Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease. The immune system attacks the body’s cell and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidney and nervous system.
Over 40 different genes predispose to SLE.
Characterized by remission and exacerbation.
SLE still an enigma where both patient and health care professionals are blind and do more harm than saving the patient. Hope in future anything can be done to save the patient from the grip of lupus,
SLE still an enigma where both patient and health care professionals are blind and do more harm than saving the patient. Hope in future anything can be done to save the patient from the grip of lupus,
Cutaneous involvement is very common in the different types of vasculitis. Skin lesions may be the only manifestation or may occur in the context of systemic disease
Cutaneous involvement is very common in the different types of vasculitis. Skin lesions may be the only manifestation or may occur in the context of systemic disease
Systemic lupus erythematosus (SLE) is an autoimmune disease. In this disease, the immune system of the body mistakenly attacks healthy tissue. It can affect the skin, joints, kidneys, brain, and other organs.
This presentation encompasses SLE as well Lupus nephritis,Antiphospholipid Syndrome and other special situation related to SLE such as SLE and Pregnancy.
Rheumatoid arthritis is the most common systemic inflammatory disease characterized by symmetrical joint involvement.
Extraarticular involvement, including rheumatoid nodules, vasculitis, eye inflammation, neurologic dysfunction, cardiopulmonary disease, lymphadenopathy, and splenomegaly, can be manifestations of the disease.
Koroner Arter Hastalığında DNA Metilasyonunun RolüBardia Farivar
Epigenetik çalışmalar, koroner arter hastalığında (CAD) DNA metilasyonunu tanımlamıştır. Kritik genlerin hücresel düzeyde CAD'ye neden olarak nasıl etkileştiği hala bilinmemektedir.
DNA metilasyonunun keşfi, araştırmacıları genomik kodlama ve hastalık fenotipindeki ilişkileri araştırmaya teşvik etti.
Son yirmi yılda, DNA metilasyonu ve CAD gelişimi arasındaki ilişki hakkında birçok bulgu olmuştur.
Kritik genlerin DNA metilasyonunun, homosistein, Alu ve Long interspersed nuclear elements 1 (LINE-1) DNA metilasyonu dahil, CAD sırasında önemli ölçüde değiştiği bulunmuştur.
The Janus kinase/Signal transducers and activators of transcription (JAK/STAT)
JAK/STAT sinyal yolu sitokinler tarafından aktifleştirilir.
Hücre farklılaşması
Hücre çoğalması
Hücre göçü
Apoptoz gibi birçok hücresel sürecin yönetilmesinde rolü vardır.
İmmün sistemi gelişimi, süt oluşumu, adipogenez gibi işlemlerin gerçekleştirilmesinde bu sinyal yolunun rolü vardır.
DNA'nın yapısı ve görevi hakkındaki önemli bilgiler 1947 yılında biyokimyacı Erwin Chargaff tarafından açıklanmıştır.
Chargaff, farklı organizmaların DNA'larının baz bileşimlerini analiz etmiş ve DNA'daki baz dizisinin türden türe değiştiğini keşfetmiştir.
1953 yılında Amerikalı James Watson ve İngiliz Francis Crick yaptıkları deneylerden ve önceki bulgularından yararlanarak DNA'nın çift sarmal modelini oluşturmuşlardır.
Mikroorganizmalar arasında gen klonlamasında bir çok aracı moleküllerden yararlanılmaktadır.
Gen klonlamasında kullanılan aracı moleküllere vektör denir.
Vektörler konakçı organizmada, bağımsız olarak replikasyon gösterirler.
Sistemik Lupus Eritematozus sebebi bilinmeyen cilt, eklem, böbrek, kalp zarı (perikard), akciğer zarı (plevra) gibi birçok doku ve organ iltihabına bağlı çok sayıda bulgularla giden, değişik seyir gösteren ve bağışıklık sisteminin bozuk çalışması sonucu ortaya çıkan bir hastalıktır.
DNA Mikroarray 'DNA çip', 'gen çip', 'genom çip', veya gen-dizi olarak da bilinen, genellikle her biri bir geni temsil eden, ayrı ayrı küçük katı yüzeye kovalent bağlarla sabitlenmiş binlerce DNA parçacıkları toplusudur.
Her DNA spotlarda 10-12 mol spesifik DNA sekansları bulunur ki “probe” yada oligo olarak bilinirler.
Bilinen her gen veya probe çip üzerinde belirli bir noktada oturup ve değişen seviyelerde floresan aktivitesi, dahil edilen genetik materyalde değişen seviyelerde gen aktivitesi gösterir.
Prob sekanslara bağlanan floresan etiketli hedef diziler bir sinyal üretir.
The Role of DNA Methylation in Coronary Artery DiseaseBardia Farivar
Epigenetic studies have identified DNA methylation in coronary artery disease (CAD). How the critical genes interact at the cellular level to cause CAD is still unknown. The discovery of DNA methylation inspired researchers to explore relationships in genomic coding and disease phenotype. In the past two decades, there have been many findings regarding the relationship between DNA methylation and CAD development, and the DNA methylation of critical genes have been found to be significantly changed during CAD, including DNA methylation at homocysteine, Alu and long Interspersed Element 1 (LINE-1) repetitive elements.
The Rho family of GTPases is a family of small G proteins. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
2. Systemic Lupus Erythematosus
Introduction:
• Systemic Lupus Erythematosus (SLE) is a complex
autoimmune disease.
• The immune system attacks the body’s cell and
tissue, resulting in inflammation and tissue
damage.
• SLE can affect any part of the body, but most often
harms the heart, joints, skin, lungs, blood vessels,
liver, kidney and nervous system.
• Over 40 different genes predispose to SLE.
• Characterized by remission and exacerbation.
3. Prevalence:
• Almost 90% of all cases occur in women.
• Overall, SLE affects women eight times more often
than it does men.
• At age 30 years, the ratio of women to men is 10:1.
• The ratio at age 65 years apeears to be about 3:1.
• The prevalence rate among women between age 15
and 64 years is 1 in 700 women.
• Symptoms usually appear between age 15 and 25
years.
• The prevalence in the general population is about
1 in 1000.
4. Etiology:
• The etiology of SLE is currently unknown, but there are environmental and
genetic factors involved.
• Environmental factors: Ultraviolet light (UVB), Alfalfa sprouts, chemicals
(hydrazines), drugs, infections (parvovirus, CMV, HCV), smoking.
• B cell activation results in increased autoantibody (mainly IgG) production to
a variety (up to 2000) of antigens (nuclear, cytoplasmic and plasma
membrane), e.g. ANA, anti-dsDNA.
• Development of and failure to remove immune complexes from the circulations
leads to deposition of complexes in the tissue, causing vasculitis and disease
(e.g. glomerulonephritis). Immune complexes also from in situ, e.g. kidney
glomerular basement membrane.
• There is impaired T cell regulation of the immune response.
5. Etiology:
Genetics
• Research indicates SLE may have a genetic link.
SLE does run in families, but no single causal gene
has been identified. Instead, multiple genes appear
to influence a person's chance of developing lupus
when triggered by environmental factors. HLA
class I, class II, and class III genes are associated
with SLE, but only classes I and II contribute
independently to increased risk of SLE.
6. Signs & Symptoms
Achy joints / arthralgia – 95%
Fever of more than 38 ℃ - 90%
Arthritis / swollen joints – 90%
Prolonged or extreme fatigue – 81%
Skin rashes – 74%
Anemia – 71%
Kidney involvement – 50%
Pain in the chest on deep breathing / pleurisy – 45%
Butterfly-shaped rash across the cheeks and nose – 42%
Sun or light sensitivity / photosensitivity – 30%
Hair loss / alopecia – 27%
Abnormal blood clotting problems – 20%
Fingers turning white and or blue in the cold – 17%
Mouth or nose ulcers – 12%
8. Pathophysiology:
• The plasma cells are producing antibodies that
are specific for self proteins, namely ds-DNA.
• Overactive B-cells. Estrogen is a stimulator of
B-cell activity.
• Suppressed regulatory function in T-cells. Lack
of T-cells.
• IL-10, also a B-cell stimulator is in high
concentration in lupus patient serum. High
concentration linked to cell damage caused by
inflammation.
• Increased levels of Ca2+ leads to spontaneous
apoptosis.
9. Pathophysiology:
• RBCs lack CR1 receptor. Decreasing the affective
removal of complexes.
• IgG is the most “pathogenic” because it forms
intermediate sized complexes that can get to the small
places and block them.
• DNA is the main antigen for which antibodies are
formed.
• Extracellular DNA has an affinity for basement
membrane where it is bound by auto-antibodies.
Classical thickening of the basement membrane.
10. Prognosis:
• Usually chronic, relapsing and unpredictable.
Remissions may last for years.
• If initial acute phase is controlled, even if very
severe (with cerebral thrombosis or severe
nephritis), the long-term prognosis is usually good.
• The 10-year survival in most developed countries
is >95%. Improved prognosis is in part due to
earlier diagnosis and more effective therapies.
• More severe disease requires more toxic therapies,
which increase risk of mortality.
11. Treatment goals
Use the drug with the:
Least side effects
Lowest dose to control disease
Long term damage prevention
• Mild disease: Avoid steroids
• Severe disease: Aggressive treatment
14. NSAIDs
Non SteroidalAnti-inflammatory Drugs
• Use to control mild to moderate pain, fever and
various inflammatory conditions, such as
rheumatoid arthritis and osteoarthritis.
• NSAIDs have analgesic, antipyretic and anti-
inflammatory properties.
• Analgesic and anti-inflammatory effects are due to
inhibition of prostaglandin synthesis.
• Antipyretic action is due to vasodilation and
inhibition of prostaglandin synthesis in the CNS.
15. NSAIDs
Non SteroidalAnti-inflammatory Drugs
• Use cautiously inpatients with a history of bleeding
disorders, GI bleeding and severe hepatic, renal or
cardiovascular disease.
• Safe use in pregnancy is not established and in
general should be avoided during the second half of
the pregnancy.
• NSAIDs prolong bleeding time and potentiate the
effect of warfarin, thrombolytic agents, some
cephalosporins and anti-platelet agents.
• NSAIDs may also decrease response to diuretics or
antihypertensive therapy.
17. CORTICOSTEROIDS
• Used for anti-inflammatory or immunosuppressant effects.
• Dosage of prednisone depends on the condition being treated and the
response of the patient.
• After a satisfactory response is obtained, dosage should be decreased
in small decrements to the lowest level that maintains an adequate
clinical response.
• The activity of the drug is thought to result at least in part from
binding with a steroid receptor.
18. CORTICOSTEROIDS
• Corticosteroids decrease inflammation by stabilizing leukocyte
lysosomal membranes, preventing release of destructive acid
hydrolases from leukocytes; inhibiting macrophage accumulation in
inflamed areas, reducing leukocyte adhesion to capillary
endothelium, reducing capillary wall permeability and edema
formation, decreasing complement components, antagonizing
histamine activity and release of kinin from substrates, reducing
fibroblast proliferation, collagen deposition and subsequent scar
tissue formation, and possibly by other mechanisms as yet unknown.
20. ANTI-MALARIALS
• Hydroxychloroquine is used as an adjunct
to corticosteroid therapy in the treatment
of discoid lupus erythematosus.
• Hydroxychloroquine therapy may lead to
the regression of skin lesions of discoid or
systemic lupus erythematosus and may
also have a beneficial effect in patients with
systemic lupus erythematosus in whom
arthritis is a prominent feature.
21. SOURCES
• Handout on Health: Systemic Lupus Erythematosus". www.niams.nih.gov. 12 June 2016
• https://en.wikipedia.org/wiki/Systemic_lupus_erythematosus
