scholarly journals New Strategies to Enhance Myocardial Regeneration: Expectations and Challenges from Preclinical Evidence

2020 ◽  
Vol 15 (8) ◽  
pp. 696-710 ◽  
Author(s):  
Erica Rurali ◽  
Maria Cristina Vinci ◽  
Beatrice Bassetti ◽  
Veronica Barbagallo ◽  
Giulio Pompilio ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Myocardial Remodeling ◽  
Physiological Conditions ◽  
Cell Efficiency ◽  
Different Types ◽  
Preclinical Trials ◽  
New Strategies

Nowadays, cardiac regeneration is an emerging topic in the cardiovascular field because of the compelling need for effective therapies for repairing or replacing cardiac tissue damaged by pathological or physiological conditions. Indeed, irreversible myocardial remodeling which follows acute myocardial infarction represents a serious burden of this century. In this context, a great improvement in pharmacological and interventional techniques is accompanied by a big challenge of cardiac regenerative medicine. In the last 20 years, several clinical trials tried to investigate the role of different types of stem cells in promoting cardiac repair. However, the promising results obtained in the preclinical trials have not yet been reproduced in patients. Thus, the development of novel strategies to improve stem cell efficiency became imperative. Here, an overview of the more recent cell types proposed for cardiac regeneration is presented, together with the most interesting approaches to enhance cell regenerative potential as well as cell-free approaches.

scholarly journals Cancer Nano-Immunotherapy from the Injection to the Target: The Role of Protein Corona

2020 ◽  
Vol 21 (2) ◽  
pp. 519
Author(s):  
Idoia Mikelez-Alonso ◽  
Antonio Aires ◽  
Aitziber L. Cortajarena
Keyword(s):  
Protein Corona ◽  
Biological Properties ◽  
Immune Reactivity ◽  
Target Tissue ◽  
Physiological Conditions ◽  
Different Types ◽  
Cancer Remission ◽  
New Strategies

Immunotherapy has become a promising cancer therapy, improving the prognosis of patients with many different types of cancer and offering the possibility for long-term cancer remission. Nevertheless, some patients do not respond to these treatments and immunotherapy has shown some limitations, such as immune system resistance or limited bioavailability of the drug. Therefore, new strategies that include the use of nanoparticles (NPs) are emerging to enhance the efficacy of immunotherapies. NPs present very different pharmacokinetic and pharmacodynamic properties compared with free drugs and enable the use of lower doses of immune-stimulating molecules, minimizing their side effects. However, NPs face issues concerning stability in physiological conditions, protein corona (PC) formation, and accumulation in the target tissue. PC formation changes the physicochemical and biological properties of the NPs and in consequence their therapeutic effect. This review summarizes the recent advances in the study of the effects of PC formation in NP-based immunotherapy. PC formation has complex effects on immunotherapy since it can diminish (“immune blinding”) or enhance the immune response in an uncontrolled manner (“immune reactivity”). Here, future perspectives of the field including the latest advances towards the use of personalized protein corona in cancer immunotherapy are also discussed.

scholarly journals Pancreatic α and β cells are globally phase-locked

2020 ◽  
Author(s):  
Huixia Ren ◽  
Yanjun Li ◽  
Chengsheng Han ◽  
Yi Yu ◽  
Bowen Shi ◽  
...  
Keyword(s):  
Islet Cells ◽  
Cell Types ◽  
Phase Oscillators ◽  
Β Cells ◽  
Oscillation Modes ◽  
Different Types ◽  
Glucagon And Insulin ◽  
Different Cell Types

ABSTRACTThe Ca2+ modulated pulsatile secretions of glucagon and insulin by pancreatic α and β cells play a key role in glucose metabolism and homeostasis. However, how different types of islet cells couple and coordinate via paracrine interactions to produce various Ca2+ oscillation patterns are still elusive. By designing a microfluidic device to facilitate long-term recording of islet Ca2+ activity at single cell level and simultaneously identifying different cell types in live islet imaging, we show heterogeneous but intrinsic Ca2+ oscillation patterns of islets upon glucose stimulation. The α and β cells oscillate in antiphase and are globally phase locked to various phase delays, causing fast, slow or mixed oscillations. A mathematical model of coupled phase oscillators quantitatively agrees with experiments and reveals the essential role of paracrine regulations in tuning the oscillation modes. Our study highlights the importance of cell-cell interactions to generate stable but tunable islet oscillation patterns.

scholarly journals Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure. Part II

2015 ◽  
Vol 82 (4) ◽  
Author(s):  
Andrea Salzano ◽  
Domenico Sirico ◽  
Michele Arcopinto ◽  
Alberto Maria Marra ◽  
Germano Guerra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Cardiac Tissue ◽  
Cell Types ◽  
Micro Rna ◽  
Future Perspective ◽  
Post Translational Modification ◽  
Progression Of Disease ◽  
Remarkable Progress ◽  
New Strategies

In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. After the evaluation of the results obtained from gene therapy and stem cells, in this part we evaluate micro- RNA, post-translational modification and microspheres based therapy.

scholarly journals Interneuron Types and Their Circuits in the Basolateral Amygdala

2021 ◽  
Vol 15 ◽  
Author(s):  
Norbert Hájos
Keyword(s):  
Basolateral Amygdala ◽  
Cell Types ◽  
Neuronal Population ◽  
Entry Site ◽  
Different Types ◽  
Network Operation ◽  
Developmental Characteristics ◽  
Cortical Regions ◽  
Multisensory Information

The basolateral amygdala (BLA) is a cortical structure based on its cell types, connectivity features, and developmental characteristics. This part of the amygdala is considered to be the main entry site of processed and multisensory information delivered via cortical and thalamic afferents. Although GABAergic inhibitory cells in the BLA comprise only 20% of the entire neuronal population, they provide essential control over proper network operation. Previous studies have uncovered that GABAergic cells in the basolateral amygdala are as diverse as those present in other cortical regions, including the hippocampus and neocortex. To understand the role of inhibitory cells in various amygdala functions, we need to reveal the connectivity and input-output features of the different types of GABAergic cells. Here, I review the recent achievements in uncovering the diversity of GABAergic cells in the basolateral amygdala with a specific focus on the microcircuit organization of these inhibitory cells.

EEG Correlation of the Discharge Properties of Identified Neurons in the Basal Forebrain

2000 ◽  
Vol 84 (3) ◽  
pp. 1627-1635 ◽  
Author(s):  
A. Duque ◽  
B. Balatoni ◽  
L. Detari ◽  
L. Zaborszky
Keyword(s):  
Basal Forebrain ◽  
Temporal Relationship ◽  
Low Voltage ◽  
Cell Types ◽  
Heterogeneous Structure ◽  
Chemical Identification ◽  
Fast Activity ◽  
Different Types ◽  
Dynamic Interplay

The basal forebrain (BF) is a heterogeneous structure located in the ventral aspect of the cerebral hemispheres. It contains cholinergic as well as different types of noncholinergic corticopetal neurons and interneurons, including GABAergic and peptidergic cells. The BF constitutes an extrathalamic route to the cortex, and its activity is associated with an increase in cortical release of the neurotransmitter acetylcholine, concomitant with electroencephalographic (EEG) low-voltage fast activity (LVFA). However, the specific role of the different BF cell types has largely remained unknown due to the lack of chemical identification of the recorded neurons. Here we show that the firing rate of immunocytochemically identified cholinergic and parvalbumin-containing neurons increase during cortical LVFA. In contrast, increased neuropeptide Y neuron firing is accompanied by cortical slow waves. Our results, furthermore, indicate that BF neurons posses a distinct temporal relationship to different EEG patterns and suggest a more dynamic interplay within BF as well as between BF and cortical circuitries than previously proposed.

scholarly journals Role of TLR4 in Neutrophil Dynamics and Functions: Contribution to Stroke Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Violeta Durán-Laforet ◽  
Carolina Peña-Martínez ◽  
Alicia García-Culebras ◽  
María Isabel Cuartero ◽  
Eng H. Lo ◽  
...  
Keyword(s):  
Inflammatory Process ◽  
Focal Cerebral Ischemia ◽  
Cell Types ◽  
Neutrophil Function ◽  
Specific Cell ◽  
Radical Oxygen Species ◽  
Physiological Conditions ◽  
Neuroprotective Strategies ◽  
Circadian Fluctuation

Background and PurposeThe immune response subsequent to an ischemic stroke is a crucial factor in its physiopathology and outcome. It is known that TLR4 is implicated in brain damage and inflammation after stroke and that TLR4 absence induces neutrophil reprogramming toward a protective phenotype in brain ischemia, but the mechanisms remain unknown. We therefore asked how the lack of TLR4 modifies neutrophil function and their contribution to the inflammatory process.MethodsIn order to assess the role of the neutrophilic TLR4 after stroke, mice that do not express TLR4 in myeloid cells (TLR4loxP/Lyz-cre) and its respective controls (TLR4loxP/loxP) were used. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery and infarct size was measured by MRI. A combination of flow cytometry and confocal microscopy was used to assess different neutrophil characteristics (circadian fluctuation, cell surface markers, cell complexity) and functions (apoptosis, microglia engulfment, phagocytosis, NETosis, oxidative burst) in both genotypes.ResultsAs previously demonstrated, mice with TLR4 lacking-neutrophils had smaller infarct volumes than control mice. Our results show that the absence of TLR4 keeps neutrophils in a steady youth status that is dysregulated, at least in part, after an ischemic insult, preventing neutrophils from their normal circadian fluctuation. TLR4-lacking neutrophils showed a higher phagocytic activity in the basal state, they were preferentially engulfed by the microglia after stroke, and they produced less radical oxygen species (ROS) in the first stage of the inflammatory process.ConclusionsTLR4 is specifically involved in neutrophil dynamics under physiological conditions as well as in stroke-induced tissue damage. This research contributes to the idea that TLR4, especially when targeted in specific cell types, is a potential target for neuroprotective strategies.

scholarly journals Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.

1991 ◽  
Vol 173 (3) ◽  
pp. 549-559 ◽  
Author(s):  
M Inaba ◽  
K Inaba ◽  
M Hosono ◽  
T Kumamoto ◽  
T Ishida ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Cell Types ◽  
Cell Sorter ◽  
Histocompatibility Complex ◽  
Different Types ◽  
Induced Tolerance ◽  
Antigen Presenting

To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a-reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs.-host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow-derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms.

scholarly journals Stage-dependent cardiac regeneration in Xenopus is regulated by thyroid hormone availability

2019 ◽  
Vol 116 (9) ◽  
pp. 3614-3623 ◽  
Author(s):  
Lindsey N. Marshall ◽  
Céline J. Vivien ◽  
Fabrice Girardot ◽  
Louise Péricard ◽  
Pierluigi Scerbo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Regenerative Process ◽  
Regenerative Capacity ◽  
Myocardial Wall ◽  
Extracellular Matrix Components ◽  
Altered Gene ◽  
Developmental Switches

Despite therapeutic advances, heart failure is the major cause of morbidity and mortality worldwide, but why cardiac regenerative capacity is lost in adult humans remains an enigma. Cardiac regenerative capacity widely varies across vertebrates. Zebrafish and newt hearts regenerate throughout life. In mice, this ability is lost in the first postnatal week, a period physiologically similar to thyroid hormone (TH)-regulated metamorphosis in anuran amphibians. We thus assessed heart regeneration in Xenopus laevis before, during, and after TH-dependent metamorphosis. We found that tadpoles display efficient cardiac regeneration, but this capacity is abrogated during the metamorphic larval-to-adult switch. Therefore, we examined the consequence of TH excess and deprivation on the efficiently regenerating tadpole heart. We found that either acute TH treatment or blocking TH production before resection significantly but differentially altered gene expression and kinetics of extracellular matrix components deposition, and negatively impacted myocardial wall closure, both resulting in an impeded regenerative process. However, neither treatment significantly influenced DNA synthesis or mitosis in cardiac tissue after amputation. Overall, our data highlight an unexplored role of TH availability in modulating the cardiac regenerative outcome, and present X. laevis as an alternative model to decipher the developmental switches underlying stage-dependent constraint on cardiac regeneration.

scholarly journals Autophagy plays a double-edged sword role in liver diseases

2021 ◽  
Author(s):  
Jing-chao Zhou ◽  
Jing-lin Wang ◽  
Hao-zhen Ren ◽  
Xiao-lei Shi
Keyword(s):  
Liver Diseases ◽  
Alcoholic Hepatitis ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Building Blocks ◽  
Cell Types ◽  
Evolutionarily Conserved ◽  
Constitutive Process ◽  
New Strategies

Abstract As a highly evolutionarily conserved process, autophagy can be found in all types of eukaryotic cells. Such a constitutive process maintains cellular homeostasis in a wide variety of cell types through the encapsulation of damaged proteins or organelles into double-membrane vesicles. Autophagy not only simply eliminates materials but also serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Previous studies have primarily recognized the role of autophagy in the degradation of dysfunctional proteins and unwanted organelles. However, there are findings of autophagy in physiological and pathological processes. In hepatocytes, autophagy is not only essential for homeostatic functions but also implicated in some diseases, such as viral hepatitis, alcoholic hepatitis, and hepatic failure. In the present review, we summarized the molecular mechanisms of autophagy and its role in several liver diseases and put forward several new strategies for the treatment of liver disease.

scholarly journals The role of melatonin in colorectal cancer treatment: a comprehensive review

2020 ◽  
Vol 12 ◽  
pp. 175883592093171
Author(s):  
Mindaugas Kvietkauskas ◽  
Viktorija Zitkute ◽  
Bettina Leber ◽  
Kestutis Strupas ◽  
Philipp Stiegler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multimodal Treatment ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Cytotoxic Effects ◽  
Comprehensive Review ◽  
Stage Disease ◽  
Different Types ◽  
New Strategies

Colorectal cancer (CRC) is one of the most common types of cancer worldwide, known as the second leading cause of cancer-related deaths annually. Currently, multimodal treatment strategies, including surgical resection, combined with chemotherapy and radiotherapy, have been used as conventional treatments in patients with CRC. However, clinical outcome of advanced stage disease remains relatively discouraging, due mainly to appearance of CRC chemoresistance, toxicity, and other detrimental side effects. New strategies to overcome these limitations are essential. During the last decades, melatonin (MLT) has been shown to be a potent antiproliferative, anti-metastatic agent with cytotoxic effects on different types of human malignancies, including CRC. Hence, this comprehensive review compiles the available experimental and clinical data analyzing the effects of MLT treatment in CRC patients and its underlying molecular mechanisms.

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