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 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 Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Moyang Lv ◽  
Wenjuan Liu
Keyword(s):  
Clinical Significance ◽  
Metabolic Disorders ◽  
Critical Role ◽  
Present Review ◽  
Molecular Characteristics ◽  
Multifunctional Protein ◽  
Mitogenic Factor ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Health And Disease

Hypoxia-induced mitogenic factor (HIMF), also known as resistin-like molecule α (RELMα) or found in inflammatory zone 1 (FIZZ1) is a member of the RELM protein family expressed in mice. It is involved in a plethora of physiological processes, including mitogenesis, angiogenesis, inflammation, and vasoconstriction. HIMF expression can be stimulated under pathological conditions and this plays a critical role in pulmonary, cardiovascular and metabolic disorders. The present review summarizes the molecular characteristics, and the physiological and pathological roles of HIMF in normal and diseased conditions. The potential clinical significance of these findings for human is also discussed.

Homeostatic Role of Autophagy in Hepatocytes

2018 ◽  
Vol 38 (04) ◽  
pp. 308-319 ◽  
Author(s):  
Bilon Khambu ◽  
Shengmin Yan ◽  
Nazmul Huda ◽  
Gang Liu ◽  
Xiao-Ming Yin
Keyword(s):  
Direct Effect ◽  
Liver Diseases ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Nutrient Supply ◽  
The Other ◽  
Chronic Liver Diseases ◽  
Physiological Processes ◽  
Abnormal Accumulation

AbstractAutophagy actively participates in the physiological process of the liver. While the direct effect of autophagy may be limited to the sequestration and degradation of a selective cargo, its overall impact can be broad, affecting many more physiological processes regulated by the particular cargo. This review will discuss two aspects of the importance of autophagy in the liver: metabolic regulation in response to feeding and starvation, and pathological consequences in the absence of autophagy. These two aspects illustrate the homeostatic functions of autophagy in the liver, one in a more direct fashion, regulating the cellular nutrient supply, and the other in a more indirect fashion, controlling the pathological signaling triggered by the abnormal accumulation of cargos. Remarkably, the hepatic pathology in autophagy-deficient livers does not seem different from that presented in other chronic liver diseases. Autophagy deficiency can be a model for the study of the relevant molecular mechanisms.

An atomic resolution study of a carbide phase in platinum

1992 ◽  
Vol 50 (1) ◽  
pp. 20-21
Author(s):  
M.J. Witcomb ◽  
M.A. O'Keefe ◽  
CJ. Echer ◽  
C. Nelson ◽  
J.H. Turner ◽  
...  
Keyword(s):  
Solid Solution ◽  
Carbon Atom ◽  
Carbide Phase ◽  
Structural Changes ◽  
Critical Role ◽  
Alloy System ◽  
Atomic Resolution ◽  
Excess Carbon ◽  
Interstitial Carbon ◽  
Resolution Study

Under normal circumstances, Pt dissolves only a very small amount of interstitial carbon in solid solution. Even so, an appropriate quench/age treatment leads to the formation of stable Pt2C {100} plate precipitates. Excess (quenched-in) vacancies play a critical role in the process by accommodating the volume and structural changes that accompany the transformation. This alloy system exhibits other interesting properties. Due to a large vacancy/carbon atom binding energy, Pt can absorb excess carbon at high temperatures in a carburizing atmosphere. In regions rich in carbon and vacancies, another carbide phase, Pt7C which undergoes an order-disorder reaction was formed. The present study of Pt carburized at 1160°C and aged at 515°C shows that other carbides in the PtxC series can be produced.

HISTOLOGICAL CHANGES IN THE INTESTINES OF POULTRY DURING FODDER INTOXICATION

2020 ◽  
Author(s):  
E.P. Dolgov ◽  
◽  
A.A. Abramov ◽  
E.V. Kuzminova ◽  
E.V. Rogaleva ◽  
...  
Keyword(s):  
Body Weight ◽  
Histological Examination ◽  
Aflatoxin B1 ◽  
Structural Changes ◽  
Clinical Manifestations ◽  
Feed Additives ◽  
The Body ◽  
Histological Changes ◽  
Beet Pulp

The article presents the data on the study of the influence of mycotoxins combination (T-2 toxin at the concentration of 0.095 mg/kg and aflatoxin B1 in the concentration of 0.019 mg/kg) on the body of quails and the results of pharmacocorrection of toxicosis with a complex consisting of beet pulp and lecithin. Structural changes in the intestines of quais at fodder mycotoxicosis are described. The use of antitoxic feed additives in poultry led to a weakening of the action of xenobiotics, which was confirmed by an increase in the safety of poultry and increase in body weight of quails, a decrease in the clinical manifestations of intoxication, as well as in positive changes in the structure of the intestine of the poultry during histological examination.

Updating long-held assumptions about fat stigma: For women, body shape plays a critical role

2020 ◽  
Author(s):  
Jaimie Krems ◽  
Steven L. Neuberg
Keyword(s):  
Body Shape ◽  
Critical Role ◽  
The Body ◽  
Theoretical Assumption ◽  
Obesity Stigma ◽  
Obese Female ◽  
Three Samples ◽  
Female Bodies ◽  
Different Parts ◽  
Fat Stigma

Heavier bodies—particularly female bodies—are stigmatized. Such fat stigma is pervasive, painful to experience, and may even facilitate weight gain, thereby perpetuating the obesity-stigma cycle. Leveraging research on functionally distinct forms of fat (deposited on different parts of the body), we propose that body shape plays an important but largely underappreciated role in fat stigma, above and beyond fat amount. Across three samples varying in participant ethnicity (White and Black Americans) and nation (U.S., India), patterns of fat stigma reveal that, as hypothesized, participants differently stigmatized equally-overweight or -obese female targets as a function of target shape, sometimes even more strongly stigmatizing targets with less rather than more body mass. Such findings suggest value in updating our understanding of fat stigma to include body shape and in querying a predominating, but often implicit, theoretical assumption that people simply view all fat as bad (and more fat as worse).

Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques

2020 ◽  
Vol 27 (3) ◽  
pp. 201-209
Author(s):  
Syed Saqib Ali ◽  
Mohammad Khalid Zia ◽  
Tooba Siddiqui ◽  
Haseeb Ahsan ◽  
Fahim Halim Khan
Keyword(s):  
Ascorbic Acid ◽  
Conformational Changes ◽  
Structural Changes ◽  
The Body ◽  
Titration Calorimetry ◽  
Spectroscopic Techniques ◽  
Human Beings ◽  
Plasma Ascorbic Acid ◽  
Dietary Antioxidant ◽  
And Function

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

Therapeutic Potential of Agonists and Antagonists of A1, A2a, A2b and A3 Adenosine Receptors

2019 ◽  
Vol 25 (26) ◽  
pp. 2892-2905 ◽  
Author(s):  
Sumit Jamwal ◽  
Ashish Mittal ◽  
Puneet Kumar ◽  
Dana M. Alhayani ◽  
Amal Al-Aboudi
Keyword(s):  
Nervous System ◽  
Therapeutic Potential ◽  
The Body ◽  
Membrane Receptors ◽  
Physiological Importance ◽  
Physiological Processes ◽  
Central Nervous Systems ◽  
Energy Consuming ◽  
Metabolic Dysfunctions ◽  
G Protein Coupled

Adenosine is a naturally occurring nucleoside and an essential component of the energy production and utilization systems of the body. Adenosine is formed by the degradation of adenosine-triphosphate (ATP) during energy-consuming processes. Adenosine regulates numerous physiological processes through activation of four subtypes of G-protein coupled membrane receptors viz. A1, A2A, A2B and A3. Its physiological importance depends on the affinity of these receptors and the extracellular concentrations reached. ATP acts as a neurotransmitter in both peripheral and central nervous systems. In the peripheral nervous system, ATP is involved in chemical transmission in sensory and autonomic ganglia, whereas in central nervous system, ATP, released from synaptic terminals, induces fast excitatory postsynaptic currents. ATP provides the energetics for all muscle movements, heart beats, nerve signals and chemical reactions inside the body. Adenosine has been traditionally considered an inhibitor of neuronal activity and a regulator of cerebral blood flow. Since adenosine is neuroprotective against excitotoxic and metabolic dysfunctions observed in neurological and ocular diseases, the search for adenosinerelated drugs regulating adenosine transporters and receptors can be important for advancement of therapeutic strategies against these diseases. This review will summarize the therapeutic potential and recent SAR and pharmacology of adenosine and its receptor agonists and antagonists.

scholarly journals Physiology and Physical Chemistry of Bile Acids

2021 ◽  
Vol 22 (4) ◽  
pp. 1780
Author(s):  
Maria Chiara di Gregorio ◽  
Jacopo Cautela ◽  
Luciano Galantini
Keyword(s):  
Physical Chemistry ◽  
Bile Acids ◽  
Material Science ◽  
Metabolic Regulation ◽  
Enterohepatic Circulation ◽  
Building Blocks ◽  
The Body ◽  
Active Molecule ◽  
Supramolecular Aggregates ◽  
Biological Field

Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical–physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bio-applications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science.

scholarly journals Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

2021 ◽  
Author(s):  
Wen-Dai Bao ◽  
Pei Pang ◽  
Xiao-Ting Zhou ◽  
Fan Hu ◽  
Wan Xiong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Gene Set Enrichment Analysis ◽  
Molecular Characteristics ◽  
Intracellular Iron

AbstractIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

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