scholarly journals The Systemic–Evolutionary Theory of the Origin of Cancer (SETOC): A New Interpretative Model of Cancer as a Complex Biological System

2019 ◽  
Vol 20 (19) ◽  
pp. 4885 ◽  
Author(s):  
Antonio Mazzocca

The Systemic–Evolutionary Theory of Cancer (SETOC) is a recently proposed theory based on two important concepts: (i) Evolution, understood as a process of cooperation and symbiosis (Margulian-like), and (ii) The system, in terms of the integration of the various cellular components, so that the whole is greater than the sum of the parts, as in any complex system. The SETOC posits that cancer is generated by the de-emergence of the “eukaryotic cell system” and by the re-emergence of cellular subsystems such as archaea-like (genetic information) and/or prokaryotic-like (mitochondria) subsystems, featuring uncoordinated behaviors. One of the consequences is a sort of “cellular regression” towards ancestral or atavistic biological functions or behaviors similar to those of protists or unicellular organisms in general. This de-emergence is caused by the progressive breakdown of the endosymbiotic cellular subsystem integration (mainly, information = nucleus and energy = mitochondria) as a consequence of long-term injuries. Known cancer-promoting factors, including inflammation, chronic fibrosis, and chronic degenerative processes, cause prolonged damage that leads to the breakdown or failure of this form of integration/endosymbiosis. In normal cells, the cellular “subsystems” must be fully integrated in order to maintain the differentiated state, and this integration is ensured by a constant energy intake. In contrast, when organ or tissue damage occurs, the constant energy intake declines, leading, over time, to energy shortage, failure of endosymbiosis, and the de-differentiated state observed in dysplasia and cancer.

immuneACCESS ◽  
2020 ◽  
Author(s):  
P Kury ◽  
M Fuhrer ◽  
S Fuchs ◽  
MR Lorenz ◽  
OB Giorgetti ◽  
...  

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Silvia Rosina ◽  
Cecilia Beatrice Chighizola ◽  
Angelo Ravelli ◽  
Rolando Cimaz

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 376
Author(s):  
Martin Röhling ◽  
Andrea Stensitzky ◽  
Camila L. P. Oliveira ◽  
Andrea Beck ◽  
Klaus Michael Braumann ◽  
...  

Although meal replacement can lead to weight reduction, there is uncertainty whether this dietary approach implemented into a lifestyle programme can improve long-term dietary intake. In this subanalysis of the Almased Concept against Overweight and Obesity and Related Health Risk (ACOORH) study (n = 463), participants with metabolic risk factors were randomly assigned to either a meal replacement-based lifestyle intervention group (INT) or a lifestyle intervention control group (CON). This subanalysis relies only on data of participants (n = 119) who returned correctly completed dietary records at baseline, and after 12 and 52 weeks. Both groups were not matched for nutrient composition at baseline. These data were further stratified by sex and also associated with weight change. INT showed a higher increase in protein intake related to the daily energy intake after 12 weeks (+6.37% [4.69; 8.04] vs. +2.48% [0.73; 4.23], p < 0.001) of intervention compared to CON. Fat and carbohydrate intake related to the daily energy intake were more strongly reduced in the INT compared to CON (both p < 0.01). After sex stratification, particularly INT-women increased their total protein intake after 12 (INT: +12.7 g vs. CON: −5.1 g, p = 0.021) and 52 weeks (INT: +5.7 g vs. CON: −16.4 g, p = 0.002) compared to CON. Protein intake was negatively associated with weight change (r = −0.421; p < 0.001) after 12 weeks. The results indicate that a protein-rich dietary strategy with a meal replacement can improve long-term nutritional intake, and was associated with weight loss.


2016 ◽  
Vol 19 (3) ◽  
pp. 371-409
Author(s):  
Yuen-Meng Wong ◽  

Real estate investment trusts (REITs) are a niche alternative investment class. Since their introduction in Asia at the turn of the millennium, the REIT market in the region has experienced phenomenal growth. In particular, the Malaysia REIT (M-REIT ) market capitalisation has seen a spectacular growth of close to 20 folds from its inception in 2005 until the end of 2013. This paper chronicles the development of the M-REIT market which is rather unique as it provides a common platform for the existence of both conventional and Islamic REITs. Empirical tests are also conducted to uncover the returns characteristics of the M-REIT market. M-REIT returns are significantly correlated with domestic stock markets but only weakly correlated with changes in interest rate, with long-term proxies having a stronger impact than short-term proxies. The results from a correlation analysis are further confirmed by regression testing which shows that M-REIT returns are most significantly driven by domestic stock market returns while only mildly by changes in interest rates and not significantly driven by returns in regional REIT markets. These findings possibly imply that M-REITs (i) subscribe more to the characteristics of equity than those of bonds, (ii) are not 'pure' yield-play instruments, (iii) are often regarded as long-term investment, and (iv) may not be fully integrated with global and regional REIT markets.


1973 ◽  
Vol 16 (2) ◽  
pp. 165-171 ◽  
Author(s):  
T. H. McClelland ◽  
T. J. Forbes

SUMMARYSixty Scottish Blackface ewes were used in a 2 × 2 factorial experiment in which two levels of metabolizable energy (ME) were given during the final 6 weeks of pregnancy. In two treatments 1600 and 2000 kcal M E were given daily over the total period while in the remaining treatments daily ME intakes were 1200 and 1600 kcal ME during the first 3 weeks of the feeding period and 2000 and 2400 kcal ME during the last 3 weeks. Digestible crude protein (DCP) intakes were constant at approximately 30 g per head daily in the constant energy treatments and 15 and 45 g per head daily in the first and second periods respectively for the low-high energy treatments.Energy intake had no statistically significant effect on lamb birth weight nor on ewe net body-weight change (change from the start of the experimental feeding period to immediately post partum). Ewes on low-high energy intakes had a significantly lower net body-weight loss than did ewes on constant energy intakes. Pattern of feeding had no significant effect on lamb birth weights. Negative nitrogen balances were found during the first feeding period where the daily DCP intake was approximately 15 g per head.


2000 ◽  
Vol 279 (5) ◽  
pp. R1805-R1812 ◽  
Author(s):  
Lisa Kelly ◽  
Silvia Morales ◽  
Brenda K. Smith ◽  
Hans-Rudolf Berthoud

The effect of capsaicin-induced chemical ablation of visceral afferents on 1-h liquid sucrose consumption was investigated in food-deprived rats. We first show that although 10% sucrose is permanently overconsumed by capsaicin-treated (CAPs) compared with vehicle-treated (VEHs) control rats, 40% sucrose is only overconsumed during the first but not subsequent 1-h exposures. Furthermore, one group of CAPs lost the overconsumption response at 20% when exposed to progressively increasing sucrose concentrations of 10–40%, and another group recovered the overconsumption response at 10% when exposed to a series of decreasing concentrations. Control rats ingested relatively constant volumes of sucrose over the range of 10, 15, and 20%, resulting in significantly different energy intakes. In contrast, CAPs generally showed a concentration-dependent decrease in volume intake, resulting in relatively constant energy intake. These results suggest that capsaicin-sensitive visceral afferents, likely from gastric distension and other preabsorptive sensors, provide major control over volume ingested. In the absence of these signals, rats initially overconsume, but rapidly learn to use other signals from capsaicin-resistant preabsorptive or postabsorptive sites, to control future intake. This redundant satiety system appears to be sensitive to the osmotic value or caloric content of the unfamiliar food, but only if this is above a threshold of about 15% sucrose.


2020 ◽  
pp. 56-57
Author(s):  
V.L. Novak ◽  
B.O. Kondratsky ◽  
S.V. Primak ◽  
O.O. Tarasyuk ◽  
O.M. Tushnitsky ◽  
...  

Objective. Analysis of issues related to the safety and quality of donated blood and its components. Materials and methods. Many years of experience of hematologists, immunologists, isoserologists, morphologists, biochemists in studying the composition, morpho-functional properties of cells and blood plasma, the use of donor blood and its components in clinical practice have made it possible to reconsider method of chemotherapy “multilateral action”. Results and discussion. One of the main axioms of modern transfusion medicine: chemotherapy should be performed strictly according to the indications and those blood components that are needed to ensure the viability of the body. The development of transfusiology has proved, with few exceptions, the inexpediency and even harmfulness of the use of whole donor blood. When using blood and its components, it is necessary to clearly consider extremely important point: the use will be in a planned manner, or in special circumstances. Blood components and blood plasma preparations have unique medicinal properties and there is currently no alternative to them. Each country is recommended to switch to self-sufficiency of blood components and their derivatives, to organize their own production structures that would meet the country’s domestic needs in blood components and preparations. The main components of the ideology of component chemotherapy are: recovery of blood component deficiency is not achieved on a “drop by drop” basis; no need to completely replace the existing deficiency of a cellular or protein component. Transfusions of blood components should be treated as a responsible invasive medical procedure – an operation that can have both immediate and long-term complications and consequences. Unreasonable transfusions of whole canned blood, especially after long periods of storage, are not only ineffective, but often pose a danger. In canned blood, during storage, complex biochemical metabolic processes take place both in cells and in plasma, which ultimately reduce the quality of both the blood itself and the morpho-functional properties of its individual components. Thus, 8-day storage of erythrocytes is the threshold after which erythrocytes begin to adversely affect the patient. Morpho-functional properties of blood components are directly dependent on the shelf life and distance of transportation. During the storage of blood and erythrocyte mass, the level of ATP decreases, on which the elasticity of the erythrocyte membrane depends. The magnitude of the negative electrical charge of the surface membrane of blood cells decreases. The number of prehemolytic forms of erythrocytes and cells that are not capable of reverse transformation increases. Within 1-4 days, leukocytes die, bacteria are released, so after this period, the greatest number of complications and reactions. Leukocytes and platelets form microaggregates at an early stage of storage, which can cause microembolism and distress syndrome. Microclots are formed, which include lysed blood cells and fibrin. The number of microclots increases every day, reaching on day 21 to 100 thousand/ml, so when transfusing it is advisable to use antiplatelet filters, rather than leukocyte. The use of bed leukofilters after a long period of storage of erythromass is not advisable, because there are no leukocytes. In addition, up to 2 % of erythrocytes are lost. The pH decreases, the content of 2,3-DFG, which is responsible for oxygen transport function (decreases by 50 % on the third day), hemolysis increases (up to 200 mg% of free hemoglobin). The concentration of potassium and ammonium ions increases. The recommended threshold for erythrocyte concentrate transfusions is a hemoglobin level of less than 70 g/l in adults and most children. It is important to use fresh-frozen plasma, erythrocyte concentrate and platelets obtained from one donor. Modern blood separators technically provide such an opportunity. Conditionally acceptable number of platelets in patients with injuries is more than 50×109/l cells, and in patients with combined brain injury is 100×109/l. Platelet concentrate obtained by the manual method from 4-5 donors leads to the development of refractoriness. With increasing shelf life of platelets, the functional properties of cells deteriorate significantly. All attempts to create the so-called artificial blood in the 19th century ended at the level of scientific developments. Synthetic and bioengineered cellular components of blood, hematopoietic factors, as well as hematopoietic stem cells are considered promising in the future. One of the possible ways to solve the problem of long-term storage of blood components, especially liquid groups, is cryopreservation of individual cells (erythrocytes) at moderately low (-20; -40; -80 ºС) and ultra-low (-165-196 ºС) temperatures, followed by deglycerization (washing), the use of special solutions for resuspension. With the development of low-temperature electric refrigeration equipment in Ukraine, this has become a reality. Conclusions. Practice has shown that both the blood itself and its components can neither be produced nor extracted as minerals, it can only be shared. All of the above indicates that blood donation is and will remain the main source of cellular components of the blood for at least the next decades.


STEMedicine ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. e43 ◽  
Author(s):  
Federico Iseppon ◽  
Manuel Arcangeletti

Pain afflicts billions of people worldwide, who suffer especially from long-term chronic pain. This gruelling condition affects the nervous system at all levels: from the brain to the spinal cord, the Dorsal Root Ganglia (DRG) and the peripheral fibres innervating the skin. The nature of the different molecular and cellular components of the somatosensory modalities, as well as the complexity of the peripheral and central circuitry are yet poorly understood. Light-based techniques such as optogenetics, in concert with the recent advances in single-cell genetic profiling, can help to elucidate the role of diverse neuronal sub-populations in the encoding of different sensory and painful stimuli by switching these neurons on and off via optically active proteins, namely opsins.  Recently, photopharmacology has emerged from the efforts made to advance optogenetics. The introduction of azo-benzene-based light-sensitive molecular switches has been applied to a wide variety of molecular targets, from ion channels and receptors to transporters, enzymes and many more, some of which are paramount for pain research and therapy. In this Review, we summarise the recent advances in the fields of optogenetics and photopharmacology and we discuss the use of light-based techniques for the study of acute and chronic pain physiology, as well as their potential for future therapeutic use to improve pain treatment.


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