Everything below concerns Neurotrophic factor. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-11-10. Where a claim depends on a specific study, the study is described rather than over-claimed.
Clinical evidence comes mainly from small studies conducted in Russia, several of which were open-label or lacked robust blinding. Reported outcomes include lower anxiety scores, changes in attention measures, and effects on asthenic states following illness. Sample sizes are typically in the tens of participants, and independent replication outside the region is scarce. Reviews published in English generally note the limited methodological quality of the underlying trials. Whether the compound produces clinically meaningful effects under rigorous conditions remains unresolved.
Proposed mechanisms center on modulation of the GABA system, but no single molecular target has been confirmed. Rodent studies report changes in GABA-A receptor expression and in the turnover of serotonin, dopamine, and norepinephrine in several brain regions. Increases in brain-derived neurotrophic factor and its receptor have also been described after repeated administration. These findings come largely from animal models, and the degree to which they describe human neurochemistry remains an open question. The mechanism is best characterized as multi-system and not fully resolved.
Regulatory status differs sharply by region. Selank holds a Russian marketing authorization, where it is supplied mainly as nasal drops, while authorities elsewhere have not approved it for medical use. Material sold internationally is therefore usually labeled as a research chemical rather than a medicine. Peer-reviewed publications come predominantly from Russian laboratories, and sample sizes are generally small. Whether the compound produces comparable effects under independent, well-controlled replication remains an open question that the broader literature has not settled.
Selank is a synthetic heptapeptide developed in Russia as a structural analogue of tuftsin, a naturally occurring immunomodulatory tetrapeptide. Its sequence, Thr-Lys-Pro-Arg-Pro-Gly-Pro, keeps the tuftsin core at the N-terminus and appends a Pro-Gly-Pro tail. Researchers at the Institute of Molecular Genetics in Moscow synthesized the compound during the 1990s while searching for peptides with combined anxiolytic and immunomodulatory activity. The added tail was intended to resist enzymatic cleavage and prolong the molecule's presence in circulation.
The compound has a calculated molecular weight near 751.9 daltons and carries a net positive charge at physiological pH because of its arginine residue. It dissolves freely in water and in common aqueous buffers, and typically appears as a white or off-white lyophilized powder. The amide backbone makes the molecule susceptible to peptidases, which limits oral use and favors intranasal or parenteral routes. Nomenclature in the literature varies: the substance is also described by the sequence abbreviation TP-7 and by a Russian trade designation.
| Property | Value | Notes |
|---|---|---|
| Route studied | Intranasal | Predominant route in published reports |
| Circulation stability | Short, minutes scale | Peptidases cleave it; the tail slows the process |
| Analytical method | RP-HPLC with mass spectrometry | Used for identity and purity assessment |
| Reported outcome domains | Anxiety and cognitive measures | Derived from small, mostly regional trials |
| Regulatory status | Marketed in Russia | Availability outside that market is limited |
Most published work on selank originates from a small number of research groups in the Russian Federation. A large share of that record appears in Russian-language journals, which limits access for readers who rely on English-indexed databases. Independent replication by laboratories outside the original research network is sparse in publicly available sources. This concentration of origin and language is a frequently noted feature when the compound is summarized in broader reviews of synthetic peptides.
Reported pharmacological effects center on reduced anxiety-like behavior in animal models and on measures of memory and learning. Proposed contributing mechanisms include modulation of GABAergic signaling, shifts in monoamine turnover, and changes in the activity of enzymes that degrade neuropeptides. Effects on the expression of genes linked to neuroplasticity have also been described. No single molecular target is widely accepted, and whether the behavioral findings arise from one pathway or several remains an open question.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed as a stabilized analogue of tuftsin, a naturally occurring tetrapeptide fragment derived from the immunoglobulin heavy chain. The additional Pro-Gly-Pro segment at the carboxyl terminus is intended to slow enzymatic cleavage. The compound is usually described in the literature as a synthetic peptide with anxiolytic and cognitive-related activity, a label that reflects a research context rather than an approved therapeutic category.
Published clinical evidence is limited. Most controlled trials were conducted in Russia, enrolled modest numbers of participants, and appeared in Russian-language journals, which restricts independent verification. Reported outcomes include lower anxiety scores, improved attention and memory measures, and changes in fatigue ratings. Reviews written in English note methodological limitations such as small samples and inconsistent endpoints. Whether the compound produces clinically meaningful benefit relative to established anxiolytics is therefore an open question rather than an established finding.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It was designed at the Institute of Molecular Genetics of the Russian Academy of Sciences as a structural analogue of tuftsin, a naturally occurring tetrapeptide fragment of the immunoglobulin heavy chain. The added Pro-Gly-Pro tail was intended to slow enzymatic degradation and extend biological activity. In Russia it is registered as an anxiolytic nasal preparation, while regulators elsewhere have not approved it for clinical use.
Outside its country of origin the compound is generally handled as a research chemical rather than an approved medicine. No regulatory approval from the United States Food and Drug Administration or the European Medicines Agency has been granted for human use. Identity and purity are normally checked by reverse-phase high-performance liquid chromatography, with mass spectrometry used to confirm the molecular mass. Lyophilised material is stored cold and desiccated, and repeated freeze-thaw cycles are avoided.
Published work on this peptide almost always uses intranasal delivery, with drops or a spray applied to the nasal mucosa. Some animal experiments have used subcutaneous or intraperitoneal injection, and a smaller number have compared routes directly. Oral administration is not a focus of the literature, because short peptides of this size are broken down by digestive enzymes and cross intestinal barriers poorly. How much of an intranasal dose reaches the bloodstream intact in humans remains an open question.
=== Disease-modifying agents === Disease-modifying antirheumatic drugs (DMARDs) are the primary treatment for RA. They are a diverse collection of drugs, grouped by use and convention. They have been found to improve symptoms, decrease joint damage, and improve overall functional abilities. DMARDs should be started early in the disease as they result in disease remission in approximately half of people and improved outcomes overall. The following drugs are considered DMARDs: methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, TNF inhibitors (certolizumab, adalimumab, infliximab and etanercept), abatacept, anakinra, and auranofin. Additionally, rituximab and tocilizumab are monoclonal antibodies and are also DMARDs. Use of tocilizumab is associated with a risk of increased cholesterol levels. The most commonly used agent is methotrexate, with other frequently used agents including sulfasalazine and leflunomide. Leflunomide is effective when used for 6–12 months, with similar effectiveness to methotrexate when used for 2 years. Sulfasalazine also appears to be most effective in the short-term treatment of rheumatoid arthritis. Hydroxychloroquine, in addition to its low toxicity profile, is considered effective for the treatment of moderate RA symptoms. Pharmacokinetic characteristics of Hydroxychloroquine are complex due to the large volume of distribution, significant tissue binding, and long terminal elimination half-life.
=== Chronic toxicity === Ingestion of melamine may lead to reproductive damage, or bladder or kidney stones, which can lead to bladder cancer. A study in 1953 reported that dogs fed 3% melamine for a year had the following changes in their urine: (1) reduced specific gravity, (2) increased output, (3) melamine crystalluria, and (4) protein and occult blood. A survey commissioned by the American Association of Veterinary Laboratory Diagnosticians suggested that crystals formed in the kidneys when melamine combined with cyanuric acid, "don't dissolve easily. They go away slowly, if at all, so there is the potential for chronic toxicity."
=== Consumption === Saffron's aroma is often described by connoisseurs as reminiscent of metallic honey with grassy or hay-like notes, while its taste has also been noted as hay-like and sweet. Consumed in large servings—more than a few threads per person per dish—saffron is experienced as bitter. Saffron also contributes a luminous yellow-orange colouring to foods. Saffron is widely used in Persian, Indian, European, and Arab cuisines. Confectioneries and liquors also often include saffron. Saffron is used in dishes ranging from the jewelled rice and khoresh of Iran, the Milanese risotto of Italy, the paella of Spain, the bouillabaisse of France, to the biryani with various meat accompaniments in South Asia. Saffron is also used in the preparation of the Golden Ham, a precious dry-cured ham made with saffron from San Gimignano in Tuscany. Common saffron substitutes include safflower (Carthamus tinctorius, which is often sold as "Portuguese saffron" or "açafrão"), annatto, and turmeric (Curcuma longa). In Medieval Europe, turmeric was also known as "Indian saffron" because of its yellow-orange colour.
As for the two cold wars thesis, the chief problem is that the two periods are incommensurable. To be sure, they were joined together by enduring ideological hostility, but in the post-World War I years Bolshevism was not a geopolitical menace. After World War II, in contrast, the Soviet Union was a superpower that combined ideological antagonism with the kind of geopolitical threat posed by Germany and Japan in the Second World War. Even with more amicable relations in the 1920s, it is conceivable that post-1945 relations would have turned out much the same. The usage of the term "Cold War" to describe the postwar tensions between the US- and Soviet-led blocs was popularized by Bernard Baruch, a US financier and an adviser to Harry Truman, who used the term during a speech before the South Carolina state legislature on April 16, 1947. Since the term "Cold War" was popularized in 1947, there has been extensive disagreement in many political and scholarly discourses on what exactly were the sources of postwar tensions. In the American historiography, there has been disagreement as to who was responsible for the quick unraveling of the wartime alliance between 1945 and 1947, and on whether the conflict between the two superpowers was inevitable or could have been avoided. Discussion of these questions has centered in large part on the works of William Appleman Williams, Walter LaFeber, Gabriel Kolko and John Lewis Gaddis.
The starch source in a beer provides the fermentable material and is a key determinant of the strength and flavour of the beer. The most common starch source used in beer is malted grain. Grain is malted by soaking it in water, allowing it to begin germination, and then drying the partially germinated grain in a kiln. Malting grain produces enzymes that will allow conversion from starches in the grain into fermentable sugars during the mash process. Different roasting times and temperatures are used to produce different colours of malt from the same grain. Darker malts will produce darker beers. Nearly all beer includes barley malt as the majority of the starch. Barley malt, in addition to being a starch source, is used because its fibrous husk aids filtration during brewing, and because it is a rich source of amylase enzymes that facilitate the conversion of starch into sugars. Other malted and unmalted grains (including wheat, rice, oats, and rye, and, less frequently, maize (corn) and sorghum) may be used. Sorghum may be used as a starch source in gluten-free beer.
Sources: en.wikipedia.org
== Corporate governance and identity == Howard Schultz was the CEO of Starbucks from 1986 to 2000. He was succeeded by Orin Smith, who ran the company for five years and positioned Starbucks as a large player in fair trade coffee (fair trade later being overturned during Kevin Johnson's leadership in 2022), increasing sales to US$5 billion. Jim Donald was CEO from 2005 to 2008, orchestrating a large-scale earnings expansion. Schultz returned as CEO during the 2008 financial crisis and spent the succeeding decade growing the company's market share, expanding its offerings, and reorienting the brand around corporate social responsibility. Kevin Johnson, who was president and chief operating officer from 2015 to 2018, succeeded Schultz as CEO in 2017. Myron E. Ullman became chairman of the firm in June 2018. Both Johnson and Ullman succeeded Howard Schultz, who served in both capacities from 2008 to 2017. Since 2018, Schultz has served as the firm's first Chairman emeritus. In March 2022, Starbucks announced that Schultz would return as CEO in April 2022 in an interim role. Later that September, Laxman Narasimhan was appointed to succeed him in April 2023, with Schultz remaining a member of the board of directors. Narasimhan assumed the position sooner than planned, in March 2023. In August 2024, he was ousted and replaced with Brian Niccol, who became the chain's CEO on September 9 after leaving his position as Chipotle's CEO. Niccol received a starting salary of $1.6 million a year and a $10 million starting bonus.
== Gene == GRP is located on chromosome 18q21. PreproGRP (the unprocessed form of GRP) is encoded in three exons separated by two introns. Alternative splicing results in multiple transcript variants encoding different isoforms.
Brimonidine is an α2 agonist medication used to treat open-angle glaucoma, ocular hypertension, and rosacea. In rosacea it improves the redness. It is used as eye drops or applied to the skin. It is also available in the fixed-dose combination medication brimonidine/timolol along with timolol maleate. Common side effects when used in the eyes include itchiness, redness, and a dry mouth. Common side effects when used on the skin include redness, burning, and headaches. More significant side effects may include allergic reactions and low blood pressure. Use in pregnancy appears to be safe. When applied to the eye it works by decreasing the amount of aqueous humor made while increasing the amount that drains from the eye. When applied to the skin it works by causing blood vessels to contract. Brimonidine was patented in 1972 and came into medical use in 1996. It is available as a generic medication. In 2023, it was the 213th most commonly prescribed medication in the United States, with more than 2 million prescriptions.
== Early life == Kevin Darnell Hart was born in Philadelphia on July 6, 1979, to Nancy Hart (died 2007) and Henry Robert Witherspoon (died 2022). He has an older brother named Robert. He was raised in a single-parent household by his mother, who worked as a systems analyst for the Office of Student Registration and Financial Services at the University of Pennsylvania. His father was a cocaine addict who was in and out of jail throughout most of Hart's childhood, prompting Hart to use humor as a way to cope with his troubled family life. His relationship with his father improved after his father recovered from his addiction. He would also later talk about his mother in his stand-up routine, portraying her as a loving yet intimidating woman. As a teenager, Hart had aspirations of becoming a basketball player. He was a participant at the La Salle basketball camp with future National Basketball Association hall of famer Kobe Bryant and future political commentator and activist Marc Lamont Hill. After graduating from George Washington High School, Hart briefly attended the Community College of Philadelphia before dropping out and moving to New York City. He spent some time working as a shoe salesman.
Sources: en.wikipedia.org
=== Other === Other physical integration methods (spray or spin coating, blending, and vacuum filtration) have been developed for paper electronics, but have yet to be implemented in paper-based microfluidic devices.
== Further reading == Bowen, W. Richard; Mohammad, A. Wahab (Aug 1998). "Diafiltration by nanofiltration: Prediction and optimization". AIChE Journal. 44 (8): 1799–1812. Bibcode:1998AIChE..44.1799R. doi:10.1002/aic.690440811. Limayem, Imène; Charcosset, Catherine; Fessi, Hatem (2004). "Purification of nanoparticle suspensions by a concentration/diafiltration process". Separation and Purification Technology. 38 (1): 1–9. doi:10.1016/j.seppur.2003.10.002. Sheth, Jignesh P.; et al. (2003). "Nanofiltration-based diafiltration process for solvent exchange in pharmaceutical manufacturing". Journal of Membrane Science. 211 (2): 251–261. doi:10.1016/s0376-7388(02)00423-4.
Typically, a wide-local excision is performed, in which the tumor is excised including a safety-margin of healthy tissue to ensure its entire removal, which is confirmed by a pathologist. In more advanced disease, a (partial) vulvectomy may need to be performed in order to remove some or all of the vulva. Advanced-stage melanomas can be treated with checkpoint inhibitors.
Nearly 20,000 suspected armed OLF members, some of which were believed to be unarmed civilians (including children) were forcibly held in military camps in three different regions for the purpose of disarming and "re-educat[ing]" them, although very few had been released by the end of 1992. Throughout this time, the country's judiciary had failed to adequately adjudicate cases or to hold the TGE and its forces accountable for rights abuses. This was largely due to disruptions such as the looming threat of a possible suspension of all judges who were associated with the former Workers' Party of Ethiopia, the abrupt resignation of the Minister of Justice, a lack of an operating police force. These types of abuses persisted throughout the remainder of the transitional period. Freedom of the press was limited; in the first half of 1994, at least twenty journalists were fined or jailed as a result of publishing content that challenged the government, a situation exacerbated by the fact that the contemporary press laws were vague and improperly implemented. Human rights organizations including the Ethiopian Human Rights Council were denied formal registration from the government but continued to process complaints and report abuses; the government accused EHRCO of being a politically-motivated group with a hidden agenda that favored opposition groups and reported false information. Individuals suspected to have been previously associated with the OLF were treated particularly harshly once they were detained in secret detention centers across the country.
===== Animals raised in captivity ===== Since TCM recognizes bear bile as a treatment compound, more than 12,000 asiatic black bears are held in bear farms. The bile is extracted through a permanent hole in the abdomen leading to the gall bladder, which can cause severe pain. This can lead to bears trying to kill themselves. As of 2012, approximately 10,000 bears are farmed in China for their bile. This practice has spurred public outcry across the country. The bile is collected from live bears via a surgical procedure. As of March 2020 bear bile as ingredient of Tan Re Qing injection remains on the list of remedies recommended for treatment of "severe cases" of COVID-19 by National Health Commission of China and the National Administration of Traditional Chinese Medicine. The tortoise (freshwater turtle, guiban) and turtle (Chinese softshell turtle, biejia) species used in traditional Chinese medicine are raised on farms, However, issues concerning the overexploitation of wild Asian turtles in China have not been completely solved.
Sources: en.wikipedia.org
Reports describe effects on GABA-A receptor expression, monoamine turnover, and neurotrophic factor levels. These are proposed mechanisms drawn mainly from animal models. No single molecular target has been established.
Intranasal delivery is the route described in most published work. It is used because the peptide is degraded quickly once it reaches circulation. Direct evidence of brain penetration in humans is lacking.
Most trials are small, regionally concentrated, and often lack rigorous blinding or placebo control. Independent replication is limited. Reviews in English generally rate the evidence as preliminary.
Selank is a synthetic seven-amino-acid peptide modeled on tuftsin, a fragment of the immunoglobulin G heavy chain. It was designed in Russia to combine anxiolytic and immunomodulatory properties in one molecule.