scholarly journals Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

2018 ◽  
Vol 19 (9) ◽  
pp. 2516 ◽  
Author(s):  
Ewelina Piktel ◽  
Ilya Levental ◽  
Bonita Durnaś ◽  
Paul Janmey ◽  
Robert Bucki
Keyword(s):  
Therapeutic Target ◽  
Animal Studies ◽  
Recent Progress ◽  
Mechanisms Of Action ◽  
Current Data ◽  
Clinical Use ◽  
Plasma Gelsolin ◽  
Beneficial Effects ◽  
Potential Biomarker ◽  
Efficacy Of Treatment

Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease

2019 ◽  
Vol 16 (8) ◽  
pp. 699-709
Author(s):  
Jessica Sarahi Alavez-Rubio ◽  
Teresa Juarez-Cedillo
Keyword(s):  
Genetic Relationship ◽  
Therapeutic Target ◽  
Drug Targets ◽  
Animal Studies ◽  
Cholesterol Acyltransferase ◽  
Cholesterol Homeostasis ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Area Of Interest ◽  
Information Gap

Background: Alzheimer´s disease (AD) is a chronic and progressive disease which impacts caregivers, families and societies physically, psychologically and economically. Currently available drugs can only improve cognitive symptoms, have no impact on progression and are not curative, so identifying and studying new drug targets is important. There are evidences which indicate disturbances in cholesterol homeostasis can be related with AD pathology, especially the compartmentation of intracellular cholesterol and cytoplasmic cholesterol esters formed by acyl-CoA: cholesterol acyltransferase 1 (ACAT1) can be implicated in the regulation of amyloid-beta (Aβ) peptide, involved in AD. Blocking ACAT1 activity, beneficial effects are obtained, so it has been suggested that ACAT1 can be a potential new therapeutic target. The present review discusses the role of cholesterol homeostasis in AD pathology, especially with ACAT inhibitors, and how they have been raised as a therapeutic approach. In addition, the genetic relationship of ACAT and AD is discussed. Conclusion: Although there are several lines of evidence from cell-based and animal studies that suggest that ACAT inhibition is an effective way of reducing cerebral Aβ, there is still an information gap in terms of mechanisms and concerns to cover before passing to the next level. Additionally, an area of interest that may be useful in understanding AD to subsequently propose new therapeutic approaches is pharmacogenetics; however, there is still a lot of missing information in this area.

scholarly journals Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?

2021 ◽  
Author(s):  
Francesco Amadeo ◽  
Katherine Trivino Cepeda ◽  
James Littlewood ◽  
Bettina Wilm ◽  
Arthur Taylor ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Therapeutic Potential ◽  
Animal Experiments ◽  
Mechanisms Of Action ◽  
Clinical Translation ◽  
Beneficial Effects ◽  
Wide Range

Mesenchymal stromal cells (MSCs) have been found to be safe and effective in a wide range of animal models of human disease. MSCs have been tested in thousands of clinical trials, but results show that while these cells appear to be safe, they tend to lack efficacy. This has raised questions about whether animal models are useful for predicting efficacy in patients. However, a problem with animal studies is that there is a lack of standardisation in the models and MSC therapy regimes used; there appears to be publication bias towards studies reporting positive outcomes; and the reproducibility of results from animal experiments tends not to be confirmed prior to clinical translation. A further problem is that while some progress has been made towards investigating the mechanisms of action (MoA) of MSCs, we still fail to understand how they work. To make progress, it is important to ensure that prior to clinical translation, the beneficial effects of MSCs in animal studies are real and can be repeated by independent research groups. We also need to understand the MoA of MSCs to assess whether their effects are likely to be beneficial across different species. In this review, we give an overview of the current clinical picture of MSC therapies and discuss what we have learned from animal studies. We also give a comprehensive update of what we know about the MoA of MSCs, particularly in relation to their role in immunomodulation.

scholarly journals Melatonin and cardiovascular disease: from mechanisms of action to potential clinical use (literature review)

2022 ◽  
Vol 20 (8) ◽  
pp. 2892
Author(s):  
O. M. Drapkina ◽  
A. V. Kontsevaya ◽  
A. V. Budnevsky ◽  
E. S. Ovsyannikov ◽  
E. S. Drobysheva ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Biological Effects ◽  
Public Health Problem ◽  
Mechanisms Of Action ◽  
Current Data ◽  
Clinical Use ◽  
Circadian Cycle ◽  
Long Time ◽  
Cyclic Processes ◽  
Cardioprotective Effects

Cardiovascular disease remains the most relevant public health problem. Most cardiovascular diseases are associated with an atherosclerosis, the development of which is associated with inflammation and endothelial dysfunction. Melatonin is a neurohormone that is synthesized mainly in the pineal gland and plays a central role in the regulation of sleep and some other body cyclic processes. For a long time, melatonin was perceived as a substance that is effective in the treatment of circadian cycle impairments. At the same time, a large number of studies have accumulated recently that demonstrate a wider range of its biological effects, including anti-inflammatory, antioxidant, antihypertensive and, possibly, hypolipidemic. The review includes current data from experimental and clinical studies demonstrating the cardioprotective effects of melatonin in atherosclerosis, myocardial ischemia, and heart failure.

scholarly journals The path toward ectogenesis: looking beyond the technical challenges

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Seppe Segers
Keyword(s):  
Neonatal Intensive Care ◽  
Animal Studies ◽  
Current Data ◽  
Safety Testing ◽  
Future Challenges ◽  
Critical Issues ◽  
Expected Benefits ◽  
Physical Impact ◽  
Biological Parenthood ◽  
Experimental Use

Abstract Background Breakthroughs in animal studies make the topic of human application of ectogenesis for medical and non-medical purposes more relevant than ever before. While current data do not yet demonstrate a reasonable expectation of clinical benefit soon, several groups are investigating the feasibility of artificial uteri for extracorporeal human gestation. Main text This paper offers the first comprehensive and up to date discussion of the most important pros and cons of human ectogenesis in light of clinical application, along with an examination of crucial ethical (and legal) issues that continued research into, and the clinical translation of, ectogenesis gives rise to. The expected benefits include advancing prenatal medicine, improving neonatal intensive care, and providing a novel pathway towards biological parenthood. This comes with important future challenges. Prior to human application, important questions have to be considered concerning translational research, experimental use of human fetuses and appropriate safety testing. Key questions are identified regarding risks to ectogenesis’ subjects, and the physical impact on the pregnant person when transfer from the uterus to the artificial womb is required. Critical issues concerning proportionality have to be considered, also in terms of equity of access, relative to the envisaged application of ectogenesis. The advent of ectogenesis also comes with crucial issues surrounding abortion, extended fetal viability and moral status of the fetus. Conclusions The development of human ectogenesis will have numerous implications for clinical practice. Prior to human testing, close consideration should be given to whether (and how) ectogenesis can be introduced as a continuation of existing neonatal care, with due attention to both safety risks to the fetus and pressures on pregnant persons to undergo experimental and/or invasive procedures. Equally important is the societal debate about the acceptable applications of ectogenesis and how access to these usages should be prioritized. It should be anticipated that clinical availability of ectogenesis, possibly first as a way to save extremely premature fetuses, may spark demand for non-medical purposes, like avoiding physical and social burdens of pregnancy.

scholarly journals The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3081
Author(s):  
Mohammad Amin Atazadegan ◽  
Mohammad Bagherniya ◽  
Gholamreza Askari ◽  
Aida Tasbandi ◽  
Amirhossein Sahebkar
Keyword(s):  
Clinical Trials ◽  
Medicinal Plants ◽  
Vascular Endothelium ◽  
Animal Studies ◽  
Natural Compounds ◽  
Herbal Products ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
Serum Homocysteine ◽  
Prevention And Treatment

Background: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. Results: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.

scholarly journals Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hu Zhu ◽  
Catherine Z. Chen ◽  
Srilatha Sakamuru ◽  
Jinghua Zhao ◽  
Deborah K. Ngan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Throughput Screening ◽  
Animal Studies ◽  
Cytopathic Effect ◽  
Mechanisms Of Action ◽  
Activity Profile ◽  
Pathway Activity ◽  
Global Pandemic ◽  
Approved Drugs

AbstractThe recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.

scholarly journals Limosilactobacillus fermentum CECT5716: Mechanisms and Therapeutic Insights

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1016
Author(s):  
María Jesús Rodríguez-Sojo ◽  
Antonio Jesús Ruiz-Malagón ◽  
María Elena Rodríguez-Cabezas ◽  
Julio Gálvez ◽  
Alba Rodríguez-Nogales
Keyword(s):  
Competitive Exclusion ◽  
Intestinal Barrier ◽  
Mechanisms Of Action ◽  
Intestinal Barrier Function ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
Host Health ◽  
Inflammatory Processes ◽  
Immunomodulatory Properties ◽  
Immunological Alterations

Probiotics microorganisms exert their health-associated activities through some of the following general actions: competitive exclusion, enhancement of intestinal barrier function, production of bacteriocins, improvement of altered microbiota, and modulation of the immune response. Among them, Limosilactobacillus fermentum CECT5716 has become one of the most promising probiotics and it has been described to possess potential beneficial effects on inflammatory processes and immunological alterations. Different studies, preclinical and clinical trials, have evidenced its anti-inflammatory and immunomodulatory properties and elucidated the precise mechanisms of action involved in its beneficial effects. Therefore, the aim of this review is to provide an updated overview of the effect on host health, mechanisms, and future therapeutic approaches.

scholarly journals Tea Polyphenols in Promotion of Human Health

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 39 ◽  
Author(s):  
Naghma Khan ◽  
Hasan Mukhtar
Keyword(s):  
Green Tea ◽  
Animal Studies ◽  
Neurological Diseases ◽  
Black Tea ◽  
Polyphenolic Compounds ◽  
Tea Polyphenols ◽  
Beneficial Effects ◽  
Gallocatechin Gallate ◽  
Prevention Of Cancer ◽  
Pharmacologically Active

Tea is the most widely used beverage worldwide. Japanese and Chinese people have been drinking tea for centuries and in Asia, it is the most consumed beverage besides water. It is a rich source of pharmacologically active molecules which have been implicated to provide diverse health benefits. The three major forms of tea are green, black and oolong tea based on the degree of fermentation. The composition of tea differs with the species, season, leaves, climate, and horticultural practices. Polyphenols are the major active compounds present in teas. The catechins are the major polyphenolic compounds in green tea, which include epigallocatechin-3-gallate (EGCG), epigallocatechin, epicatechin-3-gallate and epicatechin, gallocatechins and gallocatechin gallate. EGCG is the predominant and most studied catechin in green tea. There are numerous evidences from cell culture and animal studies that tea polyphenols have beneficial effects against several pathological diseases including cancer, diabetes and cardiovascular diseases. The polyphenolic compounds present in black tea include theaflavins and thearubigins. In this review article, we will summarize recent studies documenting the role of tea polyphenols in the prevention of cancer, diabetes, cardiovascular and neurological diseases.

scholarly journals miR-27b Suppresses Endothelial Cell Proliferation and Migration by Targeting Smad7 in Kawasaki Disease

2018 ◽  
Vol 48 (4) ◽  
pp. 1804-1814 ◽  
Author(s):  
Xing Rong ◽  
Donghui Ge ◽  
Danping Shen ◽  
Xianda Chen ◽  
Xuliang Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
Therapeutic Target ◽  
Umbilical Vein ◽  
Luciferase Reporter ◽  
Endothelial Cell Proliferation ◽  
Cell Functions ◽  
Potential Biomarker ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment.

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