If you have been reading about Carcinogenicity and want a single page that covers the useful parts, this is it: definitions, context, how it is studied, and the questions that come up repeatedly.
Last reviewed on 2026-04-29. Where a claim depends on a specific study, the study is described rather than over-claimed.
Safety concerns emerged from long-term animal studies. In rodents given the compound for extended periods, researchers found an increased incidence of certain cancers, including liver and bladder tumors. These findings contributed to the discontinuation of clinical development. Whether similar risks apply to short-term or low-level exposure in humans is not established, and controlled human safety data are limited. The relevance of high-dose rodent carcinogenicity findings to human use remains a subject of debate.
Human trials of GW501516 were small and short in duration. They examined lipid levels, glucose handling, and other metabolic markers, but the programs were halted after the animal cancer findings. No approved therapeutic product exists, and published human data are insufficient for establishing long-term safety. Reports of use for athletic performance come mainly from non-clinical settings and cannot be verified through controlled trials. Independent testing of products sold as cardarine has found inconsistent purity and labeling.
Safety discussions about cardarine frequently cite rodent carcinogenicity findings reported in the 2000s. In those studies, treated animals developed tumors at multiple sites, leading sponsors to discontinue clinical development. The relevance of these findings to humans has not been resolved, but they are a major reason the compound is not approved. Current literature emphasizes uncertainty about long-term effects and the risks of unregulated use. Regulators and health agencies have not established a safe human exposure level.
Cardarine is a synthetic compound also known as GW501516, GW-501516, and sometimes endurobol. It was developed as a selective agonist of peroxisome proliferator-activated receptor delta, a nuclear receptor involved in fatty acid oxidation and energy metabolism. The compound was studied in preclinical models for metabolic and cardiovascular conditions, but it did not become a marketed human medicine. In regulatory and anti-doping contexts, it is treated as a prohibited substance rather than a licensed medicine.
The pharmacological interest in cardarine centers on PPARδ activation and its downstream effects on lipid handling and mitochondrial function. In animal studies, PPARδ agonists have been associated with changes in exercise endurance and fatty acid utilization, though results vary by model and protocol. Human data remain sparse, and the absence of large controlled trials limits conclusions about efficacy. Researchers often describe the compound as a tool for probing PPARδ biology rather than a proven therapeutic agent.
| Property | Value | Notes |
|---|---|---|
| Primary target | PPARδ (NR1C2) | Nuclear receptor involved in lipid metabolism |
| Preclinical effect | Increased fatty acid oxidation | Observed in rodent studies |
| Key safety signal | Tumors in rodents after long-term exposure | Contributed to halted clinical development |
| Human trial status | No approved product; development stopped | Limited short-term metabolic data |
| Sport regulatory status | Prohibited at all times | WADA hormone and metabolic modulators class |
Literature on cardarine often separates receptor pharmacology from toxicology. Mechanistic papers describe PPARδ activation and gene expression changes, while safety assessments focus on carcinogenicity and species differences. Questions remain about whether rodent tumors arise through PPARδ-dependent or off-target mechanisms. Another open area is how human metabolism and exposure compare with those in animal studies. Analytical methods such as liquid chromatography–mass spectrometry are used to confirm identity in biological and product samples.
GW501516 acts as an agonist at the peroxisome proliferator-activated receptor delta, a nuclear receptor that regulates gene expression. Activation shifts transcription toward genes involved in fatty acid uptake, oxidation, and energy expenditure. The compound does not bind the androgen receptor and therefore differs from anabolic steroids and SARMs. In rodent models, this metabolic shift has been linked to increased running endurance and reduced fat accumulation. The exact downstream pathways in humans remain incompletely characterized.
Handling and quality assessment of cardarine reference material follow general laboratory practices for poorly characterized compounds. It typically appears as a white to off-white powder and is sparingly soluble in water but soluble in organic solvents such as dimethyl sulfoxide and ethanol. Storage recommendations usually specify a cool, dry, dark place, with long-term storage at low temperature and desiccation. Purity may be checked by high-performance liquid chromatography with ultraviolet detection, while identity is confirmed by mass spectrometry and nuclear magnetic resonance. No pharmacopeial monograph exists, so reported purity and stability depend on the supplier’s methods.
GW501516 acts as a selective agonist at PPARδ, a nuclear receptor that regulates transcription of genes involved in lipid handling and energy metabolism. Activation of PPARδ in preclinical models increases fatty acid oxidation, mitochondrial biogenesis, and exercise endurance in rodents. These effects have made the compound a subject of metabolic research and also a target for sport anti-doping rules. In humans, however, controlled studies are limited, and whether similar endurance or metabolic changes occur at tolerated exposures remains an open question. The receptor’s broad tissue distribution also means downstream effects may vary by organ and condition.
Detection of GW501516 in biological samples generally relies on liquid chromatography coupled with tandem mass spectrometry. Urine is a common matrix in anti-doping analysis, while blood or plasma may be used in research settings. Sample preparation can involve enzymatic hydrolysis, protein precipitation, or solid-phase extraction before instrumental analysis. Because the compound undergoes metabolism, assays may target the parent molecule, one or more metabolites, or both. Detection windows are not fixed; they depend on factors such as dose, route, individual metabolism, and assay sensitivity. Reference standards are required for accurate identification and quantification.
== Sustainable development == The Sustainable Development Index (SDI) measures the ecological efficiency of human development. Its impetus was a reaction to the UN's Human Development Index (HDI) which measures various indicators of development, but does not assess the sustainability of those underlying indicators. Countries with high human development and low ecological impact rise to the top of the SDI. Countries with low human development, and countries with high human development but high ecological impact, fall to the bottom of the SDI. The latest iteration of the index (2020) uses data from 2015, the most recent year for which data is available. In this ranking of 163 nations, Thailand ranked 44. Other ASEAN nations were ranked: Philippines, 26; Indonesia, 30; Vietnam, 42; Laos, 66; Cambodia, 77; Myanmar, 79; Malaysia, 109; Brunei, 139; and Singapore, lowest of all nations at 163.
Deionized water (DI water, DIW or de-ionized water), often synonymous with demineralized water/DM water, is water that has had almost all of its mineral ions removed, such as cations like sodium, calcium, iron, and copper, and anions such as chloride and sulfate. Deionization is a chemical process that uses specially manufactured ion-exchange resins, which exchange hydrogen and hydroxide ions for dissolved minerals, and then recombine to form water. Because most non-particulate water impurities are dissolved salts, deionization produces highly pure water that is generally similar to distilled water, with the advantage that the process is quicker and does not build up scale. However, deionization does not significantly remove uncharged organic molecules, viruses, or bacteria, except by incidental trapping in the resin. Specially made strong base anion resins can remove Gram-negative bacteria. Deionization can be done continuously and inexpensively using electrodeionization. Three types of deionization exist: co-current, counter-current, and mixed bed.
The efficiency of the ligation reactions varies depending on the specific sequence and the types of modifications made to the shortmers, as well as possible difficulties in creating a suitable template strand. As with many experimental methods, there are also issues with scalability and cost. At this point, these limitations prevent this method from being adopted as a primary oligonucleotide synthesis method.
A gelatine shot (usually called a Jell-O shot in North America and vodka jelly or jelly shot in the UK and Australia) is a shooter in which one or more liquors, usually vodka, rum, tequila, or neutral grain spirit, replaces some of the water or fruit juice that is used to congeal the gel. The American satirist and mathematician Tom Lehrer claims to have invented the gelatine shot in the 1950s while working for the National Security Agency, where he developed vodka gelatine as a way to circumvent a restriction of alcoholic beverages on base. An early published recipe for an alcoholic gelatine drink dates from 1862, found in How to Mix Drinks, or The Bon Vivant's Companion by Jerry Thomas: his recipe for "Punch Jelly" calls for the addition of isinglass or other gelatine to a punch made from cognac, rum, and lemon juice.
Nerve endings in the vagina can provide pleasurable sensations when they are stimulated during sexual activity. Women may derive pleasure from one part of the vagina, or from a feeling of closeness and fullness during vaginal penetration. Because the vagina is not rich in nerve endings, women often do not receive sufficient sexual stimulation, or orgasm, solely from vaginal penetration. Although the literature commonly cites a greater concentration of nerve endings and therefore greater sensitivity near the vaginal entrance (the outer one-third or lower third), some scientific examinations of vaginal wall innervation indicate no single area with a greater density of nerve endings. Other research indicates that only some women have a greater density of nerve endings in the anterior vaginal wall. Because of the fewer nerve endings in the vagina, childbirth pain is significantly more tolerable. Pleasure can be derived from the vagina in a variety of ways. In addition to penile penetration, pleasure can come from masturbation, fingering, or specific sex positions (such as the missionary position or the spoons sex position). Heterosexual couples may engage in fingering as a form of foreplay to incite sexual arousal or as an accompanying act, or as a type of birth control, or to preserve virginity. Less commonly, they may use non penile-vaginal sexual acts as a primary means of sexual pleasure. In contrast, lesbians and other women who have sex with women commonly engage in fingering as a main form of sexual activity.
Sources: en.wikipedia.org
First, the ancient tanners would soak the skins in water to clean and soften them. Then they would pound and scour the skin to remove any remaining flesh and fat. Hair was removed by soaking the skin in urine, painting it with an alkaline lime mixture, or simply allowing the skin to putrefy for several months then dipping it in a salt solution. After the hair was loosened, the tanners scraped it off with a knife. Once the hair was removed, the tanners would "bate" (soften) the material by pounding dung into the skin, or soaking the skin in a solution of animal brains. Bating was a fermentative process that relied on enzymes produced by bacteria found in the dung. Among the kinds of dung commonly used were those of dogs or pigeons. Historically the actual tanning process used vegetable tanning. In some variations of the process, cedar oil, alum, or tannin was applied to the skin as a tanning agent. As the skin was stretched, it would lose moisture and absorb the agent. Following the adoption in medicine of soaking gut sutures in a chromium (III) solution after 1840, it was discovered that this method could also be used with leather and thus was adopted by tanners.
=== Fibroplasia and granulation tissue formation === Simultaneously with angiogenesis, fibroblasts begin accumulating in the wound site. Fibroblasts begin entering the wound site two to five days after wounding as the inflammatory phase is ending, and their numbers peak at one to two weeks post-wounding. By the end of the first week, fibroblasts are the main cells in the wound. Fibroplasia ends two to four weeks after wounding. As a model the mechanism of fibroplasia may be conceptualised as an analogous process to angiogenesis (see above) - only the cell type involved is fibroblasts rather than endothelial cells. Initially there is a latent phase where the wound undergoes plasma exudation, inflammatory decontamination and debridement. Oedema increases the wound histologic accessibility for later fibroplastic migration. Second, as inflammation nears completion, macrophage and mast cells release fibroblast growth and chemotactic factors to activate fibroblasts from adjacent tissue. Fibroblasts at this stage loosen themselves from surrounding cells and ECM. Phagocytes further release proteases that break down the ECM of neighbouring tissue, freeing the activated fibroblasts to proliferate and migrate towards the wound. The difference between vascular sprouting and fibroblast proliferation is that the former is enhanced by hypoxia, whilst the latter is inhibited by hypoxia. The deposited fibroblastic connective tissue matures by secreting ECM into the extracellular space, forming granulation tissue (see below). Lastly collagen is deposited into the ECM.
Sausage casing, also known as sausage skin or simply casing, is the material that encloses the filling of a sausage. Natural casings are made from animal intestines or skin; artificial casings, introduced in the early 20th century, are made of collagen and cellulose. The material is then shaped via a continuous extrusion process—producing a single sausage casing of indefinite length—which is then cut into desired lengths, usually while the extrusion process continues.
Due to the very tiny and tight space at the center, only the small hydrogen of the glycine side chain is capable of interacting with the center. This contact is impossible even when a slightly bigger amino acid residue is present other than glycine.
Connective tissue diseases (also termed connective tissue disorders, or collagen vascular diseases), are medical conditions that affect connective tissue. Connective tissues protect, support, and provide structure for the body's other tissues and structures. They hold the body's structures together. Connective tissues consist of two distinct proteins: elastin and collagen. Tendons, ligaments, skin, cartilage, bone, and blood vessels are all made of collagen. Skin and ligaments also contain elastin. These proteins and the surrounding tissues may suffer damage when the connective tissues become inflamed. The two main categories of connective tissue diseases are (1) a set of relatively rare genetic disorders affecting the primary structure of connective tissue, and (2) a variety of acquired diseases where the connective tissues are the site of multiple, more or less distinct immunological and inflammatory reactions. Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities that are autoimmune in nature. Some connective tissue diseases have strong or weak genetic inheritance risks. Others may be due to environmental factors, or a combination of genetic and environmental influences.
Sources: en.wikipedia.org
Markers used to measure bone loss are not easily testable. Degradation of type I collagen releases metabolites that can be used to monitor resorption. Mutations in genes encoding collagen type 1 are known to cause a myriad of different conditions including:
A synthetic element is a known chemical element that does not occur naturally on Earth: it has been created by human manipulation of fundamental particles in a nuclear reactor, a particle accelerator, or the explosion of an atomic bomb; thus, it is called "synthetic", "artificial", or "man-made". The synthetic elements are those with atomic numbers 95–118, as shown in purple on the accompanying periodic table: these 24 elements were first created between 1944 and 2010. The mechanism for the creation of a synthetic element is to force additional protons into the nucleus of an element with an atomic number lower than 95. All known (see: Island of stability) synthetic elements are unstable, but they decay at widely varying rates; the half-lives of their longest-lived isotopes range from microseconds to millions of years. Six more elements that were first created artificially are strictly speaking not synthetic because they were later found in nature in trace quantities: technetium (43Tc), promethium (61Pm), astatine (85At), neptunium (93Np), plutonium (94Pu), and curium (96Cm); although they are sometimes classified as synthetic alongside exclusively artificial elements. The first, technetium, was created in 1937. Plutonium, first synthesized in 1940, is another such element. It is the element with the largest number of protons (atomic number) to occur in nature, but it does so in such tiny quantities that it is far more practical to synthesize it. Plutonium is known mainly for its use in atomic bombs and nuclear reactors.
For example, women's access to methadone, which suppresses cravings for drugs such as heroin, is restricted by state clinics that set appointment times for women to receive their treatment. If they miss their appointment, (which is likely: drug-addicted women may not have access to transportation and lead chaotic lives), they are denied medical care critical to their recovery. Additionally, while women of color are offered jobs as a form of government support, these jobs often do not have childcare, rendering the job impractical for mothers, who cannot leave their children at home alone. However, with respect to mandatory minimum sentencing, female offenders receive relief almost 20% more often than male offenders. In addition, female offenders, on average, receive lighter sentences than those who commit similar offenses.
Hemmer (2026) interprets Pleistocene Feliopsis palaeojavanica from the Trinil site (Indonesia) as a member of a previously unrecognized pantherine lineage that also included Miocene Pachypanthera piriyai, and interprets the studied felids as possible specialized crocodile hunters. 26 purported subfossil tiger specimens from Japan are reinterpreted as cave lions by Sun et al. (2026), indicating that cave lions were the Panthera lineage that colonized Japan during the Pleistocene. Evidence from the study of genomes of cave lions living across a time series spanning over 100,000 years, indicating that cave and modern lions were distinct evolutionary lineages with independent histories, as well as indicative of extensive population connectivity of cave lions and indicative of interbreeding of modern lions (likely from southwestern Asia) with cave lions during the Late Pleistocene, is presented by Stanton et al. (2026). Gedman et al. (2026) perform phylogenetic analyses based on paleogenomes generated from ancient DNA found in two specimens of dire wolves and report that the dire wolf lineage diverged from other canids around 4.5 million years ago, prior to the split between the black-backed jackal and other members of the subtribe Canina. Admixture analyses of the dire wolves' paleogenomes indicate hybridization between the lineage that led to the subtribe Cerdocyonina and the sister lineage to gray wolves, coyotes and dholes.
===== Alternative ===== TH2 cells play an important role in alternative macrophage activation as part of type 2 immune response against large extracellular pathogens like helminths. TH2 cells secrete IL-4 and IL-13, which activate macrophages to become M2 macrophages, also known as alternatively activated macrophages. M2 macrophages express arginase-1, an enzyme that converts arginine to ornithine and urea. Ornithine help increase smooth muscle contraction to expel the worm and also participates in tissue and wound repair. Ornithine can be further metabolized to proline, which is essential for synthesizing collagen. M2 macrophages can also decrease inflammation by producing IL-1 receptor antagonist (IL-1RA) and IL-1 receptors that do not lead to downstream inflammatory signaling (IL-1RII).
Sources: en.wikipedia.org
Rodent studies reported increased endurance and fat oxidation after GW501516 exposure. Long-term studies also found higher rates of some tumors, which led to halted development.
Small short-term human trials examined metabolic markers such as lipids and glucose. The trials did not continue after rodent cancer findings, so long-term human safety is unknown.
Controlled human trials have not established a performance benefit. Anecdotal reports exist, but they are not reliable evidence.
Cardarine is an investigational synthetic compound that acts as a PPARδ agonist. It is also known as GW501516 and has been studied mainly in preclinical research. It is not an approved medicine.