Antisense oligonucleotides are short strands of nucleic acids that bind to messenger RNA (mRNA) and inhibit gene expression. There are three main approaches for antisense oligonucleotides based on their ability to activate RNase H enzyme and resist nucleases. Antisense oligonucleotides show potential for treating various diseases like cancer, neurological disorders, and viral infections by hybridizing to target mRNA. However, challenges remain around protecting the oligonucleotides from degradation and improving cellular uptake and target specificity. Overall, antisense technology provides a novel approach for modulating gene expression and developing new therapies.
Introduction
ZNF structure and classification
ZNF’s molecular functions
Physiological role of ZNFs
Role of ZNFs in diseases
Role of ZNFs in neurodegenerative diseases
The above presentation consist of the definition of microarray, brief history, general principle of the same, the type of scanner that are used to read or to scan the microarray , type of DNA microarray and finally its various apliccation including the role of DNA microaarray in drug discovery.
molecular docking its types and de novo drug design and application and softw...GAUTAM KHUNE
This ppt deals with all the aspects related to molecular docking ,its types(rigid ,flexible and manual) and screening based on it and also deals with de novo drug design , various softwares available for docking methodologies and applications for molecular docking in new drug design
Introduction
ZNF structure and classification
ZNF’s molecular functions
Physiological role of ZNFs
Role of ZNFs in diseases
Role of ZNFs in neurodegenerative diseases
The above presentation consist of the definition of microarray, brief history, general principle of the same, the type of scanner that are used to read or to scan the microarray , type of DNA microarray and finally its various apliccation including the role of DNA microaarray in drug discovery.
molecular docking its types and de novo drug design and application and softw...GAUTAM KHUNE
This ppt deals with all the aspects related to molecular docking ,its types(rigid ,flexible and manual) and screening based on it and also deals with de novo drug design , various softwares available for docking methodologies and applications for molecular docking in new drug design
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
ZNF or Zinc Finger proteins
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold.
A genome is an organism’s complete set of DNA or complete genetic makeup, The entire DNA complement. It describes the identity and the sequence of genes of an organism.
Genomics is the study of entire genomes(structure, function, evolution, mapping, and editing of genomes)
Executing the sequencing and analysis of entire human genome enables more rapid and effective identification of disease associated genes and provide drug companies with pre validated targets.
Proteomics is the systematic high-throughput separation and characterization of proteins within biological systems./ large scale study of protein and their functions.
Proteomics measures protein expression directly, not via gene expression, thus achieving better accuracy. Current work uses 2-dimensional polyacrylamide gel electrophoresis(2D- PAGE) and mass spectrometry.
New separation and characterization technologies, such as protein microarray and high throughput chromatography are being developed.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
ZNF or Zinc Finger proteins
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold.
A genome is an organism’s complete set of DNA or complete genetic makeup, The entire DNA complement. It describes the identity and the sequence of genes of an organism.
Genomics is the study of entire genomes(structure, function, evolution, mapping, and editing of genomes)
Executing the sequencing and analysis of entire human genome enables more rapid and effective identification of disease associated genes and provide drug companies with pre validated targets.
Proteomics is the systematic high-throughput separation and characterization of proteins within biological systems./ large scale study of protein and their functions.
Proteomics measures protein expression directly, not via gene expression, thus achieving better accuracy. Current work uses 2-dimensional polyacrylamide gel electrophoresis(2D- PAGE) and mass spectrometry.
New separation and characterization technologies, such as protein microarray and high throughput chromatography are being developed.
The basic aspects of drug discovery starts from target discovery and validation further going to lead identification and optimization. In this particular slide discussion is regarding the target discovery and the tools that have been utilized in this process.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Oligonucleotide therapy - Oligonucleotide-based gene therapy (OGT) is a varia...Tripura University
Oligonucleotides are short DNA or RNA molecules, or oligomers, that have a wide range of applications in genetic testing, research, and forensics. Oligonucleotide therapy is a type of gene therapy that uses short synthetic DNA, RNA, or their chemical analogs to inactivate specific RNA or DNA targets.
HERE PRESENTS AN OLIGONUCLEOTIDE THERAPY, ITS INTRODUCTION TO OLIGONUCLEOTIDE, ITS TECHNIQUES, DEVELOPED METHODS AND THEIR APP,LICATIONS IN PHARMACEUTICAL ARE HERE DISCUSSED IN DETAIL
Antisense oligonucleotides
Antisense therapy is a form of treatment that uses antisense oligonucleotides to target messenger RNA.
(AS ONs) are synthetic DNA oligomers that hybridize to a target RNA in a sequence-specific manner. They have successfully been employed to inhibit gene expression, modulate splicing of a precursor messenger RNA, or inactivate microRNAs.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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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!
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
3. INTRODUCTION
“Antisense technology is a tool that is used for the Inhibition of gene
expression. ”
Antisense therapy is a form of treatment for genetic disorders or infections.
When the genetic sequence of a particular gene is known to be causative of
a particular disease, it is possible to synthesize a strand of nucleic acid
(DNA, RNA or a chemical analogue) that will bind to the messenger
RNA (mRNA) produced by that gene and inactivate it, effectively turning
that gene "off".
This is because mRNA has to be single stranded for it to be translated.
Alternatively, the strand might be targeted to bind a splicing site on pre-
mRNA and modify the exon content of an mRNA.
4. BASIC CONCEPT
The two complementary strands of double-stranded DNA (dsDNA) are usually
differentiated as the "sense" strand and the "antisense" strand. The DNA sense
strand looks like the messenger RNA (mRNA) the DNA sense strand itself is not
used to make protein by the cell. It is the DNA antisense strand which serves as the
source for the protein code, because, with bases complementary to the DNA sense
strand, it is used as a template for the mRNA. Since transcription results in an RNA
product complementary to the DNA template strand, the mRNA is complementary
to the DNA antisense strand. The mRNA is what is used for annulation (protein
synthesis). Hence, a base triplet 3'-TAC-5' in the DNA antisense strand can be used
as a template which will result in an 5'-AUG-3' base triplet in mRNA.
5. ANTISENSE OLIGONUCLEOTIDE
The concept of antisense oligonucleotide gene silencing was first
introduced in 1978 when Stephenson and Zamecnik (1978) used an
antisense oligonucleotide to stop viral replication in cell culture.
An antisense oligonucleotide is a single strand of nucleic acid or nucleic
acid analogs, most often an oligodeoxyribonucleotide, usually 15–20
nucleotides in length with sequence complementary to a specific target
mRNA.
The antisense oligonucleotide and target mRNA bind together via Watson–
Crick base pairing, and this hybridization leads to reduced levels of
translation of the target transcript.
7. MECHANISM
In this technique, Short segments of single stranded
RNA are introduced.
These oligonucleotides are complementary to the
mRNA, which physically bind to the mRNA.
So , they block the expression of particular gene.
In case of viruses, antisense oligonucleotides inhibit
viral replication with blocking expression of integrated
proviral genes.
Usually consist of 15–20 nucleotides.
8. Translation of mRNA may be blocked by two possible mechanisms
These are:-
1] by base specific hybridization – which prevents access by
translation machinery i.e. Hybridization arrest”.
2] by forming RNA/DNA duplex which is recognized by nuclease
RNaseH , specific or digesting RNA in an RNA/DNA duplex.
RNaseH is a non-specific endonuclease, catalyzes the cleavage of
RNA via hydrolytic mechanism.
RNaseH has ribonuclease activity cleaves the 3’-O-P bond of RNA
in a DNA/RNA duplex.
10. APPROACHES
The antisense technology can be modified in THREE
modes because of chemical modifications of the
oligonucleotides.
These modes are due to activation of RNaseH and
internucleotides linkages which do not activate enzyme.
11. 1st approach
The antisense oligonucleotides binds the target sequence causing
both “hybridisation arrest ” and “RNaseH activation”.
2nd approach
Translation arrest but they do not activate enzyme RNaseH.
Resistance against nucleuses enzyme.
eg. Oligoribonucleotides
3rd approach
It combines features of both previous approaches.
“Hybridisation arrest ” and “RNaseH activation”.
Resistance against nucleuses enzyme.
13. RNase H appears to be a ubiquitous
enzyme in eukaryotes and bacteria.
The antisense oligonucleotide
(typically a deoxyribonucleotide)
binds the target RNA to form the
heteroduplex substrate.
RNase H binds via its binding domain
at the 3′ antisense oligonucleotide/5′
RNA pole and cleaves the target RNA
approximately 7 base pairs from its
binding site.
The target mRNA is degraded,
whereas the antisense oligonucleotide
remains intact, allowing it to form
another heteroduplex substrate for
induction of RNase H cleavage.
14. 30,000
10,000
500
50
1-5
Human genome ∼
Profiling to determine
expressed genes
Profiling to determine genes
upregulated in disease
Bioinformatics
Antisense technology
Target genes
Figure : Diagramatic representation of the role of
antisense technology in drug discovery.
15. POTENTIAL ADVANTAGES
Oligonucleotides are manufactured quickly I.e.
within a week.
Sensitivity of therapy can be easily measured.
Potential to produce longer lasting responses.
Potential for enhanced binding affinity to target.
16. LIMITATIONS
Antisense agents have to be protected against
nucleolytic attack.
Large doses are required for therapeutic
response.
The difficulty in directing to a particular cells.
The half-life in plasma is short.
17. APPLICATION
Antisense oligonucleotide therapy
1. Oncology
2. CVS & CNS therapeutics
3. As antiviral and antibacterial agent.
4. Inflammation therapeutics
Other disease states like:
1. Diabetes
2. Amyotrophic lateral sclerosis(ALS)
3. Duchene muscular dystrophy
4. Asthma
5. Hair loss.
20. REFERENSES
http://en.wikipedia.org/wiki/Antisense_the
rapy
“Antisense oligonucleotid technologies in drug discovery” Tarek Aboul- Fadl
Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy,
Assiut University, Assiut 71526, Egypt.
“Antisense Oligonucleotide: Basic Concept and its Therapeutic Application”,
Dr Bharti Bhandari, Dr Deepti Chopra, Dr Neeta Wardhan, 1Department of
Physiology, AIIMS, Jodhpur, 2Department of Pharmacology, HIMSR,
JamiaHamdard, Department of Pharmacology, UCMS, Delhi, respectively.
Journal of Research in Pharmaceutical Science Volume 2 ~ Issue 3 (2014)
pp: 01-13
“Antisense technologies Improvement through novel chemical modifications”
Jens Kurreck Institut fu¨r Chemie-Biochemie, Freie Universita¨t Berlin,
Germany.