Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time.
Human Gut Mycobiota is still a mistery for us. Most of the reasearch on this topichas been conducted in the last 5 years. We are starting to comprehend the interactions with our gastrointestinal system and the virus and bacterial communities. 13% of gut microbiota in weight, about 150 species; most of them can shift from commensalism to virulent parassitosis according to our immune competence. Gut fungal overgrowth is actually underestimated in dignaosis and treatment. Many FGIDS and SIBO are frequently mixed bacteral and fungal dysbiosis
As a newly emphasized modality to treat infectious complications and also to folloew non-antibiotic regimens against infection, Probiotics has recieved more and more attention now a days.
Probiotics are live microorganisms that confer health benefits when colonize the gastrointestinal tract. The various microbial strains are now found to provide therapeutic effects through the metabolites they produce, digestion of dietary fibers, inhibition of pathogen adhesion, provide missing enzyme, maintaining homeostasis and also controlling brain activities which may lead to autism if disturbed.
Human Gut Mycobiota is still a mistery for us. Most of the reasearch on this topichas been conducted in the last 5 years. We are starting to comprehend the interactions with our gastrointestinal system and the virus and bacterial communities. 13% of gut microbiota in weight, about 150 species; most of them can shift from commensalism to virulent parassitosis according to our immune competence. Gut fungal overgrowth is actually underestimated in dignaosis and treatment. Many FGIDS and SIBO are frequently mixed bacteral and fungal dysbiosis
As a newly emphasized modality to treat infectious complications and also to folloew non-antibiotic regimens against infection, Probiotics has recieved more and more attention now a days.
Probiotics are live microorganisms that confer health benefits when colonize the gastrointestinal tract. The various microbial strains are now found to provide therapeutic effects through the metabolites they produce, digestion of dietary fibers, inhibition of pathogen adhesion, provide missing enzyme, maintaining homeostasis and also controlling brain activities which may lead to autism if disturbed.
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...Pig Farm Solution
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibrio alginolyticus and Vibrio parahaemolyticus: Current Status of Research and Challenges Ahead
Nandita Matamp and Sarita G. Bhat *
Department of Biotechnology, Cochin University of Science and Technology, Kochi-682022, Kerala, India; nandita.matamp@gmail.com
* Correspondence: saritagbhat@gmail.com; Tel.: 91-984-603-3486. Fax: 0484-257-7595
Received: 25 February 2019; Accepted: 15 March 2019; Published: 18 March 2019
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Microbiata
A main player in immunityThe microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping:
anticancer immunity,
autoimmunity, and
transplant responses
The term probiotics is a relatievly new word meaning “for life” and is currently used to name bacteria associated with beneficial effects for humans and animals. The development of resistance to range of antibiotics by some important pathogen has raised a possibility of return to pre antibiotic dark ages. So there was need of new treatment paradigm to be introduced to treat periodontal diseases. This need was fulfilled by the introduction of probiotics. Probiotics are counterparts of antibiotics thus are free from concerns for developing resistance, further they are body’s own resident flora hence are most easily adapted to host. The buzz about probiotics has become a roar but despite great promises, probiotics work is limited to gut. Periodontal works are sparse and need validation by large randomized trials. It can be said probiotics are still in “infancy” in terms of periodontal health benefits, but surely have opened door for a new paradigm of treating disease on a nano molecular mode. Novel species are likely to be added in the future as research data
accumulate. In-depth understanding of the intrinsic microbial ecological control of commensal microbiota may introduce new putative species to this discussion.
Probiotics and medicinal plants in poultry nutrition: a reviewSubmissionResearchpa
The use of medicinal plants and probiotics has recently gained interest since the ban on the use of antibiotics as growth promoters by the European Union in 2006. They are new alternatives to bridge the gap between food safety and production. Medicinal plants are cheaper and loaded with several minerals, vitamins and phytochemicals such as: alkaloids, saponin, flavonoids, phenols, tannins etc. which allows them to perform multiple biological activities. Probiotics on the other hand, repopulates the gastro intestinal tracts (GIT) with beneficial bacteria which controls the action of pathogens and control their population, thereby reducing mortality and improving general performance of an animal by Akintayo - Balogun Omolere. M and Alagbe, J.O 2020. Probiotics and medicinal plants in poultry nutrition: a review. International Journal on Integrated Education. 3, 10 (Oct. 2020), 214-221. DOI:https://doi.org/10.31149/ijie.v3i10.730 https://journals.researchparks.org/index.php/IJIE/article/view/730/703 https://journals.researchparks.org/index.php/IJIE/article/view/730
Patologie digestive, extradigestive e MicrobiotaASMaD
Presentazione a cura del Professor Giovanni Barbara - M.A.S.T.E.R. ECM in Gastroenterologia: Focus on: Microbiota e dintorni - Fondazione Santa Lucia - Roma
Microbiota: the community of micro-organisms themselves
Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time
Proteins are the most versatile macromolecules and responsible for almost all cellular functions .Protein homeostasis (or proteostasis) is state of a balanced proteome, , depends on an extensive network of different types molecular chaperones, proteolytic systems (e.g. proteosome, autophagy) and their regulators. The dysfunction in proteostasis, leading to formation of misfolded proteins or the accumulation of protein aggregates which leads to many diseases e.g. sickle cell anaemia ; neurodegenerative diseases. Also The chaperon dysfunction leads to diseases called chaperonopathy e.g. Neurodegenerative diseases, cancers. .The pharmacological intervention to treat proteostasis dysfunction diseases are pharmacological chaperones, chemical chaperon, Heat shock transcription factor-1 activator; chaperon inhibitors,proteosome inhibitors and autophagy enhancers (activators).
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...Pig Farm Solution
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibrio alginolyticus and Vibrio parahaemolyticus: Current Status of Research and Challenges Ahead
Nandita Matamp and Sarita G. Bhat *
Department of Biotechnology, Cochin University of Science and Technology, Kochi-682022, Kerala, India; nandita.matamp@gmail.com
* Correspondence: saritagbhat@gmail.com; Tel.: 91-984-603-3486. Fax: 0484-257-7595
Received: 25 February 2019; Accepted: 15 March 2019; Published: 18 March 2019
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Microbiata
A main player in immunityThe microbiome is an environmental factor in intricate symbiotic relationship with its hosts' immune system, potentially shaping:
anticancer immunity,
autoimmunity, and
transplant responses
The term probiotics is a relatievly new word meaning “for life” and is currently used to name bacteria associated with beneficial effects for humans and animals. The development of resistance to range of antibiotics by some important pathogen has raised a possibility of return to pre antibiotic dark ages. So there was need of new treatment paradigm to be introduced to treat periodontal diseases. This need was fulfilled by the introduction of probiotics. Probiotics are counterparts of antibiotics thus are free from concerns for developing resistance, further they are body’s own resident flora hence are most easily adapted to host. The buzz about probiotics has become a roar but despite great promises, probiotics work is limited to gut. Periodontal works are sparse and need validation by large randomized trials. It can be said probiotics are still in “infancy” in terms of periodontal health benefits, but surely have opened door for a new paradigm of treating disease on a nano molecular mode. Novel species are likely to be added in the future as research data
accumulate. In-depth understanding of the intrinsic microbial ecological control of commensal microbiota may introduce new putative species to this discussion.
Probiotics and medicinal plants in poultry nutrition: a reviewSubmissionResearchpa
The use of medicinal plants and probiotics has recently gained interest since the ban on the use of antibiotics as growth promoters by the European Union in 2006. They are new alternatives to bridge the gap between food safety and production. Medicinal plants are cheaper and loaded with several minerals, vitamins and phytochemicals such as: alkaloids, saponin, flavonoids, phenols, tannins etc. which allows them to perform multiple biological activities. Probiotics on the other hand, repopulates the gastro intestinal tracts (GIT) with beneficial bacteria which controls the action of pathogens and control their population, thereby reducing mortality and improving general performance of an animal by Akintayo - Balogun Omolere. M and Alagbe, J.O 2020. Probiotics and medicinal plants in poultry nutrition: a review. International Journal on Integrated Education. 3, 10 (Oct. 2020), 214-221. DOI:https://doi.org/10.31149/ijie.v3i10.730 https://journals.researchparks.org/index.php/IJIE/article/view/730/703 https://journals.researchparks.org/index.php/IJIE/article/view/730
Patologie digestive, extradigestive e MicrobiotaASMaD
Presentazione a cura del Professor Giovanni Barbara - M.A.S.T.E.R. ECM in Gastroenterologia: Focus on: Microbiota e dintorni - Fondazione Santa Lucia - Roma
Microbiota: the community of micro-organisms themselves
Microbiome: The genes and genomes of the microbiota, as well as the products of the microbiota and the host environment” [the collective genomes of the micro-organisms in a particular environment. Although the composition of the gut microbiota varies between individuals, the community in each individual is relatively stable over time
Proteins are the most versatile macromolecules and responsible for almost all cellular functions .Protein homeostasis (or proteostasis) is state of a balanced proteome, , depends on an extensive network of different types molecular chaperones, proteolytic systems (e.g. proteosome, autophagy) and their regulators. The dysfunction in proteostasis, leading to formation of misfolded proteins or the accumulation of protein aggregates which leads to many diseases e.g. sickle cell anaemia ; neurodegenerative diseases. Also The chaperon dysfunction leads to diseases called chaperonopathy e.g. Neurodegenerative diseases, cancers. .The pharmacological intervention to treat proteostasis dysfunction diseases are pharmacological chaperones, chemical chaperon, Heat shock transcription factor-1 activator; chaperon inhibitors,proteosome inhibitors and autophagy enhancers (activators).
Daptomycin is a semi-synthetic cyclic lipopeptide bactericidal antibiotic with outstanding activity against aerobic and anaerobic Gram-positive organisms including drug-resistant staphylococcai, Enterococcus spp. and Streptococci Spp
genes addiion\deeion\ediionthat lead to a therapeutic, prophylactic or diagnostic effect
Plasmid DNA
•Viral vectors
•Genetically engineered micro-organisms
•Human gene-editing technology
•Patient-derived cellular gene therapy products
cells or tissues that have been manipulated to change their biological characteristics or cells or tissues not intended to be used for the same essential/original functions in the body.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. The neglected organ
(Microbiata) therapeutic application
By
Mohie-Aldien Elsayed Sherief
Professor of pharmacology, Faculty of Medicine, Benha University
2. Intestinal microbiota
(1012-16 microorganisms ; > 1500
different species)
Total abundance of
bacteria according to the
different body sites.
Willem M de Vos et al. Gut 2022;71:1020-1032
4. The increasing number of publications on
microbiota/microbiome worldwide
February 2021 ;Qatar
Medical Journal 2020(3):4
Pubmed:microbiome Egypt: 656 results
5. Egypt probiotics market is estimated to be valued at US$-111.829 million
and is estimated to grow at a CAGR of 6.64% to reach a market size of US$-
164.442by 2025
6. The history of microbiome research from seventieth century until our days,
highlighting the shift of the paradigm from microbes as unsocial organisms causing diseases to
the holistic view of microorganisms being the center of the One Health Concept: positively
interconnecting all areas of our lives
9. Nature volume 569, pages641–648 (2019); Microbiome, Health & Biomarkers Volume 3(2); 2018
The human microbiome project (HMP)
-$170 million in funding by the NIH Common Fund from 2007 to 2016
10.
11. SCIENCE•5 Oct 2018•Vol 362, Issue 6410•pp. 33-34•DOI: 10.1126/science.aau8816
Associative links between Western lifestyle, Human conditions, and
loss of microbial diversity (LOMD).
15. Main beneficial
functions of the
human gut
microbiota.
Circles represent the three
principal classes of
functions performed by the
bacteria that inhabit the
gut. Arrows represent
causal relationships.
Abbreviation: SCFA, short
chain fatty acid
July 2011Biologics: Targets &
Therapy 5(default):71-86
DOI:10.2147/BTT.S19099
16. Microbiota diversity—a measure of how many different species and, dependent on the diversity
indices, how evenly distributed they are in the community.
Lower diversity is considered a marker of dysbiosis (microbial imbalance) in the gut and has
been found in autoimmune diseases and obesity and cardiometabolic conditions, as well as in
elderly people
17. Schematic
representation of
the role of the gut
microbiota in
health and
disease giving
some examples of
inputs and
outputs.
Ana M Valdes et al. BMJ 2018;361:bmj.k2179
IPA=indolepropionic acid;
LPS=lipopolysaccharide;
SCFA=short chain fatty acids;
TMAO=trimethylamine N-oxide
18. Taxonomic distribution, prevalence and abundance of microbial taxa that inhabit healthy
human body sites as defined in the human microbiome projects (HMP).
19. Depiction of various diseases associated with different microbiome (gut, oral, skin, vaginal)
and the major upregulated and downregulated microbes involved in said diseases
https://link.springer.com/chapter/10.1007/978-981-16-3156-6_10
20. Antibiotics affect colon flora
Jernberg C, Löfmark S, Edlund C, Jansson J. Long-term impacts of antibiotic exposure on the
human intestinal microbiota. Microbiology (Reading, England). 2010;156:3216–23.
23. Overview of candidate
biomarkers for diagnosis of gut
microbiota dysbiosis and
associated human diseases.
↓
Biomark. Med. (2021) 15(2), 139–150
decrease
30. Impact of metformin on the gut
microbiota. Various in vitro and in
vivo studies demonstrated that
metformin might exhibit glucose-
modulating effects by interacting
with the gut microbiome. Each box
presents the putative mechanism
suggested in this review
Int. J. Mol. Sci. 2021, 22, 3566.
https://doi.org/10.3390/ijms22073566
37. - They need to be ingested in a dosage high enough to cause an effect.
-The beneficial effects of a given probiotic is specific to that strain, and cannot be
regarded as general for other strains of the same species, or other species, of
bacteria or yeast.
-owing to the many unknown components presented in the donor’s samples, it also
carries the risk of transmitting pathogens or disease-causing genes to the
recipient and negative inter-actions with the recipient’s existing microbial
community,
-FMT has encountered safety issues. In March 2020, the FDA issued a safety alert following
infections with pathogenic Escherichia coli strains detected in 6 patients who received
investigational FMT products supplied by a stool bank company as treatment for C
difficile infection. Additionally, 2 patients with chronic medical conditions died after
receiving the FMT product from the stool bank; however, the FDA said the E coli infection
was not detected in the stool of 1 of the patients and it was unclear whether the infection
contributed to the death of the other. The FDA now mandates additional screening of
donor feces for these dangerous strains.25-27
- Substantial microbial community variability between individuals and the limited
long-term stabilization of a foreign microbial configuration.
-Side effects, including the following: bacterial stability and translocation, genetic
factors of individual recipients that may influence the success of FMT and bacterial
colonization, or transplant rejection similar to organ transplantation
LIMITATIONS of FMT:
38. Screening sections involved in each stage for the functional and
safety aspects of probiotics (FAO/WHO guidelines)
Probiotics and Antimicrobial Proteins (2021)
39. Animal Physiology Nutrition, Volume: 104, Issue: 6, Pages: 1835-1850, First published: 29 September 2020, DOI: (10.1111/jpn.13454)
The possible mechanisms of probiotic action.
(1) Competitive exclusion of pathogenic micro‐organisms.
(2) Production of antimicrobial substances.
(3) Competition for growth factors and nutrients.
(4) Enhancement of adhesion to intestinal mucosa.
(5) Improvement of epithelial barrier function.
(6) Improvement of secretion of IgA
40. Probiotics: 21st Century Wonder Drug Re-discovered?
Probiotics claim to resolve/reduce > 20 human maladies from diarrhea to cancer and multiple sclerosis (MS
Diarrhea Helicobacteria pylorus
Increase in Anti-allergic Cytokines Decrease in frequency of “common cold”
41. Brand name Strain Producer
Linex’ Bifidobacterium lactis BB-12 sandoz
Dicoflor Lactobacillus rhamnosus GG AGPHARMA
Enterogermina Bacillus clausii SANOFI
Enterolactis Lactobacillus casei SOFAR
Nutriflor Lactobacillus acidophilus DDS-1, Lactobacillus bulgaricus
DDS-14 Bifidobacterium bifidum, Lactobacillus rhamnosus
NUTRIGEA
Probactiol duo Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-
37 Bifidobacterium lactis Bi-07, Bifidobacterium lactis Bi-04
METAGENETICS
VSL#3 Streptococcus thermophilus, Bifidobacterium
breve, Bifidobacterium longum, Bifidobacterium infantis
lactobacillus acidophilus, Lactobacillus plantarum,
Lactobacillus paracasei, Lactobacillus delbrueckii subsp.
bulgaricus
FERRING
FARMACEUTICI
Yakult Lactobacillus casei Shirota YAKULT (Tokyo)
List of a few commercially available probiotic preparations
ink.springer.com/chapter/10.1007/978-981-16-3156-6_10/tables/1
42. Type Delivery Product phase Recent outcomes Clinical trial ID
Faecal
microbiota
transplanta
tion or
fractionate
d, partially
undefined
communiti
es
Enema
Rebiotix RBX2660
for recurrent CDI
III
29.4% relative risk reduction of CDI recurrence
compared with placebo (week 8)a
NCT03244644
(PUNCHCD3)169,170,
171,172,173
Oral capsule
Finch Therapeutics
CP101 for recurrent
CDI
II
21% relative risk reduction of CDI recurrence
compared with placebo (week 8)b
NCT03110133
(PRISM3)
Oral capsule
(Firmicutes
spores)
Seres Therapeutics
SER-109 for recurrent
CDI
III
73% relative risk reduction (week 8)
54% relative risk reduction of CDI recurrence
compared with placebo (week 24)a
NCT03183128
(ECOSPORIII)
Oral capsule
(lyophilized stool
suspension)
Rebiotix RBX7455
for recurrent CDI
I
Microbiota shifts after treatment, no CDI
recurrence in 80–100% of participants
depending on treatment (8 weeks)
NCT02981316
(ref.174
)
Prebiotics
Dietary
supplement (with
chickpea, peanut,
soybean flours
and green
banana)
Microbiota-directed
complementary food
prototype (MDCF-2)
for moderate acute
malnutrition
II
MDCF-2 increased measures of weight-for-
length and weight-for-age compared with
ready-to-use supplementary food
NCT04015999
(ref.111
)
Symbiotic
microbial
consortia
Oral capsule (40
lyophilized
isolates)
NuBiyota MET-2 for
CDI
I
Increased microbiota alpha diversity
CDI absent in 79% of participants (day 40)
NCT02865616
(ref.175
)
Oral capsule (8
lyophilized
isolates)
Vedanta Biosciences
VE303 for CDI
II
Promoted microbiota recovery in healthy
volunteers after antibiotics
NCT03788434
(CONSORTIUM)176
Examples of microbiome-based therapeutics in development and clinical trials
Microbiome-based therapeuticsnature reviews microbiology; Published: 06 January 2022
43. Studied methods of microbiota normalization in CS-born infants.
CS, C-section; FMT, faecal microbiota transplantation.
. Ann Nutr Metab; 2021 Aug 30;1-9. doi: 10.1159/000518498
44. Delivery system Pros Cons
Fermented dairy
-Affordability and easy Availability
-Ease of incorporation into daily patterns
-Additional nutritional benefits
-Enhanced bacterial survival-through upper
GI tract (100× less bacteria can be given per
dose)
-Effective in the upper GI tract
-Contains dairy proteins and
lactose
-Taste can be issue
-Not suitable when travelling
-Not suitable for vegans
Capsules
-Ease of administration
-Contain no binders
-Not therapeutic in upper GI tract
(unless opened or chewed)
-May contain allergenic excipients
-Higher cost
Tablets
-Ease of administration
-Effective in the upper GI tract
-May contain allergenic or
otherwise problematic binders and
excipients (e.g., gluten)
-Higher cost
Powders
-Effective in the upper GI tract
-Dosages can be easily adjusted
-Can be incorporated into foods or drinks
-Contain no binders
The pros and cons of different probiotic delivery systems
https://www.intechopen.com/chapters/50992
45.
46. •is chemical compounds of probiotic microbial origin including
short chain fatty acids, acetate, butyrate, and propionate mixture ,
peptides, teichoic acids, endo- and exo-polysaccharides, cell
surface proteins, vitamins, plasmalogens, and organic acidsis.
•Dosage and routes of administration follow the principles of
pharmacokinetics. Metabolites are present at most body sides and
thus suitable for different routes of administration.
•Metabolites are generally stable in the systemic circulation and
thus amenable for scalable modulation of their concentration.
•In contrast to the administration of live organisms, the effects of
some microbiome-associated metabolites are pleiotropic and
highly cell type specific. further characterization of the full effects
of different metabolites is necessary in order to understand
potential side effects of postbiotics
post-biotic / small molecule,
47. POSTBIOTICS
Molecules and metabolites produced by the gut microbiota according to the nutrients or metabolic
source and their derived compounds.
Willem M de Vos et al. Gut 2022;71:1020-1032
BSCFA, branched SCFA;
LPS, lipopolysaccharides;
PAMPs, pathogen-associated
molecular patterns;
SCFA, short chain fatty acids.
48. Colonocytes and endocrine
cells express a variety of
receptors able to sense and
transmit signals from the
microbial environment.
Willem M de Vos et al. Gut 2022;71:1020-1032
(PAMPs), Microbial/Pathogen-associated molecular
patterns .
(LPS) lipopolyscaccharides;
(eCBs), endocannabinoids .
CB1, CB2, cannabinoid receptor type 1 and type 2;
TRPV1, transient receptor potential cation channel
subfamily V member 1;
FXR, farnesoid X receptor;
AhR, aryl hydrocarbon receptor;
GPR119, GPR43, GPR41, G-protein coupled receptor 119,
43 and 41;
MYD88, myeloid differentiation primary response 88;
PPARα/γ, peroxisome proliferator-activated receptors alpha
and gamma;
TGR5, Takeda G protein-coupled receptor 5.
52. Groups Typical metabolites Typical targets Specific functions Typical diseases associated
Short-
chain fatty
acids
Acetate, propionate,
butyrate, hexanoate,
isovalerate, isobutyrate, 2-
methylpropionate,
valerate
Directly act on GPR41, GPR43,
GPR109A, GPR81, GPR91,
HDAC1 and HDAC3
Regulation of gut microbiota composition, gut
barrier integrity, appetite, energy
homeostasis, gut hormone production,
circadian clocks; inhibit proinflammatory
cytokines; stimulate water and sodium
absorption; modulate systemic immune
response
Diabetes, obesity, pancreatitis, nonalcoholic
fatty liver disease, hypertension,
atherosclerosis, chronic kidney disease,
ulcerative colitis, radiation proctitis, Crohn’s
disease, colorectal cancer, autism spectrum
disorder, sclerosis, Parkinson’s disease,
asthma, diarrhea
Bile acids Cholate, hyocholate, deoxy-
cholate, taurohyocholate,
ursodeoxycholate,
taurocholate, tauro-α-
muricholate,glycocholate,
hyodeoxycholate,tauro-β-
muricholate, lithocholate,
taurodeoxylcholate
Directly act on FXR, VDR,
PXR/SXR, constitutive
androstane receptor (CAR),
TGR5, sphingosine 1-phosphate
receptor 2 (S1PR2), formyl-
peptide receptor (FPR),
(mAChR)
Facilitate lipid and vitamin absorption;
regulation of gut microbiota composition, gut
hormones, intestinal immunity, intestinal
electrolyte and fluid balance, gut motility,
lipid homeostasis, glucose homeostasis,
amino acid homeostasis, circadian clocks;
influence neurotransmission and physiology
Primary biliary cholangitis, primary
sclerosing cholangitis, obesity, nonalcoholic
fatty liver disease, non-alcoholic
steatohepatitis, atherosclerosis, ulcerative
colitis, cancer, hepatic encephalopathy,
multiple sclerosis, Alzheimer's disease,
Parkinson's disease, traumatic brain injury,
stroke and amyotrophic lateral sclerosis
Gases H2S, H2, CO2, CH4, NO NO targets soluble guanylate
cyclase, H2S cause
conformational changes of
target proteins by sulfhydration
CH4 slows gut motility; H2S regulates gut
inflammation, motility, epithelial secretion
and susceptibility to infections; NO mediates
gastric mucosal protection and regulate
mucosal blood flow
Parkinson’s disease, colitis, ulcer
Tryptophan
and indole
derivatives
Indole-3-lactic acid, indole
acetic acid, indole-3-
acetamide, indole pyruvic
acid, indoxyl sulfuric acid,
indole, serotonin
Directly targeting on AhR and
PXR
Influence the gut microbial spore formation,
drug resistance, biofilm formation, and
virulence; regulate intestinal barrier
functions, gut hormone secretion, gut motility,
systemic immune response
Ulcerative colitis, Crohn’s disease, obesity,
stroke, mucosal candidiasis, autism spectrum
disorder, Alzheimer’s disease, Parkinson's
disease, migraine, schizophrenia, irritable
bowel syndrome
Choline
metabolites
TMA, methylamine,
dimethylglycine,
dimethylamine,
Direct target unknown, but can
activate NF-кB, protein kinase C
(PKC), NLRP3 inflammasome
Inhibits bile acid synthesis; promote
inflammation, thrombosis; affects myocardial
hypertrophy and fibrosis; exacerbates
mitochondrial dysfunction
Nonalcoholic fatty liver disease, obesity,
atherosclerosis, diabetes, heart failure,
hypertension
Vitamins Vitamin B2, Vitamin B3,
Vitamin B5, Vitamin B6,
Vitamin B9, Vitamin B12,
vitamin K
Vitamin receptors Involved in cellular metabolism; modulate
immune function and cell proliferation;
supply vitamins for hosts
Vitamin associated diseases such as
schizophrenia, autism, and dementia
Neurotrans
mitters
Dopamine, catecholamines, 5-
HT, and GABA
Adrenergic receptors, 5-HT
receptors, GABA receptors
Regulate gut motility, memory and stress
responses, immune function of nervous
system
Parkinson's disease, autism
Lipids Conjugated fatty acids,
cholesterol,
phosphatidylcholines,
triglycerides, LPS
LPS targets directly on TLR4 LPS triggers systemic inflammation;
conjugated fatty acids regulate
hyperinsulinemia, immune system,
lipoprotein profiles; cholesterol acts as
material bases for bile acid synthesis.
Diabetes, obesity, nonalcoholic fatty liver
disease, hyperinsulinemia,
hypercholesterolemia, chronic hepatitis C.
Others Ethanol; triphosadenine;
lantibiotic ( ruminococcin Aand
Triphosadenine activate P2X and
P2Y receptors
Enhance or damage gut barrier; regulate intestinal
or systemic immune response; act as antibiotics to
Fatty liver disease, C. difficile and H.
pylori infections, irritable bowel syndrome,
53. Possible diagnosis and therapy using the interaction with gut microbiome and epigenetic.
Disease Links to gut microbiome Links to epigenetics Diagnosis and therapy
Colorectal
Cancer
(CRC)
↑ abundance
of Fusobacterium
nucleatum and Providencia but
↓adabundance Lactobacillus a
nd butyrate-producing
bacteria such
as Roseburia and Fecalibacteri
um in CRC .
Butyrate, one of the most abundant
SCFAs, is well known as HDACi which
have antiangiogenic and
antimetastatic effects in cancer by
epigenetically activating tumor-
suppressor genes such
as p21 and bax or suppressing
carcinogenetic genes including Cox-2
• Oral administration
of Bifidobacterium and Bacteroides which
were suggested as therapeutic probiotics
for cancer immunotherapy .
• Butyrate or the prebiotic sources such as
acemannan in Aloe vera gel with their
chemopreventive effect.
Diabetes High ratio of
Firmicutes/Bacteroidetes in
type 2 diabetes with high
abundance of lactic acid
bacteria but low
of Faecalibacterium prausnitzii
Changes in cell wall components
such as LPS and peptidoglycan
resulting from dysbiosis are involved
in the epigenetic regulation of the
inflammatory response
• Improved diets targeting to recover
dysbiosis and epigenetic changes of pro-
inflammatory genes in metabolic syndrome
• Transplantation of gut microbiota from
lean and healthy donors to patients with
metabolic syndrome .
Obesity Decreased production of
butyrate by gut microbiota and
lower diversity of the
microbiota with low
abundance of F. prausnitzii ].
Hypomethylation at the promoter
regions of SCFAs receptor
GPR41/FFAR3 in obese patients.
• GLP-1 agonist who contributed to the
moderate increase of F. prausnitzii and the
reverse of a hypomethylation of the
promoter regions of GPR41/FFAR3 in
patients with obesity and type 2 diabetes
IBD Lower abundance
of Streptococcus and the
increased abundance
of Bacteroides, Parabacteroide
s, and Roseburia Lower
abundance of Akkermansia
muciniphila in UC patients
Hypomethylation at the differentially
methylated regions (DMR) of KHDC3L
(C6orf221) in UC patients, which
were highly correlated with the
dysbiosis Modulation of Fiaf, GPR43,
HDACs, and PPARγ expression by A.
muciniphila and propionate
• Identification of colonic mucosal DMRs
can provide epigenetical and
metagenomical targets for therapeutic
measures [107].
• Assessment of the gut microbial dysbiosis
at the early stage of CD
Epigenet. 2017, 3:2. doi: 10.21767/2472-1158.100048