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Molecular actions[edit]

@Zefr: Concerning your edit with the edit summary "questionable section, WP:OR conjecture: alter subtitle to reflect this content is research & speculation only; WP:NOTJOURNAL, WP:PRIMARY", I agree that WP:PRIMARY applies, but no medical claims are being made, so per WP:SCIRS are allowed but not encouraged. I strongly disagree that WP:NOTJOURNAL and WP:OR applies. The added text is reasonably clear and not in the lead section, so certainly is allowable. While this material may not be of interest to you, it is of interest to others. Boghog (talk) 19:22, 27 September 2016 (UTC)

Any suggestion of "molecular actions" (rather than just lab research that is underway to actually define mechanisms) infers human relevance, so WP:MEDRS does apply. Consequently, I removed this speculative, early-stage lab research here for discussion per WP:BRD. The content and sources are completely conjectural existing only as in vitro research not confirmed in humans, having low relevance per WP:NOTJOURNAL. Including this in the article is WP:OR, suggesting unproven importance. --Zefr (talk) 19:28, 27 September 2016 (UTC)
Cholesterol has recently been found to bind to and activate the estrogen-related receptor alpha (ERRα), and may be the endogenous ligand for the receptor.[1] Furthermore, statin-associated myopathy and suppression of cholesterol-induced cytokine secretion by macrophages are reduced by absence or inhibition of ERRα. As such, modulation of ERRα signaling is a key mediator in the actions of statins (by changes in cholesterol levels) and bisphosphonates.
Cholesterol has been found to bind to and affect the gating of a number of ion channels such as the nicotinic acetylcholine receptor, GABAA receptor, and the inward-rectifier potassium ion channel.[2]
@Zefr: The last sentence that you removed is supported by a secondary source and therefore should be restored. Cholesterol binding recombinant human ERRα in vitro is not a suggestion, it is a testable hypothesis that is independent of any human relevance. Hence on this specific claim, WP:MEDRS does not apply. The source goes on to discuss possible mechanisms by which statins and bisphosphonates exert there effects on bone and muscle. The fact that these medications have these effects is a medical claim that is backup by secondary sources cited by the primary source (e.g, PMID 22136934). The source goes on to discuss the mechanisms by which these drugs exert their effects. This is debatably a medical claim and hence probably should be removed. WP:OR only applies if the editor that added material was making claims that went beyond what the source stated. That was not the case here, therefore WP:OR does not apply. Finally as WP:MEDANIMAL makes clear, it is permissible to include in vitro and animal studies in Wikipedia articles as long as it is made clear that the data is preclinical. The scope of Wikipedia is wider than WP:MED, it also includes WP:MCB. Not everything must be proven in humans to be notable. Hence WP:NOTJOURNAL does not apply. Boghog (talk) 20:42, 27 September 2016 (UTC)
This edit to call the section "preclinical research" is an exaggeration, as the research has not been tested in lab animals, let alone in a human animal model that would qualify for "preclinical". WP:MEDANIMAL applies to the content in question because the implication to a typical user is that this applies to cholesterol mechanisms, but there is no in vivo proof that it does (inappropriate to include this in the Physiology section). The other content under Physiology has been demonstrated in humans, but this basic research section is years from proof in humans, so is not "preclinical". Including in vitro content to imply relevance to human cholesterol metabolism is the type of information appropriate for a journal review, but is not encyclopedic per WP:FRINGE and WP:NOTJOURNAL. --Zefr (talk) 05:08, 28 September 2016 (UTC)
The definition of preclinical is anything that is done in the laboratory. It is completely irrelevant if the research was done in lab animals or not. Hence this research is preclinical. Also if you have bothered to read the article, animal studies were in fact done. Finally as demonstrated in this previous discussion, your viewpoint has not won any converts. Boghog (talk) 05:50, 28 September 2016 (UTC)
To exclude material because it might be interpreted by some as having human relevance is ridiculous and is a form of censhorship. Boghog (talk) 06:02, 28 September 2016 (UTC)

───────────────────────── The definition of "preclinical" means that studies are "first-in-human" for dosing safety before a clinical trial is conducted. As stated here, it's a term common in the clinical trial literature. By contrast, in vitro receptor research is early-stage in the drug or mechanism discovery cycle (shown in the diagram here). This early research stage is exaggerated by your edit and subtitle selection as supposedly meaningful to physiology when it is actually years away from in vivo proof first in animals, then in humans. This is not censorship or insubstantial debate, but rather is just stating facts for an encyclopedia user, as we should be obligated to do per WP:MEDANIMAL ("in vitro and animal-model findings do not translate consistently into clinical effects in human beings") and WP:NOTJOURNAL ("A Wikipedia article should not be presented on the assumption that the reader is well-versed in the topic's field. ...language should be written in plain terms and concepts that can be understood by any literate reader of Wikipedia without any knowledge in the given field"). --Zefr (talk) 16:45, 28 September 2016 (UTC)

  • The preposition "pre" means "previous to" or "before". Preclinical does not mean first in humans. Preclinical means before humans. First in humans is a phase 1 clinical trial. A phase 1 trial is not preclinical, it is clinical. It is clear that you have no idea what you are talking about. Also in this edit with the edit summary A receptor claim is a medical claim. False. A receptor claim is a biochemical claim, not a medical claim. Boghog (talk) 20:38, 28 September 2016 (UTC)
  • This edit with the edit summary [preclinical] is not physiology. Preclinical research is not restricted to physiology. It also includes biochemistry. Again, it is painfully obvious you have no idea what you are talking about. Boghog (talk) 21:08, 28 September 2016 (UTC)
You're clearly trying to glorify in vitro research. You can't redefine the encyclopedia which states what "preclinical" means in the advances of research toward human understanding: "a stage of research that begins before clinical trials (testing in humans) can begin." "First in human" is a pilot study; anyone who has done human research - and I assume a basic biochemist or pharmacologist would not normally be involved - knows "preclinical" are the series of final steps before being tested in humans. In vitro would not be called "preclinical" because it is far from proof that the mechanism even exists in vivo, much less whether it is relevant to actual human physiology. --Zefr (talk) 21:05, 28 September 2016 (UTC)
  • The definition of what "preclinical" means directly contradicts what you wrote above, namely "preclinical" means that studies are "first-in-human". Whether it relevant to actual human physiology is irrelevant because it is not a medical claim. Finally preclinical does include in vitro. Boghog (talk) 21:22, 28 September 2016 (UTC)
  • You're clearly trying to glorify in vitro research. Not at all. All I am stating is that in vitro research is independently notable if supported by reliable sources. Furthermore as long as no medical claims are being made, there is no conflict with WP:MEDRS. You need to accept that the scope of Wikipedia is broader than WP:MED. It also includes WP:MCB. Boghog (talk) 21:32, 28 September 2016 (UTC)
  • In this edit with the edit summary: "molecular actions" are artificially determined and misrepresent that this may apply to humans; call it what it is: research. The interaction with a small molecule with an protein is not artificial. It is a fact that is independent of any relevance to humans. Since there is no medical claims made, there is no misrepresentation. Boghog (talk) 06:05, 29 September 2016 (UTC)
Continuing the debate between a molecular biologist and a physiologist... Until in vitro findings are clearly confirmed in vivo, especially in humans, showing specificity (blocking or augmenting studies) and efficacy (such as with dose-response effects), they are not facts but rather are theoretical in the process of hypothesis testing in an artificial environment variably created by researchers as explained in WP:MEDANIMAL, i.e., they are not true physiological events until proven in vivo, so are WP:UNDUE. Any putative mechanism that supposedly is part of human health or disease related to cholesterol should be held to MEDRS sourcing. The two sources used in this section are preliminary, full of conjecture and WP:PRIMARY at best. In an article like this on a topic of general interest to lay encyclopedia users, this information is premature, esoteric, jargonistic and has little value in the context of better established information elsewhere in the article per WP:NOTJOURNAL. Your insistence to include hypothetical "molecular actions" falls more into a category of persuasion trying to justify in vitro research for the encyclopedia, and therefore is WP:SYNTH and borderline WP:OR. --Zefr (talk) 16:19, 29 September 2016 (UTC)
Binding of a small molecule to a protein is not hypothetical, but a real, verifiable, fact. You previously tried arguing that it wasn't, but conesnsus is clearly against you. As long as it is supported by reliable sources, it is fair game for inclusion in an article on cholesterol. As the project banners make clear at the top of this talk page, the scope of this article not only within WP:MED, but also WP:MCB and WP:CHEMS. Boghog (talk) 16:54, 29 September 2016 (UTC)

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ok, but fixed one URL to more direct information for AHA. --Zefr (talk) 03:40, 23 November 2016 (UTC)

vegetable sources of cholesterol[edit]

Secondary metabolism : High cholesterol in tomato
A straightforward approach reveals the full cholesterol biosynthetic pathway in tomato, which is composed of ten enzymatic steps, opening the door for bioengineering of high-value molecules in crops. Phylogenetic analysis suggests that cholesterogenesis evolved from the more ancient phytosterol pathway.

Plant cholesterol biosynthetic pathway overlaps with phytosterol metabolism[edit]

The amount of cholesterol made by many plants is not negligible. Whereas cholesterogenesis in animals was elucidated decades ago, the plant pathway has remained enigmatic. Among other roles, cholesterol is a key precursor for thousands of bioactive plant metabolites