scholarly journals Methionine Nutrition and Metabolism: Insights from Animal Studies to Inform Human Nutrition

2020 ◽  
Vol 150 (Supplement_1) ◽  
pp. 2518S-2523S ◽  
Author(s):  
Rajavel Elango
Keyword(s):  
Animal Studies ◽  
Animal Feed ◽  
Lessons Learned ◽  
The Body ◽  
Methyl Donors ◽  
Transsulfuration Pathway ◽  
Indispensable Amino Acids ◽  
Rate Limiting ◽  
Plant Sources

ABSTRACT Methionine is a nutritionally indispensable amino acid, and is unique among indispensable amino acids due to its sulfur atom. Methionine is involved in cysteine synthesis via the transsulfuration pathway, which is rate limiting for the key antioxidant molecule, glutathione. Methionine is also the primary methyl donor in the body through S-adenosylmethionine via the transmethylation pathway, which is involved in the synthesis of several key metabolites including creatine and phosphatidylcholine. Methionine can also be remethylated from homocysteine, in the presence of betaine via choline and/or folate. Thus methionine demands from a dietary perspective are regulated not only by the presence of cysteine in the body, but also by the demands in vivo for the various metabolites formed from it, and also by the presence of these compounds in foods. Indeed, methionine, cysteine, and the various methyl donors/acceptors vary in human foods, and thus regulate methionine availability, especially under conditions of growth and development. Much of our understanding of methionine nutrition and metabolism arises from experiments in animal models. This is because most animal feed formulations are plant-based and plant sources are relatively low in methionine and cysteine amounts. Thus, this brief review will touch on some broad aspects of human methionine nutrition, including requirements in different life stages, disease, and bioavailability, with some examples from the insights/lessons learned from experiments initially conducted in animals.

Challenges on the effect of cell phone radiation on mammalian embryos and fetuses: a review of the literature

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Maryam Mahaldashtian ◽  
Mohammad Ali Khalili ◽  
Fatemeh Anbari ◽  
Mohammad Seify ◽  
Manuel Belli
Keyword(s):  
Embryo Development ◽  
Animal Studies ◽  
Cell Phones ◽  
Cellular Phone ◽  
The Body ◽  
Human Embryos ◽  
Success Rates ◽  
Wide Range

Summary Cell phones operate with a wide range of frequency bands and emit radiofrequency-electromagnetic radiation (RF-EMR). Concern on the possible health hazards of RF-EMR has been growing in many countries because these RF-EMR pulses may be absorbed into the body cells, directly affecting them. There are some in vitro and in vivo animal studies related to the consequences of RF-EMR exposure from cell phones on embryo development and offspring. In addition, some studies have revealed that RF-EMR from cellular phone may lead to decrease in the rates of fertilization and embryo development, as well as the risk of the developmental anomalies, other studies have reported that it does not interfere with in vitro fertilization or intracytoplasmic sperm injection success rates, or the chromosomal aberration rate. Of course, it is unethical to study the effect of waves generated from cell phones on the forming human embryos. Conversely, other mammals have many similarities to humans in terms of anatomy, physiology and genetics. Therefore, in this review we focused on the existing literature evaluating the potential effects of RF-EMR on mammalian embryonic and fetal development.

scholarly journals N-Acetyl-Cysteine supplementation lowers high homocysteine plasma levels and increases Glutathione synthesis in the trans-sulfuration pathway

2019 ◽  
Vol 13 (4) ◽  
pp. 234-240
Author(s):  
Federico Cacciapuoti
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Active Form ◽  
The Body ◽  
Glutamate Cysteine Ligase ◽  
Pathological Conditions ◽  
Transsulfuration Pathway ◽  
Antioxidant Function ◽  
Acetyl Cysteine ◽  
Rate Limiting

Glutathione (GSH), a compound derived of a combination of three amino acids – cysteine, glycine and glutamine – is the final product of homocysteine (Hcy) metabolism  in the transsulfuration pathway. The major determinants of GSH synthesis are the availability of cysteine and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). A deficiency in  transsulfuration pathway leads to excessive Hcy production (HHcy) and reduced GSH synthesis. This tripeptide, that exists in the reduced or active  form (GSH) and oxidized variant (GSH), is the main antioxidant of the  body.  Independently of its antioxidant function, the compound  has an anti-inflammatory role too, reducing the production of interleukines and the expression of TNF-alfa and iNOS synthase. A dysregulation of GSH synthesis is recognized as contributing factor to the pathogenesis of many pathological conditions. But, the insufficiency of the transsulfuration pathway is also responsible of HHcy. Besides, this condition  decreases the activity of cellular “gluthatione peroxidase”, an intracellular antioxidant enzyme that reduces hydrogen peroxide to water with the prevalence of GSSH on GSH. The consequent GSH/GSSH impaired ratio also causes some common cardiovascular and neurodegenerative disorders. In both occurrences, N-Acetyl-Cysteine (NAC) supplementation supplies the cysteine necessary for GSH synthesis and contemporarily reduces HHcy, improving  the GPx1 activity and further reducing oxidative stress.

scholarly journals Mineral Fibres and Asbestos Bodies in Human Lung Tissue: A Case Study

Minerals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 618 ◽  
Author(s):  
Di Giuseppe ◽  
Zoboli ◽  
Vigliaturo ◽  
Gieré ◽  
Bonasoni ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Animal Studies ◽  
Amorphous Layer ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
The Body ◽  
Degree Of Crystallinity ◽  
Human Lung Tissue ◽  
Improved Model

One of the open questions regarding the asbestos problem is the fate of the mineral fibres in the body once inhaled and deposited in the deep respiratory system. In this context, the present paper reports the results of an electron microscopy study of both mineral fibres and asbestos bodies found in the lung tissue of a patient who died of malignant mesothelioma due to past occupational exposure. In concert with previous in vivo animal studies, our data provide evidence that amphibole asbestos fibres are durable in the lungs, whereas chrysotile fibres are transformed into a silica‐rich product, which can be easily cleared. Amphibole fibres recovered from samples of tissue of the deceased display a high degree of crystallinity but also show a very thin amorphous layer on their surface; 31% of the fibres are coated with asbestos bodies consisting of a mixture of ferroproteins (mainly ferritin). Here, we propose an improved model for the coating process. Formation of a coating on the fibres is a defence mechanism against fibres that are longer than 10 µm and thinner than 0.5 µm, which macrophages cannot engulf. The mature asbestos bodies show signs of degradation, and the iron stored in ferritin may be released and potentially increase oxidative stress in the lung tissue.

HSF1 Promotes the Development of Endometriosis by Up-regulating PFKFB3 Expression

2020 ◽  
Author(s):  
yixin wang ◽  
jing xiu ◽  
tingting yang ◽  
chune ren ◽  
zhenhai yu
Keyword(s):  
Animal Studies ◽  
Lactic Acid Production ◽  
Glucose Consumption ◽  
The Body ◽  
Childbearing Age ◽  
Real Time Quantitative Pcr ◽  
Glucose Levels ◽  
Key Enzyme

Abstract BackgroundEndometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue (glands and stroma) outside the uterus. Endometriosis seriously affects the physical health of women of childbearing age, often causes infertility, and affects the body and mind of patients and their families.MethodsWe examined the effect of HSF1 on endometriosis through cell count, scratch and clone formation experiments. We used real-time quantitative PCR and western blotting to detect the effect of HSF1 on mRNA and protein of endometriosis cells. Collect the cell culture medium and Glucose levels and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we established a mouse model of endometriosis, and the effect of HSF1 on endometriosis was observed by inhibiting HSF1 with KRIBB11 in the mice.ResultsHSF1 is highly expressed in endometriosis and plays an indispensable role in endometriosis development in both cell and animal studies. We found that HSF1 promotes endometriosis development and glucose consumption and lactic acid production. Further research showed that HSF1 functions in endometriosis by up-regulating PFKFB3, a key enzyme in glycolysis. And the HSF1 inhibitor KRIBB11 can abrogate all of the above experimental effects both in vivo and in vitro. ConclusionsOur study shows that HSF1 plays a significant role in the occurrence and development of endometriosis, which may become a new target for the treatment of endometriosis and provide a new idea for the clinical treatment of endometriosis.

scholarly journals Minireview: Pathophysiological Roles of the TR4 Nuclear Receptor: Lessons Learned From Mice Lacking TR4

2014 ◽  
Vol 28 (6) ◽  
pp. 805-821 ◽  
Author(s):  
Shin-Jen Lin ◽  
Yanqing Zhang ◽  
Ning-Chun Liu ◽  
Dong-Rong Yang ◽  
Gonghui Li ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Bone Development ◽  
Lessons Learned ◽  
The Body ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Abstract Testicular nuclear receptor 4 (TR4), also known as NR2C2, belongs to the nuclear receptor superfamily and shares high homology with the testicular nuclear receptor 2. The natural ligands of TR4 remained unclear until the recent discoveries of several energy/lipid sensors including the polyunsaturated fatty acid metabolites, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, and their synthetic ligands, thiazolidinediones, used for treatment of diabetes. TR4 is widely expressed throughout the body and particularly concentrated in the testis, prostate, cerebellum, and hippocampus. It has been shown to play important roles in cerebellar development, forebrain myelination, folliculogenesis, gluconeogenesis, lipogenesis, muscle development, bone development, and prostate cancer progression. Here we provide a comprehensive summary of TR4 signaling including its upstream ligands/activators/suppressors, transcriptional coactivators/repressors, downstream targets, and their in vivo functions with potential impacts on TR4-related diseases. Importantly, TR4 shares similar ligands/activators with another key nuclear receptor, peroxisome proliferator-activated receptor γ, which raised several interesting questions about how these 2 nuclear receptors may collaborate with or counteract each other's function in their related diseases. Clear dissection of such molecular mechanisms and their differential roles in various diseases may help researchers to design new potential drugs with better efficacy and fewer side effects to battle TR4 and peroxisome proliferator-activated receptor γ involved diseases.

The Physiologic Activity and Mechanism of Quercetin-Like Natural Plant Flavonoids

2020 ◽  
Vol 21 (8) ◽  
pp. 654-658 ◽  
Author(s):  
Wujun Chen ◽  
Shuai Wang ◽  
Yudong Wu ◽  
Xin Shen ◽  
Shutan Xu ◽  
...  
Keyword(s):  
Experimental Studies ◽  
Normal Diet ◽  
The Body ◽  
Natural Plant ◽  
Physiological Functions ◽  
Physiologic Activity ◽  
Rate Limiting

The term “vitamin P” is an old but interesting concept. Most substances in this category belong to the family of flavonoids. “Vitamin P” has also been used to define the activity of some flavonoids, including quercetin, myricetin, and rutin. According to experimental studies, the “quercetin-like natural plant flavonoids” are beneficial to the body due to their various physiological and pharmacological activities in large doses (5 μM in vitro, 50 mg/kg in mice and 100 mg/kg in rats). The physiologically achievable concentration is 10 to 100 nM, which is quite high and hard to achieve from a normal diet. Thus, the physiologic activity and mechanism of "vitamin P" are still not clear. It should be noted that the quercetin-like natural plant flavonoids are physiological co-factors of cyclooxygenases (COXs), which are the rate-limiting key enzymes of prostaglandins. These quercetin-like natural plant flavonoids can strongly stimulate prostaglandin levels at lower doses (10 nM in vitro and in 0.1 mg/kg in vivo in rats). Although these "vitamin P" substances are not original substances in the body, their physiological functions affect the body. This review is focused on the most compelling evidence regarding the physiologic role and mechanism of quercetin-like natural plant flavonoids, which may be useful in understanding the physiological functions of "vitamin P", with the goal of focusing on the role of flavonoids in human physiological health.

scholarly journals A Review of the Health Protective Effects of Phenolic Acids against a Range of Severe Pathologic Conditions (Including Coronavirus-Based Infections)

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5405
Author(s):  
Sotirios Kiokias ◽  
Vassiliki Oreopoulou
Keyword(s):  
Phenolic Acids ◽  
Animal Studies ◽  
Viral Infections ◽  
Structural Features ◽  
Protective Effects ◽  
Naturally Occurring ◽  
Phytochemical Compounds ◽  
Plant Sources

Phenolic acids comprise a class of phytochemical compounds that can be extracted from various plant sources and are well known for their antioxidant and anti-inflammatory properties. A few of the most common naturally occurring phenolic acids (i.e., caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) have been identified as ingredients of edible botanicals (thyme, oregano, rosemary, sage, mint, etc.). Over the last decade, clinical research has focused on a number of in vitro (in human cells) and in vivo (animal) studies aimed at exploring the health protective effects of phenolic acids against the most severe human diseases. In this review paper, the authors first report on the main structural features of phenolic acids, their most important natural sources and their extraction techniques. Subsequently, the main target of this analysis is to provide an overview of the most recent clinical studies on phenolic acids that investigate their health effects against a range of severe pathologic conditions (e.g., cancer, cardiovascular diseases, hepatotoxicity, neurotoxicity, and viral infections—including coronaviruses-based ones).

scholarly journals Vascular complications of cystathionine β-synthase deficiency: future directions for homocysteine-to-hydrogen sulfide research

2011 ◽  
Vol 300 (1) ◽  
pp. H13-H26 ◽  
Author(s):  
Richard S. Beard ◽  
Shawn E. Bearden
Keyword(s):  
Hydrogen Sulfide ◽  
Animal Studies ◽  
Disease Risk ◽  
Vascular Complications ◽  
Disease Risk Factor ◽  
Positive Effects ◽  
Relative Paucity ◽  
Transsulfuration Pathway ◽  
Rate Limiting

Homocysteine (Hcy), a cardiovascular and neurovascular disease risk factor, is converted to hydrogen sulfide (H2S) through the transsulfuration pathway. H2S has attracted considerable attention in recent years for many positive effects on vascular health and homeostasis. Cystathionine β-synthase (CBS) is the first, and rate-limiting, enzyme in the transsulfuration pathway. Mutations in the CBS gene decrease enzymatic activity, which increases the plasma Hcy concentration, a condition called hyperhomocysteinemia (HHcy). Animal models of CBS deficiency have provided invaluable insights into the pathological effects of transsulfuration impairment and of both mild and severe HHcy. However, studies have also highlighted the complexity of HHcy and the need to explore the specific details of Hcy metabolism in addition to Hcy levels per se. There has been a relative paucity of work addressing the dysfunctional H2S production in CBS deficiency that may contribute to, or even create, HHcy-associated pathologies. Experiments using CBS knockout mice, both homozygous (−/−) and heterozygous (+/−), have provided 15 years of new knowledge and are the focus of this review. These murine models present the opportunity to study a specific mechanism for HHcy that matches one of the etiologies in many human patients. Therefore, the goal of this review was to integrate and highlight the critical information gained thus far from models of CBS deficiency and draw attention to critical gaps in knowledge, with particular emphasis on the modulation of H2S metabolism. We include findings from human and animal studies to identify important opportunities for future investigation that should be aimed at generating new basic and clinical understanding of the role of CBS and transsulfuration in cardiovascular and neurovascular disease.

scholarly journals Heterodimeric IL-15 in Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 837
Author(s):  
Cristina Bergamaschi ◽  
Vasiliki Stravokefalou ◽  
Dimitris Stellas ◽  
Sevasti Karaliota ◽  
Barbara K. Felber ◽  
...  
Keyword(s):  
Animal Studies ◽  
Tumor Infiltrating Lymphocytes ◽  
The Body ◽  
Single Chain ◽  
Natural Form ◽  
Memory Cd8 T Cells ◽  
Cancer Types ◽  
And Function ◽  
Infiltrating Lymphocytes

Immunotherapy has emerged as a valuable strategy for the treatment of many cancer types. Interleukin-15 (IL-15) promotes the growth and function of cytotoxic CD8+ T and natural killer (NK) cells. It also enhances leukocyte trafficking and stimulates tumor-infiltrating lymphocytes expansion and activity. Bioactive IL-15 is produced in the body as a heterodimeric cytokine, comprising the IL-15 and the so-called IL-15 receptor alpha chain that are together termed “heterodimeric IL-15” (hetIL-15). hetIL-15, closely resembling the natural form of the cytokine produced in vivo, and IL-15:IL-15Rα complex variants, such as hetIL-15Fc, N-803 and RLI, are the currently available IL-15 agents. These molecules have showed favorable pharmacokinetics and biological function in vivo in comparison to single-chain recombinant IL-15. Preclinical animal studies have supported their anti-tumor activity, suggesting IL-15 as a general method to convert “cold” tumors into “hot”, by promoting tumor lymphocyte infiltration. In clinical trials, IL-15-based therapies are overall well-tolerated and result in the expansion and activation of NK and memory CD8+ T cells. Combinations with other immunotherapies are being investigated to improve the anti-tumor efficacy of IL-15 agents in the clinic.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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