scholarly journals MicroRNAs as Important Regulators Mediate the Multiple Differentiation of Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chao Yang ◽  
Maowen Luo ◽  
Yu Chen ◽  
Min You ◽  
Qiang Chen
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Critical Role ◽  
The Body ◽  
Disease Treatment ◽  
Multipotent Stem Cells ◽  
Physiological Processes ◽  
Multiple Differentiation ◽  
Differentiation Efficiency

MicroRNAs (miRNAs) are endogenous short non-encoding RNAs which play a critical role on the output of the proteins, and influence multiple biological characteristics of the cells and physiological processes in the body. Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells and characterized by self-renewal and multidifferentiation and have been widely used for disease treatment and regenerative medicine. Meanwhile, MSCs play a critical role in maintaining homeostasis in the body, and dysfunction of MSC differentiation leads to many diseases. The differentiation of MSCs is a complex physiological process and is the result of programmed expression of a series of genes. It has been extensively proven that the differentiation process or programmed gene expression is also regulated accurately by miRNAs. The differentiation of MSCs regulated by miRNAs is also a complex, interdependent, and dynamic process, and a full understanding of the role of miRNAs will provide clues on the appropriate upregulation or downregulation of corresponding miRNAs to mediate the differentiation efficiency. This review summarizes the roles and associated signaling pathways of miRNAs in adipogenesis, chondrogenesis, and osteogenesis of MSCs, which may provide new hints on MSCs or miRNAs as therapeutic strategies for regenerative medicine and biotherapy for related diseases.

scholarly journals PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8298
Author(s):  
Hugo Christian Monroy-Ramirez ◽  
Marina Galicia-Moreno ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Arturo Santos ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Metabolic Regulation ◽  
Structural Changes ◽  
Critical Role ◽  
The Body ◽  
Molecular Characteristics ◽  
Signal Pathways ◽  
Virus Infections ◽  
Physiological Processes ◽  
Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

scholarly journals The Role of the Bone Marrow Microenvironment in the Response to Infection

2020 ◽  
Vol 11 ◽  
Author(s):  
Courtney B. Johnson ◽  
Jizhou Zhang ◽  
Daniel Lucas
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Cells ◽  
Critical Role ◽  
Primary Source ◽  
Bone Marrow Microenvironment ◽  
Future Research ◽  
Multipotent Stem Cells ◽  
Hematopoietic Stem

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

scholarly journals Paracrine interactions between epithelial cells promote colon cancer growth

2020 ◽  
Author(s):  
Guillaume Jacquemin ◽  
Annabelle Wurmser ◽  
Mathilde Huyghe ◽  
Wenjie Sun ◽  
Meghan Perkins ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Critical Role ◽  
Essential Factor ◽  
Transcriptional Responses ◽  
Tumour Formation ◽  
Different Types ◽  
The Impact

AbstractTumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (Thbs1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the Thbs1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells, promoting tumour formation and progression.

Pathogenesis as a problem of functional incompetence and imbalance in the population of T-lymphocytes

2021 ◽  
pp. 109-119
Author(s):  
Н.М. Геворкян ◽  
Н.В. Тишевская
Keyword(s):  
T Lymphocytes ◽  
Personalized Medicine ◽  
The Body ◽  
Lymphoid Cells ◽  
Human Diseases ◽  
Regulatory Role ◽  
Total Rna ◽  
Physiological Processes ◽  
Health And Disease

Цель обзора - анализ клеточной основы патогенеза различных заболеваний в свете регуляторной роли Т-лимфоцитов. Рассматривается роль поликлонального многообразия популяции Т-лимфоцитов, особых свойств этих клеток-представителей гомеостатической системы организма в физиологических процессах в норме и при патологии. Указаны перспективы терапевтического и профилактического воздействий, связанные с использованием суммарных РНК нормальных лимфоидных клеток аллогенной и ксеногенной природы. Указана также возможность создания с помощью лимфоцитарных суммарных РНК адекватных моделей заболеваний человека на пути к развитию персонифицированной медицины. This review provides an analysis of the cellular basis of the pathogenesis of various diseases in the light of the regulatory role of T-lymphocytes. The role of the polyclonal diversity of the population of T-lymphocytes, the special properties of these cells-representatives of the homeostatic system of the body, in physiological processes in health and disease is considered. Prospects for therapeutic and prophylactic effects associated with the use of total RNA of normal lymphoid cells of allogeneic and xenogenic origin are indicated. The possibility of creating, using lymphocytic total RNA, adequate models of human diseases for the development of personalized medicine is also indicated.

Adoption of students' loan schemes: the contingent role of financial knowledge

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Gloria Ocran ◽  
Livingstone Divine Caesar
Keyword(s):  
Critical Role ◽  
Financial Education ◽  
The Body ◽  
Financial Knowledge ◽  
Relative Advantage ◽  
Research Approach ◽  
Content Type ◽  
Four Dimensions ◽  
Behavioural Factors

PurposeDespite the introduction of structural reforms to the students' loan scheme (SLS) in Ghana's higher education sector, patronage is still low. This paper aims to examine the complexity of technological and behavioural factors underpinning the low rate of students' loan adoption in Ghana. It further contributes to the body of knowledge by exploring the moderating role of financial knowledge in the hypothesized relationships.Design/methodology/approachUsing a positivistic research approach, a sample of 700 tertiary students with experience in accessing SLSs were surveyed. An 88% response rate was realized and the data analysed using descriptive statistics, exploratory and confirmatory factor analysis.FindingsFour dimensions of technological factors (relative advantage, trialability, observability and compatibility) and two of behavioural factors (attitude and control behaviour) were positively related to adoption of the SLS. Financial knowledge only moderated the relationship between compatibility, attitude, behavioural control and students' loan adoption.Practical implicationsFinancial knowledge plays a critical role in influencing the investment decisions of people. Management of SLSs needs to offer financial education to targeted parents/students to clear misconceptions. It is also imperative that all other technical challenges are addressed to enhance adoption rates for the SLS. Review of guarantor requirements is needed also.Originality/valueThis paper introduces financial knowledge as a moderating variable to investigate the hypothesized relationships. It offers a developing country insight into how technological/behavioural factors and financial knowledge might be impacting adoption of SLSs.

Cell Delivery and Recirculation

2004 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Tissue Engineering ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Critical Role ◽  
Cell Movement ◽  
The Body ◽  
Associated Proteins ◽  
Adult Organism ◽  
Adenine Deaminase

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.

scholarly journals The Neural Regulation of Cancer

2020 ◽  
Vol 4 (1) ◽  
pp. 371-390
Author(s):  
Shawn Gillespie ◽  
Michelle Monje
Keyword(s):  
Nervous System ◽  
Crucial Role ◽  
The Body ◽  
Tissue Homeostasis ◽  
Neural Regulation ◽  
Physiological Processes

The nervous system is intimately involved in physiological processes from development and growth to tissue homeostasis and repair throughout the body. It logically follows that the nervous system has the potential to play analogous roles in the context of cancer. Progress toward understanding the crucial role of the nervous system in cancer has accelerated in recent years, but much remains to be learned. Here, we highlight rapidly evolving concepts in this burgeoning research space and consider next steps toward understanding and therapeutically targeting the neural regulation of cancer.

scholarly journals Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment

2020 ◽  
Vol 21 (17) ◽  
pp. 6247
Author(s):  
Yongsheng Ruan ◽  
Hye Na Kim ◽  
Heather Ogana ◽  
Yong-Mi Kim
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Stromal Cells ◽  
Critical Role ◽  
Neoplastic Disease ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Disease Therapy ◽  
Wnt Pathways

Leukemia is an aggressive hematologic neoplastic disease. Therapy-resistant leukemic stem cells (LSCs) may contribute to the relapse of the disease. LSCs are thought to be protected in the leukemia microenvironment, mainly consisting of mesenchymal stem/stromal cells (MSC), endothelial cells, and osteoblasts. Canonical and noncanonical Wnt pathways play a critical role in the maintenance of normal hematopoietic stem cells (HSC) and LSCs. In this review, we summarize recent findings on the role of Wnt signaling in leukemia and its microenvironment and provide information on the currently available strategies for targeting Wnt signaling.

scholarly journals Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning

2020 ◽  
Vol 31 (1) ◽  
pp. 267-280
Author(s):  
Rossella Breveglieri ◽  
Annalisa Bosco ◽  
Sara Borgomaneri ◽  
Alessia Tessari ◽  
Claudio Galletti ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Parietal Cortex ◽  
Magnetic Stimulation ◽  
Posterior Parietal Cortex ◽  
Critical Role ◽  
The Body ◽  
Visually Guided ◽  
Visually Guided Reaching ◽  
Posterior Parietal

Abstract Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A–hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

scholarly journals Bmal1 regulates circadian expression of cytochrome P450 3a11 and drug metabolism in mice

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Yanke Lin ◽  
Shuai Wang ◽  
Ziyue Zhou ◽  
Lianxia Guo ◽  
Fangjun Yu ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Drug Exposure ◽  
Defense Mechanism ◽  
Critical Role ◽  
The Body ◽  
Cellular Regulation ◽  
Circadian Expression ◽  
Distal Promoter ◽  
Daily Time

Abstract Metabolism is a major defense mechanism of the body against xenobiotic threats. Here we unravel a critical role of Bmal1 for circadian clock-controlled Cyp3a11 expression and xenobiotic metabolism. Bmal1 deficiency decreases the mRNA, protein and microsomal activity of Cyp3a11, and blunts their circadian rhythms in mice. A screen for Cyp3a11 regulators identifies two circadian genes Dbp and Hnf4α as potential regulatory mediators. Cell-based experiments confirm that Dbp and Hnf4α activate Cyp3a11 transcription by their binding to a D-box and a DR1 element in the Cyp3a11 promoter, respectively. Bmal1 binds to the P1 distal promoter to regulate Hnf4α transcriptionally. Cellular regulation of Cyp3a11 by Bmal1 is Dbp- and Hnf4α-dependent. Bmal1 deficiency sensitizes mice to toxicities of drugs such as aconitine and triptolide (and blunts circadian toxicity rhythmicities) due to elevated drug exposure. In summary, Bmal1 connects circadian clock and Cyp3a11 metabolism, thereby impacting drug detoxification as a function of daily time.

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