This document analyzes the potential risks of prion disease from Pfizer's COVID-19 mRNA vaccine. It finds that the vaccine's RNA sequence contains elements that could cause the proteins TDP-43 and FUS to take pathological prion confirmations linked to neurodegenerative diseases. Additionally, the vaccine-generated spike protein's interaction with ACE2 may release zinc ions in cells, which are known to facilitate prion formation of TDP-43. The author believes these factors indicate the vaccine was approved prematurely without adequate safety testing and could potentially cause more harm than the disease it is meant to prevent.
1) There are various COVID-19 vaccine candidates that target different parts of the SARS-CoV-2 spike protein, including the full-length spike protein and the receptor-binding domain (RBD).
2) Some research suggests the RBD may be a better target than the full-length spike protein due to concerns that the full protein could potentially cause immune pathology.
3) However, vaccines using the full-length spike protein aim to better mimic the natural infection and induce antibodies and T-cell responses against multiple epitopes on the spike protein.
- The mRNA-1273 vaccine induced robust antibody and neutralizing responses against SARS-CoV-2 in all participants after the first dose. A second dose led to even stronger responses, especially in the 100 μg and 250 μg groups. Systemic side effects were mostly mild or moderate. This interim report provides support for mRNA-1273 as a promising COVID-19 vaccine candidate warranting further development and evaluation.
Using SARS-CoV-2 to Teach Physiology and ScienceInsideScientific
Join Dr. Dee Silverthorn for a discussion on how the sudden appearance of the global pandemic of COVID-19 provides a unique opportunity to show students science in action as researchers and healthcare professionals around the world scramble to understand the virus and its effects on the human body. This is the third webinar in this 4-part series on how science education has evolved in the face of new challenges.
In this presentation we will explore some of the ways that we can incorporate today’s headlines into the curriculum by discussing the pathophysiology and pathology of SARS-CoV-2 infection and how it demonstrates the integration of body function across multiple organ systems. Teaching about the coronavirus pandemic also creates opportunities to have students critically analyze research studies and news reports, and to discuss ethical dilemmas such as the distribution of limited amounts of vaccine or the triage of critically ill patients when lifesaving equipment is limited. One important goal of teaching about the coronavirus pandemic is to have students learn to tolerate ambiguity, and to understand that today’s “facts” are simply our best models of what we know.
SARS-COV-2 detection by RNAscope technologyCOSMO BIO
Intense efforts are underway to develop vaccines for SARS-CoV-2. Many focus on the spike protein, which helps the virus infiltrate cells by binding the ACE2 receptor. Alternative strategies could block this receptor to prevent viral entry. Studies found SARS-CoV-2 uses ACE2 and TMPRSS2 for entry, and may use CD147 as an additional receptor. RNAscope probes target viral RNA to detect replication and localization in tissues, and can identify ACE2, TMPRSS2, and immune cell markers in infected samples.
The document summarizes the roles of ACE2 and TMPRSS2 in SARS-CoV-2 infection. It explains that SARS-CoV-2 relies on ACE2 to enter cells and TMPRSS2 to prime the viral spike protein. ACE2 catalyzes the conversion of angiotensin II and plays a role in cardiovascular function, while TMPRSS2 is involved in prostate cancer. It further discusses how ADAM17 and TMPRSS2 regulate ACE2 shedding and how their balance may impact viral infection and constitute a natural barrier when more shedding occurs. The document provides references for further reading on related topics like genetic influences on COVID-19 susceptibility and severity.
1. The document discusses research into visualizing the interaction between the HIV viral envelope and capsid protein using freeze-fracture electron microscopy.
2. The goal is to better understand how the viral envelope attaches to the capsid, which could lead to methods to disrupt this process and inhibit HIV infection.
3. Introducing a premature stop codon in the Gag protein will arrest viral bud release, allowing visualization of the arrested viral buds and interaction between the envelope and capsid.
1) There are various COVID-19 vaccine candidates that target different parts of the SARS-CoV-2 spike protein, including the full-length spike protein and the receptor-binding domain (RBD).
2) Some research suggests the RBD may be a better target than the full-length spike protein due to concerns that the full protein could potentially cause immune pathology.
3) However, vaccines using the full-length spike protein aim to better mimic the natural infection and induce antibodies and T-cell responses against multiple epitopes on the spike protein.
- The mRNA-1273 vaccine induced robust antibody and neutralizing responses against SARS-CoV-2 in all participants after the first dose. A second dose led to even stronger responses, especially in the 100 μg and 250 μg groups. Systemic side effects were mostly mild or moderate. This interim report provides support for mRNA-1273 as a promising COVID-19 vaccine candidate warranting further development and evaluation.
Using SARS-CoV-2 to Teach Physiology and ScienceInsideScientific
Join Dr. Dee Silverthorn for a discussion on how the sudden appearance of the global pandemic of COVID-19 provides a unique opportunity to show students science in action as researchers and healthcare professionals around the world scramble to understand the virus and its effects on the human body. This is the third webinar in this 4-part series on how science education has evolved in the face of new challenges.
In this presentation we will explore some of the ways that we can incorporate today’s headlines into the curriculum by discussing the pathophysiology and pathology of SARS-CoV-2 infection and how it demonstrates the integration of body function across multiple organ systems. Teaching about the coronavirus pandemic also creates opportunities to have students critically analyze research studies and news reports, and to discuss ethical dilemmas such as the distribution of limited amounts of vaccine or the triage of critically ill patients when lifesaving equipment is limited. One important goal of teaching about the coronavirus pandemic is to have students learn to tolerate ambiguity, and to understand that today’s “facts” are simply our best models of what we know.
SARS-COV-2 detection by RNAscope technologyCOSMO BIO
Intense efforts are underway to develop vaccines for SARS-CoV-2. Many focus on the spike protein, which helps the virus infiltrate cells by binding the ACE2 receptor. Alternative strategies could block this receptor to prevent viral entry. Studies found SARS-CoV-2 uses ACE2 and TMPRSS2 for entry, and may use CD147 as an additional receptor. RNAscope probes target viral RNA to detect replication and localization in tissues, and can identify ACE2, TMPRSS2, and immune cell markers in infected samples.
The document summarizes the roles of ACE2 and TMPRSS2 in SARS-CoV-2 infection. It explains that SARS-CoV-2 relies on ACE2 to enter cells and TMPRSS2 to prime the viral spike protein. ACE2 catalyzes the conversion of angiotensin II and plays a role in cardiovascular function, while TMPRSS2 is involved in prostate cancer. It further discusses how ADAM17 and TMPRSS2 regulate ACE2 shedding and how their balance may impact viral infection and constitute a natural barrier when more shedding occurs. The document provides references for further reading on related topics like genetic influences on COVID-19 susceptibility and severity.
1. The document discusses research into visualizing the interaction between the HIV viral envelope and capsid protein using freeze-fracture electron microscopy.
2. The goal is to better understand how the viral envelope attaches to the capsid, which could lead to methods to disrupt this process and inhibit HIV infection.
3. Introducing a premature stop codon in the Gag protein will arrest viral bud release, allowing visualization of the arrested viral buds and interaction between the envelope and capsid.
1) SARS-CoV is a coronavirus that emerged in 2002 causing a global pandemic. Its pathogenesis involves aberrant host innate immune responses and viral antagonism of interferon signaling.
2) Models of SARS-CoV infection like human airway epithelial cultures and mouse-adapted SARS-CoV have provided insights into innate immune pathways important for controlling SARS-CoV disease.
3) SARS-CoV encodes several proteins that antagonize type I interferon induction and signaling to evade the host innate immune response, which is an important factor in SARS pathogenesis.
Gene Therapy in Heart Failure-Egyptian critical care summit 2015Dr.Mahmoud Abbas
Gene therapy and heart failure lecture presented by Professor Sherif Mokhtar at Egyptian Critical Care Summit 2015, the leading medical event and exhibition for Critical Care Medicine in Egypt
SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination I...Guy Boulianne
This document summarizes a research study that investigated how the SARS-CoV-2 spike protein affects DNA damage repair and adaptive immunity. The main findings are:
1) The SARS-CoV-2 spike protein significantly inhibited DNA damage repair in in vitro cell line experiments by impeding the recruitment of key DNA repair proteins like BRCA1 and 53BP1 to damage sites.
2) DNA damage repair is required for effective V(D)J recombination, which generates antibody diversity in B cells and T cell receptors in T cells. Inhibiting DNA damage repair could therefore impair adaptive immunity.
3) The spike protein was found to localize in the cell nucleus, where it could interfere with DNA repair
Creative Biolabs has extensive experience in coronavirus research. Provide comprehensive high-quality coronavirus (SARS-CoV-2, SARS-CoV, MERS-CoV, etc.) related services and products.
This slide provides a brief introduction to SARS-CoV-2. If you need more knowledge, products and services related to SARS-CoV-2, please follow us.
In the past 10 years, there has been tremendous progress made in the field of gene therapy. Effective
treatments of Leber congenital amaurosis, hemophilia, and spinal muscular atrophy have been largely based on
the efficiency and safety of adeno-associated vectors. Myocardial gene therapy has been tested in patients with
heart failure using adeno-associated vectors with no safety concerns but lacking clinical improvements. Cardiac
gene therapy is adapting to the new developments in vectors, delivery systems, targets, and clinical end points and
is poised for success in the near future
SARS-CoV-2 was first identified in Wuhan, China in late 2019 and has since spread to over 200 countries. It belongs to the coronavirus family and causes the disease COVID-19. The virus enters cells through the ACE2 receptor and replicates its RNA and proteins before being released to infect other cells. Potential treatment strategies include using existing antiviral drugs, developing specific drugs that target the virus genome or proteins, and enhancing immune responses. Ongoing research focuses on antibody development, diagnostic assays, vaccines, and other medical countermeasures to treat and prevent the spread of SARS-CoV-2.
Possible drugs to fight coronavirus remdesivirRami Bechara
This can be assimilated for a small literature review. Sources include research articles, news articles and pharmaceutical websites. The drug involved in Redmesivir
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerve...InsideScientific
Mice are by far the most frequently used animal for modeling disease and developing therapeutic strategies including neurointerventions. However, due to its anatomical and physiological barriers, the brain is a difficult target for delivery of therapeutic agents. Systemic administration is plagued with marginal brain accumulation and high risk of off-target side effects.
In this webinar sponsored by Scintica Instrumentation, Dr. Piotr Walczak, Dr. Mirosław Janowski and Dr. Wojciech Lesniak address this challenge and discuss why advanced imaging is essential to perform image-guided neurointerventions.
First, Dr. Janowski provides rationale as to how imaging can be used to better understand how therapeutic agents are delivered to the brain and subsequently cleared. Next, Dr. Walczak reviews methodological and technological advances for improving precision and reproducibility of brain targeting in mice based on MRI and two-photon microscopy. Finally, Dr. Lesniak presents recently-published results using ARGUS PET/CT to quantify intra-artrial delivery of antibodies, nanobodies and poly(amidoamine) dendrimers.
Key Topics Include:
- Overview of Pre-Clinical PET/CT imaging
- Examples from applications including oncology, neurology, cardiology and dynamic imaging
- An introduction to SuperArgus PET/CT and what makes it unique
To learn more, go to:
https://insidescientific.com/webinar/precision-medicine-using-pet-image-guided-neurointervention/
Chlorogenic acid may be a potent inhibitor of dimeric SARS-CoV-2 main proteas...LucyPi1
Abstract Background: Since the emergence of coronavirus disease 2019 to date, there is no available approved drug or definitive treatment for coronavirus disease 2019 viral infection, and the identification of novel hits against therapeutic targets has become a global emergency. Echinacea purpurea is a traditional herb utilized to treat cough, fever, sore throat, respiratory tract infection, and so on as an immune stimulant. In this study, in silico molecular docking approach was used to screen phytocompounds from E. purpurea against severe acute respiratory syndrome coronavirus 2 main protease 3C-like protease (3CLpro) and severe acute respiratory syndrome coronavirus main peptidase (96% sequence similarity) to blunt the viral gene expression and viral replication. Methods: Initially, we screened phytocompounds for their druggability and ADMET property. Furthermore, x-ray crystallographic structures of main proteases 3CLpro and main peptidase having Protein Data Bank ID 6LU7 and 2GTB were used as protein targets for the identification of potential drug candidates. We performed docking using AutoDock Vina by PyRx 0.8 software. BIOVIA Discovery Studio Visualizer v2019 was used to analyze ligand-protein complex. The probable protein targets of the selected compound were predicted by BindingDB (P ≥ 0.7). STRING and Kyoto Encyclopedia of Genes and Genomes pathways are utilized to identify the molecular pathways modulated by the predicted targets (FDR ≤ 0.05), and the network interaction between compounds and protein pathways was constricted by Cytoscape 3.6.1. Results: Among all the compounds, chlorogenic acid showed druggable characteristics and scored the lowest binding energy with main protease and main peptidase via interacting with active site 1 domain amino acid residues. Interestingly, chlorogenic acid interacted with Phe140 main protease 3CLpro, which is potentially involved in the dimerization. Enrichment analysis identified chlorogenic acid to modulate insulin resistance, necroptosis, interleukin-17, tumor necrosis factor signaling pathway, legionellosis, T helper 17 cell differentiation, advanced glycation end products and receptor for advanced glycation end products, mitogen-activated protein kinase, Ras, estrogen, vascular endothelial growth factor, B-cell receptor, nuclear factor kappa B, Rap1, hypoxia inducible factor-1, phosphatidylinositide 3-kinase-Akt, insulin, mechanistic target of rapamycin, p53, retinoic acid inducible gene I like receptor, and ErbB signaling pathways. Conclusion: Chlorogenic acid may act as a potent main protease 3CLpro inhibitor and may also inhibit the severe acute respiratory syndrome coronavirus 2 dimerization, viral gene expression, and replication within the lung epithelium. Chlorogenic acid may go a long way in finding one of the multipronged solutions to tackle coronavirus disease 2019 viral infection in the future.
mRNA rather than DNA may become the nucleotide framework for new classes of drugs and vaccines. Exciting preclinical results in prophylaxis and initial clinical data in oncology suggest that mRNA technology could be translated into improvements in lung cancer and other diseases.
ACE2: From Renoprotection to a Potential
Therapy for Coronavirus Infection
ACE2: From Renoprotection to a Potential
Therapy for Coronavirus Infection
by Daniel Batlle MD
RAS Inhibitors in Hypertension and Heart Failure:
TRUTHS AND MISTRUTHS
OF TREATMENT IN THE
COVID-19 ERA
by J o r d y C o h e n , M D , M S C E
From Hypertension 2020 , American Heart Association
Copy RIght to Hypertension Session 2020 in American Heart Association
This document summarizes research into developing an anti-HIV vaccine using nucleoside-modified mRNA encoding envelope proteins. Key points:
- Researchers developed mRNA vaccines optimized for protein expression by incorporating modified nucleosides, UTRs, caps, and tails to generate HIV envelope proteins.
- Mice were primed with intradermal mRNA followed by an intramuscular protein boost to achieve strong T cell and B cell responses.
- The mRNA vaccine induced high levels of IFN-γ, TNF-α, IL-2 in antigen-specific T cells and antibody titers, demonstrating the potential of nucleoside-modified mRNA vaccines for infectious diseases like HIV.
The document summarizes the structure and replication of COVID-19. It discusses that COVID-19 is caused by SARS-CoV-2, a novel coronavirus first identified in Wuhan, China in late 2019. SARS-CoV-2 has a single-stranded RNA genome and spike proteins that give it a crown-like appearance. The virus likely originated in bats and enters cells by binding to ACE2 receptors, using its spike proteins to fuse with and enter the cell membrane. It then expresses replicase proteins and uses its RNA-dependent RNA polymerase to make copies of its genome and structural proteins, assembling new virus particles that exit the cell.
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild ...Guy Boulianne
This study systematically mapped SARS-CoV-2-specific T cell responses in various groups including unexposed individuals, exposed family members, and those with acute or convalescent COVID-19. They found that:
1) Acute-phase SARS-CoV-2-specific T cells displayed an activated cytotoxic phenotype correlated with disease severity.
2) Convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype.
3) Importantly, SARS-CoV-2-specific T cells were detectable in seronegative exposed family members and those with asymptomatic/mild COVID-19, suggesting natural exposure may prevent severe COVID-19 upon
1. Professor David Baker presented on whether ocrelizumab and cladribine should be treated like alemtuzumab in terms of COVID-19 risk.
2. Alemtuzumab causes long-term CD4 and CD8 T cell depletion and is associated with an increased risk of lung infections. Cladribine and ocrelizumab do not cause similar long-term lymphopenia.
3. Cladribine maintains T cell levels within normal ranges and has minimal monitoring requirements compared to alemtuzumab which requires frequent monitoring and hospital visits due to risks of cytokine release syndrome.
About covid variants types of variants like UK, India , South Africa ,
some information about Variant of Concern and variant of interest , the about Indian variants
- Adverse event reports for the Pfizer/BioNTech COVID-19 vaccine have exceeded 146,000, more than double the reports for all of last year. Immunological adverse events are among the highest reported and may indicate pathogenic priming could be occurring.
- The Pfizer and Moderna vaccines use mRNA to produce the SARS-CoV-2 spike protein, which binds to the ACE-2 receptor. This could disrupt the renin-angiotensin-aldosterone system regulation of blood pressure and electrolyte levels, manifesting as reported adverse events. Further study is needed on potential effects, especially in vulnerable groups.
- Natural antiviral responses against SARS-CoV-2 have been demonstrated
This document discusses the potential relationship between the SARS-CoV-2 spike protein and increased risk of thrombosis (blood clots). It summarizes several studies that found:
1) The spike protein can directly activate platelets and promote blood clotting.
2) TNF, which is increased during viral infections, provides a procoagulant stimulus that may contribute to hypercoagulable states.
3) Some COVID-19 patients have developed rare cerebral venous sinus thrombosis, and the spike protein may interact with integrins to enhance viral entry and induce a procoagulant state.
This document summarizes potential dangers of COVID-19 vaccines for children aged 12-18 based on adverse event reports. It notes that:
1) Reported adverse events following vaccination are atypically high, with over 250,000 reports including 8,500 reports for children aged 12-18, of which 17% experienced cardiovascular issues.
2) The vaccines are likely causing these adverse events as over 80% of cardiovascular, neurological, and immunological issues were reported within 1 day of vaccination.
3) The vaccines may disrupt the renin-angiotensin-aldosterone system, which regulates blood pressure and electrolytes, as the spike protein binds strongly to ACE2, a key enzyme in
1) SARS-CoV is a coronavirus that emerged in 2002 causing a global pandemic. Its pathogenesis involves aberrant host innate immune responses and viral antagonism of interferon signaling.
2) Models of SARS-CoV infection like human airway epithelial cultures and mouse-adapted SARS-CoV have provided insights into innate immune pathways important for controlling SARS-CoV disease.
3) SARS-CoV encodes several proteins that antagonize type I interferon induction and signaling to evade the host innate immune response, which is an important factor in SARS pathogenesis.
Gene Therapy in Heart Failure-Egyptian critical care summit 2015Dr.Mahmoud Abbas
Gene therapy and heart failure lecture presented by Professor Sherif Mokhtar at Egyptian Critical Care Summit 2015, the leading medical event and exhibition for Critical Care Medicine in Egypt
SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination I...Guy Boulianne
This document summarizes a research study that investigated how the SARS-CoV-2 spike protein affects DNA damage repair and adaptive immunity. The main findings are:
1) The SARS-CoV-2 spike protein significantly inhibited DNA damage repair in in vitro cell line experiments by impeding the recruitment of key DNA repair proteins like BRCA1 and 53BP1 to damage sites.
2) DNA damage repair is required for effective V(D)J recombination, which generates antibody diversity in B cells and T cell receptors in T cells. Inhibiting DNA damage repair could therefore impair adaptive immunity.
3) The spike protein was found to localize in the cell nucleus, where it could interfere with DNA repair
Creative Biolabs has extensive experience in coronavirus research. Provide comprehensive high-quality coronavirus (SARS-CoV-2, SARS-CoV, MERS-CoV, etc.) related services and products.
This slide provides a brief introduction to SARS-CoV-2. If you need more knowledge, products and services related to SARS-CoV-2, please follow us.
In the past 10 years, there has been tremendous progress made in the field of gene therapy. Effective
treatments of Leber congenital amaurosis, hemophilia, and spinal muscular atrophy have been largely based on
the efficiency and safety of adeno-associated vectors. Myocardial gene therapy has been tested in patients with
heart failure using adeno-associated vectors with no safety concerns but lacking clinical improvements. Cardiac
gene therapy is adapting to the new developments in vectors, delivery systems, targets, and clinical end points and
is poised for success in the near future
SARS-CoV-2 was first identified in Wuhan, China in late 2019 and has since spread to over 200 countries. It belongs to the coronavirus family and causes the disease COVID-19. The virus enters cells through the ACE2 receptor and replicates its RNA and proteins before being released to infect other cells. Potential treatment strategies include using existing antiviral drugs, developing specific drugs that target the virus genome or proteins, and enhancing immune responses. Ongoing research focuses on antibody development, diagnostic assays, vaccines, and other medical countermeasures to treat and prevent the spread of SARS-CoV-2.
Possible drugs to fight coronavirus remdesivirRami Bechara
This can be assimilated for a small literature review. Sources include research articles, news articles and pharmaceutical websites. The drug involved in Redmesivir
A New Frontier of Precision Medicine: Using PET for Image-Guided Neurointerve...InsideScientific
Mice are by far the most frequently used animal for modeling disease and developing therapeutic strategies including neurointerventions. However, due to its anatomical and physiological barriers, the brain is a difficult target for delivery of therapeutic agents. Systemic administration is plagued with marginal brain accumulation and high risk of off-target side effects.
In this webinar sponsored by Scintica Instrumentation, Dr. Piotr Walczak, Dr. Mirosław Janowski and Dr. Wojciech Lesniak address this challenge and discuss why advanced imaging is essential to perform image-guided neurointerventions.
First, Dr. Janowski provides rationale as to how imaging can be used to better understand how therapeutic agents are delivered to the brain and subsequently cleared. Next, Dr. Walczak reviews methodological and technological advances for improving precision and reproducibility of brain targeting in mice based on MRI and two-photon microscopy. Finally, Dr. Lesniak presents recently-published results using ARGUS PET/CT to quantify intra-artrial delivery of antibodies, nanobodies and poly(amidoamine) dendrimers.
Key Topics Include:
- Overview of Pre-Clinical PET/CT imaging
- Examples from applications including oncology, neurology, cardiology and dynamic imaging
- An introduction to SuperArgus PET/CT and what makes it unique
To learn more, go to:
https://insidescientific.com/webinar/precision-medicine-using-pet-image-guided-neurointervention/
Chlorogenic acid may be a potent inhibitor of dimeric SARS-CoV-2 main proteas...LucyPi1
Abstract Background: Since the emergence of coronavirus disease 2019 to date, there is no available approved drug or definitive treatment for coronavirus disease 2019 viral infection, and the identification of novel hits against therapeutic targets has become a global emergency. Echinacea purpurea is a traditional herb utilized to treat cough, fever, sore throat, respiratory tract infection, and so on as an immune stimulant. In this study, in silico molecular docking approach was used to screen phytocompounds from E. purpurea against severe acute respiratory syndrome coronavirus 2 main protease 3C-like protease (3CLpro) and severe acute respiratory syndrome coronavirus main peptidase (96% sequence similarity) to blunt the viral gene expression and viral replication. Methods: Initially, we screened phytocompounds for their druggability and ADMET property. Furthermore, x-ray crystallographic structures of main proteases 3CLpro and main peptidase having Protein Data Bank ID 6LU7 and 2GTB were used as protein targets for the identification of potential drug candidates. We performed docking using AutoDock Vina by PyRx 0.8 software. BIOVIA Discovery Studio Visualizer v2019 was used to analyze ligand-protein complex. The probable protein targets of the selected compound were predicted by BindingDB (P ≥ 0.7). STRING and Kyoto Encyclopedia of Genes and Genomes pathways are utilized to identify the molecular pathways modulated by the predicted targets (FDR ≤ 0.05), and the network interaction between compounds and protein pathways was constricted by Cytoscape 3.6.1. Results: Among all the compounds, chlorogenic acid showed druggable characteristics and scored the lowest binding energy with main protease and main peptidase via interacting with active site 1 domain amino acid residues. Interestingly, chlorogenic acid interacted with Phe140 main protease 3CLpro, which is potentially involved in the dimerization. Enrichment analysis identified chlorogenic acid to modulate insulin resistance, necroptosis, interleukin-17, tumor necrosis factor signaling pathway, legionellosis, T helper 17 cell differentiation, advanced glycation end products and receptor for advanced glycation end products, mitogen-activated protein kinase, Ras, estrogen, vascular endothelial growth factor, B-cell receptor, nuclear factor kappa B, Rap1, hypoxia inducible factor-1, phosphatidylinositide 3-kinase-Akt, insulin, mechanistic target of rapamycin, p53, retinoic acid inducible gene I like receptor, and ErbB signaling pathways. Conclusion: Chlorogenic acid may act as a potent main protease 3CLpro inhibitor and may also inhibit the severe acute respiratory syndrome coronavirus 2 dimerization, viral gene expression, and replication within the lung epithelium. Chlorogenic acid may go a long way in finding one of the multipronged solutions to tackle coronavirus disease 2019 viral infection in the future.
mRNA rather than DNA may become the nucleotide framework for new classes of drugs and vaccines. Exciting preclinical results in prophylaxis and initial clinical data in oncology suggest that mRNA technology could be translated into improvements in lung cancer and other diseases.
ACE2: From Renoprotection to a Potential
Therapy for Coronavirus Infection
ACE2: From Renoprotection to a Potential
Therapy for Coronavirus Infection
by Daniel Batlle MD
RAS Inhibitors in Hypertension and Heart Failure:
TRUTHS AND MISTRUTHS
OF TREATMENT IN THE
COVID-19 ERA
by J o r d y C o h e n , M D , M S C E
From Hypertension 2020 , American Heart Association
Copy RIght to Hypertension Session 2020 in American Heart Association
This document summarizes research into developing an anti-HIV vaccine using nucleoside-modified mRNA encoding envelope proteins. Key points:
- Researchers developed mRNA vaccines optimized for protein expression by incorporating modified nucleosides, UTRs, caps, and tails to generate HIV envelope proteins.
- Mice were primed with intradermal mRNA followed by an intramuscular protein boost to achieve strong T cell and B cell responses.
- The mRNA vaccine induced high levels of IFN-γ, TNF-α, IL-2 in antigen-specific T cells and antibody titers, demonstrating the potential of nucleoside-modified mRNA vaccines for infectious diseases like HIV.
The document summarizes the structure and replication of COVID-19. It discusses that COVID-19 is caused by SARS-CoV-2, a novel coronavirus first identified in Wuhan, China in late 2019. SARS-CoV-2 has a single-stranded RNA genome and spike proteins that give it a crown-like appearance. The virus likely originated in bats and enters cells by binding to ACE2 receptors, using its spike proteins to fuse with and enter the cell membrane. It then expresses replicase proteins and uses its RNA-dependent RNA polymerase to make copies of its genome and structural proteins, assembling new virus particles that exit the cell.
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild ...Guy Boulianne
This study systematically mapped SARS-CoV-2-specific T cell responses in various groups including unexposed individuals, exposed family members, and those with acute or convalescent COVID-19. They found that:
1) Acute-phase SARS-CoV-2-specific T cells displayed an activated cytotoxic phenotype correlated with disease severity.
2) Convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype.
3) Importantly, SARS-CoV-2-specific T cells were detectable in seronegative exposed family members and those with asymptomatic/mild COVID-19, suggesting natural exposure may prevent severe COVID-19 upon
1. Professor David Baker presented on whether ocrelizumab and cladribine should be treated like alemtuzumab in terms of COVID-19 risk.
2. Alemtuzumab causes long-term CD4 and CD8 T cell depletion and is associated with an increased risk of lung infections. Cladribine and ocrelizumab do not cause similar long-term lymphopenia.
3. Cladribine maintains T cell levels within normal ranges and has minimal monitoring requirements compared to alemtuzumab which requires frequent monitoring and hospital visits due to risks of cytokine release syndrome.
About covid variants types of variants like UK, India , South Africa ,
some information about Variant of Concern and variant of interest , the about Indian variants
- Adverse event reports for the Pfizer/BioNTech COVID-19 vaccine have exceeded 146,000, more than double the reports for all of last year. Immunological adverse events are among the highest reported and may indicate pathogenic priming could be occurring.
- The Pfizer and Moderna vaccines use mRNA to produce the SARS-CoV-2 spike protein, which binds to the ACE-2 receptor. This could disrupt the renin-angiotensin-aldosterone system regulation of blood pressure and electrolyte levels, manifesting as reported adverse events. Further study is needed on potential effects, especially in vulnerable groups.
- Natural antiviral responses against SARS-CoV-2 have been demonstrated
This document discusses the potential relationship between the SARS-CoV-2 spike protein and increased risk of thrombosis (blood clots). It summarizes several studies that found:
1) The spike protein can directly activate platelets and promote blood clotting.
2) TNF, which is increased during viral infections, provides a procoagulant stimulus that may contribute to hypercoagulable states.
3) Some COVID-19 patients have developed rare cerebral venous sinus thrombosis, and the spike protein may interact with integrins to enhance viral entry and induce a procoagulant state.
This document summarizes potential dangers of COVID-19 vaccines for children aged 12-18 based on adverse event reports. It notes that:
1) Reported adverse events following vaccination are atypically high, with over 250,000 reports including 8,500 reports for children aged 12-18, of which 17% experienced cardiovascular issues.
2) The vaccines are likely causing these adverse events as over 80% of cardiovascular, neurological, and immunological issues were reported within 1 day of vaccination.
3) The vaccines may disrupt the renin-angiotensin-aldosterone system, which regulates blood pressure and electrolytes, as the spike protein binds strongly to ACE2, a key enzyme in
The document discusses the potential relationship between SARS-CoV-2 spike protein and increased risk of thrombosis (blood clots). It summarizes research showing the spike protein can directly activate platelets and promote blood clotting. This may explain the increased rates of thrombosis seen in severe COVID-19 cases. The spike protein's procoagulant activity is hypothesized to be a class effect of COVID-19 vaccines, and rapid development may have prevented long term safety testing needed to verify effects. Emerging evidence suggests some post-vaccination thrombosis cases have unusual features warranting further research into potential causal links between the vaccine and these rare events.
The document discusses the relationship between COVID-19 vaccines that target the full-length spike protein versus just the receptor-binding domain (RBD), and their potential relationship to procoagulant effects and rare blood clotting issues. Some key points:
- Vaccines like AstraZeneca use the full-length spike protein in viral vectors, while others just target the RBD region.
- The spike protein plays a role in viral entry and interacts with host cell receptors like ACE2. It also has glycans that help disguise the virus.
- Studies found the AstraZeneca vaccine induces cell spikes similar to SARS-CoV-2, eliciting an immune response.
-
A Possible Role of Rosmarinic Acid against CD2 Associated Protein for the Tre...YogeshIJTSRD
Multiple sclerosis is a chronic inflammatory neurodegenerative disorder which directly affects Central Nervous System CNS . People with MS suffer with an episodic reversible memory loss during the initial stages and later it leads to the neurological deterioration. Number of research and studies has been done on the natural compounds and phytochemical compounds in order to develop the particular drug for the treatment of MS in vivo andin vitro. The present study focuses on the inhibitory effect of Rosmarinic acid against the effect of CD2 Associated protein with the help of Molecular Docking. Molecular Docking basically screens the ligand and the target protein and shows the interaction between them on the basis of the minimum binding affinities and drug likeliness properties. In our research, docking was performed between CD2 Associated protein and selected ligands with the help of docking software. Ligands were selected on the basis of their minimum Binding affinities and finally by their drug likeliness properties. Rosmarinic acid BA 5.6 was the resultant ligand of our recent study. It showed the perfect interaction with CD2 Associated protein. Therefore, we may conclude that Rosmarinic acid may act as a compound which may be used as a drug for the treatment of multiple sclerosis fromfurther in vitro and in vivostudies in future. Jitin Kumar | Tejaswee Anand | Ritika Sharma | Noopur Khare | Abhimanyu Kumar Jha | Yamini Dixit "A Possible Role of Rosmarinic Acid against CD2-Associated Protein for the Treatment of Multiple Sclerosis through in Silico Approach" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd44979.pdf Paper URL: https://www.ijtsrd.com/biological-science/biotechnology/44979/a-possible-role-of-rosmarinic-acid-against-cd2associated-protein-for-the-treatment-of-multiple-sclerosis-through-in-silico-approach/jitin-kumar
Molecular mechanism prediction analysis of compound Kushen injection in the t...LucyPi1
Abstract Background: As one of the eight effective traditional Chinese medicines for the treatment of atypical pneumonia, compound Kushen injection (CKI) played an important role in combating pneumonia caused by severe acute respiratory syndrome coronavirus 2 virus in China in 2003. CKI is known to inhibit inflammation, and its main chemical components, namely matrine and oxymatrine, can promote Th cells to recognize and eliminate viruses. In this study, network pharmacology and molecular docking were used to explore the mechanisms of CKI for treating coronavirus disease 2019. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and other related literature were used to screen CKI’s active ingredients in the blood. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Swiss Target Prediction and STITCH were used to search for potential targets of the active ingredients. The “ingredient-target” network was constructed using the Cytoscape software. The STRING online database was used to construct a target protein-protein interaction network that can be visualized and analyzed using the Cytoscape software to obtain key targets. Results: Sophocarpine, sophoridine, matrine, (+)-allomatrine, AIDS211310, and sophranol were the six active ingredients. After docking the active ingredients with severe acute respiratory syndrome coronavirus 2 3CL hydrolase and angiotensin-converting enzyme 2 (ACE2), they displayed suitable affinity, which could block viral replication and its binding to ACE2. The key targets mainly involved inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Gene Ontology enrichment analysis mainly indicated the IL-6 cytokine-mediated signaling pathway and cytokine-mediated signaling pathway. The Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis mainly indicated steroid hormone biosynthesis and the TNF signaling pathway. Conclusion: The alkaloids in CKI can block viral replication and its binding to severe acute respiratory syndrome coronavirus 2 and ACE2 receptors. They regulate the IL-6-mediated signaling pathway, TNF signaling pathway, and steroid hormone biosynthesis, thereby initiating therapeutic responses against coronavirus disease 2019.
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets. Currently, there are no proven effective therapies but remdesivir shows promise based on in vitro activity. Over 300 clinical trials are investigating potential treatments including repurposed drugs like chloroquine/hydroxychloroquine and lopinavir/ritonavir. The review summarizes the mechanisms and pharmacology of select proposed treatments and provides an overview of ongoing clinical trials.
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets, including viral entry proteins and immune pathways. Several repurposed drugs are discussed, including chloroquine/hydroxychloroquine which may inhibit viral entry and immune responses. Over 300 clinical trials are investigating potential COVID-19 treatments but currently no therapies have proven effective. The most promising is remdesivir, which has strong antiviral activity but requires further clinical trial evaluation.
Список препаратів, які тестують для лікування коронавірусу24tvua
This document discusses drug repositioning strategies to identify existing approved drugs that could potentially treat COVID-19. It analyzes host cell pathways that are important for the viral life cycle of coronaviruses like SARS-CoV-2 based on previous research. The pathways analyzed include the unfolded protein response (UPR) pathway, autophagy pathway, NLRP3 inflammasome signaling pathway, and mitochondrial permeability transition pore pathway. Based on this analysis, the document identifies 97 approved drugs that modulate these pathways and could potentially be repositioned to treat COVID-19. It emphasizes the need for further preclinical testing and analysis of electronic health records to evaluate these potential drug candidates before clinical use against COVID-19.
This document reviews potential pharmacologic treatments for COVID-19. It summarizes the virology of SARS-CoV-2 and potential drug targets. It reviews the in vitro activity and clinical experiences of repurposed drugs including chloroquine/hydroxychloroquine, lopinavir/ritonavir, and umifenovir. It also discusses investigational agents such as remdesivir. Over 300 clinical trials are evaluating potential COVID-19 treatments but currently no therapies have proven effective based on randomized clinical trial data.
The document discusses potential mechanisms for human genome integration of genetic code from SARS-CoV-2 mRNA vaccines and implications for disease. It notes that while retroviral integration of viral genetic material into host DNA was previously thought impossible, it is now known that some viruses can integrate fragments through retrotransposition. The document reviews evidence that SARS-CoV-2 sequences could be reverse transcribed and integrated into the genome, potentially contributing to conditions like autoimmune diseases, cancers, and increased LINE-1 activity in younger cells. It calls for further study of potential DNA interference by mRNA vaccines and risks to public health.
Potential therapy derived from banana protein is effective against SARS-CoV-2Creative BioMart
On January 13, 2020, a paper was published online touting the creation of a possible therapy that could be used against all known strains of the flu. A week later, the first laboratory-confirmed case of SARS-CoV-2 sparked the two-and-a-half-year COVID-19 pandemic in the United States. Interestingly, before the virus temporarily halted their work, the international team of researchers for this flu paper also investigated treatments for the coronavirus.
This document reviews pathways implicated in neurodegeneration based on genome-wide association studies of Alzheimer's disease and Parkinson's disease. It discusses several intracellular pathways including apoptosis, autophagy, and mitochondrial dysfunction. Genes involved in these pathways that are associated with Alzheimer's and Parkinson's diseases are highlighted. The document also presents a conceptual model grouping these pathways into broader categories related to intracellular mechanisms, local tissue environment influences, systemic influences, and neurodevelopment and aging.
The Clinical Potential of Influencing Nrf2 Signaling in Degenerative and Immu...LifeVantage
This document discusses the potential for targeting the Nrf2 signaling pathway to treat degenerative and immunological disorders. It begins by describing the Nrf2 transcription factor and its role in regulating antioxidant and detoxification genes via the antioxidant response element. Under normal conditions Nrf2 is bound by Keap1 and targeted for degradation, but oxidative stress or electrophiles can activate Nrf2 signaling by disrupting this interaction. The document reviews studies investigating direct Nrf2 target genes and discusses evidence that imbalances in cellular redox status contribute to disease pathogenesis. It concludes that modulating Nrf2 signaling, either through activation or inhibition, offers promise as a therapeutic strategy for various disorders by restoring redox homeostasis.
The UK has identified a new variant of SARS-CoV-2 that is spreading rapidly. This variant contains multiple mutations in the spike protein, including one called N501Y that allows it to bind more tightly to human cells. Preliminary analysis suggests this variant is up to 70% more transmissible than previous variants. National public health authorities should work to identify, isolate, and contact trace cases of the new variant to stop its spread. Increased genomic surveillance is also needed to monitor the spread and effects of this and other new variants.
This document proposes using bromhexine as a prophylactic and treatment for SARS-CoV-2. Bromhexine is a mucolytic drug that selectively inhibits the protease TMPRSS2, which plays an important role in SARS-CoV-2 cell entry. The document argues that chloroquine alone may not be effective as a prophylactic. It proposes combining a less toxic derivative of chloroquine with bromhexine to block viral entry by inhibiting both the endosomal pathway and TMPRSS2. Bromhexine has safety and affordability advantages over other TMPRSS2 inhibitors and may effectively prevent SARS-CoV-2 transmission when used as a prophylactic by inhibiting viral entry
This document provides a detailed review of the outbreak of the coronavirus. It discusses the virus's genome structure, life cycle, clinical features, diagnosis, complications/fatality rates, and preventive measures. The key points are:
- Coronavirus is a large family of RNA viruses that originated in China and has become a global pandemic.
- It has a wide range of clinical presentations, from asymptomatic to multi-organ failure. Common symptoms include fever, cough, and fatigue.
- Diagnosis is made through PCR testing of respiratory samples. Complications can include pneumonia, ARDS, sepsis, and multi-organ dysfunction.
- Preventive measures focus on infection control, isolation, hand washing, and
Similar to Covid19 rna-based-vaccines-and-the-risk-of-prion-disease-1503 (20)
1) O documento discute um livro chamado "Os Protocolos dos Sábios de Sião" que supostamente revela um plano judeu para conquistar o mundo.
2) O livro gerou grande controvérsia sobre sua autenticidade e se trata de uma falsificação para promover o anti-semitismo.
3) O documento fornece contexto sobre as várias traduções e edições do livro que apareceram na Europa e nos Estados Unidos no início do século XX.
Em 6 de julho de 2022, as Pedras-Guias da Geórgia, um monumento misterioso erguido em Elberton, Geórgia em 1980, foram alvo de uma explosão que danificou parte da estrutura. O incidente está sendo investigado como um ato de terrorismo doméstico. Após a explosão, as autoridades locais decidiram demolir o que restava do monumento por motivos de segurança. O Conselho do Condado não planeja reconstruir as Pedras-Guias.
O documento descreve o monumento das Pedras Guias da Geórgia, incluindo sua estrutura, inscrições e detalhes sobre sua construção. Foi encomendado em 1979 por um homem chamado RC Christian e construído em 1980. Contém dez diretrizes gravadas em oito idiomas e características astronômicas como marcadores de solstício e equinócio. A identidade verdadeira do patrocinador permanece desconhecida.
CLUBE DA MORTE- E-BOOK GRÁTIS O INFORMANTEELIAS OMEGA
Este documento discute a Nova Ordem Mundial (NWO) e seus objetivos. A NWO é descrita como uma conspiração global orquestrada por uma poderosa elite para estabelecer um governo mundial único. O documento também discute como a NWO está ligada a uma agenda religiosa secreta para estabelecer a adoração mundial de Lúcifer.
1) O documento discute a origem dos judeus Ashkenazi e alega que eles não são geneticamente judeus, mas descendentes de czares da região de Khazaria que se converteram ao judaísmo no século 8.
2) A família Rothschild é apontada como descendente dos judeus Ashkenazi e teria obtido controle financeiro global através de mentiras e assassinatos.
3) Várias famílias reais europeias são apontadas como tendo linhagem sanguínea dos Rothschilds.
O documento lista 45 metas do Partido Comunista para dominar o mundo, incluindo capturar partidos políticos, controlar escolas e mídia, enfraquecer a cultura e moralidade, e promover a homossexualidade e desacreditar a família e a religião. Muitas dessas metas parecem ter sido alcançadas nos EUA e Brasil nos últimos 40 anos através da infiltração marxista nos três poderes e instituições.
This document discusses George Soros and his role in destabilizing nations and supporting the drug trade. It describes how Soros launches currency attacks, funds drug legalization groups, and works to undermine sovereign governments at the behest of the British oligarchy. Soros is depicted as a key operative for the "Invisible Empire" of Britain in its efforts to maintain control over drug flows and strategic resources through covert political and economic warfare.
AGENDA GLOBAL 2030- BRASIL-manual_gt-1 (1).pdfELIAS OMEGA
O documento descreve a criação e o funcionamento de comissões para implementação dos Objetivos de Desenvolvimento Sustentável no Brasil. Inicialmente apresenta a Comissão Nacional dos ODS e sua extinção. Em seguida, detalha experiências de comissões estaduais e municipais, incluindo a primeira comissão estadual criada no Maranhão.
AGENDA GLOBAL 2030-BRASIL-guia-integracao-ods-2017_red.pdfELIAS OMEGA
Este documento fornece orientações aos municípios brasileiros sobre como incorporar os Objetivos de Desenvolvimento Sustentável (ODS) da Agenda 2030 em seus planos e gestão, incluindo a elaboração do Plano Plurianual para 2018-2021. A publicação descreve uma metodologia de sete passos para essa incorporação e dedica um capítulo a cada ODS, com questões norteadoras e sugestões de ações.
MUDANÇAS CLIMATICAS E O AUMENTO DOS URSOS POLAR 2021Proceedings_of_the_First_...ELIAS OMEGA
This document is a scanned reproduction of a book from the University of California, San Diego library that was digitized by Google as part of an effort to preserve books and make their information universally accessible online. The text contains repetitions of "University of California, San Diego library" in different languages.
O documento descreve a vida e obra do historiador brasileiro Tito Lívio Ferreira. Ele foi um pesquisador prolífico da história do Brasil e desenvolveu teses controversas, como a de que o Brasil nunca foi uma colônia portuguesa. O documento também discute as origens do Reino de Portugal e sua expansão marítima no século 15, que levou à descoberta do Brasil.
O relatório analisa as urnas eletrônicas usadas na eleição presidencial de 2022 no Brasil e encontra indícios de possível irregularidade no processo. Dois pontos cruciais são: 1) Diferenças significativas nos resultados entre modelos de urna em regiões demograficamente semelhantes, com modelos não-auditados favorecendo um candidato. 2) A possível existência de pelo menos dois códigos-fonte nas urnas, levantando dúvidas sobre a segurança e transparência do sistema. Análises detalhadas em estados nordestinos most
Os Vikings no Brasil - Jacques de Mahieu.pdfELIAS OMEGA
Este documento describe los pasos para configurar una nueva red WiFi. Explica cómo conectar el enrutador a la línea telefónica, configurar la contraseña de la red y conectar dispositivos como computadoras, teléfonos y tabletas a la red recién creada.
Este capítulo discute as diferenças entre ambientalismo legítimo e ambientalismo sectário. Ambientalismo legítimo envolve a preservação da natureza para o bem-estar humano, conforme os mandamentos de Deus no Gênesio. Ambientalismo sectário, por outro lado, usa a preservação ambiental como pretexto para promover ideologias como socialismo e anticristianismo.
O documento fornece um resumo de 3 frases ou menos sobre as seguintes informações essenciais:
1) Apresenta conhecimentos básicos sobre o SARS-CoV-2, incluindo sua classificação, proteína spike, mutações e variantes.
2) Explica brevemente como as vacinas funcionam, focando na proteína spike como alvo principal.
3) Resume os principais tipos de vacinas em desenvolvimento contra a Covid-19, incluindo vacinas de vírus ativado, inativado, subunidade proteica, vet
O documento apresenta três resoluções aprovadas pelo Encontro Nacional de Direitos Humanos do PT em dezembro de 2021. A primeira resolução discute a necessidade de recuperar os direitos humanos como elemento central da agenda política do PT. A segunda resolução fala sobre o neoliberalismo como uma agenda de revogação de direitos e sobre o governo Bolsonaro como anti-direitos humanos. A terceira resolução caracteriza a gestão da pandemia no Brasil como um genocídio que violou massivamente os direitos humanos.
O documento apresenta as diretrizes e objetivos estratégicos do Programa Nacional de Direitos Humanos 3 (PNDH-3), com foco em: 1) Interação democrática entre Estado e sociedade civil; 2) Desenvolvimento e Direitos Humanos; 3) Universalizar Direitos em um Contexto de Desigualdades; 4) Segurança Pública, Acesso à Justiça e Combate à Violência; 5) Educação e Cultura em Direitos Humanos.
Este documento apresenta a biografia do autor S.E. Castan, um brasileiro que se dedicou a pesquisar os eventos da Segunda Guerra Mundial. Ele viajou extensivamente pela Europa e Américas visitando locais históricos e entrevistando pesquisadores. O livro de Castan tem como objetivo fornecer uma perspectiva alternativa sobre a guerra, mostrando o lado alemão da história que raramente é discutido.
1) O documento discute o crescente apoio público às Nações Unidas após o fim da Guerra Fria e a Guerra do Golfo, com pesquisas mostrando que mais da metade dos americanos agora apoiam a ONU.
2) No entanto, o autor argumenta que essa crescente aceitação da ONU esconde os perigos de uma transferência de poder para um governo mundial totalitário.
3) O autor vê a crescente cooperação entre os EUA e a Rússia e a transferência de poder para a ONU como passos para
A HISTÓRIA OCULTA DO EX-PRESIDENTE DO BRASIL Luiz Inácio Lula da Silva A MÃO ...ELIAS OMEGA
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2) Lula nega as acusações e alega que nunca foi dono das propriedades, mas o Ministério Público alega ter evidências de que Lula recebeu os imóveis de empreiteiras como propina;
3) As investigações fazem parte da Operação Lava Jato e também envolvem outras pessoas lig
Philippine Edukasyong Pantahanan at Pangkabuhayan (EPP) CurriculumMJDuyan
(𝐓𝐋𝐄 𝟏𝟎𝟎) (𝐋𝐞𝐬𝐬𝐨𝐧 𝟏)-𝐏𝐫𝐞𝐥𝐢𝐦𝐬
𝐃𝐢𝐬𝐜𝐮𝐬𝐬 𝐭𝐡𝐞 𝐄𝐏𝐏 𝐂𝐮𝐫𝐫𝐢𝐜𝐮𝐥𝐮𝐦 𝐢𝐧 𝐭𝐡𝐞 𝐏𝐡𝐢𝐥𝐢𝐩𝐩𝐢𝐧𝐞𝐬:
- Understand the goals and objectives of the Edukasyong Pantahanan at Pangkabuhayan (EPP) curriculum, recognizing its importance in fostering practical life skills and values among students. Students will also be able to identify the key components and subjects covered, such as agriculture, home economics, industrial arts, and information and communication technology.
𝐄𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐍𝐚𝐭𝐮𝐫𝐞 𝐚𝐧𝐝 𝐒𝐜𝐨𝐩𝐞 𝐨𝐟 𝐚𝐧 𝐄𝐧𝐭𝐫𝐞𝐩𝐫𝐞𝐧𝐞𝐮𝐫:
-Define entrepreneurship, distinguishing it from general business activities by emphasizing its focus on innovation, risk-taking, and value creation. Students will describe the characteristics and traits of successful entrepreneurs, including their roles and responsibilities, and discuss the broader economic and social impacts of entrepreneurial activities on both local and global scales.
Communicating effectively and consistently with students can help them feel at ease during their learning experience and provide the instructor with a communication trail to track the course's progress. This workshop will take you through constructing an engaging course container to facilitate effective communication.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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This document provides an overview of wound healing, its functions, stages, mechanisms, factors affecting it, and complications.
A wound is a break in the integrity of the skin or tissues, which may be associated with disruption of the structure and function.
Healing is the body’s response to injury in an attempt to restore normal structure and functions.
Healing can occur in two ways: Regeneration and Repair
There are 4 phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. This document also describes the mechanism of wound healing. Factors that affect healing include infection, uncontrolled diabetes, poor nutrition, age, anemia, the presence of foreign bodies, etc.
Complications of wound healing like infection, hyperpigmentation of scar, contractures, and keloid formation.
1. Volume 5 | Issue 1 | 1 of 3
Microbiol Infect Dis, 2021
COVID-19 RNA Based Vaccines and the Risk of Prion Disease
Classen Immunotherapies, Inc., 3637 Rockdale Road, Manchester,
MD 21102, E-mail: classen@vaccines.net.
J. Bart Classen, MD*
Citation: Classen JB. COVID-19 RNA Based Vaccines and the Risk of Prion Disease. Microbiol Infect Dis. 2021; 5(1): 1-3.
Research Article
ABSTRACT
Development of new vaccine technology has been plagued with problems in the past. The current RNA based SARS-
CoV-2 vaccines were approved in the US using an emergency order without extensive long term safety testing. In
this paper the Pfizer COVID-19 vaccine was evaluated for the potential to induce prion-based disease in vaccine
recipients. The RNA sequence of the vaccine as well as the spike protein target interaction were analyzed for the
potential to convert intracellular RNA binding proteins TAR DNA binding protein (TDP-43) and Fused in Sarcoma
(FUS) into their pathologic prion conformations. The results indicate that the vaccine RNA has specific sequences
that may induce TDP-43 and FUS to fold into their pathologic prion confirmations. In the current analysis a total
of sixteen UG tandem repeats (ΨGΨG) were identified and additional UG (ΨG) rich sequences were identified. Two
GGΨA sequences were found. Potential G Quadruplex sequences are possibly present but a more sophisticated
computer program is needed to verify these. Furthermore, the spike protein, created by the translation of the vaccine
RNA, binds angiotensin converting enzyme 2 (ACE2), a zinc containing enzyme. This interaction has the potential
to increase intracellular zinc. Zinc ions have been shown to cause the transformation of TDP-43 to its pathologic
prion configuration. The folding of TDP-43 and FUS into their pathologic prion confirmations is known to cause
ALS, front temporal lobar degeneration, Alzheimer’s disease and other neurological degenerative diseases. The
enclosed finding as well as additional potential risks leads the author to believe that regulatory approval of the
RNA based vaccines for SARS-CoV-2 was premature and that the vaccine may cause much more harm than benefit.
*
Correspondence:
J. Bart Classen, MD, Classen Immunotherapies, Inc., 3637
Rockdale Road, Manchester, MD 21102, Tel: 410-377-8526.
Received: 27 December 2020; Accepted: 18 January 2021
Microbiology & Infectious Diseases
ISSN 2639-9458
Keywords
COVID-19, Vaccines, Diabetes, Immunity.
Introduction
Vaccines have been found to cause a host of chronic, late developing
adverse events. Some adverse events like type 1 diabetes may not
occur until 3-4 years after a vaccine is administered [1]. In the
example of type 1 diabetes the frequency of cases of adverse events
may surpass the frequency of cases of severe infectious disease
the vaccine was designed to prevent. Given that type 1 diabetes is
only one of many immune mediated diseases potentially caused by
vaccines, chronic late occurring adverse events are a serious public
health issue.
The advent of new vaccine technology creates new potential
mechanisms of vaccine adverse events. For example, the first
killed polio vaccine actually caused polio in recipients because
the up scaled manufacturing process did not effectively kill
the polio virus before it was injected into patients. RNA based
vaccines offers special risks of inducing specific adverse events.
One such potential adverse event is prion based diseases caused
by activation of intrinsic proteins to form prions. A wealth of
knowledge has been published on a class of RNA binding proteins
shown to participating in causing a number of neurological
diseases including Alzheimer’s disease and ALS. TDP-43 and
FUS are among the best studied of these proteins [2].
The Pfizer RNA based COVID-19 vaccine was approved by the
US FDA under an emergency use authorization without long term
safety data. Because of concerns about the safety of this vaccine a
study was performed to determine if the vaccine could potentially
induce prion based disease.
Methods
Pfizer’s RNA based vaccine against COVID-19 was evaluated for
the potential to convert TDP-43 and or FUS to their prion based
2. Volume 5 | Issue 1 | 2 of 3
Microbiol Infect Dis, 2021
disease causing states. The vaccine RNA was analyzed for the
presence of sequences that can activate TDP-43 and FUS. The
interaction of the transcribed spike protein with its target was
analyzed to determine if this action could also activate TDP-43
and FUS.
Results
Analysis of the Pfizer vaccine against COVID-19 identified two
potentialriskfactorsforinducingpriondiseaseishumans.TheRNA
sequence in the vaccine [3] contains sequences believed to induce
TDP-43 and FUS to aggregate in their prion based conformation
leading to the development of common neurodegerative diseases.
In particular it has been shown that RNA sequences GGUA [4],
UG rich sequences [5], UG tandem repeats [6], and G Quadruplex
sequences [7], have increased affinity to bind TDP-43 and or
FUS and may cause TDP-43 or FUS to take their pathologic
configurations in the cytoplasm. In the current analysis a total of
sixteen UG tandem repeats (ΨGΨG) were identified and additional
UG (ΨG) rich sequences were identified. Two GGΨA sequences
were found. G Quadruplex sequences are possibly present but
sophisticated computer programs are needed to verify these.
The spike protein encoded by the vaccine binds angiotensin
converting enzyme 2 (ACE2), an enzyme which contains zinc
molecules [8]. The binding of spike protein to ACE2 has the
potential to release the zinc molecule, an ion that causes TDP-43
to assume its pathologic prion transformation [9].
Discussion
There is an old saying in medicine that “the cure may be worse
than the disease.” The phrase can be applied to vaccines. In the
current paper the concern is raised that the RNA based COVID
vaccines have the potential to cause more disease than the
epidemic of COVID-19. This paper focuses on a novel potential
adverse event mechanism causing prion disease which could be
even more common and debilitating than the viral infection the
vaccine is designed to prevent. While this paper focuses on one
potential adverse event there are multiple other potential fatal
adverse events as discussed below.
Over the last two decades there has been a concern among certain
scientists that prions could be used as bioweapons. More recently
there has been a concern that ubiquitous intracellular molecules
could be activated to cause prion disease including Alzheimer’s
disease, ALS and other neurodegenerative diseases. This concern
originates due to potential for misuse of research data on the
mechanisms by which certain RNA binding proteins like TDP-43,
FUS and others can be activated to form disease causing prions.
The fact that this research, which could be used for bioweapons
development, is funded by private organizations including the Bill
and Melinda Gates Foundation, and Ellison Medical Foundation
[2] without national/international oversight is also a concern.
In the past, for example, there were prohibitions for publishing
information pertaining to construction of nuclear bombs.
Published data has shown that there are several different factors that
can contribute to the conversion of certain RNA binding proteins
including TDP-43, FUS and related molecules to their pathologic
states. These RNA binding proteins have many functions and are
found in both the nucleus and the cytoplasm.These binding proteins
have amino acid regions, binding motifs that bind specific RNA
sequences. Binding to certain RNA sequences when the proteins
are in the cytoplasm is believed to causes the molecules to fold in
certain ways leading to pathologic aggregation and prion formation
in the cytoplasm [2]. The current analysis indicates Pfizer's RNA
based COVID-19 vaccine contains many of these RNA sequences
that have been shown to have high affinity for TDP-43 or FUS
and have the potential to induce chronic degenerative neurological
diseases.
Zinc binding to the RNA recognition motif of TDP-43 is another
mechanism leading to formation of amyloid like aggregations [9].
The viral spike protein, coded by the vaccine RNAsequence, binds
ACE2 an enzyme containing zinc molecules [8]. This interaction
has the potential to increase intracellular zinc levels leading to
prion disease. The initial binding could be between spike proteins
on the surface of the cell transfected by the vaccine and ACE2
on the surface of an adjacent cell. The resulting complex may
become internalized. Alternatively, the interaction could initially
take place in the cytoplasm of a cell that makesACE2 and has been
transfected with the vaccine RNA coding for the spike protein.
The interaction is quite concerning given the belief that the virus
causing COVID-19, SARS-CoV-2, is a bioweapon [10,11] and it
is possible that the viral spike protein may have been designed to
cause prion disease.
Another related concern is that the Pfizer vaccine uses a unique
RNA nucleoside 1-methyl-3'-pseudouridylyl (Ψ). According to
FDA briefing documents, this nucleoside was chosen to reduce
activation of the innate immune system [12]. RNA molecules
containing this nucleoside will undoubtedly have altered binding
[13]. Unfortunately, the effect on TDP-43, FUS and other RNA
binding proteins is not published. The use of this nucleoside in
a vaccine can potentially enhance the binding affinity of RNA
sequences capable of causing TDP-43 and FUS to assume toxic
configurations.
There are many other potential adverse events that can be induced
by the novel RNA based vaccines against COVID-19. The vaccine
places a novel molecule, spike protein, in/on the surface of host
cells. This spike protein is a potential receptor for another possibly
novel infectious agent. If those who argue that the COVID-19 is
actually a bioweapon are correct, then a second potentially more
dangerous virus may be released that binds spike protein found on
the host cells of vaccine recipients. Data is not publicly available
to provide information on how long the vaccine RNA is translated
in the vaccine recipient and how long after translation the spike
protein will be present in the recipient’s cells. Such studies
pertaining to in vivo expression will be complex and challenging.
Genetic diversity protects species from mass casualties caused by
infectious agents. One individual may be killed by a virus while