This document summarizes a presentation on microRNAs in Alzheimer's disease and depression. It discusses the characteristics of microRNAs, how they can serve as biomarkers for disease detection and monitoring treatment response. Specific microRNAs have been associated with Alzheimer's and depression. The presentation analyzes studies identifying microRNAs differently expressed in Alzheimer's and depression. A few microRNAs are common to both conditions. Gene therapy techniques can be used to up-regulate or down-regulate microRNA levels as a potential treatment approach.
Circulating Biomarkers for Alzheimer's Disease: Neurodegenerative Disorders ...QIAGEN
Alzheimer's disease (AD) is a complex neurodegenerative disorder. Circulating miRNAs hold great promise in the discovery of non-invasive and novel biomarkers for AD diagnosis and prognosis. This slideshow presents the role of miRNAs in AD and details current progress in biomarker discovery. Various tools for pathway-focused and genome-wide miRNA expression profiling, miRNA functional studies and target identification are also included.
Circulating Biomarkers for Alzheimer's Disease: Neurodegenerative Disorders ...QIAGEN
Alzheimer's disease (AD) is a complex neurodegenerative disorder. Circulating miRNAs hold great promise in the discovery of non-invasive and novel biomarkers for AD diagnosis and prognosis. This slideshow presents the role of miRNAs in AD and details current progress in biomarker discovery. Various tools for pathway-focused and genome-wide miRNA expression profiling, miRNA functional studies and target identification are also included.
Chair, Suresh S. Ramalingam, MD, FACP, FASCO, Arjun Balar, MD, Yelena Janjigian, MD, and Kurt A. Schalper, MD, PhD, prepared useful Practice Aids pertaining to PD-L1 expression as a cancer immunotherapy biomarker for this CME/MOC/CC activity titled “Revisiting PD-L1 as an Immunotherapy Biomarker Across the Cancer Spectrum: Current and Emerging Standards of Testing, Scoring, and Assay Interpretation.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC information, and to apply for credit, please visit us at http://bit.ly/3t8iyRk. CME/MOC/CC credit will be available until May 10, 2022.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
DNA Methylation: An Essential Element in Epigenetics Facts and TechnologiesQIAGEN
Check out this slide deck from Dr. Thorsten Singer and Dr. Ralf Peist to learn about DNA methylation in epigenetics, from its significance in cancer to strategies for studying it.
Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell and repeatedly divides to become a cancer
Chemicals which initiate this process is called chemical carcinogens
Chemicals which increase the effectiveness of carcinogens is called co-carcinogens
REGULATORY BACKGROUND
ROLE OF PROTO-ONCOGENES AND TUMOR SUPPRESSOR GENES
ACTIVATION OF PROTO ONCOGENES
OXIDATIVE STRESS IN CARCINOGENESIS
OECD guidelines
451- Carcinogenecity studies
453- Combined chronic toxicity/carcinogenecity
ICH guidelines
S1A- Guideline on the need for carcinogenicity studies of
pharmaceuticals
S1B- Testing for carcinogenicity of pharmaceuticals
S1C- Dose selection for carcinogenicity studies of pharmaceuticals
This ppt will provide you a brief yet effective information about major types of biomarkers, their definitions, their significance in disease dignosis & treatment, how they are being & are developed to be used as an effective dignostic tool for Cancer & their other future implications in other fields of medicine.
The Journal of Biomarkers in Drug Development (JBDD) promotes rigorous research that makes a significant contribution in advancing knowledge for Biomarkers in Drug Development. JBDD includes all major themes pertaining to Biomarkers used in Drug Development.
Chair, Suresh S. Ramalingam, MD, FACP, FASCO, Arjun Balar, MD, Yelena Janjigian, MD, and Kurt A. Schalper, MD, PhD, prepared useful Practice Aids pertaining to PD-L1 expression as a cancer immunotherapy biomarker for this CME/MOC/CC activity titled “Revisiting PD-L1 as an Immunotherapy Biomarker Across the Cancer Spectrum: Current and Emerging Standards of Testing, Scoring, and Assay Interpretation.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/CC information, and to apply for credit, please visit us at http://bit.ly/3t8iyRk. CME/MOC/CC credit will be available until May 10, 2022.
I have described in this presentation the critical points in the maturation of small non-coding RNA especially miRNA and its role in the development and diagnosis of specific psychiatric disorders
DNA Methylation: An Essential Element in Epigenetics Facts and TechnologiesQIAGEN
Check out this slide deck from Dr. Thorsten Singer and Dr. Ralf Peist to learn about DNA methylation in epigenetics, from its significance in cancer to strategies for studying it.
Carcinogenesis refers to the process by which a normal cell is transformed into a malignant cell and repeatedly divides to become a cancer
Chemicals which initiate this process is called chemical carcinogens
Chemicals which increase the effectiveness of carcinogens is called co-carcinogens
REGULATORY BACKGROUND
ROLE OF PROTO-ONCOGENES AND TUMOR SUPPRESSOR GENES
ACTIVATION OF PROTO ONCOGENES
OXIDATIVE STRESS IN CARCINOGENESIS
OECD guidelines
451- Carcinogenecity studies
453- Combined chronic toxicity/carcinogenecity
ICH guidelines
S1A- Guideline on the need for carcinogenicity studies of
pharmaceuticals
S1B- Testing for carcinogenicity of pharmaceuticals
S1C- Dose selection for carcinogenicity studies of pharmaceuticals
This ppt will provide you a brief yet effective information about major types of biomarkers, their definitions, their significance in disease dignosis & treatment, how they are being & are developed to be used as an effective dignostic tool for Cancer & their other future implications in other fields of medicine.
The Journal of Biomarkers in Drug Development (JBDD) promotes rigorous research that makes a significant contribution in advancing knowledge for Biomarkers in Drug Development. JBDD includes all major themes pertaining to Biomarkers used in Drug Development.
Parkinson's disease is a brain disorder that progressively affects a person’s ability to control body movements, caused by a disorder of certain nerve cells in a part of the brain that produces dopamine, a chemical messenger the brain uses to help direct and control body movement.
Early diagnosis of Parkinson's disease gives you the best chance of a longer, healthier life. This presentation covers the information about biomarkers for Parkinson Diseases which include biological, physiological and imagine candidate / novel biomarkers.
Biomarkers to Diagnostics – The Essential Tool Box for Drug Development - Presentation delivered by Johan Luthman, Vice President, Neuroscience Clinical Development, Eisai Pharmaceuticals at the marcus evans Evolution Summit Fall 2015 in Las Vegas
Development of multivariate classifiers in cancerMehis Pold
Short presentation about development of multivariate classifiers to predict chemotherapy treatment responses in breast cancer. The steps of workflow are briefly described and the results indicate that expression data on micro-RNA in breast cancer alone are not sufficient to predict treatment responses.
Integrative transcriptomics to study non-coding RNA functionsMaté Ongenaert
Integrative transcriptomics to study non-coding RNA functions
by dr. ir. Pieter Mestdagh - Center for Medical Genetics, Ghent University
Over the last years, non-coding RNAs (e.g. microRNAs and long non-coding RNAs) have emerged as an important layer of the transcriptome. In order to elucidate their function in disease biology, multiple tools have been developed, ranging from miRNA target prediction algorithms to the more advanced integrative genomics approaches. Through the combination of multiple layers of information, integrative genomics allows a more accurate and comprehensive assessment of non-coding RNA functions in human disease. In this presentation, I will discuss different approaches on how to combine multi-level transcriptome data in order to functionally characterize non-coding RNA networks.
Preface about Anti Aging Medicine, what it is, who can do this practice and how is the latest news. From many sources, including Prof. dr. Wimpie Pangkahila, Sp.And ' lecturers. Presented in Update Pain Management, Nutrition and Stem Cell Therapy, Solo Paragon, 6th Feb 2016
microRNA for Clinical Research and Tumor AnalysisBioGenex
The discovery of microRNAs [miRNAs] has been one of the defining developments in cancer biology over the past decade. miRNAs are short, single stranded 20-22 nucleotide long, non-coding RNAs that regulate gene expression and have fundamental roles in Cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. BioGenex solved the inherent difficulties in visualizing miRNAs in spatial context by using a propriety technology to synthesize modified, high-affinity oligonucleotides, labelling miRNA probes with multiple reporter molecules and developing a fully-integrated miRNA-ISH workflow solution allowing high throughput analysis of miRNA in the spatial context.
Acute myeloid leukemia (AML) is a hematopoietic malignancy with a dismal outcome in the majority of cases. A detailed understanding of the genetic alterations and gene expression changes that contribute to its pathogenesis is important to improve prognostication, disease monitoring, and therapy. In this context, leukemia-associated misexpression of microRNAs (miRNAs) has been studied, but no coherent picture has emerged yet, thus warranting further investigations.
Total RNA Discovery for RNA Biomarker Development WebinarQIAGEN
Precision medicine offers to transform patient care by targeting treatment to those with most to gain. To date the most significant advances have been at the level of DNA, for example, the use of somatic DNA alterations as diagnostic indicators of disease and for prediction of pharmacodynamic response. Development of RNA expression signatures as biomarkers has been more problematic. While RNA expression analysis has yielded valuable insights into the biological mechanisms of disease, RNA is a more unstable molecule than DNA, and more easily damaged or degraded during sample collection and isolation. In addition, RNA levels are inherently dynamic and gene expression signatures are extraordinarily complex. Recently, much progress has been made in identifying key changes in gene expression in cancer and other diseases, as well as identifying expression signatures in circulating nucleic acid that have the potential to be developed into diagnostic and prognostic indicators.
definition of epidemiological marker-specific protein polysacharide antigens,genes incase of microorganisms...its features,different types like phenotypic and genotypic markers i,its description,uses,advantages,disadvantages etc.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
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Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journey
I International Symposium: Neurobiology and Biomarkers of Brain Aging - Micro rna in alzheimer’s disease and depression
1. I International Symposium: Neurobiology and
Biomarkers of Brain Aging
microRNA in Alzheimer’s
disease and Depression
Ana Paula Mendes Silva
PhD Student
Federal University of Minas Gerais/UFMG
4. CChhaarraacctteerriissttiiccss
• Non-coding RNA
microRNAs mediate translational
repression or mRNA degradation
Post-transcriptional regulators of
miRNA
gene expression
18 to 22-nucleotides-long
http://mcb.berkeley.edu/labs/he/Research.htm
5. CChhaarraacctteerriissttiiccss
• Horizontal transfer of miRNAs by secreted
extracellular vesicles -> intercellular communication
http://circres.ahajournals.org/content/110/3/483.abstract
7. CChhaarraacctteerriissttiiccss
• Multiple miRNAs can target a single mRNA
BDNF
hsa-miR-1
hsa-miR-206
hsa-miR-613
hsa-miR-374b
hsa-miR-495
hsa-miR-374a
hsa-miR-10a
hsa-miR-195
hsa-miR-216b
hsa-miR-30a
hsa-miR-122
hsa-miR-30e
8. BBiioommaarrkkeerr
• A biomarker is an indicator of physiological,
biochemical, or anatomic parameter
BBiioollooggiiccaall
PPrroocceesssseess
PPaatthhoollooggiiccaall
PPrroocceesssseess
TThheerraappeeuuttiicc
IInntteerrvveennttiioonn
9. BBiioommaarrkkeerr
• miRNAs can be detected in serum, plasma,
urine, and other biological fluids
BBooddyy fflluuiiddss
http://www.mirnabodymap.org/
10. AAddvvaannttaaggeess
• Horizontal transfer
• Mature miRNAs are small
• Stable molecules
• Resistant to RNA degradation
• Highly conserved among species
11. AAddvvaannttaaggeess
• Differentiate pathological phenotypes
• Provide global disease profiling
• Customized treatment:
– Rational drug selection
– Monitoring response to therapy
• Alows risk stratification
12. AAddvvaannttaaggeess
• Noninvasive biomarkers
• Positive impact in patient comfort
• Can lead to early diagnosis
• Might enable patients to get on treatments earlier,
preventing the devastanting effects of the disease
13. LLiimmiittaattiioonnss
• It’s difficult to measure each miRNA contribuition to
the disease
• The presence of miRNAs in collected fluids does not
directly indicate the inhibition of the translation
process
• Although a single miRNA can be related with multiple
pathologies it does not necessarily mean that all the
pathologies will develop
• Cost of miRNA sequencing
14. MMeettaa--aannaallyyssiiss
Identification
Records identified through Web of
Science
Included Eligibility Screening
Records identified through
PubMed
Records identified through
SCOPUS
416 AD Records after duplicates removed
176 D
Records screened
Records excluded, because they
are reviews, book chapters,
meeting abstracts, descriptive
articles and protocoll papers
Full-text articles accessed for
eligibility
Full-text articles excluded,
miRNAs specific cell, animal
models and the blood of
patients under the use of any
medication
6 AD Studies included in the analysis
3 D
http://www.prisma-statement.org/
15. AAllzzhheeiimmeerr’’ss ddiisseeaassee
• The words used to identify the miRNAs related to
Alzheimer’s were: Alzheimer’s disease and miRNA.
• Identified 77 miRNAs differently expressed
21. MMaajjoorr ddeepprreessssiivvee ddiissoorrddeerr
• The words used to identify the miRNAs related to
depression were: (Major depressive disorder OR
depressive disorder OR depression) and miRNA.
• Identified 32 miRNAs differently expressed
26. GGeennee tthheerraappyy
• Up-regulated
– AntagomiRs are used to decrease the levels of
specific miRNA
• Down-regulated
– Synthetic RNAs or siRNAs are used to increase the
levels
Good Afternoon. My name is Ana Paula, I am a phD student in Molecular Medicine at the Federal University of Minas Gerais.
First of all, I’d like to say it’s na honor to be invited to presente and discuss the work i have been developing. It’s na excelente opportunity for us to exchange and work on some of our doubts.
The objetive of my work is to identify the miRNAs that assist in early diagnosis of Alzheimer’s disease and major depressive disorder.
In this way, It’s importante for us to know about characteristics of this molecule.
Why is it considered a biomarker?
What are the advantages and limitations of using miRNAs?
Which one of them, among those already found in literature, are related to Alzheimer’s disease and depression.
And what is the future perspective of miRNas gene therapy?
In order to have na overview of the process involving the study of biomarkers, as seen in miRNAs, we need to understand their biogenesis mechanisms.
Where in the body can they be foud?
What are the extraction methodologies used?
Which tools are available and how should they be used to quantify the miRNAs expression?
What are the clinical applications of this biomarker in prognosis, diagnosis and customized gene therapy?
The miRNas are included in the non-coding RNA Family. Each molecule is 18 to 22 nucleotides-long.
Their basic function is to regulate mRNA repression and degradation throughout the translation process. Repression works as a physical mechanism to prevent association between rRNA and mRNA. The complete degradation happens after the complex RISC associates itself with the mRNA. Thus, the miRNAs are post-transcriptional regulators of gene expression.
The miRNAs are produced inside the cellular nucleus. They may act on the cytoplasm of the cell that produces them. They may be transferred horizontally by exosome, microvesicles, associated to HDL or proteins such as Argonauta.
One of the most important characteristics of miRNAs is that a single miRNAs can target multiple mRNAs. A single miRNA can interfere in a variety of physiological mechanism in gene expression. Characterizing a large amount of regulation mechanisms, involving multiple genes. As an example we have the miRNA-130b which is involved in the regulation of 116 genes and we also have the let-7d which is involved in the regulation of 126 genes.
In adition, different miRNAs can have the same target mRNA, which makes the global study of the regulation mechanism in a single gene even more complex. Differently from when we study the relationship between a mRNA and its gene.
Therefore, the miRNAs could indicate the regulation genes, possibly associated with diseases such as Alzheimer’s and depression.
a single mRNA can also be targeted by multiple miRNAs
One of the most important characteristics of miRNAs is that a single miRNAs can target multiple mRNAs. A single miRNA can interfere in a variety of physiological mechanism in gene expression. Characterizing a large amount of regulation mechanisms, involving multiple genes. As an example we have the miRNA-130b which is involved in the regulation of 116 genes and we also have the let-7d which is involved in the regulation of 126 genes.
In adition, different miRNAs can have the same target mRNA, which makes the global study of the regulation mechanism in a single gene even more complex. Differently from when we study the relationship between a mRNA and its gene.
Therefore, the miRNAs could indicate the regulation genes, possibly associated with diseases such as Alzheimer’s and depression.
a single mRNA can also be targeted by multiple miRNAs
A biomarker is an indicator of physiological, biochemical, or anatomic parameter. And that can objectively be measured in normal biologic processes, pathological processes, or responses to a therapeutic intervention. The extraction and quantifying process of biomarkers should be easy and guaranteed. Thus, the employ of miRNAs as a biomarker of these diseases.
miRNAs can be easily detected and extract from serum, plasma, urine, and other biological fluids.
And according to literature, they may be associated with many diseases such as cancer and neurodegenerative processes.
Considering all of characteristics discussed, we are able to list the advantages and limitations of using miRNAs to identify diseases.
The most relevant advantages when comparing miRNAs to proteins and mRNAs are:
It is easiers to transfer miRNAs horizontally, which alows the gathering of miRNAs from cells or fluid that are not directly related to a pathology, avoiding the necessity of biopsis.
They are small molecules
miRNAs have more stability, since they are transported inside microvesicles or associated with proteins. Thus, they are more resistant to RNA degradation.
Furthermore their molecules have a high rate of conservation among species, making them easier to study, even in animal models.
They assist in defferentiating the methabolic process of diseases thathave the same pathological phenotype and that are not necessarily regulated by the same miRNAs or genes.
Once we identify the miRNAs involved in the pathology, we may characterize the global regulation profile of the disease.
It alows a customized treatment, based on the individual profile of the pathology, alowing the selection of specific drugs and the monitoring of the therapy results.
By doing this they diminsh the necessity of biopsis made from affected tissue.
It’s a non-invasive biomarker for the diagnosis of many neurodegenerative diseases.
It contributes positively for the wellbeing of the patient.
The early diagnosis is possible through the identification of the target miRNAs in body fluids. Thus, there is no need to wait for the disease to evolve before satrting treatment.
These biomarkers prevent the worst effects of the disease, effects such as massive cell death.
It’s difficult to measured the individual miRNA contribution in the development of the disease. Because there are many genes involved in the pathology and many miRNAs regulate a single gene.
The presence of miRNAs in collected fluid does not directly indicate the inhibition of the translation process.
Although a single miRNA can be related with multiple pathologies it does not necessarily mean that all the pathologies will develop.
The cost of miRNA’s sequencing is still too high to be done in laboratorial scale.
In order to understand the regulation mechanisms of gene expression in Alzheimer’s disease and depression we performed a meta-analysis following the parameters of prisma guidelines. We aimed to identify the miRNAs, which have already been described in literature, that are involved in both pathologies,.
Initially we used specific key – words to identify records in databases such as Web of Science, Pubmed and SCOPUS.
Finally, we collected only the miRNAs data with p-value under 5% and fold change greater than 1.5.
The words used to identify the miRNAs related to Alzheimer’s were: Alzheimer’s disease and miRNA.
Through the identification of six studies we found 77 miRNAs express themselves differently in elder patients with Alzheimer than when compared to normal patients. Which are listed in the chart below.
The words used to identify the miRNAs related to depression were: (Major depressive disorder OR depressive disorder OR depression) and miRNA.
We identified of 3 studies and found 32 miRNAs expressed differently in elder patients with depression when compared to normal patients. They are related in the chart below.
Individually, eachone acts upon the gene expression of 2000 to 8000 genes. Being that of all of these genes, 155 of them are regulated by 8 miRNAs in common.
The network between these 155 genes shows us how complex the gene regulation is.
Antagomirs relacionados aos miRNAs -> down-regulated
Utilização de miRNas -> up-regulated
I hope i was able to show you how my work is importante and i hope to be able to answer to the following questions