This document discusses non-coding RNAs (ncRNAs) as potential targets for drug discovery. It begins by defining ncRNAs and describing their types and functions. Several types of ncRNAs are involved in diseases like cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are discussed in more detail, including their biogenesis, mechanisms of action, and roles in various diseases. The role of ncRNA in regulating immune signaling pathways during Mycobacterium tuberculosis infection is also covered. Finally, the potential for using miRNAs as diagnostic and therapeutic markers is presented.
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
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.
This slide is about the basics of mRNA-based therapy. The content includes: definition of mRNA, timeline of mRNA therapeutics, action mechanism and development strategies of mRNA drugs, therapeutic mRNA applications, and the related services provided by Creative Biolabs.
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
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of specific mRNA molecules. Two types of small ribonucleic acid (RNA) molecules – microRNA (miRNA) and small interfering RNA (siRNA) – are central to RNA interference.
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.
This slide is about the basics of mRNA-based therapy. The content includes: definition of mRNA, timeline of mRNA therapeutics, action mechanism and development strategies of mRNA drugs, therapeutic mRNA applications, and the related services provided by Creative Biolabs.
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.
Follow us on: Pinterest
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
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.
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
3. ncRNA a transcriptional junk?
Though 80% of the human genome is
transcribed into RNA, majority of RNA
lacks protein coding potential.
Non coding RNA- RNA molecule that
functions without being translated into a
protein.
Initially considered as “Transcriptional
noise”, “Junk DNA”, “Dark genomic
matter”
Research in the past two decades has
provided convincing evidence favouring
biological roles for different types of
ncRNA in various diseases.
3
Bernard et al. Molecular biotechnology.2010
DNA RNA PROTEIN
Translation
Transcription
4. Types of ncRNA
4
Genome
Tanscriptome
Non coding
RNAs
(>80%)
Coding
RNAs
(<3%) mRNA Proteins
ncRNA
Regulatory
Small
ncRNAs(<200nt)
Long
ncRNAs(>200nt)
House
keeping
rRNA, tRNA
snRNA, snoRNA
5. Function category Role Functions
Protein synthesis
tRNA Transport of amino acids to ribosomes
rRNA Constituent of ribosomes
Transcriptional
modification, DNA
replication
snoRNA rRNA modification
snRNA Pre-mRNA splicing, rRNA processing
Regulation of gene
expression
miRNA Modulate the post-transcriptional gene expression by binding to specific
mRNA
siRNA Repress the gene expression after transcription(RNA interference)
piRNA Inhibits the function of transposon through PIWI protein
xiRNA Inactivate an X chromosome
pRNA Mediate transcriptional gene silencing and activation
lincRNA Repress the transcriptome response depend on p53
tiRNA Regulation of transcription by targeting epigenetic silencing complexes
circRNA Act as miR sponge
5
6. ncRNA- Role in disease
• ncRNA have significant role in various
physiological and pathological processes.
• Differential expression of miRNA result in
either upregulation or downregulation of
their targets
• Interact with DNA, RNA or proteins to
modulate cellular process
• Potential to regulate various diseases like
cancer, neuro-degenerative, infectious,
autoimmune diseases and many more.
6
Dysregulation of miRNA is
by;
Downregulation of miRNA
expression due to mutation or
transcriptional downregulation
Overexpression of miRNA
Mutation in 3’UTR of
mRNA affect miRNA binding
site
Mutation in mRNA itself
7. miRNA
RNA induced silencing complex(RISC)
complex targets the mRNA transcript
based on sequence complementarity b/w
miRNA sequence and 3’ UTR of target
mRNA.
Binding leads to mRNA degradation if
homology b/w miRNA and mRNA is
extensive.
If less, deadenylation followed by
translation prevention.
Endogenous single-stranded
sncRNA that are 18-25 nt in
length
7
Winter et al. Nat Cell Biol. 11,2009
miR biogenesis and action
8. miRNA and Cancer
• miRNA binds to 3’UTR of target genes that regulates
the cellular processes like apoptosis, cell cycle,
development, differentiation and metabolism.
• Cancer associated miR are either tumor-suppressor or
oncogenic.
• Therapeutic strategies that modulate the expression of
miRNAs in tumor acts by replenishing endogenously
depleted miRNAs(mimics) or inhibiting overexpressed
miRNA through inhibitors usually by Oligonucleotide
based approach.
• miR-7 mediated downregulation of Pak1 inhibits the
progression of breast cancer
8
Tumor-suppressor miR
• miR-34a
• miR-145
• let-7 family
Oncogenic miR
• miR-21
• miR-155
miR-200c
10. lncRNA RNA polymerase II
transcripts lacks an ORF
and are >200 nucleotides
Mechanism of actions
Types of lncRNA
10
Uchida and Dimmeler. Circ Res.2015 X Zhang. Biorg Chem;92.2019
12. Role of ncRNA in regulation of immune response
to mycobacterium tuberculosis
Differential expression of miRs upon infection with M.tb regulates host
signalling pathways linked to inflammation, autophagy, apoptosis and
polarization of macrophages.
M.tb utilize host miR to promote pathogenicity.
Host-induced miR augment antibacterial processes.
Targeting miR is an emerging option for host-directed therapies.
In TB, the host-pathogen interaction impacts processes such as;
Apoptosis
Autophagy
Cytokine production
macrophage polarization
12
Therapeutic exploration
• Manipulation of apoptosis by miRNA
agonists/antagonists
• miRNA-directed therapeutics to augment
autophagy
• Inflammatory response in macrophages
can be regulated by targeting miRNAs
which interfere with pathways linked to
macrophage polarization
13. miRNA-mediated Regulation of phagocytosis
During infection of macrophages with M.tb there is an increase in miR-
142-3p which directly targets N-wiskott-Aldrich syndrome protein (N-
WASp) to inhibit actin assembly
miRNA –mediated regulation of autophagy
Downregulation of Ca2+ by miR-27a-targets the Ca2+ transporter, voltage-
dependent calcium channel subunit alpha2delta to limit Ca2+ entry into the
cytoplasm-inhibits autophagy promoting survival of M.tb in
macrophages.
13
14. miRNA as diagnostic and therapeutic markers
• Examining miRNA profile in TB patients prior to and following
treatment. A Change is associated with therapeutic response.
• miR profile in serum can be used as a biomarker for diagnosis(eg. miR
125a-5p elevated in Tb, miR-16 decrease in MDT)
14
Exosomal miR
as diagnostic
marker
• miR-484
• miR-425
• miR-96-3-p
15. Function ncRNA Actions
Etiology
miR 155-5p
miR 29-3p
Inhibition of innate immunity
miR 20b-5p
miR 21-5p
Suppression of inflammation
miR 125 a-3p
miR 144-5p
Inhibition of phagosome maturation and
autophagy
miR 155-5p
miR 582-5p
Apoptosis inhibition
Diagnosis
miR 17-5p
miR 20b-5p
Upregulation in TB patients
miR 320-a
miR 22-3p
Downregulation
Treatment
lncRNAs NEAT 1
lncRNAs NEAT 2
Downregulation during drug treatment, linked
with disease improvement
15
16. REFERENCES
1. Almatroudi A et al. Non-Coding RNAs in Tuberculosis Epidemiology: Platforms
and Approaches for Investigating the Genome's Dark Matter. Int J Mol Sci. 2022.
2. Singh et al. Role of various non-coding RNAs in EMT, cancer and metastasis:
Recent trends and future prospective. Adv in cancer biology-metastasis;4:2022.
3. X. Zhang et al. The role of long noncoding RNA in major human disease.
Bioorganic chemistry;92.2019.
4. Toden et al. Non-coding RNAs and potential therapeutic targeting in cancer;
Biochim Biophys Acta Rev Cancer;1875(1).2021.
5. Palazzo AF and Lee ES. Non-coding RNA: What is functional and what is junk?;
Frontiers in genetics.2015.
6. Wei Li et al. the roles of host noncoding RNAs in mycobacterium tuberculosis
infection; Front.Immunol. May 2021.
16
17. • 7. Miura, Shiori & Himaki, Takehiro & Takahashi, Junko & Iwahashi, Hitoshi.the
role of transcriptomics: physiological equivalence based on gene expression
profiles. Reviews in Agricultural Science.2017
• 8. Winter, J., Jung, S., Keller, S. et al. Many roads to maturity: microRNA
biogenesis pathways and their regulation. Nat Cell Biol 11, 228–234 (2009)
17