This document summarizes research on peptides and aging conducted by Prof. Vladimir Khavinson and his colleagues. It describes several key findings:
1. Certain peptides have been found to increase lifespan and healthspan in animal studies by regulating gene expression and protein synthesis. These peptides show tissue-specific effects and are considered safe.
2. Peptide preparations developed from various tissues (thymus, pineal gland, etc.) have been used to treat over 15 million patients to prevent and treat age-related diseases.
3. Studies demonstrate that peptides can modulate immune function, suppress cancer growth, reduce induced carcinogenesis, protect against DNA damage, and increase stress resistance.
4. Research further suggests peptides may
O documento fornece informações sobre critérios gerais para escolha do tipo de polímero elastomérico. Ele discute a importância de obter dados técnicos e comerciais sobre o artefato, e usa gráficos e tabelas para ajudar na escolha da família de polímero baseada em propriedades como resistência ao calor e inchamento. Também fornece detalhes sobre características e aplicações típicas de diferentes famílias de borrachas.
FOOD AND NUTRACEUTICALS REGULATION IN INDIAChandanBV2
This document provides an overview of regulations for nutraceuticals and functional foods in India. It discusses key terms like nutraceuticals and functional foods. It outlines the history and timeline of food regulations in India, describing various national laws established. It explains the Food Safety and Standard Act of 2006, which aims to establish a single reference point for all food safety matters. The document also discusses licensing and registration requirements for nutraceuticals under FSSAI, labeling requirements, and the regulatory requirements for entering the Indian nutraceutical market.
Why Using Zebrafish for BioMedical Research and Drug Discovery?Jens-Ole Bock
Zebrafish is a vertebrate whose genome is completely sequenced; who shares a similar physiology to humans, including many equivalent organs; who offers with a growing battery of genetic tools, which combined with organism’s transparency, permits the tracing of cells and easy genetic manipulation (CRISPR).
These characteristics help ensure that information acquired through zebrafish is more accurate and informative than that obtained by in vitro assays, and thus easier to extrapolate to human biology.
Organs-on-a-chip are microfluidic cell culture chips that mimic human organs. They are about the size of an AA battery and contain channels lined with living human cells on a transparent chip. This allows scientists to observe cell behavior and responses under physiological conditions, including fluid flow and mechanical forces. Organs-on-chips can help address issues with drug development by providing more accurate and predictive models of how drugs will interact with human organs before clinical trials. They have the potential to reduce drug development costs and timelines compared to current animal models and cell cultures.
This document discusses the use of animal models in biomedical research. It describes how animals are used to study human disease and test potential treatments in order to advance human health without risking harm to people. Common animal models mentioned include mice, rats, dogs, primates, and rabbits, which can provide insights into conditions like heart disease, cancer, neurological disorders, and infectious diseases. However, the use of animals in research also raises ethical issues, as it often involves invasive procedures that can cause pain and distress. Large numbers of animals are required for activities like vaccine production and drug testing, but only a small percentage of potential treatments ultimately succeed.
Alternative to Animal Experiment ModelsDr Jayant Rai
The document discusses alternatives to animal experimentation. It provides an overview of animal experimentation, including its historical use and current regulatory guidelines. Some key uses of animals in experimentation include education, research, cosmetic testing, and toxicology testing. The document then discusses the development of alternatives such as in vitro techniques like cell cultures, microorganism studies, computer simulations, and epidemiological research that can replace or reduce animal use. It provides examples of specific alternative tests and methods that have been validated including embryonic stem cell tests, the Ames test, and skin patch tests. Overall, the document promotes developing and validating alternative methods to animal testing that satisfy the principles of replacement, reduction and refinement of animal use.
Regulatory strategy for medical device start-upsRina Nir
The document discusses regulatory considerations for medical device startups. It notes that the regulatory environment will significantly impact business plans by influencing budgets, timelines, staffing needs and more. Startups must thoroughly assess their regulatory situation and strategy to navigate the complex approval processes in both the US and EU. Later slides provide more details on specific regulatory pathways, standards, and trends to consider for medical device development.
Peptides are short chains of amino acids linked by peptide bonds. They are distinguished from proteins by typically containing fewer than 50 amino acid units. Peptides are formed through condensation reactions between carboxyl and amino groups of separate amino acids, releasing a water molecule. Peptide bonds are rigid and planar, contributing to protein structure stability. Peptides serve many important biological functions and can be classified based on their production method, including through ribosomal translation, nonribosomal synthesis, and enzymatic digestion of proteins in foods. Bioactive peptides derived from food proteins can have beneficial effects like lowering blood pressure, cholesterol, and antimicrobial properties.
O documento fornece informações sobre critérios gerais para escolha do tipo de polímero elastomérico. Ele discute a importância de obter dados técnicos e comerciais sobre o artefato, e usa gráficos e tabelas para ajudar na escolha da família de polímero baseada em propriedades como resistência ao calor e inchamento. Também fornece detalhes sobre características e aplicações típicas de diferentes famílias de borrachas.
FOOD AND NUTRACEUTICALS REGULATION IN INDIAChandanBV2
This document provides an overview of regulations for nutraceuticals and functional foods in India. It discusses key terms like nutraceuticals and functional foods. It outlines the history and timeline of food regulations in India, describing various national laws established. It explains the Food Safety and Standard Act of 2006, which aims to establish a single reference point for all food safety matters. The document also discusses licensing and registration requirements for nutraceuticals under FSSAI, labeling requirements, and the regulatory requirements for entering the Indian nutraceutical market.
Why Using Zebrafish for BioMedical Research and Drug Discovery?Jens-Ole Bock
Zebrafish is a vertebrate whose genome is completely sequenced; who shares a similar physiology to humans, including many equivalent organs; who offers with a growing battery of genetic tools, which combined with organism’s transparency, permits the tracing of cells and easy genetic manipulation (CRISPR).
These characteristics help ensure that information acquired through zebrafish is more accurate and informative than that obtained by in vitro assays, and thus easier to extrapolate to human biology.
Organs-on-a-chip are microfluidic cell culture chips that mimic human organs. They are about the size of an AA battery and contain channels lined with living human cells on a transparent chip. This allows scientists to observe cell behavior and responses under physiological conditions, including fluid flow and mechanical forces. Organs-on-chips can help address issues with drug development by providing more accurate and predictive models of how drugs will interact with human organs before clinical trials. They have the potential to reduce drug development costs and timelines compared to current animal models and cell cultures.
This document discusses the use of animal models in biomedical research. It describes how animals are used to study human disease and test potential treatments in order to advance human health without risking harm to people. Common animal models mentioned include mice, rats, dogs, primates, and rabbits, which can provide insights into conditions like heart disease, cancer, neurological disorders, and infectious diseases. However, the use of animals in research also raises ethical issues, as it often involves invasive procedures that can cause pain and distress. Large numbers of animals are required for activities like vaccine production and drug testing, but only a small percentage of potential treatments ultimately succeed.
Alternative to Animal Experiment ModelsDr Jayant Rai
The document discusses alternatives to animal experimentation. It provides an overview of animal experimentation, including its historical use and current regulatory guidelines. Some key uses of animals in experimentation include education, research, cosmetic testing, and toxicology testing. The document then discusses the development of alternatives such as in vitro techniques like cell cultures, microorganism studies, computer simulations, and epidemiological research that can replace or reduce animal use. It provides examples of specific alternative tests and methods that have been validated including embryonic stem cell tests, the Ames test, and skin patch tests. Overall, the document promotes developing and validating alternative methods to animal testing that satisfy the principles of replacement, reduction and refinement of animal use.
Regulatory strategy for medical device start-upsRina Nir
The document discusses regulatory considerations for medical device startups. It notes that the regulatory environment will significantly impact business plans by influencing budgets, timelines, staffing needs and more. Startups must thoroughly assess their regulatory situation and strategy to navigate the complex approval processes in both the US and EU. Later slides provide more details on specific regulatory pathways, standards, and trends to consider for medical device development.
Peptides are short chains of amino acids linked by peptide bonds. They are distinguished from proteins by typically containing fewer than 50 amino acid units. Peptides are formed through condensation reactions between carboxyl and amino groups of separate amino acids, releasing a water molecule. Peptide bonds are rigid and planar, contributing to protein structure stability. Peptides serve many important biological functions and can be classified based on their production method, including through ribosomal translation, nonribosomal synthesis, and enzymatic digestion of proteins in foods. Bioactive peptides derived from food proteins can have beneficial effects like lowering blood pressure, cholesterol, and antimicrobial properties.
Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,...KineMed, Inc.
The document discusses using measurements of causal pathways to improve predictability in disease outcomes and drug development. It outlines some key challenges, including the fundamental unpredictability of complex biological systems and high attrition rates in pharmaceutical development. The author proposes that measuring the activity of disease-driving processes, or "causal pathways", could help navigate this complexity and transform medicine development by providing a link between molecular targets and whole system outcomes. Examples of causal pathways for various diseases are given, and new kinetic technologies for measuring dynamic proteomes and metabolic water fluxes are described.
The biology of Aging in Insects From Drosphila to other insects and back.pptxArchana Ramanji
This particular presentation describes aging in insects and explains the mechanisms underlying it, particularly in Drosophila including eusocial insects.
This document discusses a study on the effects of micronutrient supplementation on male subfertility. It notes that sperm quality and male fertility have been declining. The study examined 132 men who took a daily supplement of various micronutrients for 3 months, finding a 25.8% pregnancy rate. This was higher than the 14.8% rate among the 73 men in a control group who did not take supplements. The document concludes that a lack of micronutrients may cause declining sperm quality and quality can be improved with micronutrient supplementation based on this study and others discussed.
‘From Molecular to Systems Nutrition. Lessons from mouse to man’ NUGO Dublin...Norwich Research Park
1. The document discusses the role of nutrition challenges and sensing mechanisms in adaptation and disease. It summarizes research on how different diets affect gene expression, organ function, and disease development using mouse models.
2. One study found that a weekly alternating diet between calorie restriction and a medium-fat diet in mice protected the liver from fatty liver disease compared to mice fed a constant medium-fat or calorie-restricted diet.
3. The research suggests unsaturated fats may be more efficiently taken up in the small intestine, activating nutrient sensing pathways and preventing organ overload and early disease development, compared to saturated fats.
Modulating Oncometabolic Syndrome: Integrative Diet & Nutrition to Complement...Jeanne M Wallace PhD
Presentation by Jeanne M. Wallace, PhD, CNC, at CMBM's Food as Medicine conference, Indianapolis 2013. Oncometabolic Syndrome is a cluster of metabolic factors that influence the growth and progression of cancer. Standard lab testing can be used to assess nutritional factors that may influence cancer outcomes, tailor a protocol to an individual's unique needs, and evaluate the efficacy of the nutrition intervention in modulating these factors.
Steven M. Kornblau is a professor of medicine at UT MD Anderson Cancer Center who specializes in hematology and oncology. He completed his medical training at MD Anderson from 1988-1991 and has been a faculty member there since 1991. Dr. Kornblau's research focuses on protein expression patterns in blood cancers. He also runs one of the largest tissue repositories for leukemia and myeloma in the world. The document discusses myelofibrosis, its diagnosis, prognosis, driver mutations, complications, and traditional and newer treatment options like ruxolitinib.
This section provides an overview of key molecular biology concepts:
- DNA exists in a condensed chromatin structure with histones to fit in the nucleus. Histone modifications regulate gene expression.
- Mitochondria have their own circular DNA separate from nuclear DNA.
- DNA methylation and histone modifications like methylation and acetylation can alter gene expression without changing DNA sequence. Dysregulated epigenetic modifications are implicated in diseases.
- Nucleotides are composed of a nitrogenous base, a pentose sugar, and a phosphate. Purines and pyrimidines differ in their ring structures. DNA contains thymine while RNA contains uracil.
Androgens & Cardiovascular Diseases in Women: From Basic Research to Clinical...InsideScientific
Join Dr. Licy Yanes-Cardozo as she expands on her research exploring the role of androgens on cardiovascular physiology in cis and transgender patients.
Women have higher plasma concentrations of androgens than estrogens, yet the role of androgens in physiological processes and diseases is not completely understood. High levels of androgens in women are associated with a negative cardiometabolic profile, whereas in men, low levels of androgens are associated with an increased incidence of cardiovascular diseases.The biology behind androgens’ sex difference is not completely understood.
In this webinar, Dr. Yanes-Cardozo discusses two clinical situations that are associated with high levels of androgens. Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in reproductive-aged women, is associated with a modest elevation of plasma levels of androgens. In transmen individuals (female to male), plasma concentrations of androgens are elevated to achieve similar levels found in cisgender men and much higher than in PCOS women. The role that these two different plasma concentrations play in cardiovascular physiology and pathophysiology remains unclear. Gaps and opportunities in basic research and clinical practice are highlighted.
Key Topics Include:
- Review the key role of androgens in cardiovascular pathophysiology
- Discuss potential mechanisms by which androgens mediate a deleterious cardiometabolic profile in females
- Interpret gaps and opportunities in basic and clinical practice in conditions of androgen excess
The document provides an overview of the field of biotechnology, including its history, key areas and applications. It discusses topics like genetic engineering, recombinant DNA technology, transgenic plants and animals, DNA microarrays, bioinformatics, and careers in biotechnology. The future prospects of biotechnology in addressing global challenges like food security and healthcare are also highlighted.
П. Сутерс "Проявления инсулинорезистентности и гликемический контроль в интен...rnw-aspen
Доклад с 15 Межрегиональной научно-практической конференции "Искусственное питание и инфузионная терапия больных в медицине критических состояний" 21-22 мая 2015 г
Protein kinases play an important role in cell signaling and are implicated in many human diseases. There are over 500 protein kinase genes in the human genome, with around 30% associated with tumor suppression and 100 associated with oncogenesis. Protein kinases function through reversible phosphorylation of other proteins and are involved in key cellular processes like growth, differentiation, survival and death. Dysregulation of kinases, through overexpression, mutation or chromosomal translocation, can lead to uncontrolled cell growth and cancer development. Targeting dysregulated kinases through monoclonal antibodies or small molecule inhibitors is an important therapeutic strategy for diseases like cancer. Further characterization of the many unexplored kinases may open new targets for drug development.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
This document describes using computational methods to identify potential drug candidates that can inhibit breast cancer metastatic beta arrestin 2 (ARRB2). Ensemble-based virtual screening and pharmacophore modeling were used to screen drug molecules from the DrugBank database and identify top candidates. The 15 molecules with best binding were further analyzed with molecular dynamics simulations. The results suggest two molecules as the best ARRB2 inhibitor candidates based on their binding affinity and stability in simulations. The study provides a framework for discovering novel ARRB2 inhibitors using integrated computational approaches.
My Prostate Cancer Story by Paul SchellhammerTony Crispino
With permission of Dr. Schellhammer this slide deck should be interesting to any PCa patient. Dr. Schellhammer is a former president of the American Urological Association and a leading authority on prostate cancer. He has fought i long battle. He and his colleague, Paul Lange operated on each other and had vastly different results.
dkNET Webinar: An Encyclopedia of the Adipose Tissue Secretome to Identify Me...dkNET
Presenter: Paul Cohen, MD, PhD, Albert Resnick, M.D. Associate Professor, Rockefeller University
Abstract
White and brown adipocytes not only play a central role in energy storage and combustion but are also dynamic secretory cells that secrete signaling molecules linking levels of energy stores to vital physiological systems. Disruption of the signaling properties of adipocytes, as occurs in obesity, contributes to insulin resistance, type 2 diabetes, and other metabolic disorders. Fat cells have been estimated to secrete over 1,000 polypeptides and microproteins and an even larger number of small molecule metabolites. The great majority of the adipocyte secretome has not been defined or characterized. A major obstacle has been the lack of suitable technologies to quantitatively identify circulating proteins and metabolites, determine their cellular origin, and elucidate their function. Building on key innovations in chemical biology and mass spectrometry, our team is generating an encyclopedia of the white and brown adipocyte secretome in mouse models and humans. Our work has the potential to identify new secreted mediators with roles in obesity, type 2 diabetes, and metabolic diseases, provide a crucial resource for researchers and clinicians, and lead to new biomarkers and therapies.
The top 3 key questions that this resource can answer:
1. What techniques can be used to characterize the secretome of a cell type in vitro and in vivo?
2. What is the full complement of proteins and metabolites secreted by different kinds of adipocytes?
3. How should one prioritize uncharacterized secreted mediators for functional study?
Resource link: https://secrepedia.org/
Upcoming webinars schedule: https://dknet.org/about/webinar
Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer. It consists of autologous dendritic cells activated ex vivo with a recombinant fusion protein and infused back to the patient to stimulate an immune response against prostate cancer cells. Clinical trials demonstrated a significant survival benefit for patients treated with Sipuleucel-T compared to placebo. Dendreon is preparing for the commercial launch of Provenge in the US and EU, which will require a major manufacturing and logistics effort to process and deliver the personalized immunotherapy to thousands of patients.
1. Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer that works by activating antigen-presenting cells and T-cells against prostatic acid phosphatase.
2. Clinical trials showed Provenge improved overall survival in metastatic castration-resistant prostate cancer patients.
3. Manufacturing and delivering Provenge presents logistical challenges due to its personalized nature that Dendreon aims to address through an advanced planning system and partnerships.
The document summarizes current diagnosis and treatment strategies for neuroendocrine tumors. It discusses the classification and grading of neuroendocrine tumors based on primary tumor site and biomarkers like Ki67. Imaging techniques like octreoscan, MIBG scintigraphy, and PET using tracers like 18F-DOPA and 68Ga-DOTA-octreotide are described. Treatment options discussed include surgery, medical therapies like somatostatin analogs, chemotherapy, targeted radionuclide therapy using 177Lu-DOTA-octreotate and peptide receptor radionuclide therapy.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,...KineMed, Inc.
The document discusses using measurements of causal pathways to improve predictability in disease outcomes and drug development. It outlines some key challenges, including the fundamental unpredictability of complex biological systems and high attrition rates in pharmaceutical development. The author proposes that measuring the activity of disease-driving processes, or "causal pathways", could help navigate this complexity and transform medicine development by providing a link between molecular targets and whole system outcomes. Examples of causal pathways for various diseases are given, and new kinetic technologies for measuring dynamic proteomes and metabolic water fluxes are described.
The biology of Aging in Insects From Drosphila to other insects and back.pptxArchana Ramanji
This particular presentation describes aging in insects and explains the mechanisms underlying it, particularly in Drosophila including eusocial insects.
This document discusses a study on the effects of micronutrient supplementation on male subfertility. It notes that sperm quality and male fertility have been declining. The study examined 132 men who took a daily supplement of various micronutrients for 3 months, finding a 25.8% pregnancy rate. This was higher than the 14.8% rate among the 73 men in a control group who did not take supplements. The document concludes that a lack of micronutrients may cause declining sperm quality and quality can be improved with micronutrient supplementation based on this study and others discussed.
‘From Molecular to Systems Nutrition. Lessons from mouse to man’ NUGO Dublin...Norwich Research Park
1. The document discusses the role of nutrition challenges and sensing mechanisms in adaptation and disease. It summarizes research on how different diets affect gene expression, organ function, and disease development using mouse models.
2. One study found that a weekly alternating diet between calorie restriction and a medium-fat diet in mice protected the liver from fatty liver disease compared to mice fed a constant medium-fat or calorie-restricted diet.
3. The research suggests unsaturated fats may be more efficiently taken up in the small intestine, activating nutrient sensing pathways and preventing organ overload and early disease development, compared to saturated fats.
Modulating Oncometabolic Syndrome: Integrative Diet & Nutrition to Complement...Jeanne M Wallace PhD
Presentation by Jeanne M. Wallace, PhD, CNC, at CMBM's Food as Medicine conference, Indianapolis 2013. Oncometabolic Syndrome is a cluster of metabolic factors that influence the growth and progression of cancer. Standard lab testing can be used to assess nutritional factors that may influence cancer outcomes, tailor a protocol to an individual's unique needs, and evaluate the efficacy of the nutrition intervention in modulating these factors.
Steven M. Kornblau is a professor of medicine at UT MD Anderson Cancer Center who specializes in hematology and oncology. He completed his medical training at MD Anderson from 1988-1991 and has been a faculty member there since 1991. Dr. Kornblau's research focuses on protein expression patterns in blood cancers. He also runs one of the largest tissue repositories for leukemia and myeloma in the world. The document discusses myelofibrosis, its diagnosis, prognosis, driver mutations, complications, and traditional and newer treatment options like ruxolitinib.
This section provides an overview of key molecular biology concepts:
- DNA exists in a condensed chromatin structure with histones to fit in the nucleus. Histone modifications regulate gene expression.
- Mitochondria have their own circular DNA separate from nuclear DNA.
- DNA methylation and histone modifications like methylation and acetylation can alter gene expression without changing DNA sequence. Dysregulated epigenetic modifications are implicated in diseases.
- Nucleotides are composed of a nitrogenous base, a pentose sugar, and a phosphate. Purines and pyrimidines differ in their ring structures. DNA contains thymine while RNA contains uracil.
Androgens & Cardiovascular Diseases in Women: From Basic Research to Clinical...InsideScientific
Join Dr. Licy Yanes-Cardozo as she expands on her research exploring the role of androgens on cardiovascular physiology in cis and transgender patients.
Women have higher plasma concentrations of androgens than estrogens, yet the role of androgens in physiological processes and diseases is not completely understood. High levels of androgens in women are associated with a negative cardiometabolic profile, whereas in men, low levels of androgens are associated with an increased incidence of cardiovascular diseases.The biology behind androgens’ sex difference is not completely understood.
In this webinar, Dr. Yanes-Cardozo discusses two clinical situations that are associated with high levels of androgens. Polycystic Ovary Syndrome (PCOS), the most common endocrine disorder in reproductive-aged women, is associated with a modest elevation of plasma levels of androgens. In transmen individuals (female to male), plasma concentrations of androgens are elevated to achieve similar levels found in cisgender men and much higher than in PCOS women. The role that these two different plasma concentrations play in cardiovascular physiology and pathophysiology remains unclear. Gaps and opportunities in basic research and clinical practice are highlighted.
Key Topics Include:
- Review the key role of androgens in cardiovascular pathophysiology
- Discuss potential mechanisms by which androgens mediate a deleterious cardiometabolic profile in females
- Interpret gaps and opportunities in basic and clinical practice in conditions of androgen excess
The document provides an overview of the field of biotechnology, including its history, key areas and applications. It discusses topics like genetic engineering, recombinant DNA technology, transgenic plants and animals, DNA microarrays, bioinformatics, and careers in biotechnology. The future prospects of biotechnology in addressing global challenges like food security and healthcare are also highlighted.
П. Сутерс "Проявления инсулинорезистентности и гликемический контроль в интен...rnw-aspen
Доклад с 15 Межрегиональной научно-практической конференции "Искусственное питание и инфузионная терапия больных в медицине критических состояний" 21-22 мая 2015 г
Protein kinases play an important role in cell signaling and are implicated in many human diseases. There are over 500 protein kinase genes in the human genome, with around 30% associated with tumor suppression and 100 associated with oncogenesis. Protein kinases function through reversible phosphorylation of other proteins and are involved in key cellular processes like growth, differentiation, survival and death. Dysregulation of kinases, through overexpression, mutation or chromosomal translocation, can lead to uncontrolled cell growth and cancer development. Targeting dysregulated kinases through monoclonal antibodies or small molecule inhibitors is an important therapeutic strategy for diseases like cancer. Further characterization of the many unexplored kinases may open new targets for drug development.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
This document describes using computational methods to identify potential drug candidates that can inhibit breast cancer metastatic beta arrestin 2 (ARRB2). Ensemble-based virtual screening and pharmacophore modeling were used to screen drug molecules from the DrugBank database and identify top candidates. The 15 molecules with best binding were further analyzed with molecular dynamics simulations. The results suggest two molecules as the best ARRB2 inhibitor candidates based on their binding affinity and stability in simulations. The study provides a framework for discovering novel ARRB2 inhibitors using integrated computational approaches.
My Prostate Cancer Story by Paul SchellhammerTony Crispino
With permission of Dr. Schellhammer this slide deck should be interesting to any PCa patient. Dr. Schellhammer is a former president of the American Urological Association and a leading authority on prostate cancer. He has fought i long battle. He and his colleague, Paul Lange operated on each other and had vastly different results.
dkNET Webinar: An Encyclopedia of the Adipose Tissue Secretome to Identify Me...dkNET
Presenter: Paul Cohen, MD, PhD, Albert Resnick, M.D. Associate Professor, Rockefeller University
Abstract
White and brown adipocytes not only play a central role in energy storage and combustion but are also dynamic secretory cells that secrete signaling molecules linking levels of energy stores to vital physiological systems. Disruption of the signaling properties of adipocytes, as occurs in obesity, contributes to insulin resistance, type 2 diabetes, and other metabolic disorders. Fat cells have been estimated to secrete over 1,000 polypeptides and microproteins and an even larger number of small molecule metabolites. The great majority of the adipocyte secretome has not been defined or characterized. A major obstacle has been the lack of suitable technologies to quantitatively identify circulating proteins and metabolites, determine their cellular origin, and elucidate their function. Building on key innovations in chemical biology and mass spectrometry, our team is generating an encyclopedia of the white and brown adipocyte secretome in mouse models and humans. Our work has the potential to identify new secreted mediators with roles in obesity, type 2 diabetes, and metabolic diseases, provide a crucial resource for researchers and clinicians, and lead to new biomarkers and therapies.
The top 3 key questions that this resource can answer:
1. What techniques can be used to characterize the secretome of a cell type in vitro and in vivo?
2. What is the full complement of proteins and metabolites secreted by different kinds of adipocytes?
3. How should one prioritize uncharacterized secreted mediators for functional study?
Resource link: https://secrepedia.org/
Upcoming webinars schedule: https://dknet.org/about/webinar
Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer. It consists of autologous dendritic cells activated ex vivo with a recombinant fusion protein and infused back to the patient to stimulate an immune response against prostate cancer cells. Clinical trials demonstrated a significant survival benefit for patients treated with Sipuleucel-T compared to placebo. Dendreon is preparing for the commercial launch of Provenge in the US and EU, which will require a major manufacturing and logistics effort to process and deliver the personalized immunotherapy to thousands of patients.
1. Sipuleucel-T (Provenge) is an autologous cellular immunotherapy for asymptomatic metastatic prostate cancer that works by activating antigen-presenting cells and T-cells against prostatic acid phosphatase.
2. Clinical trials showed Provenge improved overall survival in metastatic castration-resistant prostate cancer patients.
3. Manufacturing and delivering Provenge presents logistical challenges due to its personalized nature that Dendreon aims to address through an advanced planning system and partnerships.
The document summarizes current diagnosis and treatment strategies for neuroendocrine tumors. It discusses the classification and grading of neuroendocrine tumors based on primary tumor site and biomarkers like Ki67. Imaging techniques like octreoscan, MIBG scintigraphy, and PET using tracers like 18F-DOPA and 68Ga-DOTA-octreotide are described. Treatment options discussed include surgery, medical therapies like somatostatin analogs, chemotherapy, targeted radionuclide therapy using 177Lu-DOTA-octreotate and peptide receptor radionuclide therapy.
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
1. Peptides, Genome, Ageing
Prof. Vladimir Khavinson, M.D.,Ph.D.
Director of the St. Petersburg Institute of
Bioregulation and Gerontology
Member of the Russian Academy of Sciences
I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences
Saint Petersburg Institute of Bioregulation and Gerontology
http://www.khavinson.ru
khavinson@gerontology.ru
2. Interrelation of life style, disease, work, ecology,
genetics and biological ageing
Ageing
Disease
Life style
WorkEcology
Genetics
3. Population aged 60 and over in the main world
regions 1960 – 2020
Source: UN unit of population
4. Documented centenarians
Country Age Name Date of birth Date of death
France 122 Jeanne Calment 23.02.1875 04.08.1997
Japan 120 Sigechio Izumi 29.06.1865 21.02.1986
Russia 117 Semennikova Varvara 10.05.1890 09.03.2008
USA 114 Martha Graham 12.1844 25.06.1959
Great Britain 114 Martha Eliza Williams 02.06.1873 02.06.1987
Canada 113 Pierre Joubert 15.07.1701 16.11.1814
Spain 112 Joseph Salas Mateo 14.06.1860 27.02.1973
France 112 Augustine Tessier 02.10.1869 09.03.1981
5. Potential increase in the average human lifespan up
to specific limit (biological reserve)
Khavinson V. Peptidergic regulation of ageing (2009)
7. The expression of transcription proteins (PAX1) in
epithelial cells of human thymus
Khavinson V. Peptidergic regulation of ageing (2009)
* - p<0.05 as compared to group 1
Immunofluorescence laser confocal microscopy, x400
Red fluorescence – Rodamin G
Green fluorescence – FITC
8. Age-related changes in the expression of
signal molecules in human thymus
Markers
Area of expression, %
60-74 years 75-89 years >90 years
Ki67 0.58±0.07 0.19±0.03* 0.07±0.02*
Р53 4.51±0.11 9.32±0.43* 4.41±0.20
AIF 0.07±0.02 1.35±0.02* 2.61±0.31*
MMP2 0.58±0.07 0.19±0.03* 0.07±0.02*
MMP9 4.51±0.11 9.32±0.43* 4.41±0.20
CGRP 0.07±0.02 1.35±0.02* 2.61±0.31*
CD4 2.70±0.54 1.58±0.18* 0.32±0.07*
CD5 2.48±0.31 1.66±0.31 1.05±0.12*
CD8 3.88±0.52 3.91±0.49 1.84±0.32*
CD20 0.69±0.12 0.56±0.11 0.65±0.13
- р<0.05 as compared to corresponding indices in the group of patients aged 60-74*
9. Protein synthesis in hepatocytes of rats
of different age
Khavinson V. Peptides and ageing (2002)
- p<0.05 as compared to the 3-month old rats; - p<0.05 as compared to the 9-month old rats* **
10. Adverse factors
(stress, harmful
environment, radiation,etc.)
Decreased gene
activity
Decreased protein
synthesis
Decreased functions
of organs
Decreased vital
activity
Peptides
(small proteins)
Recovery
Pathological processes
and accelerated ageing
Peptide bioregulation of vital activity
11. 1. Natural origin
2. Tissue-specific action
3. Safe to use
4. Microdoses
5. Availability of the product
St. Petersburg Institute of Bioregulation and Gerontology
1. Peptide preparations (over 30)
2. Peptide biologically active food supplements (over 40)
3. Peptide cosmetic products (over 10)
Characteristics of the peptides
12. Over 15 million patients were treated with these pharmaceuticals both for prevention
and treatment of different pathological states (1982 – 2014).
Cytomedins® - peptide geroprotectors
(pharmaceuticals)
Preparation
(State Pharmacopoeia of the
Russian Federation)
Source of the
peptides
Patents
Thymalin®
(1982)
Thymus
Morozov V., Khavinson V.
US Patent № 5,070,076 (1991)
Epithalamin®
(1990)
Pineal gland
Khavinson V. et al.
RU Patent № 944191 (1993)
Prostatilen®
(1992)
Prostate gland
Khavinson V. et al.
RU Patent № 1417244 (1993)
Cortexin®
(1999)
Brain
Khavinson V. et al.
RU Patent № 1298979 (1993)
Retinalamin®
(1999)
Retina
Khavinson V. et al.
RU Patent № 1436305 (1993)
13. Cytogens® - synthetic peptides
(pharmaceutical and food supplements)
Preparations Structure
Correction of
functions
Patents
Thymogen® Glu-Trp Immune system
Morozov V., Khavinson V.
US Patent № 5,538,951 (1996)
Vilon® Lys-Glu
Regeneration
processes
Khavinson V. et al.
US Patent № 6,642,201 (1996)
Vesugen® Lys-Glu-Asp Vessels
Khavinson V. et al.
US Patent № 7,851,449 (2010)
Livagen® Lys-Glu-Asp-Ala Liver
Khavinson V.
US Patent № 7,101,854 (2006)
Epitalon® Ala-Glu-Asp-Gly Endocrine system
Khavinson V.
US Patent № 6,727,227 (2004)
Bronchogen® Ala-Glu-Asp-Leu
Bronchopulmonary
system
Khavinson V. et al.
US Patent № 7,625,870 (2009)
Pancragen® Lys-Glu-Asp-Trp Pancreas
Khavinson V. et al.
US Patent № 7,491,703 (2009)
Cardiogen® Ala-Glu-Asp-Arg
Cardiovascular
system
Khavinson V. et al.
US Patent № 7,662,789 (2010)
14. Peptide tissue (gene)-specific regulation
Khavinson V. Bull. Exp. Biol. Med. (2002)
- p<0.05 as compared to the control*
15. Livagen increases protein synthesis in rat
hepatocytes
Khavinson V. Neuroendocrinology Lett. (2002)
3 months 24 months
- p<0.05 as compared to the control*
16. Peptide immune modulators
(Saint Petersburg Institute of Bioregulation and Gerontology)
Preparation Structure Patents
Thymalin® Polypeptides from
thymus
Morozov V., Khavinson V.
US Patent № 5,070,076 (1991)
Thymogen®
Glu-Trp
Morozov V., Khavinson V.
US Patent № 5,538,951 (1996)
Vilon®
Lys-Glu
Khavinson V. et al.
US Patent № 6,642,201 (1996)
Crystagen®
Glu-Asp-Pro
Khavinson V. et al.
US Patent № 8,057,810 (2011)
17. Similarity in structures of the peptide
immune modulators
Preparation Structure Publications
Vilon Lys-Glu (Morozov V., Khavinson V.,1997)
Splenopentin Arg-Lys-Glu-Val-Tyr (Audhya G. et al., 1984)
Thymosin alpha-1
(ACE)-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu- Ile-
Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-
Glu-Ala-Glu-Asn
19. The influence of Vilon (KE) on the expression of signal
molecules in dissociated human thymus cultures
- p<0.05 as compared to the control
0
1
2
3
4
CD4 CD5
Areaofexpression,%
* *
Control Vilon
*
20. The influence of Vilon on CD5 expression
in dissociated human thymus cultures
Control Vilon
Immunohistochemistry with hematoxylin and eosin stain, х200
21. The influence of Vilon on differentiation of CD4+CD8+
thymocytes into CD4+ lymphocytes
Flowcytometry
Vilon
74,7%
19,4%
Control
96,7%
1,2%
23. Peptides suppress the cellular growth curve of
human B-cell lymphoblastic leukemia
0
10,000
20,000
30,000
40,000
50,000
60,000
0 2 4 6 8 10
Numberofcellsin1ml
time, days
контроль АЕ-0 АВ-0 Т-34Vilon Chonluten
(EDG)
*
*
*
*
- p<0.05 as compared to the control
Control Epitalon
Peptide concentration – 20 ng/ml
Namalva line cells, 6th passage
*
24. Control Chonluten, 20 ng/ ml
Life light microscopy, х 100, 3rd day of the experiment
The peptide decreases the number of B-cells
of human lymphoblastic leukemia
(Namalva line, 6th passage)
25. 0
20
40
60
80
100
120
140
160
180
контроль АЕ-0 АВ-0 Т-34
a0,h Peptides increase average doubling time of cell
population of human B-cell lymphoblastic leukemia
(Namalva line, 6th passage)
0
0
ln
2ln
M
M
t
a
t
a0 – average doubling time of
cell population, h
t – time of logarithmic phase of
culture growth, h
Mt - number of cells at the
moment of time t
M0 - number of cells at the
initial time
*
*
*
- p<0.05 as compared to the control
Control Epitalon Vilon Chonluten
*
26. *
*
Peptides increase CD3 expression in cell population
culture of human B-cell lymphoblastic leukemia
(Namalva line, 6th passage)
- p<0.05 as compared to the control
0
0.25
0.5
0.75
1
контроль AE-0 AB-0 Т-34
CD3 area of expression, %
Epitalon Vilon ChonlutenControl
СD3 – marker of Т-lymphocyte
*
*
*
27. Control Vilon, 20 ng/ ml
Light microscopy, immunocitochemistry with haematoxylin coloration, х 200
Peptides increase CD3 expression in cell population
culture of human B-cell lymphoblastic leukemia
(Namalva line, 6th passage)
28. Peptides decrease induced carcinogenesis in
animals
Anisimov V., Khavinson V. Biogerontology (2010)
- р<0.05 as compared to the control*
30. The influence of peptides on chromatin in human
lymphocytes
Khavinson V., Malinin V. Gerontological aspects of genome peptide regulation (2005)
- p<0.05 as compared to the control (20-40 years old); - p<0.05 as compared to the control (75-88 years old)
* **
31. - p<0.001 as compared to the control; - p<0.05 as compared to the control
Anisimov V. et al. International J. Cancer (2002)
Peptides suppress HER-2/neu oncogene expression
in transgenic mice
* **
32. Epitalon increases telomere length and the limit of
fibroblasts division
Anisimov V., Khavinson V. Biogerontology (2010)
- p<0.05 as compared to the control*
33. Retinal peptides induce the differentiation of
polypotent ectoderm of Xenopus laevis
Khavinson V. Peptidergic regulation of ageing (2009)
34. - р<0.05 as compared to the young animals, placebo; - р<0.05 as compared to the old animals, placebo
Epitalon increases melatonin synthesis in old
monkeys
Melatoninlevelinbloodin3p.m.
(ng/ml)
6-8 years
(young monkeys)
Placebo
Epitalon
20-26 years
Khavinson V. et al. Neuroendocrinology Lett. (2001)
* **
35. Ezhekort (EDG) decreases apoptosis
2. mito-GPF expression in human gastric epithelial cells
1. mito-GPF expression in mice fibroblasts
Control H. Pylori + EzhekortH. Pylori
Control H. Pylori + EzhekortH. Pylori
Confocal microscopy, х400
Confocal microscopy, х600
36. Ezhekort increases the expression of marker WNT5A
in culture of human gastric epithelial cells
- р < 0.05 as compared to the control; - р < 0.05 as compared to H. рylori
WNT5Aareaexpression,%
Control H. pylori H. pylori + H. pylori +
Ezhekort Clacid
* **
37. Ezhekort increases the expression of KRT14 protein
(cytoskeleton marker) in culture of human gastric
epithelial cells
KRT14areaexpression,%
- р < 0.05 as compared to the control; - р < 0.05 as compared to H. рylori
Control H. pylori H. pylori + H. pylori +
peptide Clacid
* **
38. Ezhekort decreases the expression of mRNA signal
molecules in gastric mucous membrane
*
*
*
*
TNFα - tumor necrosis factor, SOD – superoxide dismutase, Cox-2 – cyclooxygenase
mRNAsignalmolecule
expression,c.u.
Control Gastric ulcer Gastric ulcer + Gastric ulcer +
peptide сlacid
- p<0.05 – as compared to the control
TNFα SOD Cox-2
Khavinson V., et al. Bull. Exp. Biol. Med. (2011)
*
*
*
*
*
39. Pathomorphosis of induced gastric ulcers, х 20
Ezhekort contributes to epithelialization
of gastric ulcer
Control Ezhekort
Pyogenic infiltrate of
leukocytes in ulcer
Ulcer Ulcer healing
Khavinson V., et al. Bull. Exp. Biol. Med. (2011)
40. Ezhekort decreases the mRNA gene expression in
gastric mucous membrane
iNOS – NO-synthase 2 (inducible), eNOS - endothelial NO-synthase,
HSP70 - heat shock protein, NF kappa b-p65 - transcription factor
0
100
200
300
400
500
600
iNOS cNOS HSP70 NF kappa b-p65
Signalingmoleculesexpression
comparedtothecontrole,%
Control Gastric ulcer Gastric ulcer + peptide Gastric ulcer + clacide
*
*
* *
** ** ** ** ** ** ** **
- р < 0.05 as compared to the control; - р < 0.05 as compared to the gastric ulcer* **
41. The influence of Pancragen on glucose content in the
blood of rats with alloxan-induced diabetes (treatment)
Animal
group
Glucose concentration in blood (mg %)
Initial
level
In 15 days
after
alloxan
injection
8th day of
Pancragen
course
After the completion of Pancragen course (days)
9 28 44 58
Control
(NaCl)
84.0±5.7 345.0±15.4 360.0±12.3 351.4±11.2 375.7±11.2
347.2±12.
8
332.1±13.7
n 10 10 9 7 5 5 3
Pancragen 81.1±3.8 333.6±12.4 254.5±16.2* 183.9 ±10.5* 221.5±11.2* 210.8±9.3* 198.9±11.5*
n 11 11 11 9 8 8 7
- p < 0.001 as compared to the control*
42. Pancragen decreases glucose content in the blood of
rats with alloxan-induced diabetes
(prevention and treatment)
Animal
group
Glucose concentration in blood (mg %)
Initial
level
7th day of
Pancragen
course
(1st course)
After alloxan injection (days)
14
21 28
402nd Pancragen course
(from 18th till 28th day)
Control
(NaCl)
82.7 ± 0.9 96.4 ± 1.0 333.7 ± 55.8* 345.6 ± 57.8* 156.4 ± 26.4* 405.0±89.8*
n 7 7 6 5 5 4
Pancragen 76.8 ± 1.1 94.0 ± 0.8 261.5 ± 39.5** 159.0 ± 32.6** 77.3 ± 1.3** 107.7±6.4**
n 8 8 8 6 6 6
- p < 0.001 as compared to the initial level; - p < 0.02 as compared to the control* **
43. Pancragen increases insulin content in blood of rats
with alloxan-induced diabetes
Animal group
Insulin content in the blood (μMU/ml)
Initial level
8th day of the
treatment of
alloxan diabetes
After alloxan injection (days)
9 18 44
Control
(NaCl)
24.3 ± 2.1 0.8 ± 0.25 0 0 0
n 8 8 6 5 5
Pancragen 23.8 ± 2.8 3.1 ± 1.1* 3.2 ± 0.5** 4.3 ± 0.5** 3.9 ± 1.1**
n 10 10 7 7 7
- p < 0.05 as compared to the initial level; - p < 0.001 as compared to the control* **
44. Pancragen (KEDW) increases the protein expression
in senescent pancreatic cells
Peptide KEDW stimulates the expression of β-cell differentiation factors (Nkx2.2, Pax4)
in human pancreatic cell cultures
0
0.5
1
1.5
2
control peptide AEDL
(control)
peptide KEDW
Geneexpressoin,units
0
0.2
0.4
0.6
0.8
1
control peptide AEDL
(control)
peptide KEDW
Geneexpression,units
*
*
Pax4Nkx2.2
Proteinexpression,%
Proteinexpression,%
Khavinson V. Advances in Gerontology (2013)
- р<0.05 as compared to the control*
45. Peptide KEDW stimulates the expression of
acinar differentiation factor Ptf1a in human
pancreatic cell cultures
Peptide KEDW stimulates the expression of
α-cell differentiation factor Pax6 in human
pancreatic cell cultures
0
0.5
1
1.5
2
2.5
3
control peptide AEDL
(control)
peptide KEDW
Geneexpression,units
0
0.5
1
1.5
2
control peptide AEDL
(control)
peptide KEDW
Geneexpression,units
Ptf1a
Pax6
Proteinexpression,%Proteinexpression,%
Khavinson V. Advances in Gerontology (2013)
Pancragen increases the protein expression
in senescent pancreatic cells
*
*
- р<0.05 as compared to the control*
46. Pancragen increases the expression of
differentiation factor Pax6 in senescent pancreatic cells
Immunocytochemistry, х200,
aged (14th passage) cell culture of human pancreas “MIA PaCa-2”
Control Peptide KEDW
Khavinson V. Advances in Gerontology (2013)
47. Peptides increase average lifespan
(the results of 25 experiments)
Death of
control animals (0)
Khavinson V. Peptidergic regulation of ageing (2009)
- р<0.05 as compared to the control*
Inrespecttothecontrol(0)
48. The influence of peptide bioregulators
on mice lifespan
Khavinson V. Peptides and ageing (2002)
- р<0.05 as compared to the control*
49. Peptides increase organism vital resource
Biological Activity Publications
Increase in the protein synthesis in rat hepatocytes
by 42.9%
Khavinson V. Peptides and
ageing. NEL (2002)
Increase in the growth of explants in organotypic
cultures of cells of the animal by 22-42%
Khavinson V. Peptides and
ageing. NEL (2002)
Increase of the amount of optional heterochromatin
in lymphocytes of elderly people by 42.4%
Khavinson V. et al. NEL (2003)
Increase in the number of divisions of human
fibroblasts by 42.5% and a 2.4-fold increase in the
average length of telomeres
Khavinson V. et al. Bul. Exp.
Biol. Med. (2004)
Increase in the lifespan of animals by 20-40% and
maximal lifespan by 42.3%
Anisimov V., Khavinson V.
Biogerontology (2010),
Anisimov V. et al. Mech. Ageing
Dev. (2001)
A 3.1-fold decrease in the frequency of tumors
induced by a carcinogenic agent in animals
Anisimov V., Khavinson V.
Biogerontology (2010)
53. The structures of peptides (3D models)
Conformations of the peptides Ala-Glu-Asp-Gly (Epitalon), Glu-Asp-Gly (Chonluten),
Lys-Glu (Vilon) with optimal minimization energy.
Red colour indicates oxygen molecules, blue – nitrogen molecules, black – carbon
molecules, light grey - polar hydrogen molecules. Nonpolar hydrogen molecules are
not displayed
Epitalon Chonluten Vilon
54. Penetration of FITC-labeled peptide
into HeLa cells
Fedoreeva L. et al. Biochemistry (2010)
6-hour cell incubation with
FITC-labeled peptide (1,2 х 10-6 М)
А, C –
staining of
DAPI nuclei
(DNA
identification)
B, D –
fluorescence
A B
C D
Control
FITC-tag peptide
55. The influence of peptides on hydrolysis of
fluorescence-labelled deoxyribooligonucleotide with
endonuclease WEN1
B - Bronchogen
(Ala-Glu-Asp-Leu)
C - Cardiogen
(Lys-Glu-Asp-Arg)
E - Epitalon
(Ala-Glu-Asp-Gly)
Khavinson V. et al. Bull. Exp. Biol. Med. (2011)
P - Pancragen
(Lys-Glu-Asp-Trp)
Oligo
Oligo+WEN1
Oligo+WEN1+Е
Oligo+WEN1+B
Oligo+WEN1+P
Oligo+WEN1+C
Oligonucleotide - (5’) FAM – CGC CGC CAG GCG CCG CCG CG (3’)
(FAM – carboxyfluorescein)
56. Fedoreeva L. et al. Biochemistry (2011)
The influence of Bronchogen (ADEL) on
deoxyribooligonucleotide fluorescence with CNG
and CG sites which could be metilated
Length wave, nm
Fluorescenceintensity,units
Control
Bronchogen
(various
concentrations)
Bronchogen suppresses
fluorescence
(5’ ) (FAM)-cg-ccg-cca-ggc-gcc-gcc-gcg (3’)
57. HPLS of peptide and DNA on sefandex G-25 in
physiological solution at room temperature
Khavinson V. et al. Bull. Exp. Biol. Med. (2006)
58. DNA - Pancragen (KEDW) interaction
(spectrophotometric method)
220 240 260 280 300 320 340
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
1,6
1,8
2,0
оптическаяплотнсть
длина волны, нм
ДНК
С(KEDW)/C(ДНК)=1
С(KEDW)/C(ДНК)=2
С(KEDW)/C(ДНК)=5
С(KEDW)/C(ДНК)=10
Opticaldensity,units
Wave length, nm
DNA
C(KEDW)/C(DNA)=1
C(KEDW)/C(DNA)=2
C(KEDW)/C(DNA)=5
C(KEDW)/C(DNA)=10
The peptide influences the secondary structure of the macromolecule.
Changes in DNA spectral properties are observed in KEDW presence.
59. DNA - KEDW interaction
(viscosimetry method)
0,0 0,5 1,0 1,5
0,0
0,2
0,4
0,6
0,8
1,0
1,2
[(r
-1)/C]
(r
-1)/C
концентрация пептида *10-4, М
0
KEDW
приведеннаявязкостьRelativeviscosity,units
Concentration of the peptide, x10-4 M
KEDW binding with DNA leads to the decreased viscosity.
Thus the peptide influences the tertiary DNA structure.
60. Local separation of strands [poly (dA-dT):poly(dA-
dT)] as a result of DNA double helix melting
Khavinson V. et al. Bull. Exp. Biol. Med. (2008)
61. Local separation of strands [poly (dA-dT):poly(dA-
dT)] as a result of DNA double helix melting
Khavinson V. et al. Bull. Exp. Biol. Med. (2008)
62. Model of DNA-peptide complex
Pancragen
Vilon
Major groove
5’-GGCAGG-3’
3’-CCGTCC-5’
neutrally charged part of DNA
positively charged part of DNA
negatively charged part of DNA
63. Pancragen sites of binding in gene promoter regions
Red colour indicates Pancragen sites of binding
Gene Gene regulatory region, range -499 to 100 bp GenBank №
Pdx1
ATCAAATGCTTCTGACCTAGAGAGCTGGGTCTGCAAACTTTTTTTTTATCGTATTCCGCAACAGTTAAATAAAAAATTAAAAACTCA
ACATGTCTCCTTGTAAACTACATCAATTAACAAACACACTATGTCCATTATCAAATATAATAGAAAAAATATAGGAAAATAGAAAAT
AGAAAAATATAGGAAAATAGAAACTTTTAAGCCACGGTGAAAATGTTTCTATAAATGAGTGGTTCTAATGTTTTCGTGAGCGCCCAT
TTTGGGGAGCACCGCCAGCTGCCCGTTCAGGAGTGTGCAGCAAACTCAGCTGAGAGAGAAAATTGGAACAAAAGCAGGTGCTCGCGG
GTACCTGGGCCTAGCCTCTTAGTGCGGCCAGCCAGGCCAATCACGGCCCCCGGCTGAACCACGTGGGGCCCCGCGGAGCCTATGGTG
CGGCGGCCGGCCCGCCGGTCCGCGCTGGCTGTGGGTTCCCTCTGAGATCAGTGCGGAGCTGTCAAAGCGAGCAGGGGTGGCGCCGGG
AGTGGGAACGCCACACAGTGCCAAATCCCCGGCTCCAGCTCCCGACTCCCGGCTCCCGGCTCCCGGCTCCCGGTGCCC
NM_000209.3
Pax6
GGCCCGAAGCCGCCGAGAGAGCTCGGGACAGCGCAGGACCAGGCAGCCGCTCGCTCTCCTGTCACCTTAACTGCAGGCTCCGAGGGG
CGCCTTTGGAGTGTACTGAGGTGTGTCCTAATCGTGCGGCATTCAACAAATGGACTTCTGGTGTGTGGTCAGAAGAGAAAAGCCATT
TACTTACTTTCCTCCCCGGTTTTCTGGCAACAGCTGAAGGGGAGCTGCCTCCGTGGACTGAGCAGACCCAGGAGAGGGAGTCGTGGT
GCGGAGACACACGCACCACACACAGATGACCGGTGGCACACACGACACACGCTGACATACCGACATCGCCAGTGGGACACACACACA
CACACACACACACACACACACACACACAGAGAGAGAGAGAGAATCCCTCCCAGCATTGGTCATCCGCCCCCCCACCCAGGCTTCCAC
TCCCCCTCCCCTCTTATCTCCCCTGGCTTCCCCTCCTCTCGGGCGCTGCGAAAAGCAGCCGCACTTAGTCAACAAATGGCACGTGGG
AGAAGTTGGTGAGTGTTTGGTGAGGACTCTTCAGGGCTTTTCACAAGAACCCTCTGTACACAAAGTAAGTGGCGTGTT
NM_000280
Pax4
GCCAGCTCTCAAAGAAAGCAGCTTGCGTTGACAGCCTGGGGGCAGCAAGGATGCAGTCTCCCAGGAGAGGATGCACTCGGTGGTGGG
AAGCCAGGCTGGAGGGGCCTGAGTGACCCTCTCCACAGGCGGGCAGGGCAGTGGGAGAGGTGGTGTGTGGATACCTCTGTCTCACGC
CCAGGGATCAGCAGCATGAACCAGCTTGGGGGGCTCTTTGTGAATGGCCGGCCCCTGCCTCTGGATACCCGGCAGCAGATTGTGCGG
CTAGCAGTCAGTGGAATGCGGCCCTGTGACATCTCACGGATCCTTAAGGTAATGGGCCAGCACCTTTACCCAGTGATGGGGACAGGA
AGCAGGGAGAAAGGGCTCCTCTGAAGGCAAGAGCCTGGGGCTGTTGCAGGCTCTGAGGGCTTCTGGGACTTGGGTCACTTCCTGGGA
GATCCTCTCGGAGGTTGAAAAGGGGAGCCTCAGGCCCTCAAAGGTGAGGCTGGACTCCCGACTTCATGGCCTGGTCCAGTAAGTCTT
GGCTTTGTCTTATAGCCTCCTCCTGTCCCAGGGACACTCTCCTTCCTTCTGCCCATCATGCCTCACCTGTCCCTGCTT
NM_006193
Nkx2.2
TCCCCTCCTCCTCCCCACCCCCACCTTTTTTAAGATGCAATTTGTTAAAACGGCCCTTTCAAGTGTGTGGACTCGCGAGCGACGCGG
TGGCCCTTTGTATGTAAATACTGGGTTTAAAAAAAAAAAGGCTCGCCCCGTCTTTGCAATTAATTGACACGTTACACCTCTCATCTT
GCTCTAGAGGGCCGTTGGCTGGGAGCGCGGAGCTCCCCAAAACCCACAATTTCACATCTGCAAATACTGTCTTCATCCACTTGACTC
CCAAGACCCGCCCACACGTGGCCAACCTTTGCGTTTTTAATGTCTCTTCCCCCTTTTTTCCACCCTTCTCCCGCTCCCTCTCTCGCT
CCCCCTCCCTCCCTCTTTCTTTCCCTCCCTCCCTCTCTTTCTCCCCCTCTCCCCGCCTCCCCAGGTTCGTGAGTGGAGCCCAGCCTT
ATATGGACTGATCGCTCGGGCAATGGCCCATTTTTTCCTCGCCACCAGCCGCCACCGCGCGCCGAGCGGCCGCCGGAGCCCGAGCTG
ACGCCGCCTTGGCACCCCTCCTGGAGTTAGAAACTAAGGCCGGGGCCCGCGGCGCTCGGCGCGCAGGCCGCCCGGCTT
NM_002509.3
Foxa2
CGAAGCTCCGTGTCTGCCATCTCGCCTGTCTTCTGCCACCATCGCCCCCAATTTTGGACAGGTGGGCTGGATGCCCACTAGTTCCTA
TGCATTCTCTGTGTCTGAGGGGGTGGGTACAGGGCTGGATCCCCAAGGTCCAGCCAGGTTTTCAGAACCAAGAAAGAGCCTCCACAT
CCAAACACCTGCAATATCCCCCCACTCCAAATCTGGGCTCACAGGCTAACCCAGAACAGAAGACAATTTTTGAACCCAAGAGCTGCT
GGGGAAATAAAAGTATACGATTGCTGGAGTTTCTAATTTCTATTAAGCAGTCCCTCTGGAAGACAGAGAGGACAGAGACGCTCTTGA
AGTCAACTCCATATGCCCCATCATTGATTCCTGGATTCTTCTCTCCTCACCCCTCCCTCCCCACCTCCTGCCCTGTTTGTTTTAGTT
ACGAAATGCTGTGGGCACCTCGGTTGTGACTGAAAAGTAACCTTGAAACACGCCGGCCTGAATATCAGAGACAAATCTCAGCCTCCC
AACCGTCGGCCGCTGCTAGAGGGGCTGCTTGCGCCAGGCGCCGGCCGCCCCACTGCGGGTCCCTGGCGGCCGGTGTCT
NM_153675.2
64. Mechanism of peptide regulation of the living matter
development
Khavinson V. Peptidergic regulation of ageing (2009)
65. The role of peptides in the cycle of DNA, RNA and
protein biosynthesis
Khavinson V. Peptidergic regulation of ageing (2009)
66. Peptide regulation of protein synthesis
(proposed mechanism)
Peptide activates selective gene transcription during its binding with DNA. This can lead to mRNA formation and
the synthesis of apoptotic, proliferative and differentiation proteins. This increases cell resource and slows down
cellular senescence.
Khavinson V. et al. Biology Bulletin Reviews (2013)
68. The influence of peptide
bioregulators on morbidity of the
employees
(40-60 years) “Avtovaz” (Tolyatti)
when exposed to harmful factors.
Main group (450 employees)
received injections during 30 days
(10 injections sequentially), to
improve the functions of brain -
Cortexin, and to immune system -
Thymalin, normalize endocrine
system – Epithalamin.
Control group (400 employees)
received injections during 30 days
(10 injections sequentially) of
vitamins B 12, C, D.
69. Changes in morbidity levels
The observation period - 1 year
Control group Acute respiratory
diseases
Total
morbidity
2.4 times
2.8 times
70. The influence of peptide bioregulators on ageing rate
of the employees under the influence of adverse
factors
Administration of the bioregulators - 300 people, Control (multivitamins) - 200 people
The observation period - 1 year
- p<0.05 as compared to the control*
Ageingrateindex(years)
Ageing rate index = biologic age/due biological age
Control Peptide Peptide Complex of
bioregulation bioregulation peptide bioregulation
of brain of vessels of brain and vessels
71. The influence of peptide
bioregulators on morbidity of
employees of «Gazprom» under the
influence of adverse factors
Main group (11 192 employees)
received a complex of 6 peptide
bioregulators to improve the
functional state of immune system,
brain, blood vessels, bronchi, liver,
cartilage tissue (in capsules for oral
administration).
Control group (3 000 employees)
received multivitamins for 30 days
(for oral administration).
72. Changes in morbidity levels
The observation period - 1 year
Control group Acute respiratory
diseases
Total
morbidity
2.7 times
2.3 times
73. The influence of peptide bioregulators on mortality in
elderly and senile age patients
Khavinson V., Morozov V. Neuroendocrinology Lett. (2003)
44,1
22,3
81,8
45,8
33,3
*
*
*
Observation period - 12 years Observation period - 6 years
Elderly
(60-74 years)
Senile age patients
(75-89 years)
Mortality,%
- Control - Epithalamin - Epithalamin + Thymalin
- p<0.05 as compared to the control*
74. The influence of Epithalamin on survival of elderly
patients
Indices
Control group
(Basic treatment)
Main group
(Basic treatment
+ Epithalamin)
Number of patients 40 39
Age of patients before the
study
65.1 ± 1.1 64.5 ± 0.9
Survival rate at 15 years 16 (40%) 26 (66.7%)*
The cause of death of the
patients (myocardial
infarction or stroke (%)
83.3 46.2*
Korkushko O. et.al. (2011)
- p<0.05 as compared to the control*
75. The influence of Epithalamin on survival of elderly
patients
Korkushko O. et.al. (2011)
40
50
60
70
80
90
100
1992 1995 1996 1997 2000 2003 2007
*
*
*
*
Survivalrate(%)
Basic therapy + complex of peptide bioregulators
Basic therapy (control)
- p<0.05 as compared to the control*
76. Epithalamin increases melatonin level
in elderly people
Khavinson V. Peptidergic regulation of ageing (2009)
- p<0.05 as compared to the healthy people*
77. The influence of Epithalamin on telomere length
Age of
patients,
years
Normal limits of
telomere length
(b.p.)
Administration of Epithalamin
Initial value After administration
5-10 13.88-15.89 ـ ـ
25-30 11.78-13.78 ـ ـ
45-50 9.67-11.68 10.53±0.97 11.97±1.32*
60-65 8.09-10.10 9.32±0.82 10.83±1.12*
75-80 6.51-8.52 ـ ـ
90-95 4.93-6.94 ـ ـ
Tsuji A. et al. Forensic Science International. (2002)
Bekaert S. et al. Anticancer Research. (2005)
- p<0.05 as compared to the initial values*
78. Pineal Gland Preparations
Epithalamin (Epinorm) – peptide complex with molecular weight 1000-
5000 Da extracted from cattle pineal gland. The preparation is produced in
flacons (ampoules) by 10 mg for intramuscular administration.
Course of treatment takes 5-10 days (1 injection daily).
Epitalon – Ala-Glu-Asp-Gly tetrapeptide. The preparation is produced in
ampoules by 100 µg for intramuscular administration. Course of treatment
takes 10 days (1 injection daily).
Endoluten – peptide complex with molecular weight 1000-5000 Da extracted
from cattle pineal gland. The preparation is produced in
capsules by 10 mg for oral administration.
Course of treatment takes 10-20 days (by 2 capsules daily).
79. Age, years
(norm)
Investigation
Telomere length (b.p.)
Peptide Preparations
Epithalamin Epitalon Endoluten
60-65
(8.09-10.10)
Initial value
9.32 ± 0.82
(n=25)
9.61 ± 0.93
(n=19)
9.43 ± 1.12
(n=21)
After treatment 10.83 ± 1.12 * 10.72 ± 1.21 * 10.62 ± 1.32 *
75-80
(6.51-8.52)
Initial value
7.33 ± 0.81
(n=21)
7.51 ± 0.91
(n=17)
7.63 ± 0.98
(n=18)
After treatment 8.73 ± 0.78 * 8.91 ± 1.11 * 8.66 ± 1.21 *
The influence of Pineal Gland Preparations on
telomere length in patients’ blood cells
- p<0.05 as compared to the initial indices*
80. Age, years Investigation
6-OHMS excretion (ng/h)
Peptide Preparation
Epithalamin Epitalon Endoluten
60-65
Initial value
410 ± 38
(n=21)
445 ± 43
(n=19)
428 ± 47
(n=17)
After treatment 933 ± 86 * 915 ± 97 * 820 ± 92 *
75-80
Initial value
363 ± 41
(n=18)
371 ± 35
(n=22)
348 ± 43
(n=21)
After treatment 690 ± 63 * 615 ± 71 * 580 ± 62 *
The influence Pineal Gland Preparations on the
melatonin metabolite 6-OHMS excretion
normal limits for people aged 30-39– 1020-1900 ng/h
- p<0.05 as compared to the initial indices*
81. Enhancement of life resource in the elderly people
after application of peptides
Korkushko O. et.al. (2002, 2006)
INDICES
CHANGES
(after treatment with
peptides)
Intensity of the changes
(*)
Physical performance Enhancement 1.8 – 1.9-fold
Fatigability in case of physical
activity
Decrease 2.3 – 2.5-fold
Short memory Improvement by 56%
ARD and flu frequency Decrease 2.4-fold
T-lymphocytes function Enhancement by 24-43%
Total antioxidant activity Enhancement by 53%
Melatonin in the blood Enhancement 2.4-fold
Telomeres length Enhancement 14-16%
Bone tissue density Enhancement In 73-83% of the patients
Survival rate
15years of observation
Enhancement by 67%
- p<0.05 as compared to the control*
82. Enhancement of human vital resource
The application of peptide bioregulators contributed to
significant decrease in ageing rate in patients (aged 40-55
years) exposed to harmful factors and increase in survival
rate of elderly patients (observation period - 15 years), which is
evidenced by:
1. Improved physical capacity
2. Reduced ageing rate of cardiovascular system
3. Normalized metabolism
4. Improved brain function
5. Increased resistance to viral diseases
84. Expected results of the programme
Medical significance
Social significance
• Increase in working capacity
• Reducing the rate of ageing
• Normalization of metabolism
• Brain function improvment
• Reduction in general morbidity
• Reduction of infectious diseases during epidemics
• Reducing the incidence of work-related diseases
• Slowdown the accelerated ageing of population
• Improvement of quality of life and extending
working life
• Improvement of economic efficiency of
workforce
85. Complex of the main peptides to enhance the
resource and prevent age-related disorders
Pinealon (brain)
Vesugen (vessels)
Crystagen(thymus)
Chonluten (lungs)
Ovagen (liver)
Cartalax (cartilage)
The scheme of treatment:
1. Pinealon, Vesugen – 10 days
2. Crystagen, Chonluten – 10 days
3. Ovagen, Cartalax – 10 days
Total 30 days
Health assessment is
conducted before the
application and
repeated in 4 months.
This is followed by mathematical processing, statistics and
recommendations. Recommended 2 courses each year.
86. Enhancement of vital resource of Russian Olympic
team in rhythmic gymnastics
left to right: А. Shumilova (coach), D. Kondakova, A. Zaripova (coach), J. Lukonina,
Prof. V.Khavinson, E.Kanaeva, V. Schtelbaums (coach),
I. Viner-Usmanova (main coach of team, honored coach of Russia),
О. Buyanova (coach), D. Dmitrieva
87. Peptide application areas
Domestic
animals
Synthetic
preparations
Synthetic Medical
cosmetology
Aviculture
Sportsmen
products
Natural
preparations
Natural Preventive
cosmetology
Animal
husbandry
Functional
foods and
beverages
Preparations
Biologically
active
supplements
Cosmetology Veterinary Nutrition
88. Conclusion
Theoretical, experimental and clinical investigations
have shown the role of signal small peptides in
epigenetic regulation of gene expression, protein
synthesis, life resource and life span increase.
89. Researchers of the St. Petersburg Institute of
Bioregulation and Gerontology
Left to right - Professors:
Ariev A., Baranovsky A., Anisimov V., Khavinson V., Kozina L., Chalisova N., Kvetnaia T., Trofimova S.,
Kheifits V., Morozov V., Baluzek M., Malinin V., Shataeva L., Kozlov K., Kvetnoy I., Ryzhak G.
90. Prof. Khavinson and the team of the Laboratory of Biogerontology
of the St. Petersburg Institute of Bioregulation and Gerontology
Left to right Khalimov R., Prof. Khavinson V., Prof. Kvetnaia T., Basharina V.;
Dr. Tarnovskaya S., Plotnikova E., Dr. Linkova N.
91. The institutions where the main studies were
conducted
S.M. Kirov Military Medical Academy
(1977-1991), Principal investigator of the Russian Academy of Sciences
Prof. V. Khavinson
St. Petersburg Institute of Bioregulation and Gerontology
(1992-2015), Principal investigator of the Russian Academy of Sciences
Prof. V. Khavinson
N.N. Petrov Institute of Oncology
(1977-2015), Principal investigator of the Russian Academy of Sciences
Prof. V. Anisimov
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov
Moscow State University
(2008-2015), Principal investigator of the Russian Academy of Sciences
Prof. B. Vanyushin
Institute of Gerontology of National Academy of Medical Science of Ukraine
(1992-2015), Principal investigator of the Academy of Medical Sciences of
Ukraine
Prof. O. Korkushko
92. The institutions where some of the studies were
conducted
National Institute on Ageing (Baltimore, the USA)
Italian National Research Center on Ageing (Ancona, Italy)
Institute of Anatomy, Ludwig-Maximilians-University of Munich
(Munich, Germany)
Prince Felipe Research Center (Valencia, Spain)
University of Antwerp, Department of Biomedical Sciences
(Antwerp, Belgium)