1. The document discusses research into how inhibition of TXNRD or SOD1 can overcome resistance to β-lapachone that is mediated by NRF2. Stable cell lines were generated for experiments using lentiviral transduction.
2. Western blot and fluorescence techniques were used to analyze protein expression and localization. Nuclear isolation was also utilized. Results showed that overexpression of KEAP1 or NRF2 led to resistance to β-lapachone. Silencing NRF2 reduced this resistance.
3. Depletion of catalase did not affect β-lapachone sensitivity, but inhibition of TXNRD with auranofin increased DNA damage and cell death in response to β-lap
Nrf2 Transcription Factor- Nuclear Factor- Erythroid 2 related factor)PHARMA IQ EDUCATION
1. Nrf2- transcription factor
2. Reactive Oxygen Species
3. Free Radicals
4. Antioxidant Defence Mechanism
5. Function of Nrf2 receptor
6. Protein structural domain of Nrf2
7. Protein structural domain of Keap1
8. Physiological Role pf Nrf2
9.
THANK YOU
brief overview on oligonucleotide, oligonucleoside and its application in medicine. given the basic knowledge as well about the DNA and its composition.
Nrf2 Transcription Factor- Nuclear Factor- Erythroid 2 related factor)PHARMA IQ EDUCATION
1. Nrf2- transcription factor
2. Reactive Oxygen Species
3. Free Radicals
4. Antioxidant Defence Mechanism
5. Function of Nrf2 receptor
6. Protein structural domain of Nrf2
7. Protein structural domain of Keap1
8. Physiological Role pf Nrf2
9.
THANK YOU
brief overview on oligonucleotide, oligonucleoside and its application in medicine. given the basic knowledge as well about the DNA and its composition.
RNAi is a highly specific post-transcriptional gene silencing process, a powerful tool for functional genomics. This guide includes protocol reviews, handy tips and troubleshooting help.
This course required us to present an article which prof gave us randomly. And my article is a review paper related to TLR signaling! I upload here just hope that it can be useful for someone who is interested in this approach for studyding TLR signaling dynamics based on Synthetic ligands!
Many thanks for your look at my presentation and leave some comments if I got mistakes inside!
RNAi is a highly specific post-transcriptional gene silencing process, a powerful tool for functional genomics. This guide includes protocol reviews, handy tips and troubleshooting help.
This course required us to present an article which prof gave us randomly. And my article is a review paper related to TLR signaling! I upload here just hope that it can be useful for someone who is interested in this approach for studyding TLR signaling dynamics based on Synthetic ligands!
Many thanks for your look at my presentation and leave some comments if I got mistakes inside!
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!
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
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
- 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
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Seminario Biologia molecular
1. 1
María Alejandra Alvarez Betin
Third semester of Medicine
Universidad Pontificia Bolivariana.
Teacher: Lina Maria Martinez Sanchez.
2. Introduction
NRF2: protein that controls the way in which certain
genes are expressed, acts as the primary cellular barrier
against the harmful effects of oxidative stress by
regulating the expression of cytoprotective genes when
it is next to Protein 1 associated with EACH similar to
Kelch
β- LAPACHONE: is an ortho naphthoquinone, with
potential antineoplastic and radiosensitizing activity, is
bioactivated creating a oxidoreduction that generates
high levels of superoxide.
2
3. Introduction
TXNRD: Thioredoxin reductase is a major
antioxidant and redox regulator in mammalian
cells, it has roles in preventing and
promoting/sustaining cancer.
SOD1: this gene provides instructions for
making the enzyme superoxide dismutase.
This enzyme attaches to molecules of copper
and zinc to break down toxic, charged oxygen
molecules
6. Cell line generation
6
For what?
Used to obtain information on
the relationship between the
activation / inhibition of
different pathways and their
effects on gene expression
Basis
Stable cell lines were
generated via lentiviral
transduction for 6h. Twenty-
four hours after transduction,
puromycin was added to the
growth medium for 72 h to
select for infected cells.
KEEP1 WT
KEEP1 MUT
7. Western Blot
7
For what?
It is used to study proteins,
estimate their size and
confirm the presence of post-
translational modifications.
Basis
Electrophoresis to separate
proteins
they are transferred to the
surface of a membrane and
exposed to an antibody.
Antibody binding is detected
using a radioactive or chemical
marker.
8. Fluorescence
8
For what?
Visualization and study of the
cellular location of biological
structures that have been
previously excited
quantification and
determination of total
antioxidant capacity
Basis
distribution of an antigen in a
group of cells to direct
fluorescent markers to a
target molecule and observe
through microscopy
9. Nuclear isolation
9
For what?
studying processes such as
nuclear-cytoplasmic shuttling,
and protein–chromatin or
nuclear protein–protein
interactions in response to
diverse stimuli
Basis
dissolution of the cytoplasmic
membrane, using a low
concentration of a nonionic
detergent and fast
centrifugation steps.
10. Results
10
FIG 1
KEAP1MUT cell lines
displayed uniformly high
NQO1 protein levels,
while protein levels of
NQO1 in KEAP1WT cells
were highly variable
Overexpression of
KEAP1 C273S and
NRF2 T80K led to the
accumulation of NRF2,
which promoted
resistance to β-
lapachone exposure
NRF2 silencing by
shRNAs markedly
reduced resistance to
β-lapachone in H460
cells (KEAP1MUT)(
11. 11
Results FIG 2
A time-dependent
accumulation of DNA
damage in H1299 cells
(KEAP1 WT).
KEAP1WT cells
accumulated γ-H2AX
following β-lapachone
exposure
12. 12
Results FIG 2
In H1299 cells promoted
resistance to βlapachone-
induced DNA damage and
decreased accumulation
of ROS
shRNA-mediated silencing of
NRF2 in H460 and HCC15 cells
increased γ-H2AX levels
following β-lapachone exposure
13. 13
Results FIG 3
Depletion of catalase did not
affect the β-lapachone
sensitivity of NSCLC cells.
auranofin significantly
increased β-lapachone-
induced cell death and DNA
damage in KEAP1MUT cells
14. DISCUSSION
14
Author
D. Zhang, J. Rennhack,
E.R. Andrechek, C.E.
Rockwell, K.T. Liby,
what he said
Aberrant NRF2 activation
promotes resistance to
therapeutics that rely on
the production of ROS.
Or
A.P. Lundberg, et al Isobutyl-
deoxynyboquinone (IB-
DNQ) is being developed
for clinical use
I.S. Harris, et al KEAP1MUT cells were
highly resistant to
auranofin compared to
KEAP1WT cells
15. 15
CONCLUSION
• I think it is a good investigation because it is about helping people
with cancer which is a really degenerative and complicated disease
for the patient and their family
• I consider that with the molecular biology they could realize more
studies with organisms like the B-lapachone that are not as
invasive as chemotherapy
Para examinar la influencia de las mutaciones KEAP1 / NRF2 en la respuesta de NSCLC al tratamiento con β-lapachona, evaluamos la eficacia citotóxica de β-lapachone en un panel de dieciséis líneas celulares de NSCLC, siete de las cuales se caracterizan por la activación de mutaciones de KEAP1. Además, incluimos las células InthestudyCalu3, que albergan una variante polimórfica de NQO1 (NQO1 * 3) que da como resultado niveles de enzimas 95% más bajos.
F-determinar si la resistencia a β-lapachona dependía de NRF2, las células H1299 (KEAP1WT) se infectaron con un virus que codifica una mutación inactivadora de KEAP1 (C273S) o una mutación de ganancia de función NRF2 (T80K), para promover la activación aberrante de NRF2
De acuerdo con nuestros hallazgos anteriores, la sobreexpresión de KEAP1C273S y NRF2T80K pero no KEAP1WT condujo a la acumulación de NRF2, que promovió la resistencia a la exposición a β-lapachona
G-H460 (KEAP1 MUT) infectados con virus que codifican shRNA contra NRF2 (shNRF2) o un control de shRNA, el silenciamiento de NRF2 por shRNA redujo notablemente la resistencia a β-lapachona en células H460 (KEAP1MUT) (Fig. 1G).
A continuación, evaluamos si las células KEAP1MUT estaban protegidas contra el daño del ADN inducido por β-lapachona [27,40]. Controlamos los niveles de H2A.X fosforilado (γ-H2AX), un marcador molecular sensible del daño en el ADN. Observamos una acumulación de daño de ADN dependiente del tiempo en las células H1299 (KEAP1WT), mientras que las células A549 (KEAP1MUT) no exhibieron un aumento de γ-H2AX después del tratamiento de 2 h con β-lapachona 3 μM
E- la expresión ectópica de KEAP1C273S o NRF2T80K en células H1299(WT) también promovió la resistencia al daño del ADN inducido por βlapachona y la disminución de la acumulación de ROS (Fig. 2E, F y S2A). (E) Evaluación del daño en el ADN de las células H1299 (KEAP1 WT) infectadas con un vector vacío (Control) o un virus que codifica la expresión de NRF2 T80K. A la izquierda, las células se expusieron a 2, 3 o 4 μM de β-lapachona. Niveles de proteínas de NRF2, NQO1, H2AX total (control de carga), Tubulina (control de carga) y el marcador de daño de ADNγ-H2AX (pS139)
G-
B- Ensayos de supervivencia de un panel de células NSCLC mutantes KEAP1 infectadas con virus que codifican shRNAs contra SOD1 (1, 2) o con un shRNA de control (shCTL). Las células NSCLC se trataron con vehículo (DMSO al 0,012%) o con β-lapachona 3 μM durante 2 h. La viabilidad celular se evaluó 48 h después del tratamiento. Se realizó la prueba estadística ANOVA unidireccional, seguida de la prueba de comparación múltiple de Dunnett.
D-