scholarly journals Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriana M. De Mendoza ◽  
Soňa Michlíková ◽  
Johann Berger ◽  
Jens Karschau ◽  
Leoni A. Kunz-Schughart ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Collateral Damage ◽  
Hyperthermia Treatment ◽  
Reversible Process ◽  
Technological Advances ◽  
Thermal Enhancement ◽  
Main Driver ◽  
Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

scholarly journals Effect of Processing on Fish Protein Antigenicity and Allergenicity

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 969
Author(s):  
Xingyi Jiang ◽  
Qinchun Rao
Keyword(s):  
Fish Species ◽  
Protein Denaturation ◽  
Ex Vivo ◽  
Protein Solubility ◽  
Future Research ◽  
Food Protein ◽  
In Vivo Evaluation ◽  
Fish Allergy

Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.

scholarly journals Definition of a minimal munc18c domain that interacts with syntaxin 4

2000 ◽  
Vol 350 (3) ◽  
pp. 741-746 ◽  
Author(s):  
Julian GRUSOVIN ◽  
Violet STOICHEVSKA ◽  
Keith H. GOUGH ◽  
Katrina NUNAN ◽  
Colin W. WARD ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Full Length ◽  
Yeast Two Hybrid ◽  
Protein Protein Interaction ◽  
Interaction Studies ◽  
Syntaxin 4 ◽  
Definition Of ◽  
Two Hybrid

munc18c is a critical protein involved in trafficking events associated with syntaxin 4 and which also mediates inhibitory effects on vesicle docking and/or fusion. To investigate the domains of munc18c responsible for its interaction with syntaxin 4, fragments of munc18c were generated and their interaction with syntaxin 4 examined in vivo by the yeast two-hybrid assay. In vitro protein–protein interaction studies were then used to confirm that the interaction between the proteins was direct. Full-length munc18c1–592, munc18c1–139 and munc18c1–225, but not munc18c226–592, munc18c1–100, munc18c43–139 or munc18c66–139, interacted with the cytoplasmic portion of syntaxin 4, Stx42–273, as assessed by yeast two-hybrid assay of growth on nutritionally deficient media and by β-galactosidase reporter induction. The N-terminal predicted helix-a-helix-b-helix-c region of syntaxin 4, Stx429–157, failed to interact with full-length munc18c1–592, indicating that a larger portion of syntaxin 4 is necessary for the interaction. The yeast two-hybrid results were confirmed by protein–protein interaction studies between Stx42–273 and glutathione S-transferase fusion proteins of munc18c. Full-length munc18c1–592, munc18c1–139 and munc18c1–225 interacted with Stx42–273 whereas munc18c1–100 did not, consistent with the yeast two-hybrid data. These data thus identify a region of munc18c between residues 1 and 139 as a minimal domain for its interaction with syntaxin 4.

scholarly journals Anti-Inflammatory Effects of 3-Formyl, 7-Flavonols Derivatives by Microwave Enhanced Chemistry Assisted - Vilsmeier Haack Synthesis

2019 ◽  
Vol 12 (04) ◽  
pp. 1779-1791
Author(s):  
M. Karpakavalli ◽  
A.Y. Sangilimuthu ◽  
A.Usha Raja Nanthini ◽  
G.Nagaraja Perumal ◽  
S. Mohan ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Population Increase ◽  
Spectral Studies ◽  
Dimethyl Formamide ◽  
Mass Spectral ◽  
Paw Oedema ◽  
Rf Values ◽  
Anti Inflammatory

In the modern medicines the novel and active molecules are essential to act against various diseases and increase the needs day by day due to population increase. In view of that, we attempt to make a variety of synthetic molecules against inflammation by a new and popular greener microwave assisted and faster method such as Microwave Enhanced Chemistry assisted Vilsmeier Haack Synthesis (MEC-VHS). In this paper, we report the synthesis of nitro- dinitro- and acetyl- derivatives of 3- formyl, 7-flavonols using MEC-VHS techniques against inflammation as anti-inflammatory agent. These derivatives were synthesized via pinkish formylation complex of dimethyl formamide and phosphorous oxychloride by microwave irradiation resulted as suspension by base. The re-crystallized products were characterized through Co-TLC, λmax, IR, HPTLC, 1HNMR, CHN analysis and mass spectral studies. The HPTLC finger print profiles obtained were of with a prominent single peak and with a matching Rf values compared to that obtained by an ordinary Co-TLC technique. All the synthesized compounds were screened for their anti-inflammatory activity by in vitro protein denaturation method and in vivo carrageenan induced paw oedema method and it was found that all the compounds excepting the un-substituted 3-formyl, 7-flavonols gave an equi- or more potent activity as compared to that of the standard.

scholarly journals BIOGENESIS OF MITOCHONDRIA

1969 ◽  
Vol 42 (2) ◽  
pp. 377-391 ◽  
Author(s):  
G. M. Kellerman ◽  
D. R. Biggs ◽  
Anthony W. Linnane
Keyword(s):  
Unsaturated Fatty Acids ◽  
Mitochondrial Protein ◽  
Mitochondrial Membranes ◽  
Phylogenetic Implications ◽  
Obligate Aerobic ◽  
Biogenesis Of Mitochondria ◽  
Citric Acid Cycle Enzymes ◽  
Definition Of

Growth under conditions of oxygen restriction results in a generalized decrease in the definition of the mitochondrial membranes, a decrease in the mitochondrial cytochromes, and a decrease in citric acid cycle enzymes of the obligate aerobic yeast Candida parapsilosis. Addition of unsaturated fatty acids and ergosterol to cultures exposed to limited oxygen results in improved definition of the mitochondrial membranes and an increase in the total mitochondrial cytochrome content of the cells. Euflavine completely inhibits mitochondrial protein synthesis in vitro. Its in vivo effect is to cause the formation of giant mitochondrial profiles with apparently intact outer membranes and modified internal membranes; the cristae (in-folds) appear only as apparently disorganized remnants while the remainder of the inner membrane seems intact. Cytochromes a, a3, b, and c1 are not synthesized by the cells in the presence of euflavine. Ethidium appears to have effects identical to those of euflavine, whereas chloramphenicol, lincomycin, and erythromycin have similar effects in principle but they are less marked. The effects of all the inhibitors are freely reversible after removal of the drugs. The results are discussed in terms of a functionally three-membrane model of the mitochondrion. In addition, the phylogenetic implications of the observed differences between this organism and the facultative anaerobic yeasts are considered.

scholarly journals Induction and Maturation of Hepatocyte-Like Cells In Vitro: Focus on Technological Advances and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye Xie ◽  
Jia Yao ◽  
Weilin Jin ◽  
Longfei Ren ◽  
Xun Li
Keyword(s):  
Genetic Manipulation ◽  
Toxicity Testing ◽  
Basic Research ◽  
Drug Approval ◽  
Cell Types ◽  
Comprehensive Overview ◽  
Technological Advances ◽  
Degree Of Differentiation

Limited by the poor proliferation and restricted sources of adult hepatocytes, there is an urgent need to find substitutes for proliferation and cultivation of mature hepatocytes in vitro for use in disease treatment, drug approval, and toxicity testing. Hepatocyte-like cells (HLCs), which originate from undifferentiated stem cells or modified adult cells, are considered good candidates because of their advantages in terms of cell source and in vitro expansion ability. However, the majority of induced HLCs are in an immature state, and their degree of differentiation is heterogeneous, diminishing their usability in basic research and limiting their clinical application. Therefore, various methods have been developed to promote the maturation of HLCs, including chemical approaches, alteration of cell culture systems, and genetic manipulation, to meet the needs of in vivo transplantation and in vitro model establishment. This review proposes different cell types for the induction of HLCs, and provide a comprehensive overview of various techniques to promote the generation and maturation of HLCs in vitro.

Optimization of Oxygen Delivery within Hydrogels

2021 ◽  
Author(s):  
Sophia M Mavris ◽  
Laura M Hansen
Keyword(s):  
Tissue Engineering ◽  
Oxygen Transport ◽  
Current Medical ◽  
The Body ◽  
Clinical Translation ◽  
Technological Innovations ◽  
Technological Advances ◽  
Cell Sources

Abstract The field of tissue engineering has been continuously evolving since its inception over three decades ago with numerous new advancements in biomaterials and cell sources and widening applications to most tissues in the body. Despite the substantial promise and great opportunities for the advancement of current medical therapies and procedures, the field has yet to capture wide clinical translation due to some remaining challenges, including oxygen availability within constructs, both in vitro and in vivo. While this insufficiency of nutrients, specifically oxygen, is a limitation within the current frameworks of this field, the literature shows promise in new technological advances to efficiently provide adequate delivery of nutrients to cells. This review attempts to capture the most recent advances in the field of oxygen transport in hydrogel-based tissue engineering, including a comparison of current research as it pertains to the modeling, sensing, and optimization of oxygen within hydrogel constructs as well as new technological innovations to overcome traditional diffusion-based limitations. The application of these findings can further the advancement and development of better hydrogel-based tissue engineered constructs for future clinical translation and adoption.

scholarly journals In Vitro Anti-Inflammatory and In Vivo Antiarthritic Activities of Aqueous and Ethanolic Extracts of Dissotis thollonii Cogn. (Melastomataceae) in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Stephanie Flore Djuichou Nguemnang ◽  
Eric Gonzal Tsafack ◽  
Marius Mbiantcha ◽  
Ateufack Gilbert ◽  
Albert Donatien Atsamo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Denaturation ◽  
Inflammatory Diseases ◽  
Ros Production ◽  
Zymosan A ◽  
Ethanolic Extracts ◽  
Anti Inflammatory ◽  
Promising Source

Dissotis thollonii Cogn. (Melastomataceae) is a tropical plant widely used in traditional Cameroonian medicine to relieve and treat many pathologies. It is widespread in the western region where it is used to treat typhoid fever, gastrointestinal disorders, and inflammatory diseases. The purpose of this study is to scientifically demonstrate the anti-inflammatory and antiarthritic properties of the aqueous and ethanolic extracts of the leaves of Dissotis thollonii. The anti-inflammatory properties were evaluated in vitro by inhibition tests for cyclooxygenase, 5-lipoxygenase, protein denaturation, extracellular ROS production, and cell proliferation; while antiarthritic properties were evaluated in vivo in rats using the zymosan A-induced monoarthritis test and the CFA-induced polyarthritis model. This study shows that aqueous and ethanolic extracts at a concentration of 1000 μg/ml inhibit the activity of cyclooxygenase (47.07% and 63.36%) and 5-lipoxygenase (66.79% and 77.7%) and protein denaturation (42.51% and 44.44%). Similarly, both extracts inhibited extracellular ROS production (IC50 = 5.74 μg/ml and 2.96 μg/ml for polymorphonuclear leukocytes, 7.47 μg/ml and 3.28 μg ml for peritoneal macrophages of mouse) and cell proliferation (IC50 = 16.89 μg/ml and 3.29 μg/ml). At a dose of 500 mg/kg, aqueous and ethanolic extracts significantly reduce edema induced by zymosan A (69.30% and 81.80%) and CFA (71.85% and 79.03%). At the same dose, both extracts decreased sensitivity to mechanical hyperalgesia with 69.00% and 70.35% inhibition, respectively. Systemic and histological analyzes show that both extracts maintain the studied parameters very close to normal and greatly restored the normal architecture of the joint in animals. Dissotis thollonii would therefore be a very promising source for the treatment of inflammatory diseases.

scholarly journals Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000337 ◽  
Author(s):  
Lorenzo Galluzzi ◽  
Ilio Vitale ◽  
Sarah Warren ◽  
Sandy Adjemian ◽  
Patrizia Agostinis ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Adaptive Immune Response ◽  
Operational Definition ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Regulated Cell Death ◽  
Definition Of

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Glucose homeostasis and hypothalamic-pituitary-adrenocortical axis during development in rats

1990 ◽  
Vol 259 (5) ◽  
pp. E601-E613 ◽  
Author(s):  
E. P. Widmaier
Keyword(s):  
Stress Responses ◽  
Adrenocorticotropic Hormone ◽  
Glucose Sensor ◽  
Adult Life ◽  
Glucose Sensing ◽  
Physiological Data ◽  
Compensatory Mechanisms ◽  
Definition Of

Glucoprivation represents a model stress in which activation of different stress responses at different ages can be monitored both in vivo and in vitro. Physiological data indicate rat brain contains a liver/pancreas-type glucose sensor, yet no biochemical or immunocytochemical evidence exists for such a sensor. Young rats appear to lack normal hypothalamic glucose-sensing ability and do not show typical secretory patterns of corticotropin-releasing factor, adrenocorticotropic hormone, or corticosterone after experimentally induced glucoprivation. However, they hypersecrete catecholamines and glucagon (compared with adults) and thrive on fuel sources other than glucose that are abundant after birth. High steroid levels during the first 24 h after birth may be critical for inducing gluconeogenic enzymes and promoting differentiation of tissues like pancreas. Neonatal rats also have unique control systems to combat the damaging effects of other stresses like hypoxia; these systems may disappear in adults. Thus the definition of stress may change during development, and the compensatory mechanisms employed to combat stress change from neonatal to adult life and are intricately related to the metabolic needs of the animal.

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