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Pathol Res Pract. 2012 Jul 15;208(7):377-81. doi: 10.1016/j.prp.2012.04.006. Epub 2012 Jun 8.

The influence of physical activity in the progression of experimental lung cancer in mice

Renato Batista Paceli 1Rodrigo Nunes CalCarlos Henrique Ferreira dos SantosJosé Antonio CordeiroCassiano Merussi NeivaKazuo Kawano NagaminePatrícia Maluf Cury


Impact_Fator-wise_Top100Science_Journals

GRUPO_AF1 – GROUP AFA1 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 1 – GROUP AFAN1 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO_AF2 – GROUP AFA2 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

GRUPO AFAN 2 – GROUP AFAN 2 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

Slides – mestrado – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

CARCINÓGENO DMBA EM MODELOS EXPERIMENTAIS

DMBA CARCINOGEN IN EXPERIMENTAL MODELS

Avaliação da influência da atividade física aeróbia e anaeróbia na progressão do câncer de pulmão experimental – Summary – Resumo – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto

https://pubmed.ncbi.nlm.nih.gov/22683274/

Abstract

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb – C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.

@ ´´Harvard is a founding member of the Association of American Universities[130] and remains a preeminent research university with “very high” research activity (R1) and comprehensive doctoral programs across the arts, sciences, engineering, and medicine according to the Carnegie Classification.[90] With Harvard Medical School consistently ranking first among medical schools for research,[131] biomedical research is an area of particular strength for the university. More than 11,000 faculty members and over 1,600 medical and graduate students contribute to discovery and innovation at Harvard Medical School as well as its 15 affiliated hospitals and research institutes.[132] Harvard Medical School and its affiliates attracted $1.65 billion in competitive research grants from the National Institutes of Health in 2019, more than twice as much as any other university.[133]´´

https://www.nature.com/articles/s42255-019-0162-4

High-protein diets boost artery-clogging plaque, mouse study shows

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High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy

Nature Metabolism volume 2, pages110–125(2020)Cite this article

Abstract

High-protein diets are commonly utilized for weight loss, yet they have been reported to raise cardiovascular risk. The mechanisms underlying this risk are unknown. Here, we show that dietary protein drives atherosclerosis and lesion complexity. Protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mammalian target of rapamycin (mTOR) signalling. This is causal in plaque progression, because the effects of dietary protein are abrogated in macrophage-specific Raptor-null mice. Mechanistically, we find amino acids exacerbate macrophage apoptosis induced by atherogenic lipids, a process that involves mammalian target of rapamycin complex 1 (mTORC1)-dependent inhibition of mitochondrial autophagy (mitophagy), accumulation of dysfunctional mitochondria and mitochondrial apoptosis. Using macrophage-specific mTORC1- and autophagy-deficient mice, we confirm this amino acid–mTORC1–autophagy signalling axis in vivo. Our data provide insights into the deleterious impact of excessive protein ingestion on macrophages and atherosclerotic progression. Incorporation of these concepts in clinical studies is important to define the vascular effects of protein-based weight loss regimens.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request. Source data for Figs. 4 and 8 and Extended Data Figs. 34 and 6 are provided with the paper.

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Acknowledgements

This work was supported by National Institutes of Health grant no. R01 HL125838, VA MERIT I01 BX003415, American Diabetes Association grant no. 1-18-IBS-029, Washington University Diabetic Cardiovascular Disease Center and Diabetes Research Center grant no. P30 DK020579, Washington University Mass Spectrometry core grant nos. P41GM103422 and P30DK056341, and the Foundation for Barnes-Jewish Hospital.

Author information

Affiliations

  1. Department of Medicine, Cardiovascular Division, Washington University School of Medicine, St Louis, MO, USA
    • Xiangyu Zhang
    • , Ismail Sergin
    • , Trent D. Evans
    • , Se-Jin Jeong
    • , Astrid Rodriguez-Velez
    • , Divya Kapoor
    • , Sunny Chen
    • , Eric Song
    • , Karyn B. Holloway
    • , Abhinav Diwan
    • , Nathan O. Stitziel
    • , Joel D. Schilling
    •  & Babak Razani
  2. John Cochran VA Medical Center, St Louis, MO, USA
    • Xiangyu Zhang
    • , Se-Jin Jeong
    • , Divya Kapoor
    • , Karyn B. Holloway
    •  & Abhinav Diwan
  3. Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St Louis, MO, USA
    • Jan R. Crowley
    •  & Irfan J. Lodhi
  4. University Health Network, Peter Munk Cardiac Center, University of Toronto, Toronto, Ontario, Canada
    • Slava Epelman
  5. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    • Conrad C. Weihl
  6. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA
    • Daping Fan
  7. Department of Nutrition, Washington University School of Medicine, St Louis, MO, USA
    • Bettina Mittendorfer
    •  & Babak Razani
  8. Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, USA
    • Joel D. Schilling
    •  & Babak Razani

Contributions

X.Z. and B.R. designed the studies and wrote the manuscript. X.Z., I.S., T.D.E., S.J., A.R., D.K., S.C., E.S., K.B.H. and J.R.C. performed and analysed the experiments. X.Z. and I.S. prepared the figures. D.K., S.E., C.C.W., A.D., D.F., B.M., N.O.S., J.D.S., I.J.L. and B.R. provided the reagents, advised on the experimental design and performed critical reading of the manuscript.

Corresponding author

Correspondence to Babak Razani.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Primary Handling Editor: Pooja Jha.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 High Protein diets increase atherosclerotic plaque formation and plaque complexity without altering serum metabolites.

(a) Average daily food intake over 1 week for ApoE-KO mice fed a standard Western diet (n = 5) or high protein Western diet (n = 5) (b–d) Cohorts of ApoE-KO mice were placed on a standard Western diet (Std. WD) or high protein Western diet (HP WD) and after 8 weeks, (b) Body composition (fat and lean weights) (Std. WD: n = 4; HP WD: n = 5), (c) glucose tolerance test (GTT) and glucose AUC (Std. WD: n = 7; HP WD: n = 9), and (d) serum cholesterol, glucose, triglycerides, and free fatty acids (Std. WD: n = 11; HP WD: n = 14) were measured. (e) Quantification of atherosclerotic plaque burden using Oil Red O-stained aortic root sections from mice fed standard or high protein Western diets for 16 weeks; representative roots shown on right (Std. WD: n = 12; HP WD: n = 11). (f) Measurements of serum cholesterol in cohorts of ApoE-KO mice after 16 weeks of standard or high protein Western diets (Std WD: n = 6; HP WD: n = 8). (g-i) Plaque composition quantified by immunofluorescence staining of aortic root sections for (g) macrophage (MOMA-2+) (Std. WD: n = 12; HP WD: n = 13), (h) apoptosis (TUNEL+) (Std. WD: n = 13; HP WD: n = 13), (i) and necrotic core (acellular) (Std. WD: n = 13; HP WD: n = 13). For all graphs, data are presented as mean ±SEM. *P < 0.05, **P < 0.01, ***P < 0.001, two-tailed unpaired t-test.

Extended Data Fig. 2 Levels of select L-amino acids in serum, aorta, and splenic macrophages after high protein challenge.

(a) Serum levels of 8 L-amino acids by mass spectrometry from mice fed standard or high protein Western diets for 8 weeks (Std. WD: n = 8; HP WD: n = 8). (b–d) Time course measurement of the levels of 8 L-amino acids in serum (n = 3) (b), splenic macrophages (n = 2) (c), and atherosclerotic aortas (n = 2) (d) by mass spectrometry after high protein gavage. For all graphs, data are presented as mean ±SEM. *P < 0.05, **P < 0.01, ***P < 0.001, two-tailed unpaired t-test for a and one-way ANOVA with Dunnett’s test for b–d.

Extended Data Fig. 3 Leucine is amongst the best amino acid inducers of mTOR signaling in cultured primary macrophages.

(a, b) Immunoblot analysis of thioglycollate-elicited peritoneal macrophages (PMACs) (a) and bone marrow derived macrophages (BMDM) (b) after 30min of incubation with amino acid-free or regular/amino acid-sufficient medium to assess mTORC1 signaling using phospho- and total S6K and S6 levels as readouts. (c) Representative immunofluorescence images of BMDMs after 15min of incubation with amino acid-free or regular/amino acid-sufficient medium to assess co-localization between mTOR and Lamp2. (d, e) Immunoblot analysis of macrophages after 30min of incubation with regular medium or amino acid-free medium with and without 20 different L-amino acids to assess mTORC1 signaling using phospho- and total S6 levels as readouts. Representative blots (d) and quantification of pS6/total S6 ratio for five independent experiments (e). The best three mTOR inducers and three non-inducers are listed at right. (f, g) Immunofluorescence imaging of macrophages after 15min of incubation with regular medium or amino acid-free medium with and without the best three mTOR inducers and non-inducers to assess co-localization between mTOR and Lamp2. Representative images (f) and quantification of the mTOR/Lamp2 co-localization (+aa: n = 42; -aa: n = 74; Leu: n = 26; Arg: n = 38; Glu: n = 12; Gln: n = 34; Phe: n = 37; Thr: n = 43 cells) (g). For all graphs, data are presented as mean ±SEM. Source data

Extended Data Fig. 4 Body weight and common serum metabolites of control and mϕRaptor KO mice fed a standard or LCHP Western diet.

(a) Immunoblot analysis of control and Raptor KO macrophages after 30min of incubation with regular medium or amino acid-free medium with and without leucine to assess mTORC1 activity using phospho- and total S6K and S6 as readouts. (b) Immunofluorescence imaging of macrophages after 15min of incubation with regular medium or amino acid-free medium with and without leucine to assess co-localization between mTOR and Lamp2. Representative images (left) and quantification of the mTOR/Lamp2 co-localization (right) (Control: +aa: n = 42; -aa: n = 52; Leu: n = 44; ATG5 KO: +aa: n = 27; -aa: n = 40; Leu: n = 43 cells). (c) Total body weights of control (n = 22) and mϕRaptor-KO mice (n = 18) (all on ApoE-KO background) fed a standard Western diet for 8 weeks. (d) Measurements of serum cholesterol, glucose, triglycerides, and free fatty acids in control and mϕRaptor-KO mice after 8 weeks of Western diet feeding (n = 15–25 per group). (e) Measurements of serum cholesterol, glucose, triglycerides, and free fatty acids in cohorts of mϕRaptor-KO mice (on ApoE-null background) fed a standard Western diet or high protein Western diet for 8 weeks (n = 15 per group). For all graphs, data are presented as mean ±SEM. *P < 0.05, **P < 0.01, one-way ANOVA with Tukey’s test for b, two-tailed unpaired t-test for cSource data

Extended Data Fig. 5 Leucine-mediated activation of mTORC1 synergizes with atherogenic lipids to induce mitochondrial-dependent apoptosis in macrophages.

(a, b) Control and Raptor-KO macrophages were treated with vehicle, 500µg/ml cholesterol crystals (CC) with or without leucine and apoptosis assessed by Caspase-3/7 immunofluorescence staining. Shown are (a) representative images and (b) quantification of >103 cells from acquired images (Control: -aa: n = 11; Leu: n = 9; cc: n = 11; cc+Leu: n = 11; Raptor-KO: n = 11 image fields). For all graphs, data are presented as mean ±SEM. *P < 0.05, ***P < 0.001, one-way ANOVA with Tukey’s test.

Extended Data Fig. 6 Leucine-mediated activation of mTORC1 inhibits autophagy in macrophages.

(a) Immunoblot analysis of phospho- and total ULK1 levels in macrophages incubated with amino acid-free medium with and without leucine for the indicated times. (b, c) The autophagy marker LC3 was evaluated in macrophages incubated with regular medium or amino acid-free medium with and without leucine for 30 minutes using (b) immunoblot analysis or (c) quantification of LC3 intensity (+aa: n = 52; -aa: n = 52; Leu: n = 52 cells) and number of puncta (+aa: n = 97; -aa: n = 87; Leu: n = 97 cells) by immunofluorescence microscopy. (d) Phospho- and total ULK1 levels were determined in Control and Raptor KO macrophages incubated with regular medium or amino acid-free medium with and without leucine for 30 minutes. (e) LC3 levels in control and Raptor KO macrophages incubated with vehicle or 100nM Bafilomycin for 2 hours. (f) LC3 intensity (Control: +aa: n = 39; -aa: n = 27; Leu: n = 30; Raptor-KO: +aa: n = 31; -aa: n = 30; Leu: n = 30 cells) and number of puncta (n = 52 cells/group) were analyzed by immunofluorescence microscopy in control and Raptor KO macrophages incubated with regular medium or amino acid-free medium with and without leucine for 30 minutes. (g) Quantification of LC3 intensity by immunofluorescence microscopy in control and ATG5-KO macrophages incubated with regular medium or amino acid-free medium with and without leucine for 30 minutes (Control: +aa: n = 52; -aa: n = 50; Leu: n = 51; ATG5 KO: +aa: n = 36; -aa: n = 35; Leu: n = 47 cells). (h) ATG5-KO macrophages were co-incubated with vehicle or CC ± leucine and percent of caspase 3/7-positive cells were quantified in >103 cells from acquired images (-aa: n = 13; -aa+cc: n = 11; Leu: n = 10; Leu+ cc.: n = 12 image fields). For all graphs, data presented as mean ±SEM. *P < 0.05, one-way ANOVA with Tukey’s test. Source Data

Extended Data Fig. 7 Common serum metabolites of mϕRaptor-KO and dual mϕRaptor/mϕATG5-KO (DKO) mice fed a standard Western diet.

Measurements of serum cholesterol, glucose, triglycerides, and free fatty acids in cohorts of mϕRaptor-KO (n = 18) and mϕRaptor/ mϕATG5-KO (DKO) mice (n = 14) (all on ApoE-null background) fed a standard Western diet for 8 weeks.

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Source Data Extended Data Fig. 3

Unprocessed western blots of Extended Data Fig. 3

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Source Data Extended Data Fig. 6

Unprocessed western blots of Extended Data Fig. 6

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Zhang, X., Sergin, I., Evans, T.D. et al. High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy. Nat Metab 2, 110–125 (2020). https://doi.org/10.1038/s42255-019-0162-4

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Increase in heart attack risk from protein rich diet

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High-protein diets may help people lose weight and build muscle, but a new study in mice suggests they have a down side: They lead to more plaque in the arteries. Further, the new research shows that high-protein diets spur unstable plaque — the kind most prone to rupturing and causing blocked arteries. More plaque buildup in the arteries, particularly if it’s unstable, increases the risk of heart attack.The new study appears in the journal Nature Metabolism.

“There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years,” said senior author. “But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health.”

The researchers studied mice fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries. According to the senior author, mice must eat a high-fat diet to develop arterial plaque. Therefore, some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

“A couple of scoops of protein powder in a milkshake or a smoothie adds something like 40 grams of protein — almost equivalent to the daily recommended intake,” the senior author said. “To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet — keeping the fat constant. Protein went from 15% to 46% of calories for these mice.”

The mice on the high-fat, high-protein diet developed worse atherosclerosis — about 30% more plaque in the arteries — than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

“This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques,” the senior author said. “In other words, our study shows how and why dietary protein leads to the development of unstable plaques.”

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by the team and other groups has shown that immune cells called macrophages work to clean up plaque in arteries. But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

“In mice on the high-protein diet, their plaques were a macrophage graveyard,” the senior author said. “Many dead cells in the core of the plaque make it extremely unstable and prone to rupture. As blood flows past the plaque, that force — especially in the context of high blood pressure — puts a lot of stress on it. This situation is a recipe for a heart attack.”

To understand how high dietary protein might increase plaque complexity, the authors studied the path protein takes after it has been digested — broken down into its original building blocks, called amino acids.

The team found that excess amino acids from a high-protein diet activate a protein in macrophages called mTOR, which tells the cell to grow rather than go about its housecleaning tasks. The signals from mTOR shut down the cells’ ability to clean up the toxic waste of the plaque, and this sets off a chain of events that results in macrophage death. The researchers found that certain amino acids, especially leucine and arginine, were more potent in activating mTOR — and derailing macrophages from their cleanup duties, leading to cell death — than other amino acids.

“Leucine is particularly high in red meat, compared with, say, fish or plant sources of protein,” the senior author said. “A future study might look at high-protein diets with different amino acid contents to see if that could have an effect on plaque complexity. Cell death is the key feature of plaque instability. If you could stop these cells from dying, you might not make the plaque smaller, but you would reduce its instability.

“This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease,” the author said.

https://medicine.wustl.edu/news/high-protein-diets-boost-artery-clogging-plaque-mouse-study-shows/

https://www.nature.com/articles/s42255-019-0162-4 Edited January 25th 2020

 

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  4. Greetings,

    I want to share some very important information that’s been spreading all over the internet relating to our future well being.

    We’re on the horizon of a future of a one world cashless society where we will be mandated to have an RFID microchip inserted in our body. This microchip will hold all our data and we will lose our privacy due to the tracking power.

    Even bigger news than this, did you know that this was predicted almost two thousand years in the past by a man named Jesus? Have doubts? Keep reading to see… This may be the most important thing you will read.

    • “And he(the false prophet) causeth all, the small and the great, and the rich and the poor, and the free and the bond, that there be given them a mark on their right hand, or upon their forehead; and that no man should be able to buy or to sell, save he that hath the mark, even the name of the beast or the number of his name. Here is wisdom. He that hath understanding, let him count the number of the beast; for it is the number of a man: and his number is Six hundred and sixty and six” (Revelation 13:16-18 ASV)..

    Speaking on the last times, this could only be pointing to a cashless society, which we have yet to see, but we are getting close to. How come? Otherwise we would be able to buy or sell without taking the mark among each other if tangible money was still valid. It logically deduces itself to this conclusion.

    The mark can’t be spiritual, because the word references two different physical places. If it was to be spiritual, the text would only conclude one place.

    Here is it where it all starts coming together. It is astonishing how on target the scriptures are in the matter of this RFID chip. These are notes from a man named Carl Sanders who labored with a team of engineers to help invent the RFID microchip in the 90’s.

    Carl Sanders sat in 17 New World Order conferences with heads of state officials such as Henry Kissinger and Bob Gates of the CIA to talk about their agenda on how to bring about this one-world system. The US government commissioned Mr. Sanders to design a microchip for identifying and controlling the peoples of the world-a microchip that could be inserted under the skin with a hypodermic needle(a quick, convenient procedure that would be progressively received by the people).

    Carl Sanders, with a team of engineers behind him, with U.S. grant monies provided by tax dollars, took on this challenge and produced a RFID chip that’s powered by a lithium battery, rechargeable by means of the temperature changes in our skin. Without the understanding of the biblical scriptures (Mr. Sanders was not a follower of Christ at the time), these engineers spent one and a half million dollars conduction research on the best and most convenient location to have the RFID microchip placed below the skin.

    These researchers discovered that the forehead and the back of the hand(the two spots Revelation says the mark will be received) aren’t only the most convenient spots, but are additionally the only viable spots for rapid, consistent temperature fluctuations within the skin to recharge the lithium battery. The RFID chip is approximately seven millimeters in length, .75 millimeters in diameter, about the dimensions of a grain of rice. It’s capable of storing many pages of information about you. All your basic history, work records, crime data, health history, and financial records will be saved on this chip.

    Mr. Sanders believes that this RFID chip, which he remorsefully helped invent, is the “beast’s mark” mentioned in Revelation 13:16-18. The Greek word for “mark” is “charagma,” which is defined as a “scratch or etching.” Additionally it’s interesting to observe that the number 666 is in fact a word in the original Greek language. The word is “chi xi stigma,” with the last part, “stigma,” additionally meaning “to stick or prick. Mr. Sanders believes that is referring to the use of a hypodermic needle being poked in the human flesh to insert the RFID chip.”

    Mr. Sanders reached out to a doctor asking what would occur if the lithium contained within the RFID microchip leaked into the human body. The physician answered by saying a terrible sore would arise in that spot. This is what the book of Revelation says:

    “And the first went and poured out his bowl into the land— and a bad and evil sore came upon the people having the mark of the beast and the ones giving worship to his image” (Revelation 16:2 DLNT).

    The Bible tells us that we cannot buy or sell without having the mark, or the number of its name. This number of the beast being 666. The Bible tells us to count the number 666. How do we calculate 666?

    This is where it gets really interesting. Counting the number of the beast 666 has been long debated throughout the history of the world, but has now been made known in these last times by God. What you will read confirms itself with the word of God the real meaning to calculate six-six-six.

    Through God’s Holy word, God uses the number 3 for confirming things. Here are a few examples:

    “For there are three that bear witness in heaven: the Father, the Word, and the Holy Spirit; and these three are one” (1 John 5:7 NKJV).

    “and that He was buried, and that He rose again the third day according to the Scriptures” (1 Corinthians 15:4 NKJV).

    “…Holy, holy, holy, Lord God Almighty, Who was and is and is to come!” (Revelation 4:8 NKJV).

    Now what is interesting is the the mark of the beast is described in detail in 3 distinct verses (Revelation 13:16,17,18), and each verse lists three different examples of the given subject. The last 3 being the number 6 used 3 times in a row. Here is a key point to solving how to count the number 666.

    What does it mean to calculate? It means to add up. So how could we add up 666? Call back to mind my earlier key point regarding God confirming in 3’s. So logically, what would be the most sensible way to add up the number 666? To add it up equally in threes based off the number. We cannot count it equally as 600+60+6, this would also revert us back to the beginning. We are not able to count it as 600+600+600, or 60+60+60, because there are no zeroes in between or at the end of 666. The only rational option is 6+6+6=18. What is fascinating is that the verse that reveals for us to count the number itself is verse 18, being the third verse out of three verses that describe the mark of the beast. Now what is 18 divided by 3? 6. So 3×6=18, or 6+6+6=18.

    Another interesting point is the only two other combinations (making a combined total of three possible combinations) for placing a “+” symbol in between the sixes are 66+6=72, and 6+66=72. Count both 72’s together and you get 144. Why the number 144 is interesting is because the verse following Revelation 13:18 is the first time in scripture where the 144,000 are being mentioned in detail:

    “Then I looked, and behold, a Lamb standing on Mount Zion, and with Him one hundred and forty-four thousand, having His Father’s name written on their foreheads…” (Revelation 14:1).

    Now if you add up all 3 values by counting 666 by moving the plus symbol around in all three possible combinations, it would be 72+72+18=162. What is fascinating about the number 162, is, if you divide 144,000 by 162, you get 888. The name of Jesus in Greek gematria calculates to 888. The New Testament was written in Greek. Revelation 14:1 not only mentions the 144,000, but also the Lamb of God being Jesus Christ.

    Now what is interesting about the number for Jesus, 888, is that if you apply this same formula, you get 8+8+8=24. Why the number 24? Revelation chapter 4 tells us there are 24 elders seated around the throne of God. This is the same throne where Jesus sits:

    “Immediately I was in the Spirit; and behold, a throne set in heaven, and One sat on the throne. And He who sat there was like a jasper and a sardius stone in appearance; and there was a rainbow around the throne, in appearance like an emerald. Around the throne were twenty-four thrones, and on the thrones I saw twenty-four elders sitting, clothed in white robes; and they had crowns of gold on their heads” (Revelation 4:2-4).

    Now if you take 8+8+8=24, and 8+88=96, and 88+8=96, you get 24+96+96=216. Take 144,000 divided by 216 and you get 666. Take into account that this was the exact formulation to get the value 162 out of counting 666 that brought about the numeral 888 when dividing 144,000 by 162. It is perpetual.

    With using the identical formula of counting by including the plus symbol in between the numbers, why do all these numbers relate in such a way?

    Another interesting factor to be aware is that if you add up all the numbers from 1 to 36, it totals 666. The number 36, as in three sixes? Could this be a hint that we must add up three sixes instead of perceiving the number as six-hundred sixty six?

    So what might this mean? We all know in this world we are identified by numbers in numerous forms. Starting from our birth certificates to social security, also with our drivers license, being recognized based on a system of ruler ship. So it is plausible that this RFID chip will comprise a brand new identification that has a total of 18 characters.

    Could this be the identification of the beast, the number of its name? The one-world beast system that’s recognized by 18 characters? This would fit the scriptures that speaks of a mark that we ought to have to buy or sell in our right hand or forehead, and that it additionally incorporates the number of the beast, throughout a future cashless money society.

    Go to: https://biblefreedom.com to see all the proof!

    The Holy scriptures warns us in the end times that a false prophet will rise up doing miraculous signs to deceive many to receive the beasts mark:

    “Then the beast was captured, and with him the false prophet who worked signs in his presence, by which he deceived those who received the mark of the beast and those who worshiped his image” (Revelation 19:20).

    No matter the cost, DO NOT TAKE IT!

    “Then a third angel followed them, saying with a loud voice, “If anyone worships the beast and his image, and receives his mark on his forehead or on his hand, he himself shall also drink of the wine of the wrath of God, which is poured out full strength into the cup of His indignation. He shall be tormented with fire and brimstone in the presence of the holy angels and in the presence of the Lamb. And the smoke of their torment ascends forever and ever; and they have no rest day or night, who worship the beast and his image, and whoever receives the mark of his name” (Revelation 14:9-11).

    We are dwelling in very prophetic times with very important Biblical prophecies coming to pass. When Donald Trump acknowledged Jerusalem as capital of Israel on December 6th of ’17, this was a huge step to bring about the Third Temple foretold within the Holy Bible.

    God’s holy Word’s alerts us that the Antichrist will seat himself in this temple:

    “…and the man of sin is revealed, the son of perdition, who opposes and exalts himself above all that is called God or that is worshiped, so that he sits as God in the temple of God, showing himself that he is God” (2 Thessalonians 2:3-4).

    Within the Islamic religion, they have a man called the Mahdi, referred to as their messiah who they are waiting to appear. There are various testimonies from individuals online who believe this man will be Barack Obama who may be the biblical Antichrist. I have had strange dreams about Barack. He got on stage claiming to be a follower of Christ with no affiliation to the Muslim faith, but was later revealed by his family that he indeed is a religious Muslim.

    His actual birth name is stated to be Barry Soetoro, and he had his name switched to Barack Obama. Is there any significance to this?

    Jesus says, “And He said to them, ‘I saw Satan fall like lightning from heaven'” (Luke 10:18).

    In Hebrew, the name “Barack” means “lighting”, and the usage of “Bama” (Strongs Hebrew phrase 1116) is used to refer to the “heights” of heaven.

    The following day after the election of Barack Obama (11/04/08), the triumphing pick three lotto numbers in Illinois (Obama’s home state) for 11/5/08 were 666.

    Obama was a U.S. senator for the state of Illinois, and his zip code was 60606.

    Regardless, whomsoever seats themselves in the future Third Temple in Jerusalem, declaring themselves to be God IS THE ANTICHRIST. DO NOT BE LEAD ASTRAY.

    Why do we need Jesus Christ?

    “for all have sinned and fall short of the glory of God” (Romans 2:23).

    “For the wages of sin is death, but the gift of God is eternal life in Christ Jesus our Lord” (Romans 6:23).

    Our good works cannot save us from our sins. If we step in front of a judge in the court of law, being guilty for committing a crime, the judge will not judge us by the good that we have done, rather the crimes we’ve committed. If we as fallen humanity, created in God’s image, pose this kind of moral justice, how much greater a perfect, righteous, and Holy creator?

    God has introduced to us His ethical law’s through the ten commandments received by Moses at Mt. Siani. These laws were not given so we can be justified, but so that we could see the need for the savior. They’re the mirror of God’s character of what He has put in each and every one of us, with our conscious bearing witness that we all know that it is an offense to steal, lie, dishonor our mother and father, and so forth.

    We can attempt to comply with all the moral laws of the 10 commandments, however we’ll by no means catch up to them to be justified before a Holy God. The same word of the law given to Moses manifested as flesh over 2000 years ago within the body of Jesus Christ. He came to be our justification by perfectly fulfilling the law, living a sinless life that solely God may fulfill.

    The space between us and the law of God can by no means be reconciled by our very own merit, but the arm of Jesus is stretched out by the grace and mercy of God. And if we’re to grab on, by means of faith in Him, He’ll pull us forward being the one to justify us. As inside the court of law, if somebody steps in and pays your fine, even though you are guilty, the judge can do what is legal and just and let you go free. This is what Jesus did nearly 2000 years ago on the cross. It was a legal transaction being fulfilled in the spiritual realm by the shedding of His blood, with His last words being, “…It is finished!…” (John 19:30).

    Now why did Jesus have to die for us?

    Due to the fact that God is Holy and just, the wrath that belongs to us could not be overlooked. Through the perfect righteousness and justice of God’s character, it ought to be reconciled, it must be quenched and satisfied.

    For God takes no pleasure in the death of the wicked (Ezekiel 18:23). This is why in Isaiah chapter 53, the place it speaks of the coming Messiah and His soul being a sacrifice for our sins, why it says it pleased God to crush His only begotten Son.

    This is because the wrath that we deserve was justified by being poured out upon His Son. For if it were to be poured out upon us who’ve earned it, we would all perish and go to hell. God created a means of escape by pouring it out on His Son who’s soul could not be left in Hades, however was raised and seated on the right hand of God in power.

    So now after we put on the Lord Jesus Christ (Romans 13:14), God no longer see’s the person who deserves His wrath, but the glorious image of His perfect Son residing in us, justifying us as if we acquired the wrath we deserve, making a means of escape from the curse of death.

    Now what we must do is repent and trust in the savior, confessing and forsaking our sins. That is not just a head knowledge of believing in Jesus, howeverrather receiving His words, taking them to heart. In which we no longer live to practice sin, however turn away from our sins and exercise righteousness:

    “Do you not know that the unrighteous will not inherit the kingdom of God? Do not be deceived. Neither fornicators, nor idolaters, nor adulterers, nor homosexuals, nor sodomites, nor thieves, nor covetous, nor drunkards, nor revilers, nor extortioners will inherit the kingdom of God. And such were some of you. But you were washed, but you were sanctified, but you were justified in the name of the Lord Jesus and by the Spirit of our God” (1 Corinthians 6:9-11).

    By doing so we may come to be transformed into the image of God by faith in His Son Christ Jesus Who’s willing to offer the Holy Spirit to people who ask of Him:

    “Most assuredly, I(Jesus) say to you, unless one is born of water and the Spirit, he cannot enter the kingdom of God. That which is born of the flesh is flesh, and that which is born of the Spirit is spirit. Do not marvel that I said to you, ‘You must be born again.’ (John 3:5-6).

    “But you are not in the flesh but in the Spirit, if indeed the Spirit of God dwells in you. Now if anyone does not have the Spirit of Christ, he is not His” (Romans 8:9).

    Now what are you waiting for? Our Father in heaven only wishes the best for us, restoring all the pieces this world has stolen from us. That is what it means to be “holy”. To be made whole.

    He’s waiting to listen to you. That God given tongue to speak language, by using faith, pray to Him, ask Him to forgive you by confessing your sins and be willing to forsake them; that you accept the sacrifice of His Son Jesus on the cross, and that you want His Holy Spirit residing inside you transforming you into a child of the living God.

    Jesus says, “but whoever drinks of the water that I shall give him(the Holy Spirit) will never thirst. But the water that I shall give him will become in him a fountain of water springing up into everlasting life.”

    Did you realize that Jesus spoke more about hell than anyone else in God’s word, even more than He spoke about heaven?! For this very reason He was brought forth to die for us, to save us from this place that we deserve.

    He describes hell as a actual place where,

    “Their worm does not die
    And the fire is not quenched” (Mark 9:44).

    And where,

    “There will be weeping and gnashing of teeth…” (Luke 13:28).

    Jesus tells us who to fear,

    “And do not fear those who kill the body but cannot kill the soul. But rather fear Him who is able to destroy both soul and body in hell” (Matthew 10:28).

    “Now I saw a new heaven and a new earth, for the first heaven and the first earth had passed away. Also there was no more sea. Then I, John, saw the holy city, New Jerusalem, coming down out of heaven from God, prepared as a bride adorned for her husband. And I heard a loud voice from heaven saying, ‘Behold, the tabernacle of God is with men, and He will dwell with them, and they shall be His people. God Himself will be with them and be their God. And God will wipe away every tear from their eyes; there shall be no more death, nor sorrow, nor crying. There shall be no more pain, for the former things have passed away.’

    Then He who sat on the throne said, ‘Behold, I make all things new.’ And He said to me, ‘Write, for these words are true and faithful.’

    And He said to me, ‘It is done! I am the Alpha and the Omega, the Beginning and the End. I will give of the fountain of the water of life freely to him who thirsts. He who overcomes shall inherit all things, and I will be his God and he shall be My son. But the cowardly, unbelieving, abominable, murderers, sexually immoral, sorcerers, idolaters, and all liars shall have their part in the lake which burns with fire and brimstone, which is the second death.'” (Revelation 21:1-8).

    Out of all of the world religions, how can we make certain the Bible has it all right? The scientific data has established and continues to support that the universe once had a beginning in which space, time and matter had been created. Many know this as the big bang.

    “The non-biblical religions tell us that god or god’s create within space and time that eternally exist. The Bible stands alone and says that time and space don’t exist until God creates the universe.” – Astronomer(Phd) Hugh Ross

    The Bible not only got it correct that space, time and matter all came into existence at the beginning of the universe, it additionally states in 7 different places that the universe is is continuing to expand thousands of years earlier than scientists discovered these facts.

    Did you already know that the actual Noah’s Ark was found in the place where the Bible informed us it’d be with the correct dimensions? As well as proof for the destruction of Sodom & Gomorrah and the Exodus account of the Red Sea crossing?

    The Bible is the most translated and studied historical document in the history of the world, packed with predictive prophecies, matching what we discover in the book of nature. Wouldn’t you expect God’s word to be so?

    This information and more can all be found here: https://biblefreedom.com

    The Lord is calling you!

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