peptidase cleavage comes up often in conversation and rarely with the context attached. Here we lay out the basics in order, then work through the practical considerations.
Last reviewed on 2025-11-30. Where a claim depends on a specific study, the study is described rather than over-claimed.
Development took place during the 1980s at institutes of the Russian Academy of Sciences, where peptide fragments of ACTH were screened for cognitive and neuroprotective effects. The compound received regulatory approval in Russia as a nasal preparation, marketed for conditions such as ischemic stroke, transient ischemic attacks, and optic nerve disorders. Registration in other countries has not followed. Most published clinical reports originate from a small number of Russian research groups, and independent replication outside that setting remains limited. The regulatory status therefore differs sharply between Russia and the rest of the world.
Laboratory work points toward modulation of neurotrophic signaling, particularly expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal tissue. Studies also describe effects on monoamine turnover, inflammatory mediators, and oxidative markers. These observations come mainly from animal models and cultured cells, so the causal chain in humans is not firmly established. Whether the reported molecular changes translate into measurable clinical benefit is an open question. Reviews generally present the mechanism as plausible rather than demonstrated.
Clinical evidence consists largely of small trials with modest sample sizes, often without independent replication. Reported endpoints include cognitive scores, recovery after stroke, and visual function, but study designs vary widely and few trials meet contemporary reporting standards. Systematic reviewers have noted a high risk of bias in several of these reports. No large multicenter trial conducted outside Russia has been published. The compound is therefore best described as investigational in most jurisdictions, with its clinical role still unresolved.
Published studies examine a fairly narrow set of endpoints. Rodent experiments commonly measure maze learning, infarct volume after induced ischemia, and tissue levels of neurotrophic factors. Clinical reports from Russian centres describe attention, memory and recovery scores in patients after stroke or transient ischemic attack. Most of those human studies are small and few have been repeated by independent groups. Outcome measures differ between studies, which limits direct comparison.
Circulation time for the peptide is short because peptidases cleave it readily. The Pro-Gly-Pro tail is thought to slow breakdown compared with the bare ACTH fragment, but the gain appears modest. Absorption after intranasal dosing is limited, and only a fraction of a dose is expected to reach the central nervous system. Laboratory concentrations therefore sit well above levels achieved systemically, a gap that complicates translation from bench findings to clinical claims.
The mechanisms attributed to semax are inferred from animal and cell studies rather than traced to one confirmed target. The most frequently cited pathway involves increased expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal and cortical tissue. Some work points to engagement of melanocortin receptors, particularly MC4, which the parent ACTH fragment can activate. Effects on dopaminergic and serotonergic signalling have also been reported. No single account explains all observed results, and the relative weight of each pathway remains unsettled.
| Property | Value | Notes |
|---|---|---|
| Sequence | Met-Glu-His-Phe-Pro-Gly-Pro | Heptapeptide; ACTH(4-10) analog extended at C-terminus |
| Molecular mass | ~813.9 Da | Free peptide, unmodified |
| Appearance | White to off-white powder | Typical lyophilized solid |
| Solubility | Soluble in water and saline | Also soluble in common aqueous buffers |
| Storage (solid) | -20 °C, desiccated | Protect from moisture and repeated thawing |
Regulatory status varies sharply by country. Semax is registered for medical use in Russia, where it appears in formularies as a nasal solution, and it also holds registration in a small number of neighbouring states. It has no approval from the United States Food and Drug Administration or the European Medicines Agency, and it is not a scheduled controlled substance in most jurisdictions. Elsewhere it circulates mainly as laboratory material, so purity documentation comes from suppliers rather than from a national pharmacopoeia.
Semax is a synthetic peptide created in the Soviet Union during the early 1980s by researchers working in Moscow. It was built from the short adrenocorticotropic hormone fragment known as ACTH(4-10), and the chain was then extended with three additional amino acids. The resulting molecule was named semax and entered clinical use in Russia in 1994. It is generally described as a nootropic and neuroprotective agent rather than as a hormone analogue.
The parent fragment ACTH(4-10) carries the sequence Met-Glu-His-Phe-Arg-Trp-Gly. Semax replaces the arginine and tryptophan positions with a proline-glycine-proline tail, giving Met-Glu-His-Phe-Pro-Gly-Pro. That change removes residues associated with adrenal stimulation, so the peptide does not drive cortisol release the way full ACTH does. This distinction shapes how the compound is grouped in the literature, where it sits with neuropeptides and peptide neuromodulators rather than with corticosteroids.
Solid semax is typically supplied as a lyophilised powder that is hygroscopic and sensitive to moisture, light, and repeated temperature cycling. Long-term storage of the dry peptide is generally recommended at approximately -20 degrees Celsius, while shorter working periods may use refrigeration at 2 to 8 degrees Celsius. Vials should remain tightly closed and desiccated when brought to room temperature, because condensation can damage the material before it is weighed. Dividing a batch into aliquots is preferable to thawing one container repeatedly.
Dissolution is normally performed in water, phosphate-buffered saline, or normal saline, since the peptide is freely soluble in aqueous media and is rarely handled with strong organic solvents. Solution pH should be kept near neutral, because extreme acidity or alkalinity accelerates backbone hydrolysis and encourages oxidation of the methionine side chain. Once dissolved, the material is less stable than the dry powder and is commonly divided into single-use portions and frozen. Buffers containing primary amines, such as Tris, are often avoided because of possible side reactions.
Many of the city's leading merchants were involved in smuggling at this time, illicitly exporting goods like foodstuffs and leather, while under-declaring imports of wine. In 1574 Elizabeth I visited the city during her Royal Progress through the western counties. The city burgesses spent over one thousand pounds on preparations and entertainments, most of which was raised by special rate assessments. In 1577 the explorer Martin Frobisher arrived in the city with two ships and samples of ore, which proved to be worthless. He also brought, according to Latimer "three savages, doubtless Esqiumaux, clothed in deerskins, but all of them died within a month of their arrival." Bristol sent three ships to the Royal Navy fleet against the Spanish Armada in 1588, and also supplied two levies of men to the defending land forces. Despite appeals to the Privy Council no reimbursement was made for these supplies. The corporation also had to repair the walls and gates of the city. The castle had fallen into disuse in the late Tudor era, but the City authorities had no control over royal property and the precincts became a refuge for lawbreakers. Anne of Denmark came to Bristol in June 1613 and was welcomed by the mayor Abel Kitchin. The visit featured a pageant on the river, with an English ship attacked by Turkish galleys, which the queen watched from the Canon's Marsh meadow near the cathedral. An English victory was signalled by the release of six bladders of pig's blood poured out of the ship's scupper holes.
doi:10.1086/590941. PMID 18665816. Wikidata Q45138244. Rajan P Adhikari; Cook, Gregory Murray; Lamont, Iain; Selwyn Lang; Heffernan, Helen Mary; John M B Smith (2002). "Phenotypic and molecular characterization of community occurring, Western Samoan phage pattern methicillin-resistant Staphylococcus aureus". Journal of Antimicrobial Chemotherapy. 50 (6): 825–831. doi:10.1093/jac/dkf242. PMID 12461000. Wikidata Q40686052.
Structure/function analysis established that a fusion protein containing Cut domains 1 and 2 linked to a nuclear localization signal (C1C2-NLS) is rapidly recruited to DNA damage and is sufficient to accelerate the repair oxidative DNA damage and mono-alkylated bases in genomic DNA. Since the C1C2-NLS protein is devoid of transcription activation potential, these results suggest that Cut domains are directly involved in DNA repair.
Malnutrition-related diabetes mellitus (MRDM), also known as Type 5 diabetes and formerly as Type J diabetes, is a type of diabetes mellitus characterized by reduced insulin production (similar to Type 1 diabetes). However, in MRDM, the insulin deficiency is primarily linked to childhood malnutrition rather than autoimmune damage to the pancreatic beta cells. Unlike Type 1 diabetes, patients with Type 5 diabetes do not develop ketonuria or ketosis.
Sources: en.wikipedia.org
Galen believed that the arterial blood was created by venous blood passing from the left ventricle to the right by passing through 'pores' in the interventricular septum, air passed from the lungs via the pulmonary artery to the left side of the heart. As the arterial blood was created 'sooty' vapors were created and passed to the lungs also via the pulmonary artery to be exhaled. In addition, Ibn al-Nafis had an insight into what would become a larger theory of the capillary circulation. He stated that "there must be small communications or pores (manafidh in Arabic) between the pulmonary artery and vein," a prediction that preceded the discovery of the capillary system by more than 400 years. Ibn al-Nafis' theory, however, was confined to blood transit in the lungs and did not extend to the entire body. Finally, William Harvey, a pupil of Hieronymus Fabricius (who had earlier described the valves of the veins without recognizing their function), performed a sequence of experiments, and published Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus in 1628, which "demonstrated that there had to be a direct connection between the venous and arterial systems throughout the body, and not just the lungs. Most importantly, he argued that the beat of the heart produced a continuous circulation of blood through minute connections at the extremities of the body.
=== Planting === The sacred lotus requires a nutrient-rich and loam soil. In the beginning of the summer period (from March until May in the northern hemisphere), a small part of rhizome with at least one eye is either planted in ponds or directly into a flooded field. It can also be propagated via seeds or buds. Furthermore, tissue culture is a promising propagation method for the future to produce high volumes of uniform, true-to-type, disease-free materials. The first step of cultivation is to plough the dry field. One round of manure is applied after ten days, before flooding the field. To support a quick initial growth, the water level is relatively low and increases when plants grow. Then a maximum of approximately 4,000 per hectare (1,600/acre) with grid spacing of 1.2 by 2 metres (3 ft 11 in × 6 ft 7 in) are used to plant directly into the mud 10–15 cm (3+7⁄8–5+7⁄8 in) below the soil surface.
=== Skeleton === Because feathers are often associated with birds, feathered dinosaurs are often touted as the missing link between birds and dinosaurs. However, the multiple skeletal features also shared by the two groups represent another important line of evidence for paleontologists. Areas of the skeleton with important similarities include the neck, pubis, wrist (semi-lunate carpal), arm and pectoral girdle, furcula (wishbone), and breast bone. Comparison of bird and dinosaur skeletons through cladistic analysis strengthens the case for the link.
As a standard method for analysis, mass spectrometers have reached other planets and moons. Two were taken to Mars by the Viking program. In early 2005 the Cassini–Huygens mission delivered a specialized GC-MS instrument aboard the Huygens probe through the atmosphere of Titan, the largest moon of the planet Saturn. This instrument analyzed atmospheric samples along its descent trajectory and was able to vaporize and analyze samples of Titan's frozen, hydrocarbon covered surface once the probe had landed. These measurements compare the abundance of isotope(s) of each particle comparatively to earth's natural abundance. Also on board the Cassini–Huygens spacecraft was an ion and neutral mass spectrometer which had been taking measurements of Titan's atmospheric composition as well as the composition of Enceladus' plumes. A Thermal and Evolved Gas Analyzer mass spectrometer was carried by the Mars Phoenix Lander launched in 2007. Mass spectrometers are also widely used in space missions to measure the composition of plasmas. For example, the Cassini spacecraft carried the Cassini Plasma Spectrometer (CAPS), which measured the mass of ions in Saturn's magnetosphere.
Historically Druzes, by large, sent their children to Protestant schools and accepted an implicit orientation toward Britain. Many of the first graduates of the Syrian Protestant College in Beirut, the forerunner of AUB, were Druze, who over generations maintain an affinity to AUB. At the Catholic schools and universities (such as Notre Dame University–Louaize) in Lebanon, Christian and Druze students study and socialise together. Moreover, many members of the Druze political and cultural elite received their education in Christian institutions. Notable Druze figures who studied at these institutions include Abbas Halabi, Asad Al Faqih, Majid Arslan, Marwan Hamadeh, Manal Abdel Samad, and Kamal Jumblatt, who attended the prestigious Collège Saint Joseph – Antoura. Marriage outside the Druze faith is rare and is strongly discouraged, and Druze can face serious social consequences if he or she converts to another faith to marry a non-Druze. According to Simon Haddad of Notre Dame University–Louaize "if a Druze marries a Christian or Muslim, they could both be ostracized and marginalized by their community, and this could have very serious consequences if the couple works in town". While according to United Nations High Commissioner for Refugees report: "Conversely, a source contacted by the Research Directorate of Canada's Immigration and Refugee Board in September 1998 advised that "there would be no problem for a mixed Druze/Orthodox Christian couple to live a normal life in Lebanon today"".
Sources: en.wikipedia.org
Many herbs are applied topically to the skin in a variety of forms. Essential oil extracts can be applied to the skin, usually diluted in a carrier oil. Many essential oils can burn the skin or are simply too high dose used straight; diluting them in olive oil or another food grade oil such as almond oil can allow these to be used safely as a topical. Salves, oils, balms, creams, and lotions are other forms of topical delivery mechanisms. Most topical applications are oil extractions of herbs. Taking a food-grade oil and soaking herbs in it for anywhere from weeks to months allows certain phytochemicals to be extracted into the oil. This oil can then be made into salves, creams, lotions, or simply used as an oil for topical application. Many massage oils, antibacterial salves, and wound healing compounds are made this way. Inhalation, as in aromatherapy, can be used as a treatment.
His first feud as champion was against Vince McMahon's wrestler On Raw the following night, McMahon presented him with a new championship belt and warned Austin that he did not approve of his rebellious nature, desiring a "corporate champion"; Austin responded with Dude Love, defeating him at Unforgiven: In Your House, and Over the Edge: In Your House. Austin lost the WWF Championship to Kane in a First Blood match. Austin regained the title the next night on Raw. After defeating The Undertaker at SummerSlam, the title was vacated after a controversial finish during a Triple Threat match at Breakdown: In Your House between The Undertaker, Kane and Austin. At Rock Bottom: In Your House, Austin defeated The Undertaker in a Buried Alive match after Kane performed a Tombstone Piledriver on The Undertaker which sent him into the grave. With this victory, Austin qualified for the 1999 Royal Rumble. Austin's next appearance after this would be the January 4, 1999, edition of Raw, where he would come out to help Mankind defeat The Rock to become the WWF Champion by striking The Rock in the face with a steel chair and draping Mankind's body over him.
=== Observations of thin graphite layers and related structures === Transmission electron microscopy (TEM) images of thin graphite samples consisting of a few graphene layers were published by G. Ruess and F. Vogt in 1948. Eventually, single layers were also observed directly. Single layers of graphite were also observed by transmission electron microscopy within bulk materials, particularly inside soot obtained by chemical exfoliation. From 1961 to 1962, Hanns-Peter Boehm published a study of extremely thin flakes of graphite. The study measured flakes as small as ~0.4 nm, which is around 3 atomic layers of amorphous carbon. This was the best possible resolution for TEMs in the 1960s. However, it is impossible to distinguish between suspended monolayer and multilayer graphene by their TEM contrasts, and the only known method is to analyze the relative intensities of various diffraction spots. The first reliable TEM observations of monolayers are likely given in references 24 and 26 of Geim and Novoselov's 2007 review. In 1975, van Bommel et al. epitaxially grew a single layer of graphite on top of silicon carbide. Others grew single layers of carbon atoms on other materials. This "epitaxial graphene" consists of a single-atom-thick hexagonal lattice of sp2-bonded carbon atoms, as in free-standing graphene.
==== MMP ==== Another major contributor to angiogenesis is matrix metalloproteinase (MMP). MMPs help degrade the proteins that keep the vessel walls solid. This proteolysis allows the endothelial cells to escape into the interstitial matrix as seen in sprouting angiogenesis. Inhibition of MMPs prevents the formation of new capillaries. These enzymes are highly regulated during the vessel formation process because destruction of the extracellular matrix would decrease the integrity of the microvasculature.
Sources: en.wikipedia.org
Semax is a synthetic seven-amino-acid peptide derived from a fragment of corticotropin. It is used in Russia as a nasal preparation, while elsewhere it is studied as a research compound. It is not approved as a medicine in most countries.
Its sequence corresponds to the 4-10 region of corticotropin extended by three residues. This fragment lacks the region responsible for adrenal steroid release, so it is explored for neural rather than hormonal effects. The relationship explains the compound's classification among ACTH-derived peptides.
It holds approval in Russia for several neurological indications as a nasal spray or drop formulation. Regulatory agencies in the United States and the European Union have not approved it. Products sold elsewhere are generally labeled for research use only.
It consists mainly of animal experiments and small clinical reports, with much of the clinical material published in Russian-language journals. Large independent trials are scarce. Separating reliable effects from chance findings is consequently difficult.