New Insights Into Gut-Bacteria-Derived Indole and Its Derivatives in Intestinal and Liver Diseases

The interaction between host and microorganism widely affects the immune and metabolic status. Indole and its derivatives are metabolites produced by the metabolism of tryptophan catalyzed by intestinal microorganisms. By activating nuclear receptors, regulating intestinal hormones, and affecting the biological effects of bacteria as signaling molecules, indole and its derivatives maintain intestinal homeostasis and impact liver metabolism and the immune response, which shows good therapeutic prospects. We reviewed recent studies on indole and its derivatives, including related metabolism, the influence of diets and intestinal commensal bacteria, and the targets and mechanisms in pathological conditions, especially progress in therapeutic strategies. New research insights into indoles will facilitate a better understanding of their druggability and application in intestinal and liver diseases.

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Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

Nutrients ◽

10.3390/nu10091135 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1135 ◽

Cited By ~ 16

Author(s):

Francesca Bonomini ◽

Elisa Borsani ◽

Gaia Favero ◽

Luigi Rodella ◽

Rita Rezzani

Keyword(s):

Liver Diseases ◽

Molecular Mechanisms ◽

Antioxidant Properties ◽

Therapeutic Strategies ◽

Beneficial Effects ◽

Pathological Conditions ◽

Positive Effect ◽

And Oxidative Stress

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

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Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.672455 ◽

2021 ◽

Vol 12 ◽

Author(s):

Agata Matejuk ◽

Arthur A. Vandenbark ◽

Halina Offner

Keyword(s):

Immune Response ◽

Nervous System ◽

Cross Talk ◽

Immune Cells ◽

Peripheral Circulation ◽

Therapeutic Strategies ◽

Organ Function ◽

The Central Nervous System ◽

Health And Disease ◽

New Research

The immune system's role is much more than merely recognizing self vs. non-self and involves maintaining homeostasis and integrity of the organism starting from early development to ensure proper organ function later in life. Unlike other systems, the central nervous system (CNS) is separated from the peripheral immune machinery that, for decades, has been envisioned almost entirely as detrimental to the nervous system. New research changes this view and shows that blood-borne immune cells (both adaptive and innate) can provide homeostatic support to the CNS via neuroimmune communication. Neurodegeneration is mostly viewed through the lens of the resident brain immune populations with little attention to peripheral circulation. For example, cognition declines with impairment of peripheral adaptive immunity but not with the removal of microglia. Therapeutic failures of agents targeting the neuroinflammation framework (inhibiting immune response), especially in neurodegenerative disorders, call for a reconsideration of immune response contributions. It is crucial to understand cross-talk between the CNS and the immune system in health and disease to decipher neurodestructive and neuroprotective immune mechanisms for more efficient therapeutic strategies.

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Faculty Opinions recommendation of Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14221957.15735057 ◽

2012 ◽

Author(s):

Ganes Sen ◽

Saurabh Chattopadhyay

Keyword(s):

Immune Response ◽

Experimental Colitis ◽

Commensal Bacteria ◽

Antiviral Signaling ◽

Signaling Protein ◽

Mitochondrial Antiviral Signaling ◽

Mitochondrial Antiviral Signaling Protein

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Is Immune Response Relevant in Interstitial Lung Disease?

Current Immunology Reviews ◽

10.2174/1573395516999200914143054 ◽

2020 ◽

Vol 16 (1) ◽

pp. 18-27

Author(s):

Manzoor M. Khan

Keyword(s):

Immune Response ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Lung Fibrosis ◽

Lymphocytic Infiltration ◽

Therapeutic Strategies ◽

Mediators Of Inflammation ◽

Acquired Immune Responses ◽

Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

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Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

Pathogens and Disease ◽

10.1093/femspd/ftab008 ◽

2021 ◽

Author(s):

Haidi Karam-Allah Ramadan ◽

Gamal Badr ◽

Nancy K Ramadan ◽

Aml Sayed

Keyword(s):

Immune Response ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Responses ◽

Signaling Pathways ◽

Liver Diseases ◽

Stat Signaling ◽

Chronic Hcv ◽

Direct Acting

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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COVID-19: Unmasking Emerging SARS-CoV-2 Variants, Vaccines and Therapeutic Strategies

Biomolecules ◽

10.3390/biom11070993 ◽

2021 ◽

Vol 11 (7) ◽

pp. 993

Author(s):

Renuka Raman ◽

Krishna J. Patel ◽

Kishu Ranjan

Keyword(s):

Immune Response ◽

Monoclonal Antibodies ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Viral Vector ◽

Therapeutic Strategies ◽

Convincing Evidence ◽

Plasma Therapy ◽

Therapeutic Monoclonal Antibodies ◽

Increased Susceptibility

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

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Ellagitannins, Gallotannins and their Metabolites- The Contribution to the Anti-Inflammatory Effect of Food Products and Medicinal Plants

Current Medicinal Chemistry ◽

10.2174/0929867323666160919111559 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4946-4967 ◽

Cited By ~ 18

Author(s):

Anna K. Kiss ◽

Jakub P. Piwowarski

Keyword(s):

Immune Response ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Health Effects ◽

Biological Effects ◽

Food Products ◽

Anti Inflammatory ◽

The Impact

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products’ phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs’ bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs’ metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.

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Macrophages produce somnogenic and pyrogenic muramyl peptides during digestion of staphylococci

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.260.1.r126 ◽

1991 ◽

Vol 260 (1) ◽

pp. R126-R133 ◽

Cited By ~ 2

Author(s):

L. Johannsen ◽

J. Wecke ◽

F. Obal ◽

J. M. Krueger

Keyword(s):

Immune Response ◽

Body Temperature ◽

Bacterial Cell ◽

Cell Walls ◽

Mammalian Cells ◽

Slow Wave Sleep ◽

Biological Effects ◽

Biologically Active ◽

Chromatographic Behavior ◽

Bacterial Cell Walls

Muramyl peptides have a variety of biological effects in mammals, including enhancement of the immune response, sleep, and body temperature. Although mammals lack biosynthetic pathways for muramyl peptides, they are found in mammals and are well known as components of bacterial cell walls. This suggests that phagocytic mammalian cells digest bacterial cell walls and produce biologically active muramyl peptides. Staphylococcal cell walls were radioactively labeled during growth of the bacteria. During the digestion of these radiolabeled bacteria, murine bone marrow macrophages produced low-molecular-weight substances that coeluted chromatographically with the radioactive cell wall marker. Further separation of these substances using reversed-phase high-performance liquid chromatography resulted in the isolation of substances with high specific biological activity. Intracerebroventricular injection of rabbits with these substances induced an increase in slow-wave sleep and body temperature and a suppression of rapid-eye-movement sleep. The characteristics of the biological responses and the chromatographic behavior of the active components are consistent with those of muramyl peptides. The ability of macrophages to tailor muramyl peptides from peptidoglycan may provide an amplification step for the immune response. Muramyl peptides released by macrophages may also act as mediators for various facets of the acute phase response elicited by bacterial infections such as fever and sleep.

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Genetic polymorphisms mediating behavioural and immune response to pathogens may moderate the impact of the COVID-19 pandemic: a pilot study

10.1101/2020.06.03.20120998 ◽

2020 ◽

Author(s):

Ravi Philip Rajkumar

Keyword(s):

Immune Response ◽

Pilot Study ◽

Immune Responses ◽

Genetic Variants ◽

Mortality Rates ◽

Therapeutic Strategies ◽

Published Data ◽

Entire World ◽

S Allele ◽

The Impact

AbstractBackgroundThe COVID-19 pandemic has affected the entire world, but there are wide variations in prevalence and mortality across nations. Genetic variants which influence behavioural or immune responses to pathogens, selected for by pathogen pressure, may influence this variability. Two relevant polymorphisms in this context are the s allele of the serotonin transporter promoter (5-HTTLPR) and the G allele of the interleukin-6 gene (IL-6 rs1800795).MethodsThe frequencies of the 5-HTTLPR s allele and IL-6 rs1800795 G allele were obtained from published data. The correlations between these allele frequencies and the prevalence and mortality rates of COVID-19 were examined across 44 nations.ResultsThe IL-6 rs1800795 G allele was negatively correlated with COVID-19 prevalence (ρ = −0.466, p < 0.01) and mortality (ρ = −0.591, p<0.001) across nations. The 5-HTTLPR s allele was negatively correlated with COVID-19 mortality rates (ρ = −0.437, p = 0.023).ConclusionsThese results suggest that a significant relationship exists between genetic variants that influence behavioural and immune responses to pathogens and indices of the impact of COVID-19 across nations. Further investigation of these variants and their correlates may permit the development of better preventive or therapeutic strategies in the management of the COVID-19 pandemic.

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The Role of Immune-Related miRNAs in the Pathology of Kidney Transplantation

Biomolecules ◽

10.3390/biom11081198 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1198

Author(s):

Emanuela Boštjančič ◽

Željka Večerić-Haler ◽

Nika Kojc

Keyword(s):

Immune Response ◽

Kidney Transplantation ◽

Kidney Diseases ◽

Experimental Models ◽

Regulatory Rna ◽

Limited Data ◽

Pathological Conditions ◽

Monitoring Response ◽

Disease Specific

MicroRNAs (miRNAs) are members of the non-coding regulatory RNA family that play pivotal roles in physiological and pathological conditions, including immune response. They are particularly interesting as promising therapeutic targets, prognostic and diagnostic markers due to their easy detection in body fluids and stability. There is accumulating evidence that different miRNAs provide disease-specific signatures in liquid samples of distinct kidney injuries. Using experimental models and human samples, there have been numerous suggestions that immune-related miRNAs are also important contributors to the development of different kidney diseases as well as important markers for monitoring response after kidney transplantation. However, there are limited data for understanding their function in the molecular pathways of allograft pathologies. In our review, we focused on microRNAs that are related to different aspects of immune response after kidney transplantation.

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