Tuberculosis infection is #1 cause of death among HIV patients in the developing countries. Drugs must not only inhibit tuberculosis but also inhibit HIV infection. Sophisticated searches in #Elsevier #PathwayStudio knowledge graph revealed that several FDA approved drugs have appropriate therapeutic profile.
Pharmacokinetics And Pharmacodynamic of Biotechnology Drugs - Trilok ShahareTrilok Shahare
This document discusses the pharmacokinetics and pharmacodynamics of biotechnology drugs. It begins by defining pharmacokinetics as the study of what the body does to a drug and pharmacodynamics as the study of a drug's biochemical and physiological effects. The document then examines various types of biotechnology products including proteins and peptides, monoclonal antibodies, oligonucleotides, vaccines, and gene therapies. It provides examples and applications of each type of biotechnology drug.
Application of PROTAC In The New Field of Attenuated Vaccines.pdfDoriaFang
Researchers developed a live attenuated influenza A virus vaccine using proteolysis targeting chimera (PROTAC) technology to degrade viral proteins through the endogenous ubiquitin-proteasome system of host cells.
The development of an HIV vaccine faces significant challenges including viral diversity, establishment of viral reservoirs, and immune evasion. Current vaccine strategies aim to elicit broadly neutralizing antibodies or enhance cellular immunity through various approaches including recombinant proteins, viral vectors, and DNA vaccines. While two vaccine concepts have undergone efficacy trials, neither provided protective effects. Ongoing research continues through clinical trials evaluating prime-boost regimens combining DNA vaccines and viral vectors.
NPF: AIDS 2010 Refresher for Vienna JournalistsDaric Snyder
This document provides a summary of a refresher course on HIV/AIDS for journalists. It covers HIV/AIDS from both a medical/scientific perspective and a public health perspective. From a medical perspective, it explains how HIV infects and destroys CD4 cells, eventually overcoming the immune system. From a public health perspective, it discusses populations vulnerable to HIV, modes of transmission, and prevention strategies at both personal and societal levels. It emphasizes that until a vaccine or cure is developed, prevention must be the focus. The document compares the perspectives of medicine and public health and stresses journalists' important role in educating the public about HIV/AIDS.
immunobiology of hiv virus human immunodeficeincy virusAkshay Raj
HIV infects and destroys CD4+ T cells, weakening the immune system and leading to AIDS. It is transmitted through sexual contact, blood transfusions, or from mother to child. While some can suppress the virus for many years, treatment aims to control progression, as there is no cure. HIV evades immunity through antigenic mutations and hiding from antibodies, exploiting the immune system it evolved to overcome. Immunotherapy and antiretroviral drugs target different stages of the viral lifecycle, but combination treatment is required to suppress HIV long-term.
1. An estimated 1.1 million people in the US are living with HIV, including nearly 181,000 who are unaware of their infection. The number living with HIV has increased over the past decade while new annual infections have remained stable at around 50,000.
2. MSM (men who have sex with men) continue to have the highest burden of HIV infection, and African Americans continue to be disproportionately affected.
3. In 2011, nearly 49,000 people were diagnosed with HIV and over 32,000 were diagnosed with AIDS in the US. Over 1.1 million people in the US have been diagnosed with AIDS since the start of the epidemic.
Pharmacokinetics And Pharmacodynamic of Biotechnology Drugs - Trilok ShahareTrilok Shahare
This document discusses the pharmacokinetics and pharmacodynamics of biotechnology drugs. It begins by defining pharmacokinetics as the study of what the body does to a drug and pharmacodynamics as the study of a drug's biochemical and physiological effects. The document then examines various types of biotechnology products including proteins and peptides, monoclonal antibodies, oligonucleotides, vaccines, and gene therapies. It provides examples and applications of each type of biotechnology drug.
Application of PROTAC In The New Field of Attenuated Vaccines.pdfDoriaFang
Researchers developed a live attenuated influenza A virus vaccine using proteolysis targeting chimera (PROTAC) technology to degrade viral proteins through the endogenous ubiquitin-proteasome system of host cells.
The development of an HIV vaccine faces significant challenges including viral diversity, establishment of viral reservoirs, and immune evasion. Current vaccine strategies aim to elicit broadly neutralizing antibodies or enhance cellular immunity through various approaches including recombinant proteins, viral vectors, and DNA vaccines. While two vaccine concepts have undergone efficacy trials, neither provided protective effects. Ongoing research continues through clinical trials evaluating prime-boost regimens combining DNA vaccines and viral vectors.
NPF: AIDS 2010 Refresher for Vienna JournalistsDaric Snyder
This document provides a summary of a refresher course on HIV/AIDS for journalists. It covers HIV/AIDS from both a medical/scientific perspective and a public health perspective. From a medical perspective, it explains how HIV infects and destroys CD4 cells, eventually overcoming the immune system. From a public health perspective, it discusses populations vulnerable to HIV, modes of transmission, and prevention strategies at both personal and societal levels. It emphasizes that until a vaccine or cure is developed, prevention must be the focus. The document compares the perspectives of medicine and public health and stresses journalists' important role in educating the public about HIV/AIDS.
immunobiology of hiv virus human immunodeficeincy virusAkshay Raj
HIV infects and destroys CD4+ T cells, weakening the immune system and leading to AIDS. It is transmitted through sexual contact, blood transfusions, or from mother to child. While some can suppress the virus for many years, treatment aims to control progression, as there is no cure. HIV evades immunity through antigenic mutations and hiding from antibodies, exploiting the immune system it evolved to overcome. Immunotherapy and antiretroviral drugs target different stages of the viral lifecycle, but combination treatment is required to suppress HIV long-term.
1. An estimated 1.1 million people in the US are living with HIV, including nearly 181,000 who are unaware of their infection. The number living with HIV has increased over the past decade while new annual infections have remained stable at around 50,000.
2. MSM (men who have sex with men) continue to have the highest burden of HIV infection, and African Americans continue to be disproportionately affected.
3. In 2011, nearly 49,000 people were diagnosed with HIV and over 32,000 were diagnosed with AIDS in the US. Over 1.1 million people in the US have been diagnosed with AIDS since the start of the epidemic.
This document provides information about malaria vaccines. It discusses the context of malaria globally and the need for a vaccine. Several potential vaccine candidates target different stages of the malaria parasite's lifecycle, including sporozoites, infected hepatocytes, and erythrocytic stages. Developing an effective vaccine is challenging due to the parasite's diversity and complexity. The most promising current candidate is RTS,S, which provides some protection against malaria in clinical trials but is not fully effective.
diversified species genetic information and a wide
range of antibodies information and one-stop customized service at https://modelorg-ab.creative-biolabs.com/
This document discusses the evolution of HIV and resistance to treatment over time. It explains that HIV has a high mutation rate which allows it to quickly evolve resistance to individual drugs. While highly active antiretroviral therapy (HAART) was able to suppress viral loads, it did not reduce them to zero, allowing HIV to rebound once treatment is stopped. This ongoing ability of HIV to evolve resistance presents ethical challenges and ensures that a cure will not be easily achieved.
This document provides an overview of recent advances in HIV/AIDS treatment. It discusses how combination antiretroviral therapy pills have simplified treatment regimens. New drug classes such as entry inhibitors and integrase inhibitors have been developed that target different parts of the viral lifecycle. Studies have also shown benefits of starting antiretroviral treatment earlier, even before symptoms develop. Vaccine research continues in an effort to develop a preventive vaccine, with some studies showing a limited level of effectiveness.
The Diagnostic & Testing virtual conference held on the 11th June 2020 was an inspiring event examining the role of both molecular and rapid diagnostics in tackling disease, infection and reducing the impact of COVID-19 within our communities and hospitals. The virtual conference explored how health professionals, academics and industry are driving diagnostic and testing usage within laboratories, pharmacies and community practice.
The conference built upon the UK Diagnostics Summit held annually in London discussed how diagnostics and testing are tackling COVID-19, the technology in development, accuracy of COVID-19 tests as well as exploring current testing methods for cancer, diabetes, sepsis, urinary tract infections and HAI’S.
Antibiotic resistance is the ability of bacteria to resist the effects of an antibiotic. It is one of the world’s biggest public health problems We now know that an increasing number of patients are infected by micro-organisms which have developed a resistance to antimicrobial agents. This resistance is now a real threat to public health in world wide.
This document provides an overview of HIV vaccines, including definitions, estimates of herd immunity thresholds for different diseases, types of vaccines, strategies for preventive and therapeutic HIV vaccines, and summaries of clinical trials. It discusses DNA vaccines, viral vector vaccines, dendritic cell vaccines, therapeutic vaccine candidates, and the Canadian HIV Vaccines Initiative.
This document provides information on HIV and AIDS. It begins with an introduction that defines HIV as the human immunodeficiency virus. It then discusses the two types of HIV viruses, HIV-1 and HIV-2, and what AIDS stands for. The document continues by describing the morphology of HIV, its genes and antigens, viral entry and replication cycle, transmission methods, pathogenesis, stages of infection, opportunistic infections, laboratory diagnosis methods, and current antiretroviral treatment options.
This document provides an overview of laboratory diagnosis of AIDS, including:
1) The structure of HIV and the humoral and cellular immune response to HIV are described.
2) Diagnosis of AIDS involves antibody detection using screening tests like ELISA and confirmatory tests like Western blot. Antigen detection tests like p24 antigen capture and PCR are also used.
3) Laboratory monitoring of anti-retroviral therapy includes measuring CD4+ T cell counts, HIV RNA levels, and testing for HIV drug resistance.
1) Nanorobots could potentially be used to treat AIDS by recognizing and converting HIV-infected white blood cells back to their original form, maintaining a constant level of immune cells and allowing the patient to defend against diseases.
2) The nanorobot would use a DNA sensor to identify HIV-infected cells and an RNA converter to change the cell's RNA and reverse the HIV infection. It would be powered by metabolizing glucose and oxygen or external acoustic power.
3) Key challenges in using nanorobots for this approach include their size needing to be small enough to avoid blocking blood flow while still performing tasks, using biocompatible materials like diamond or carbon that don't trigger an immune response, and
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The document provides an overview of HIV and AIDS, including:
- HIV is a virus that weakens the immune system and can lead to AIDS if untreated. There are two types, HIV-1 being more prevalent.
- It is typically transmitted sexually, through blood/needles, or mother-to-child. Diagnosis involves antibody tests like ELISA and confirmation with Western Blot.
- If left untreated, it can take 10-15 years for HIV to develop into AIDS. Antiretroviral treatment can slow disease progression. Current global statistics and highest prevalence areas are mentioned.
HIV attacks and weakens the immune system by destroying CD4+ T cells. This leaves the body vulnerable to opportunistic infections and diseases. AIDS is the final stage of HIV infection where the CD4+ cell count drops below 200, resulting in life-threatening illnesses. There are two types of HIV - HIV-1 is the predominant global type while HIV-2 is less common and concentrated in West Africa. Both can be transmitted sexually, through blood exposure, and from mother to child, ultimately causing AIDS if left untreated.
This document discusses the laboratory diagnosis of HIV infection. It describes how HIV is transmitted and classified as a retrovirus. The viral structure and genome are explained. HIV attaches to host cells via CD4 receptors and coreceptors before integrating into the host DNA. This leads to a latent period before viral replication and release of new virions. The immune response is discussed, including antibody production and cytotoxic T cells. However, HIV can evade the immune system through mutations and downregulation of MHC molecules. This ultimately results in a decline in CD4+ T cells and progression to AIDS.
This study aimed to identify genes undergoing short-term positive selection in Verotoxigenic Escherichia coli (VTEC) using the software program Timezone. Timezone was used to analyze genomes of VTEC serotypes O157, O104, O111 as well as commensal and pathogenic strains. Genes with evidence of short-term selection, such as parallel hotspot mutations, were identified. Many results were associated with virulence factors involved in bacteriophages, cell motility and the membrane, agreeing with other studies on VTEC pathogenesis.
Pharmacokinetics study influences the
Decided route of administration for a specific medication
the amount and the frequency of each dose and its dosing intervals.
1) A team at Scripps Research Institute proposes permanently suppressing latent HIV rather than trying to eliminate all viral reservoirs through "shock and kill" strategies, which have not worked.
2) The team used a derivative of cortistatin to inhibit the HIV transcription factor tat and suppress viral replication in cells from HIV patients on antiretroviral therapy (ART). When ART was withdrawn, viral rebound was reduced by over 90% compared to without the inhibitor.
3) This approach aims to accumulate repressive epigenetic marks at the HIV promoter through tat inhibition, preventing viral reactivation even when strong inducers are used. If successful in further tests, it could lead to a functional cure for HIV
Measuring parameters of Bovine Enterovirus infectionMatthew Dower
1) Four assays were performed to measure parameters of bovine enterovirus infection: plaque assay, TCID50 assay, viral protein assay, and intracellular viral RNA assay.
2) The plaque assay showed that virus titer increased with time as more replication cycles occurred.
3) The viral protein assay indicated variation in viral proteins produced at different time points of infection.
4) Unfortunately, the intracellular viral RNA assay did not detect any RNA from samples.
An analytic study of the fractional order model of HIV-1 virus and CD4+ T-cel...IJECEIAES
In this article, we study the fractional mathematical model of HIV-1 infection of CD4+ T-cells, by studying a system of fractional differential equations of first order with some initial conditions, we study the changing effect of many parameters. The fractional derivative is described in the caputo sense. The adomian decomposition method (Shortly, ADM) method was used to calculate an approximate solution for the system under study. The nonlinear term is dealt with the help of Adomian polynomials. Numerical results are presented with graphical justifications to show the accuracy of the proposed methods.
Knowledge graph applications for cosmetics industryAnton Yuryev
This document summarizes three use cases for Elsevier's deep reading AI and biology knowledge graph. The first use case identifies UV-absorbing compounds for skin care by annotating over 684,000 compounds with relevant cell processes and diseases. The second use case identifies compounds that can modulate estrogen production by analyzing relevant metabolic pathways and regulation networks. The third use case performs transcriptomics analysis of androgenic alopecia to build a regulatory network model and identify new drug targets using differential expression analysis and sub-network enrichment.
Five drug development strategies to combat SARS-CoV2Anton Yuryev
Slides were presented at webinar on “Opportunities & Challenges in Drug Discovery and Development” organised by Elsevier in collaboration with Dr Reddy’s Institute of Life Sciences, Hyderabad on July 16th,2020
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This document provides information about malaria vaccines. It discusses the context of malaria globally and the need for a vaccine. Several potential vaccine candidates target different stages of the malaria parasite's lifecycle, including sporozoites, infected hepatocytes, and erythrocytic stages. Developing an effective vaccine is challenging due to the parasite's diversity and complexity. The most promising current candidate is RTS,S, which provides some protection against malaria in clinical trials but is not fully effective.
diversified species genetic information and a wide
range of antibodies information and one-stop customized service at https://modelorg-ab.creative-biolabs.com/
This document discusses the evolution of HIV and resistance to treatment over time. It explains that HIV has a high mutation rate which allows it to quickly evolve resistance to individual drugs. While highly active antiretroviral therapy (HAART) was able to suppress viral loads, it did not reduce them to zero, allowing HIV to rebound once treatment is stopped. This ongoing ability of HIV to evolve resistance presents ethical challenges and ensures that a cure will not be easily achieved.
This document provides an overview of recent advances in HIV/AIDS treatment. It discusses how combination antiretroviral therapy pills have simplified treatment regimens. New drug classes such as entry inhibitors and integrase inhibitors have been developed that target different parts of the viral lifecycle. Studies have also shown benefits of starting antiretroviral treatment earlier, even before symptoms develop. Vaccine research continues in an effort to develop a preventive vaccine, with some studies showing a limited level of effectiveness.
The Diagnostic & Testing virtual conference held on the 11th June 2020 was an inspiring event examining the role of both molecular and rapid diagnostics in tackling disease, infection and reducing the impact of COVID-19 within our communities and hospitals. The virtual conference explored how health professionals, academics and industry are driving diagnostic and testing usage within laboratories, pharmacies and community practice.
The conference built upon the UK Diagnostics Summit held annually in London discussed how diagnostics and testing are tackling COVID-19, the technology in development, accuracy of COVID-19 tests as well as exploring current testing methods for cancer, diabetes, sepsis, urinary tract infections and HAI’S.
Antibiotic resistance is the ability of bacteria to resist the effects of an antibiotic. It is one of the world’s biggest public health problems We now know that an increasing number of patients are infected by micro-organisms which have developed a resistance to antimicrobial agents. This resistance is now a real threat to public health in world wide.
This document provides an overview of HIV vaccines, including definitions, estimates of herd immunity thresholds for different diseases, types of vaccines, strategies for preventive and therapeutic HIV vaccines, and summaries of clinical trials. It discusses DNA vaccines, viral vector vaccines, dendritic cell vaccines, therapeutic vaccine candidates, and the Canadian HIV Vaccines Initiative.
This document provides information on HIV and AIDS. It begins with an introduction that defines HIV as the human immunodeficiency virus. It then discusses the two types of HIV viruses, HIV-1 and HIV-2, and what AIDS stands for. The document continues by describing the morphology of HIV, its genes and antigens, viral entry and replication cycle, transmission methods, pathogenesis, stages of infection, opportunistic infections, laboratory diagnosis methods, and current antiretroviral treatment options.
This document provides an overview of laboratory diagnosis of AIDS, including:
1) The structure of HIV and the humoral and cellular immune response to HIV are described.
2) Diagnosis of AIDS involves antibody detection using screening tests like ELISA and confirmatory tests like Western blot. Antigen detection tests like p24 antigen capture and PCR are also used.
3) Laboratory monitoring of anti-retroviral therapy includes measuring CD4+ T cell counts, HIV RNA levels, and testing for HIV drug resistance.
1) Nanorobots could potentially be used to treat AIDS by recognizing and converting HIV-infected white blood cells back to their original form, maintaining a constant level of immune cells and allowing the patient to defend against diseases.
2) The nanorobot would use a DNA sensor to identify HIV-infected cells and an RNA converter to change the cell's RNA and reverse the HIV infection. It would be powered by metabolizing glucose and oxygen or external acoustic power.
3) Key challenges in using nanorobots for this approach include their size needing to be small enough to avoid blocking blood flow while still performing tasks, using biocompatible materials like diamond or carbon that don't trigger an immune response, and
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The document provides an overview of HIV and AIDS, including:
- HIV is a virus that weakens the immune system and can lead to AIDS if untreated. There are two types, HIV-1 being more prevalent.
- It is typically transmitted sexually, through blood/needles, or mother-to-child. Diagnosis involves antibody tests like ELISA and confirmation with Western Blot.
- If left untreated, it can take 10-15 years for HIV to develop into AIDS. Antiretroviral treatment can slow disease progression. Current global statistics and highest prevalence areas are mentioned.
HIV attacks and weakens the immune system by destroying CD4+ T cells. This leaves the body vulnerable to opportunistic infections and diseases. AIDS is the final stage of HIV infection where the CD4+ cell count drops below 200, resulting in life-threatening illnesses. There are two types of HIV - HIV-1 is the predominant global type while HIV-2 is less common and concentrated in West Africa. Both can be transmitted sexually, through blood exposure, and from mother to child, ultimately causing AIDS if left untreated.
This document discusses the laboratory diagnosis of HIV infection. It describes how HIV is transmitted and classified as a retrovirus. The viral structure and genome are explained. HIV attaches to host cells via CD4 receptors and coreceptors before integrating into the host DNA. This leads to a latent period before viral replication and release of new virions. The immune response is discussed, including antibody production and cytotoxic T cells. However, HIV can evade the immune system through mutations and downregulation of MHC molecules. This ultimately results in a decline in CD4+ T cells and progression to AIDS.
This study aimed to identify genes undergoing short-term positive selection in Verotoxigenic Escherichia coli (VTEC) using the software program Timezone. Timezone was used to analyze genomes of VTEC serotypes O157, O104, O111 as well as commensal and pathogenic strains. Genes with evidence of short-term selection, such as parallel hotspot mutations, were identified. Many results were associated with virulence factors involved in bacteriophages, cell motility and the membrane, agreeing with other studies on VTEC pathogenesis.
Pharmacokinetics study influences the
Decided route of administration for a specific medication
the amount and the frequency of each dose and its dosing intervals.
1) A team at Scripps Research Institute proposes permanently suppressing latent HIV rather than trying to eliminate all viral reservoirs through "shock and kill" strategies, which have not worked.
2) The team used a derivative of cortistatin to inhibit the HIV transcription factor tat and suppress viral replication in cells from HIV patients on antiretroviral therapy (ART). When ART was withdrawn, viral rebound was reduced by over 90% compared to without the inhibitor.
3) This approach aims to accumulate repressive epigenetic marks at the HIV promoter through tat inhibition, preventing viral reactivation even when strong inducers are used. If successful in further tests, it could lead to a functional cure for HIV
Measuring parameters of Bovine Enterovirus infectionMatthew Dower
1) Four assays were performed to measure parameters of bovine enterovirus infection: plaque assay, TCID50 assay, viral protein assay, and intracellular viral RNA assay.
2) The plaque assay showed that virus titer increased with time as more replication cycles occurred.
3) The viral protein assay indicated variation in viral proteins produced at different time points of infection.
4) Unfortunately, the intracellular viral RNA assay did not detect any RNA from samples.
An analytic study of the fractional order model of HIV-1 virus and CD4+ T-cel...IJECEIAES
In this article, we study the fractional mathematical model of HIV-1 infection of CD4+ T-cells, by studying a system of fractional differential equations of first order with some initial conditions, we study the changing effect of many parameters. The fractional derivative is described in the caputo sense. The adomian decomposition method (Shortly, ADM) method was used to calculate an approximate solution for the system under study. The nonlinear term is dealt with the help of Adomian polynomials. Numerical results are presented with graphical justifications to show the accuracy of the proposed methods.
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Knowledge graph applications for cosmetics industryAnton Yuryev
This document summarizes three use cases for Elsevier's deep reading AI and biology knowledge graph. The first use case identifies UV-absorbing compounds for skin care by annotating over 684,000 compounds with relevant cell processes and diseases. The second use case identifies compounds that can modulate estrogen production by analyzing relevant metabolic pathways and regulation networks. The third use case performs transcriptomics analysis of androgenic alopecia to build a regulatory network model and identify new drug targets using differential expression analysis and sub-network enrichment.
Five drug development strategies to combat SARS-CoV2Anton Yuryev
Slides were presented at webinar on “Opportunities & Challenges in Drug Discovery and Development” organised by Elsevier in collaboration with Dr Reddy’s Institute of Life Sciences, Hyderabad on July 16th,2020
Drugs predicted to bind #COVID19 proteins by computational dockingAnton Yuryev
Drugs predicted by computational ligand docking to bind COVID19 proteins from Wu et al 2020, Kandeel et al 2020, Joshi et al 2020, Adem et al 2020 articles
Genetic variations linked to Acute Respiratory Distress syndromeAnton Yuryev
The list of rs Identifiers linked by to ARDS in peer-reviewed scientific literature. This list can help determine individuals at risk to develop severe symptoms from COVID19 infection
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BenevolentAI has reported three AAK1 and GAK kinase inhibitors effective against #coronavirus #COVID19. I publish the list of 35 approved drugs and lead compounds that can inhibit AAK1 and GAK kinases and therefore can be effective against #COVID19. Drugs were found in #Elsevier #PathwayStudio and #Reaxys knowledgebases. To find more drugs that can be effective against #COVID19 please visit #Elsevier Coronavirus Information Center or read my blog about atrategies to find more drugs for #coronavirus
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This presentation demonstrates how to use Elsevier Text Mining to analyze a patient's microbiome profile from Aperiomics and interpret the results. Multiple Search is used to identify bacterial species from the patient's throat and stool that have been linked to her lung and bowel problems in medical literature. Species linked to her conditions include Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus parainfluenzae, and Fusobacterium nucleatum in her throat and Bacteroides vulgatus in her stool. Multiple Search also identifies protective species in her stool like Bifidobacterium longum and Faecalibacterium prausnitzii. Antibiotics and probiotics are then suggested
The document analyzes the tumor transcriptomics profile of a patient with stage IV gallbladder cancer. It identifies the top 200 most significantly activated expression regulators in the patient's tumor using sub-network enrichment analysis software. Key regulators identified include histone deacetylases and DNA methyltransferases. The analysis suggests treatment with the HDAC inhibitor vorinostat and discusses how activated regulators like HDACs, PDCD1, and CTLA4 may be contributing to tumor proliferation and immune evasion. Graphical summaries show pathways enriched with active regulators in the tumor related to cancer hallmarks like histone modification and immune response evasion.
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Elsevier helps malaria research with comprehensive Plasmodium biology databaseAnton Yuryev
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Elsevier has significantly reduced the cost of drug development for rare diseases through drug repurposing. They have brought together knowledge about drug targets, effects, and disease biology to identify drugs and nutraceuticals approved by the FDA that could potentially be repositioned to treat rare diseases, eliminating the need for new drug development and clinical trials. Using automated queries of Elsevier knowledgebases, they can provide summaries of potential treatments for a given rare disease, including key researchers and institutions, relevant drug targets, and approved drugs that may be effective - reducing the cost of repositioning existing drugs to under $500,000.
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Profiling how Immune inhibitors Secreted by Melanoma affect NK & other immune...Anton Yuryev
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2) Elsevier's Professional Services team leverages Elsevier's capabilities to provide customized data management and analysis solutions.
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Pathway analysis for personalized oncologyAnton Yuryev
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2) Calculating pathway activity signatures which are short allows better patient classification compared to single targets. Pathway activity also allows selection of drugs that inhibit the active pathway.
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Microstomia, characterized by an abnormally small oral aperture, presents significant challenges in prosthodontic treatment, including limited access for examination, difficulties in impression making, and challenges with prosthesis insertion and removal. To manage these issues, customized impression techniques using sectional trays and elastomeric materials are employed. Prostheses may be designed in segments or with flexible materials to facilitate handling. Minimally invasive procedures and the use of digital technologies can enhance patient comfort. Education and training for patients on prosthesis care and maintenance are crucial for compliance. Regular follow-up and a multidisciplinary approach, involving collaboration with other specialists, ensure comprehensive care and improved quality of life for microstomia patients.
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Drug re-positioning for tuberculosis infection in HIV/ADS patients
1. Anti-tuberculosis drugs for HIV patients
Prepared by Anton Yuryev, Ph.D., Elsevier Professional Services on February 15th
2018
Disclaimer: Data in Pathway Studio and in PharmaPendium is regular updated by Elsevier. Therefore
the reproduction of workflows from this report may produce additional findings that are different from
the results in this report.
Contents
Mechanism for development of tuberculosis (TB) in HIV patients...............................................................1
Finding drugs inhibiting both HIV infection and TB in Pathway Studio........................................................2
Figure 1: Chemical compounds known to inhibit both TB and HIV found in Pathway Studio..............2
Figure 2: Approved drugs inhibiting HIV infection, tuberculosis infection and activating
macrophages are on the top row .........................................................................................................3
Finding drugs inhibiting HIV infection of alveolar macrophages using Pathway Studio curated pathway
collection.......................................................................................................................................................3
Finding proteins expressed in alveolar macrophages...............................................................................3
Finding proteins expressed in alveolar macrophages inhibiting HIV infection.........................................3
Figure 3: Proteins expressed in alveolar macrophages regulating HIV infection ................................4
Identification of curated pathways inhibiting HIV infection in alveolar macrophages and corresponding
drug agonists.............................................................................................................................................4
Table 1: Drugs activating “Alveolar Macrophages Dysfunction” pathway...............................................5
Finding HIV-inhibiting macrophage-activating proteins and drugs outside curated pathways ...................5
Figure 4: NFE2L2 agonists found in Pathway Studio.................................................................................5
Finding drugs positively regulating concepts related to Macrophage Activation and M2 Polarization in
Pathway Studio .............................................................................................................................................6
Figure 5: Additional drugs activating macrophages not found by previous workflows .......................6
Conclusion.....................................................................................................................................................6
Table2: Pathway Studio concepts relevant to Macrophage Activation and M2 Polarization ......................8
Table 3: Complete list of drugs inhibiting HIV infection of macrophages found by this white paper........12
Mechanism for development of tuberculosis (TB) in HIV patients
Mechanism of TB-HIV interaction is well understood on cellular level. In brief, HIV can infect T-cells and
macrophages using CD4 and CCR2/4/5 receptors for entry. HIV infection of immune cell leads to the
attenuation of their function and globally compromised immune system. TB uses alveolar macrophages
for entry into the organism. If macrophages are healthy TB infection becomes latent and bacteria can
live capsulized inside alveolar macrophage phagosomes for years without causing health problems. HIV-
2. compromised macrophages cannot control TB replication and allow its malignant spreading into many
organs where TB forms granulomas from immune cells around infected resident macrophages.
Granulomas subsequently transform into tubercles. It is known that TB does not enter macrophages in
certain organs such as heart, skeletal muscles, pancreas, or thyroid. HIV does not infect M2 polarized
anti-inflammatory macrophages in all tissues, however, prolonged M2 polarization leads to the
accumulation of IL10 which causes macrophages deactivation and increases CCR5 expression on
monocytes. Down-regulation of macrophages and T-cells by HIV eventually leads to immune system
failure and AIDS. IL10 is also known to facilitate pathogen survival in macrophages thus promoting TB
infection. Therefore, drugs against TB infection in HIV patient must activate macrophage function, or
prevent virus infection of macrophages, or inhibit IL10 production.
Finding drugs inhibiting both HIV infection and TB in Pathway Studio
To find drugs inhibiting both types of infection let’s first find relevant disease entities in Pathway Studio.
Search for HIV using basic search box located on top of Pathway Studio interface finds several hundred
molecules, pathways and diseases. You can sort search results by “Total connectivity” column to find
most informative HIV-related disease concepts: “HIV infection”, “HIV-1 infection”, “Acquired
Immunodeficiency Syndrome”. Move them into empty pathway, perform another basic search for
“tuberculosis” and move “Tuberculosis” disease entity into the same pathway with HIV entities. Select
one of HIV-related diseases and “Tuberculosis” disease entity and find drugs inhibiting both diseases
using Add->Network builder dialog with settings “Common regulators” filtered for entity Small Molecule
and relation type ClinicalTrial or Regulation with Effect negative. Repeat “Common regulators” search
for all pairs of “Tuberculosis” with another HIV-related entity. The approach should yield more than 200
chemical entities as shown on Figure 1.
Figure 1: Chemical compounds known to inhibit both TB and HIV found in Pathway Studio
To select only approved drugs in this pathway you can either add column “PharmaPendium ID” to Entity
view table of the pathway or paste the following advanced graphical language query into advanced
search “Search query” box:
objectType='Small Molecule' AND "PharmaPendium ID" != null AND MemberOf (select Network WHERE
Name = 'TB+HIV drugs')
Make sure to replace 'TB+HIV drugs' with the name of your pathway. To find drugs inhibiting TB
infection in HIV patients through activation of macrophages find relevant “Macrophage” Cell entities
3. using basic search and add them to the same pathway and use Network builder option “Find direct
interactions” option with filter for Regulation relation type with Effect positive. Filtering results for
macrophage activators should find at least 27 chemical entities. 18 of them are true drugs and nine are
metabolites that are also approved for therapeutic applications and therefore have PharmaPendium ID.
Figure 2: Approved drugs inhibiting HIV infection, inhibiting tuberculosis, and activating
macrophages are shown in the top row
Finding drugs inhibiting HIV infection of alveolar macrophages using
Pathway Studio curated pathway collection
Finding proteins expressed in alveolar macrophages
To find proteins expressed in alveolar macrophages add “Alveolar macrophages” entity to new pathway
and use Add->Network Builder option “Expand pathway” filtered for entity types: Protein, Functional
Class, Complex and filtered for Relation type “CellExpression”. This search will find more than 100
proteins.
Finding alveolar macrophages proteins that inhibit HIV infection
Some alveolar macrophages proteins contribute to HIV infection while others prevent it. Drugs that can
inhibit proteins contributing to HIV infection are likely immune-suppressants inhibiting macrophage
function. They can only further weaken immune system that is already handicapped by HIV and TB
infection. Therefore you should search for drugs that activate proteins preventing HIV infection. To find
such proteins add HIV-related diseases to the pathway containing proteins expressed in alveolar
macrophages. Select “HIV infection”, “HIV-1 infection”, “Acquired Immunodeficiency Syndrome” on the
pathway and use menu option Add->Relation between selected and unselected entities to connect them
with proteins expressed in alveolar macrophages.
To find proteins that inhibit HIV infection visualize Effect sign in relations using menu option Style->Color
relations->By Effect. Align all red-colored relations with Effect negative horizontally using Align menu
option. Align all green-colored relations with Effect positive horizontally using Align menu option in a
different row. Inspect sentences supporting all remaining grayed-out relations to find which effect a
4. protein has on HIV infection. Move all proteins inhibiting HIV next to the proteins linked by red-colored
relations. Reading supporting sentence is often enough to understand the nature of effect but
sometime you will need to open the original article containing the sentence to gain an insight about
effect sign. This effort should yield you more than 35 proteins expressed in alveolar macrophages that
negatively affect HIV infection. While curating for effect is the longest step in this workflow it effectively
substitutes for browsing several hundred scientific articles. It will take less than one hour in Pathway
Studio compared with days of reading thus improving your reading productivity more than 10 times.
Figure 3: Proteins expressed in alveolar macrophages regulating HIV infection
Proteins contributing to HIV infection are shown at the top of the diagram. Proteins preventing HIV
infection are shown at the bottom of the diagram.
Identification of curated pathways inhibiting HIV infection in alveolar
macrophages and their drug agonists
To find curated pathways containing proteins inhibiting HIV infection in alveolar macrophages select
these proteins in the pathway and use Tools->Enrichment analysis of selected entities menu option.
Because alveolar macrophages are components of both blood and lung organ systems you should
specify both of these systems in Gene Set Categories box by browsing to Organ systems taxonomy
branch in Anatomical Index pathway classification. This search should find more than 70 curated
pathways. You should look through top 10-20 hits in the search results to find most relevant pathways.
For this white paper two pathways were selected for finding drugs: “Anti-Inflammatory Function of
Macrophage M2 Lineage” and “Alveolar Macrophages Dysfunction”. Macrophage M2 polarization
pathway has been expected from the mechanism of TB-HIV interaction described above. “Alveolar
Macrophages Dysfunction” pathway belongs to COPD (Chronic Obstructive Pulmonary Disease) pathway
collection. The Notes section in the Properties for this pathway says that “Macrophages are believed to
play a pivotal role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Their
numbers are increased (5-10 fold) in the airways, lung parenchyma, bronchoalveolar lavage fluid, and
sputum of smokers and patients with COPD”. Thus, this pathway depicts how macrophages are
chronically activated in COPD by various endogenous signals provoked by tobacco smoking and air
pollutants.
5. To find drugs activating alveolar macrophages or their M2 polarization select receptors responsible for
signal transduction into macrophages on both pathways and expand using Add->Network Builder option
“Expand pathway” filtered for Small Molecules and DirectRegulation with Effect positive. Receptors in
“Anti-Inflammatory Function of Macrophage M2 Lineage” pathway have not yielded any drugs for this
tutorial, while receptors responsible for chronic macrophage activation in COPD have drug agonists
listed in Table 1.
Table 1: Drugs activating “Alveolar Macrophages Dysfunction” pathway
Name Target in
pathway
Reported anti-HIV activity URN PharmaPendium ID
ivermectin P2RX5 4 publications, 1 clinical trial urn:agi-cas:70288-86-7 Ivermectin
polymyxin B P2RX7 1 clinical trial urn:agi-cas:1404-26-8 Polymyxin B
isoflurane P2RX7 urn:agi-cas:26675-46-7 Isoflurane
hemin TLR2 3 publications urn:agi-cas:16009-13-5 Hemin
bleomycin TLR2 12 clinical trials urn:agi-cas:11056-06-7 Bleomycin
paclitaxel TLR4 4 publications, 1 clinical trial
against AIDS-Kaposi's sarcoma
urn:agi-cas:33069-62-4 Paclitaxel
imiquimod TLR4 2 clinical trials against AIDS-anal
cancer
urn:agi-cas:99011-02-6 Imiquimod
Finding drugs for HIV-inhibiting macrophage-activating proteins not
included in curated pathways
More drugs activating alveolar macrophages can be found by inspecting individual proteins from the
bottom of Figure 3 that do not belong to “anti-Inflammatory Function of Macrophage M2 Lineage” or
“Alveolar Macrophages Dysfunction” pathways. For example, activation of NFE2L2 protein was recently
shown to protect macrophages from HIV infection by inhibiting oxidative stress caused by HIV. NFE2L2
agonists can be found in Pathway Studio by expanding NFE2L2 using Add->Network Builder towards
Small Molecules by DirectRegulation relation with Effect=positive. Figure 4 shows NFE2L2 agonists that
are cheap and can be readily available in poor countries. Additionally, one publication suggests that
NFE2L2 activation may help macrophages to also combat TB infection.
Figure 4: NFE2L2 agonists found in Pathway Studio
6. Finding drugs positively regulating other concepts related to
Macrophage Activation and M2 Polarization in Pathway Studio
Additional drugs activating macrophages or their M2 polarization can be found by expanding relevant
concepts using Add->Network builder towards Small Molecules by Regulation relation with
Effect=positive or as inhibitors of the concepts opposing macrophage activation and M2 polarization
Table 2 shows 165 concepts relevant for macrophage function that can be expanded towards drug. You
should expand only towards Small molecules than have PharmaPendium ID. Use “Add condition” link in
Network builder dialog to add “PharmaPendium ID” != null condition to your query. Alternatively, you
can create a group of all PharmaPendium drugs and then use filter for Specific Pathways or Entity List
available on the last page of Network builder dialog.
Figure 5: Additional drugs activating macrophages not found by previous workflows
Conclusion
We found 61 drugs, 20 food supplements from plants, and 24 human metabolites that potentially can
reduce risk of TB infection in HIV patients (Table 3). They activate alveolar macrophages and reduce risk
of their HIV infection which in turn hampers macrophages resistance to TB. Not all potential drugs have
been found by this tutorial. However, the tutorial demonstrates and validates principals for finding ant-
TB drugs for HIV patients. The approach was validated by finding Vitamin D3, which is the standard
supplement in combating TB infection in HIV patients. Tutorial also found Interferon gamma-1b that
was tested as aerosol treatment to activate alveolar macrophages in HIV patients. The workflow can be
repeated in Pathway Studio for other proteins and concepts that were omitted from the consideration
in this white paper to find even more potential anti-TB drugs for HIV patients.
7. Not every drug found by this tutorial can be used against HIV. Additional filtering criteria should be
applied to select the best drugs. For example, imiquimod can only be applied topically and therefore
cannot activate macrophages in the lung. DMSO is only approved for organ transplant conservation. TB
infection is wide-spread among HIV patients in the developing countries. Therefore drug availability and
cost must be additional criteria for drug selection. Food supplements and metabolites may be the
cheapest way to prevent tuberculosis in HIV positive population in poor countries.
8. Table2: Pathway Studio concepts relevant to Macrophage Activation and
M2 Polarization
Name Object Type Total
Connectivity
Drug action
alveolar macrophage Cell 2410 must activate
M1 macrophage Cell 843 must activate
M2 macrophage Cell 1370 must activate
macrophage Cell 12605 must activate
monocyte-macrophage precursor cell Cell 9 must activate
alveolar macrophage adhesion Cell Process 7 must activate
alveolar macrophage aggregation Cell Process 6 must activate
alveolar macrophage apoptosis Cell Process 50 must inhibit
alveolar macrophage autophagy Cell Process 2 must activate
alveolar macrophage chemotaxis Cell Process 10 must activate
alveolar macrophage count Cell Process 87 must activate
alveolar macrophage cytotoxicity Cell Process 6 must activate
alveolar macrophage damage Cell Process 9 must inhibit
alveolar macrophage death Cell Process 20 must inhibit
alveolar macrophage destruction Cell Process 2 must inhibit
alveolar macrophage development Cell Process 17 must activate
alveolar macrophage differentiation Cell Process 9 must activate
alveolar macrophage distribution Cell Process 2 must activate
alveolar macrophage division Cell Process 4 must activate
alveolar macrophage fate commitment Cell Process 2 must activate
alveolar macrophage formation Cell Process 5 must activate
alveolar macrophage function Cell Process 121 must activate
alveolar macrophage growth Cell Process 7 must activate
alveolar macrophage homeostasis Cell Process 7 must activate
alveolar macrophage infiltration Cell Process 13 must activate
alveolar macrophage interaction Cell Process 6 must activate
alveolar macrophage invasion Cell Process 3 must activate
alveolar macrophage localization Cell Process 2 must activate
alveolar macrophage migration Cell Process 21 must activate
alveolar macrophage motility Cell Process 5 must activate
alveolar macrophage phagocytosis Cell Process 74 must activate
alveolar macrophage phenotype Cell Process 41 must activate
alveolar macrophage polarity Cell Process 18 must activate
alveolar macrophage population Cell Process 29 must activate
alveolar macrophage priming Cell Process 7 must activate
alveolar macrophage proliferation Cell Process 18 must activate
alveolar macrophage proliferative response Cell Process 2 must activate
alveolar macrophage ratio Cell Process 3
9. alveolar macrophage recognition Cell Process 3 must activate
alveolar macrophage regeneration Cell Process 2 must activate
alveolar macrophage renewal Cell Process 2 must activate
alveolar macrophage repertoire Cell Process 3 must activate
alveolar macrophage sequestration Cell Process 3 must activate
alveolar macrophage size Cell Process 3 must activate
alveolar macrophage spreading Cell Process 5 must activate
alveolar macrophage structure Cell Process 2 must activate
alveolar macrophage survival Cell Process 9 must activate
alveolar macrophage viability Cell Process 7 must activate
M1 macrophage chemotaxis Cell Process 4 must activate
M1 macrophage count Cell Process 32 must activate
M1 macrophage cytotoxicity Cell Process 3 must activate
M1 macrophage dedifferentiation Cell Process 2 must inhibit
M1 macrophage development Cell Process 14 must activate
M1 macrophage differentiation Cell Process 20 must activate
M1 macrophage formation Cell Process 15 must activate
M1 macrophage function Cell Process 23 must activate
M1 macrophage infiltration Cell Process 31 must activate
M1 macrophage migration Cell Process 6 must activate
M1 macrophage phenotype Cell Process 70 must activate
M1 macrophage polarity Cell Process 148 must activate
M1 macrophage population Cell Process 11 must activate
M1 macrophage proliferation Cell Process 4 must activate
M1 macrophage ratio Cell Process 7 must activate
M1 macrophage repertoire Cell Process 4 must activate
M1 macrophage stress Cell Process 2 must inhibit
M1 macrophage survival Cell Process 6 must activate
M2 macrophage apoptosis Cell Process 2 must inhibit
M2 macrophage count Cell Process 60 must activate
M2 macrophage death Cell Process 3 must inhibit
M2 macrophage development Cell Process 44 must activate
M2 macrophage differentiation Cell Process 56 must activate
M2 macrophage formation Cell Process 33 must activate
M2 macrophage function Cell Process 38 must activate
M2 macrophage growth Cell Process 2 must activate
M2 macrophage infiltration Cell Process 14 must activate
M2 macrophage migration Cell Process 11 must activate
M2 macrophage phenotype Cell Process 132 must activate
M2 macrophage polarity Cell Process 237 must activate
M2 macrophage population Cell Process 24 must activate
M2 macrophage proliferation Cell Process 12 must activate
10. M2 macrophage ratio Cell Process 5 must activate
M2 macrophage regeneration Cell Process 3 must activate
M2 macrophage repertoire Cell Process 2 must activate
M2 macrophage survival Cell Process 3 must activate
macrophage activation Cell Process 1694 must activate
macrophage adhesion Cell Process 403 must activate
macrophage agglutination Cell Process 2 must activate
macrophage aggregation Cell Process 66 must activate
macrophage antigen processing and presentation Cell Process 0 must activate
macrophage apoptosis Cell Process 850 must inhibit
macrophage architecture Cell Process 2 must activate
macrophage autophagy Cell Process 60 must activate
macrophage chemotaxis Cell Process 407 must activate
macrophage clonal anergy Cell Process 2 must inhibit
macrophage communication Cell Process 7 must activate
macrophage compartmentalization Cell Process 2 must activate
macrophage contact Cell Process 11 must activate
macrophage count Cell Process 820 must activate
macrophage cytotoxicity Cell Process 58 must activate
macrophage damage Cell Process 77 must inhibit
macrophage death Cell Process 322 must inhibit
macrophage dedifferentiation Cell Process 3 must inhibit
macrophage destruction Cell Process 13 must inhibit
macrophage development Cell Process 286 must activate
macrophage diapedesis Cell Process 6 must activate
macrophage differentiation Cell Process 789 must activate
macrophage disruption Cell Process 11 must inhibit
macrophage distribution Cell Process 25 must activate
macrophage division Cell Process 33 must activate
macrophage elongation Cell Process 8 must activate
macrophage enlargement Cell Process 2 must activate
macrophage extravasation Cell Process 31 must activate
macrophage fate Cell Process 25 must activate
macrophage fate commitment Cell Process 17 must activate
macrophage fate specification Cell Process 4 must activate
macrophage formation Cell Process 194 must activate
macrophage function Cell Process 1471 must activate
macrophage fusion Cell Process 141 must activate
macrophage growth Cell Process 141 must activate
macrophage homeostasis Cell Process 44 must activate
macrophage homing Cell Process 45 must activate
macrophage infiltration Cell Process 726 must activate
11. macrophage interaction Cell Process 121 must activate
macrophage invasion Cell Process 162 must activate
macrophage lifespan Cell Process 2 must activate
macrophage localization Cell Process 23 must activate
macrophage mediated cytotoxicity Cell Process 20 must activate
macrophage migration Cell Process 950 must activate
macrophage migration inhibition Cell Process 43 must inhibit
macrophage morphogenesis Cell Process 2 must activate
macrophage motility Cell Process 143 must activate
macrophage motion Cell Process 50 must activate
macrophage phagocytosis Cell Process 556 must activate
macrophage phenotype Cell Process 596 must activate
macrophage polarity Cell Process 709 must activate
macrophage population Cell Process 438 must activate
macrophage priming Cell Process 64 must activate
macrophage proliferation Cell Process 471 must activate
macrophage proliferative response Cell Process 5 must activate
macrophage ratio Cell Process 19
macrophage recognition Cell Process 75 must activate
macrophage regeneration Cell Process 7 must activate
macrophage renewal Cell Process 15 must activate
macrophage repertoire Cell Process 39 must activate
macrophage response Cell Process 287 must activate
macrophage selection Cell Process 3 must activate
macrophage senescence Cell Process 4 must activate
macrophage sequestration Cell Process 63 must activate
macrophage size Cell Process 24 must activate
macrophage spreading Cell Process 120 must activate
macrophage stress Cell Process 12 must activate
macrophage structure Cell Process 4 must activate
macrophage survival Cell Process 256 must activate
macrophage tethering Cell Process 5 must activate
macrophage transdifferentiation Cell Process 7 must activate
macrophage transendothelial migration Cell Process 63 must activate
macrophage transepithelial migration Cell Process 6 must activate
macrophage viability Cell Process 157 must activate
macrophage volume Cell Process 4 must activate
monocyte macrophage differentiation Cell Process 139 must activate
myeloblast macrophage differentiation Cell Process 2 must activate
myeloid cell macrophage differentiation Cell Process 13 must activate
myeloid progenitor cell macrophage differentiation Cell Process 2 must activate
neutrophil macrophage differentiation Cell Process 3 must activate
12. stem cell macrophage differentiation Cell Process 2 must activate
Table 3: Complete list of drugs inhibiting HIV infection of macrophages
found in this white paper
Name Connectivity Class Target HIV
inhibition
TB
inhibition
albendazole 486 Drug Macrophage Yes Yes
amikacin 324 Drug Macrophage Yes Yes
atorvastatin 2553 Drug Macrophage Yes Yes
azithromycin 1201 Drug Macrophage Yes Yes
caspofungin 268 Drug Macrophage Yes Yes
CGP 75355 235 Drug Macrophage Yes Yes
cisplatin 5050 Drug Macrophage Yes Yes
dexamethasone 7253 Drug Macrophage Yes Yes
DMSO 2255 Drug Macrophage Yes Yes
doxorubicin 4635 Drug Macrophage Yes Yes
erythromycin 1147 Drug Macrophage Yes Yes
iohexol 212 Drug Macrophage Yes Yes
isoniazid 574 Drug Macrophage Yes Yes
ivermectin 587 Drug P2RX4 Yes Yes
lentinan 303 Drug Macrophage Yes Yes
prednisolone 2330 Drug Macrophage Yes Yes
prednisone 2134 Drug Macrophage Yes Yes
primaquine 264 Drug Macrophage Yes Yes
pyrazinamide 205 Drug Macrophage Yes Yes
rifabutin 166 Drug Macrophage Yes Yes
ritonavir 830 Drug Macrophage Yes Yes
sulfasalazine 877 Drug Macrophage Yes Yes
valproic acid 3771 Drug Macrophage Yes Yes
warfarin 1127 Drug Macrophage Yes Yes
curcumin 4678 Supplement NFE2L2 Yes Yes
epigallocatechin-3-gallate 3052 Supplement NFE2L2 Yes Yes
genistein 3547 Supplement NFE2L2 Yes Yes
arginine 4584 Metabolite Macrophage Yes Yes
ascorbic acid 4373 Metabolite Macrophage Yes Yes
cysteine 3316 Metabolite Macrophage Yes Yes
folate 2940 Metabolite Macrophage Yes Yes
interferon gamma-1b 86 Metabolite Macrophage Yes Yes
lactate 4227 Metabolite Macrophage Yes Yes
niacin 1402 Metabolite Macrophage Yes Yes
13. polylactic acid 289 Metabolite Macrophage Yes Yes
prostaglandin E2 6120 Metabolite Macrophage Yes Yes
vitamin D3 2076 Metabolite Macrophage Yes Yes
bleomycin 1909 Drug TLR2 Yes
colchicine 1937 Drug Macrophage Yes
dimethyl fumarate 711 Drug NFE2L2 Yes
D-penicillamine 617 Drug Macrophage Yes
exenatide 1505 Drug Macrophage Yes
haloperidol 1801 Drug Macrophage Yes
imiquimod 1066 Drug TLR4 Yes
irinotecan 1040 Drug Macrophage Yes
lenalidomide 1060 Drug Macrophage Yes
levamisole 697 Drug Macrophage Yes
paclitaxel 3552 Drug TLR4 Yes
pioglitazone 2345 Drug Macrophage Yes
polymyxin B 623 Drug P2RX7 Yes
rapamycin 5459 Drug Macrophage Yes
simvastatin 3207 Drug Macrophage Yes
sulforaphane 1548 Drug NFE2L2 Yes
tert-butylhydroquinone 511 Drug NFE2L2 Yes
fisetin 810 Supplement NFE2L2 Yes
pterostilbene 536 Supplement NFE2L2 Yes
pyridostigmine 404 Supplement Macrophage Yes
resveratrol 4647 Supplement NFE2L2 Yes
rosiglitazone 2782 Supplement Macrophage Yes
9-cis-retinoic acid 877 Metabolite Macrophage Yes
cadmium 3573 Metabolite NFE2L2 Yes
estradiol 6534 Metabolite Macrophage Yes
heme 2115 Metabolite NFE2L2 Yes
hemin 1221 Metabolite TLR2 Yes
lipoic acid 1764 Metabolite NFE2L2 Yes
melatonin 5009 Metabolite NFE2L2 Yes
methionine 2264 Metabolite Macrophage Yes
retinoic acid 6995 Metabolite Macrophage Yes
deferoxamine 1539 Drug Macrophage Yes
quercetin 3203 Supplement NFE2L2 Yes
glutamine 3099 Metabolite Macrophage Yes
3H-1,2-dithiole-3-thione 174 Drug NFE2L2
bardoxolone 63 Drug NFE2L2
clioquinol 309 Drug Macrophage
dichloroacetate 738 Drug Macrophage
diethyl maleate 310 Drug NFE2L2
14. docetaxel 1501 Drug Macrophage
everolimus 1641 Drug Macrophage
FTY720 1780 Drug Macrophage
gadodiamide 114 Drug Macrophage
glatiramer acetate 633 Drug Macrophage
isoflurane 1666 Drug P2RX7
isoproterenol 2563 Drug Macrophage
lixisenatide 136 Drug Macrophage
MG132 2544 Drug NFE2L2
nitrogen mustard 380 Drug Macrophage
oltipraz 325 Drug NFE2L2
paraquat 1139 Drug NFE2L2
thiazolidinediones 1483 Drug Macrophage
triamcinolone acetonide 724 Drug Macrophage
butylated hydroxyanisole 468 Supplement NFE2L2
carnosic acid 479 Supplement NFE2L2
CDDO-Im 261 Supplement NFE2L2
CDDO-Me 491 Supplement NFE2L2
cinnamaldehyde 565 Supplement NFE2L2
ellagic acid 868 Supplement Macrophage
hydroxytyrosol 446 Supplement NFE2L2
indigo carmine 95 Supplement Macrophage
isoliquiritigenin 546 Supplement NFE2L2
phenethyl isothiocyanate 587 Supplement NFE2L2
urethane 495 Supplement Macrophage
15d-PGJ2 1313 Metabolite NFE2L2
4-hydroxynonenal 1163 Metabolite NFE2L2
calcitriol 4333 Metabolite Macrophage
triiodothyronine 3131 Metabolite Macrophage