scholarly journals Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Ruzhou Zhao ◽  
Xingcheng Zhao ◽  
Xiaobo Wang ◽  
Yanqi Liu ◽  
Jie Yang ◽  
...  

AbstractRapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.

1959 ◽  
Vol 197 (6) ◽  
pp. 1357-1358 ◽  
Author(s):  
J. Davidović ◽  
Ines Wesley

Rats cooled to a rectal temperature of 20°C were permitted to rewarm at a simulated altitude of 11,500 m. A greater survival rate was observed in animals so treated than in controls not previously exposed to hypothermia. The loss of hypoxic tolerance was more pronounced within the range of 28°–36°C than in the range of 22°–28°C. The depth of cooling has a notable influence on the tolerance to hypoxia during rewarming when the body temperature of 33°C is reached. Thus far, the most resistant were rats cooled by the closed vessel technique to 18°C and those cooled by immersion to 22°C. The mechanism of this interesting phenomenon is unknown.


2020 ◽  
Vol 472 (11) ◽  
pp. 1619-1630
Author(s):  
Ru-Zhou Zhao ◽  
Xiao-Bo Wang ◽  
Shuai Jiang ◽  
Ning-Yu Ru ◽  
Bo Jiao ◽  
...  

1988 ◽  
Vol 20 (4-5) ◽  
pp. 101-108 ◽  
Author(s):  
R. C. Clifft ◽  
M. T. Garrett

Now that oxygen production facilities can be controlled to match the requirements of the dissolution system, improved oxygen dissolution control can result in significant cost savings for oxygen activated sludge plants. This paper examines the potential cost savings of the vacuum exhaust control (VEC) strategy for the City of Houston, Texas 69th Street Treatment Complex. The VEC strategy involves operating a closed-tank reactor slightly below atmospheric pressure and using an exhaust apparatus to remove gas from the last stage of the reactor. Computer simulations for one carbonaceous reactor at the 69th Street Complex are presented for the VEC and conventional control strategies. At 80% of design loading the VEC strategy was found to provide an oxygen utilization efficiency of 94.9% as compared to 77.0% for the conventional control method. At design capacity the oxygen utilization efficiency for VEC and conventional control was found to be 92.3% and 79.5%, respectively. Based on the expected turn-down capability of Houston's oxygen production faciilities, the simulations indicate that the VEC strategy will more than double the possible cost savings of the conventional control method.


2020 ◽  
Vol 14 (2) ◽  
pp. 108-125
Author(s):  
Apoorva Singh ◽  
Nimisha

: Skin cancer, among the various kinds of cancers, is a type that emerges from skin due to the growth of abnormal cells. These cells are capable of spreading and invading the other parts of the body. The occurrence of non-melanoma and melanoma, which are the major types of skin cancers, has increased over the past decades. Exposure to ultraviolet radiations (UV) is the main associative cause of skin cancer. UV exposure can inactivate tumor suppressor genes while activating various oncogenes. The conventional techniques like surgical removal, chemotherapy and radiation therapy lack the potential for targeting cancer cells and harm the normal cells. However, the novel therapeutics show promising improvements in the effectiveness of treatment, survival rates and better quality of life for patients. Different methodologies are involved in the skin cancer therapeutics for delivering the active ingredients to the target sites. Nano carriers are very efficient as they have the ability to improve the stability of drugs and further enhance their penetration into the tumor cells. The recent developments and research in nanotechnology have entitled several targeting and therapeutic agents to be incorporated into nanoparticles for an enhancive treatment of skin cancer. To protect the research works in the field of nanolipoidal systems various patents have been introduced. Some of the patents acknowledge responsive liposomes for specific targeting, nanocarriers for the delivery or co-delivery of chemotherapeutics, nucleic acids as well as photosensitizers. Further recent patents on the novel delivery systems have also been included here.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jiajia Wang ◽  
Jitao Li ◽  
Qianqian Ge ◽  
Zhao Chen ◽  
Jian Li

The Exopalaemon carinicauda could be a useful crustacean laboratory animal in many research fields. We newly established an inbred line of Exopalaemon carinicauda named EC4 inbred line by brother×sister mating and keeping to F11 generation. Trends in heterozygosity in the process of producing EC4 inbred line were examined through the characterization of polymorphisms based on gene frequencies of SNP and EST-SSR loci. The results demonstrated that the number of alleles (N), observed heterozygosity (Ho), expected heterozygosity (He), and polymorphism information content (PIC) gradually decreased with the increase of inbreeding generations. The genetic detection results indicated that 9 (29.03%, 9/31) of the SNP loci and 15 (32.61%, 15/46) of the EST-SSR loci were homozygous in F11 generation of EC4 inbred line. The variation of the growth-related traits, the immune responses, and antioxidant status were described in experimental full-sibling inbred populations of E. carinicauda at five levels of inbreeding coefficient (F=0.785, F=0.816, F=0.859, F=0.886, F=0.908) under controlled laboratory conditions. The body weight, body length, and survival rate in EC4 inbred line of all generations were less than the control population. Inbreeding affected the antibacterial activity, phenoloxidase (PO) activity, and superoxide dismutase (SOD) which decreased at the eleventh generation of EC4 inbred line. This study demonstrated that inbreeding had a negative effect on the economic traits and immune response, but our inbred line was established successfully until F11 and confirmed by genetic detection using SNP and EST-SSR loci.


Hygiene ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 56-68
Author(s):  
Cinzia Casu ◽  
Giovanna Mosaico ◽  
Valentino Natoli ◽  
Antonio Scarano ◽  
Felice Lorusso ◽  
...  

The tongue is able to quickly reflect the state of health or disease of the human body. Tongue inspection is an important diagnostic approach. It is a unique method that allows to explore the pathogenesis of diseases based on the guiding principles of the holistic concept that involves the observation of changes in the lining of the tongue in order to understand the physiological functions and pathological changes of the body. It is a potential method of screening and early detection of cancer. However, the subjective inspection of the tongue has a low reliability index, and therefore computerized systems of acquisition of diagnostic bioinformation have been developed to analyze the lining of the tongue. Next-generation sequencing technology is used to determine the V2–V4 hypervariable regions of 16S rRNA to study the microbiota. A lot of neoplasms are identified only at an advanced phase, while in the early stages, many subjects remain in an asymptomatic form. On the contrary, the early diagnosis is able to increase the prognosis of cancer and improve the survival rates of subjects. Evidently, it is necessary to develop new strategies in oral medicine for the early diagnosis of diseases, and the diagnosis of the tongue as a minimally invasive method is certainly one of them.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zdenek Andrysik ◽  
Heather Bender ◽  
Matthew D. Galbraith ◽  
Joaquin M. Espinosa

AbstractCellular adaptation to hypoxia is a hallmark of cancer, but the relative contribution of hypoxia-inducible factors (HIFs) versus other oxygen sensors to tumorigenesis is unclear. We employ a multi-omics pipeline including measurements of nascent RNA to characterize transcriptional changes upon acute hypoxia. We identify an immediate early transcriptional response that is strongly dependent on HIF1A and the kinase activity of its cofactor CDK8, includes indirect repression of MYC targets, and is highly conserved across cancer types. HIF1A drives this acute response via conserved high-occupancy enhancers. Genetic screen data indicates that, in normoxia, HIF1A displays strong cell-autonomous tumor suppressive effects through a gene module mediating mTOR inhibition. Conversely, in advanced malignancies, expression of a module of HIF1A targets involved in collagen remodeling is associated with poor prognosis across diverse cancer types. In this work, we provide a valuable resource for investigating context-dependent roles of HIF1A and its targets in cancer biology.


2021 ◽  
Vol 19 (1) ◽  
pp. 55-63
Author(s):  
Vera V. Marysheva ◽  
Vladimir V. Mikheev ◽  
Petr D. Shabanov

PURPOSE: To study the effect of amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) on the resistance of male outbred mice to acute hypoxia with hypercapnia under conditions of isolated functioning of one from the hemispheres, as well as both hemispheres of the brain. METHODS: A model of acute hypoxia with hypercapnia (canned hypoxia) was used in mice of the same mass, the lifespan of all animals was determined. Temporary shutdown of the cortex of one of the hemispheres or both hemispheres was achieved by epidural application of filter paper moistened with 25% potassium chloride solution, creating a spreading depression according to Leao. Amtizol, 2-aminobenzthiazole (2-ABT) and 2-amino-4-acetylthiazolo[5,4-b]indole (BM-606) at equimolar doses of 25, 32.5, and 50 mg/kg, respectively were used as pharmacological analyzers, the compounds were injected intraperitoneally 30 min before the hypoxic episode. RESULTS: It was shown that, in contrast to amtizol, 2-ABT and VM-606 increase the life time of experimental animals when any hemisphere is turned off. The use of drugs when both hemispheres were turned off revealed that amtizol has approximately equal effect on the brain and the rest of the body, in 2-ABT antihypoxic activity is 1/3 associated with the brain, in VM-606 exclusively with the brain. CONCLUSION: The experimental model used in this work makes it possible to quite easily evaluate the effect of either one drug or compare several drugs, their role in the functioning of the cerebral hemispheres, on which part of the sample highly resistant or low resistant to hypoxia they have the greatest effect.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.


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