27 research outputs found
Novel RGD/polyamines – Synthesis and Study of Antitumor Activity // Нови RGD/полиамини – синтез и проучване на противотуморна активност
No full textЗлокачествените новообразувания са на едно от първите места по честота на заболяванията, водещи до смърт и са основен проблем на общественото здравеопазване. В България наред с хипертонията и сърдечно-съдовите заболявания, онкологичните се определят като едни от най-рисковите.
Един от основните проблеми при лечението на туморни заболявания е, че лекарствата не са селективни по отношение на раковите и на нормалните клетки.
С цел оптимизиране на терапията се използва нов подход за лекарствен дизайн - комбиниране на два или повече фармакологични ефекта в един лиганд. Новополучената молекула запазва ефикасността на терапията на отделните вещества (синергичен ефект, по-ниски дози и малък брой странични ефекти).
Представеното научно изследване в настоящата дисертация е в основата си с фундаментален характер. Научната му значимост се състои в обогатяване на съществуващите знания в областта на целенасочения синтез на биологично активни пептиди и проучване на тяхната активност.
В резултат на проведения синтез са получени 13 пептидни аналога на RGD, изследвано е цитотоксичното и антипролиферативното действие на подбрани молекули, извършен е сравнителен анализ на ефектите им върху ракови и неракови клетки
Получените резултати могат да послужат за последващи надграждащи проучвания с цел разработване на подходяща лекарствена форма за перорален прием.Malignant neoplasms are one of the leading causes of death and significant public health problems. Along with hypertension and cardiovascular disease, cancer is defined as one of the riskiest in Bulgaria.
One of the main problems in treating tumours is that drugs are not selective for cancer and normal cells.
In order to optimize the therapy, a new approach to drug design is used - combining two or more pharmacological effects in one ligand. The newly obtained molecule retains the efficacy of the therapy of the individual substances (synergistic effect, lower doses, and a small number of side effects).
The research presented in this dissertation is fundamentally fundamental. Its scientific significance lies in the enrichment of existing knowledge in the field of targeted synthesis of biologically active peptides and the study of their activity.
As a result of the synthesis, 13 peptide analogues of RGD were obtained, the cytotoxic and antiproliferative action of selected molecules was studied, and a comparative analysis of their effects on cancer and non-cancer cells was performed.
The results may be used for subsequent follow-up studies to develop an appropriate oral dosage form
Machine Learning-Based Prediction of Rule Violations for Drug-Likeness Assessment in Peptide Molecules Using Random Forest Models
No full textPeptide therapeutics often fall outside classical small-molecule heuristics, such as Lipinski’s Rule of Five (Ro5), motivating the development of adapted filters and data-driven approaches to early drug-likeness assessment. We curated >300 k drug (small and peptide) and non-drug molecules from PubChem, extracted key molecular descriptors with RDKit, and generated three rule-violation counters for Ro5, the peptide-oriented beyond-Ro5 (bRo5) extension, and Muegge’s criteria. Random Forest (RF) classifier and regressor models (with 10, 20, and 30 trees) were trained and evaluated. Predictions for 26 peptide test molecules were compared with those from SwissADME, Molinspiration, and manual calculations. Model metrics were uniformly high (Ro5 accuracy/precision/recall = 1.0; Muegge ≈ 0.99), indicating effective learning. Ro5 violation counts matched reference values for 23/26 peptides; the remaining cases differed by +1 violation, reflecting larger structures and platform limits. bRo5 predictions showed near-complete agreement with manual values; minor discrepancies occurred in isolated peptides. Muegge’s predictions were internally consistent but tended to underestimate SwissADME by ~1 violation in several molecules. Four peptides (ML13–16) satisfied bRo5 boundaries; three also fully met Ro5. RF models thus provide fast and reliable in silico filters for peptide drug-likeness and can support the prioritisation of orally developable candidates
Microphones as Airspeed Sensors for Micro Air Vehicles
No full textThis project proposes and evaluates a novel concept for an airspeed instrument aimed at small hybrid unmanned aerial vehicles. The working principle is to relate the power spectra of the wall-pressure fluctuations beneath the turbulent boundary layer formed over the vehicle’s body to its airspeed. The instrument consists of two microphones, flush mounted on the UAV’s nose cone, that capture the pseudo-sound caused by the coherent turbulent structures, and a micro-controller that processes the signals from the microphones and computes the airspeed. Dedicated models were constructed, using data obtained from wind tunnel and flight experiments, that take the power spectra of the microphones’ signals as an input and provide the airspeed as an output. The model structure is a feed-forward neural network with a single hidden layer, trained using a second-order gradient descent algorithm, following a supervised learning approach. The models were validated using only flight data, with the best one achieving a mean approximation error of 0.043 m/s and having a standard deviation of 1.039 m/s. It was also shown that the airspeed could be successfully predicted for a wide range of angles of attack, given that they are known, thus necessitating the vehicle to be equipped with a dedicated angle of attack sensor.Aerospace Engineerin
Socialisme, Communisme, Totalitarisme : quelle différence pour une recherche historique du point de vue moral ?
No full textThe essay focuses on recent developments in the field of history of socialist/ communist regime in Bulgaria. The author considers this form of disciplinary knowledge as a set of discourses and draws his research material from a number of interviews with researchers (mostly historians, but also anthropologists and sociologists) in the field. The attempt is made to elucidate the “moral base” and potential political implications of the existing demarcation and differentiation between different approaches to this still burning subject. The accent is put on the individual (and collective) choice of labeling the epoch – socialism, communism, or totalitarianism. Those three labels are used in order to construct three ideal types of historical-sociological research and to indicate the methodological specificities of every type of research as well as itsparticular objects of study. Finally a point is made on the danger which a close relationship between a study and politics represents to the relative research autonomy
Pharmacological application of Portulaca Oleracea
Get PDFТученицата е космополитен вид и родът Portulaca принадлежи към семейство Portulacaceae, малко семейство с 21 рода и 580 вида, и е разпространено космополитно, среща се основно в Америка и някои видове са открити в Арабия. Ботаническото наименование на тученицата е Portulaca oleracea.Тя е разпространена широко в тропичните и субтропичните региони на света, използва се за храна, като саксийна билка и се добавя към супи и салати в средиземноморските и тропичните азиатски държави.Тя е в списъка на Световната здравна организация като едно от най-използваните медицински растения и е даден терминът „глобална панацея`. Китайският фолклор я описва като „зеленчук за дълъг живот` и се използва от хиляди години в традиционната китайска медицина. Тученицата има висок потенциал да бъде използвана като храна за хора и животни и като фармакологичен агент в медицината.Тученицата също осигурява източник на хранителни ползи, дължащи се на нейните омега-3 мастни киселини и антиоксидантни свойства. Тученицата е един от най-богатите зелени растителни източници на омега-3 мастни киселини. Тя намалява нивата на холестерол и триглицериди, повишава полезните високоплътностни липопротеини.Много от съставните на тученицата са били изолирани, включително флавоноиди, алкалоиди, мастни киселини, терпеноиди, полизахариди, витамини, стероли, протеини и минерали. Тученицата е била използвана в народната медицина в много страни като антипиретик, антисептик, противоглистно и т.н. Тя проявява широк обхват от фармакологични ефекти, включително антибактериално, антиулцерогенно, противовъзпалително, антиоксидантно и ранозаздравяващо свойство.Тученицата намалява телесното тегло, серумните свободни мастни киселини и хиперинсулинемията. Полизахариди от тученица проявяват някои биологични активности като противоракова, антиоксидантна, противовъзпалителна и имуноповишаваща.Purslane is a cosmopolitan species and Portulaca family belongs to the family Portulacaceae, a small family with 21 genera and 580 species, which is widespread, occurring mainly in America and some species found in Arabia. The botanical name of purslane is Portulaca oleracea.It is widely distributed in tropical and subtropical regions of the world, used as food, as a pot herb and added to soups and salads in the Mediterranean and tropical Asian countries.It is featured in the list of the World Health Organization as one of the most used medicinal plants and given the term `global panacea.` Chinese folklore describes it as `a vegetable of longevity` and it has been used for thousands of years in traditional Chinese medicine.Purslane has a high potential to be used as food for humans and animals and can be used as a pharmacological agent in medicine.Purslane also provides a source of nutritional benefits due to its omega-3 fatty acid, and antioxidant properties. Purslane is one of the richest sources of green vegetable omega-3 fatty acid. It reduces cholesterol and triglycerides, increases beneficial high-density lipoprotein.Many of the components of purslane have been isolated, including flavonoids, alkaloids, fatty acids, terpenoids, polysaccharides, vitamins, sterols, proteins and minerals.Purslane has been used in folk medicine in many countries as an antipyretic, antiseptic, anthelmintic, etc. It exhibits a wide range of pharmacological effects, including antibacterial, antiulcerogenic, anti-inflammatory, antioxidant and wound-healing properties. Purslane reduces body weight, serum free fatty acids and hyperinsulinemia. It also increases insulin sensitivity and relieves glucose tolerance disorders.The polysaccharides of purslane exhibit some biological activities, such as anticancer, antioxidant, anti-inflammatory and immunostimulating properties
Composition and administration of emu oil
Get PDFМаслото от ему се добива от щраусоподобни нелетящи птици, характерни за територията на Австралия. Извлича се от голямо струпване на мазнини, намиращо се на гърба на птицата.Съставът на маслото от ему дава обяснение на изключителните му свойства. Състои се главно от ненаситени мастни киселини - олеинова, линоленова и алфа-линоленова. Съдържа и наситени мастни киселини - палмитинова, стеаринова, миристинова, арахидонова, гадоелинова. Богато е и на витамини А, Е и F.Доказано е, че маслото от ему е мощен трансдермален агент, който може да проникне дълбоко в кожата и ефектът му не е само върху повърхностните слоеве. Маслото е ефективно за широко приложение. То има противовъзпалително, антибактериално и антиалергично действие, повишава клетъчното възпроизвеждане, прониква бързо и дълбоко в кожата и не запушва порите.Може да се прилага за:• успокояване и намаляване на възпалението, свързано с акне, дерматит, екзема, псориазис;• намаляване на възпалението и подуването на мускули и стави при артрит;• заличаване на белези от скорошни рани и превенция срещу стрии; • изгаряния;• овлажняване на суха и напукана кожа, редуцира бръчки и петна;• активира космените фоликули на скалпа и стимулира растежа на нова коса;• за масаж при хронични травми.Доказано е отсъствието на странични ефекти при прилагането на масло от ему.Поради трансдермалните му способности то може да увеличи ползите от други продукти, използвани едновременно. Съчетава се добре с гел от алое, масло от нар, масло от семена на шипка, масло от карите, рициново масло, водорасли и морски колаген, кокосово масло, витамини А, Е, D, глюкозамин. То е добър емулгатор и се смесва успешно с други масла и вода, без да оставя мазен филм върху кожата или скалпа.Emu oil is obtained from birds belonging to the ostrich family during processing. They typically live in Australia. The oil is extracted from the oil mass located on the back of the bird.Emu oil has extraordinary properties. It consists mainly of polyunsaturated fatty acids , oleic acid and omega 9, and saturated fatty acids - palmitic acid, stearic acid, miristic acid, arachidonic acid, gadoleic acid. It is also rich in vitamins A, E and F.It has been proven that emu oil is a powerful deep tissue agent and its positive qualities go far beyond benefiting surface layers of the skin. The oil has a broad spectrum of uses because of its anti- inflammatory, anti-bacterial and anti-allergic properties. Emu oil regenerates cellular activity and does not block pores.It can be used for:• Reducing inflammation connected to acne, dermatitis, eczema and psoriasis;• Reducing inflammation and swelling of muscles and joints , relieving arthritis pain;• Healing of scars and burns;• Protecting against stretch marks;• Moisturizing dry and cracked skin;• Reducing the appearance of stretch marks;• Activating hair follicles on scalp to stimulate hair growth;• Massage in chronic muscle pain and long-term injuries.Emu oil combines well with other products due to its deep tissue penetration qualities. It works in balance with aloe, pomegranate oil, rose hip oil, shea butter, castor oil, seaweed and marine collagen, coconut oil, vitamins A, E, D and glucosamine. It blends successfully with other oils and water without leaving greasy residue on skin and scalp
Prevention and treatment of degenerative changes of the locomotor system with natural products
No full textDegenerative diseases are progressive destructive processes that leave lasting damage in the body. These are the most common articular damages.Degenerative bone diseases are caused by wear and tear of the joints in everyday life. They also cause friction, which is highly painful. Knee and hip joints are affected. NSAIDs are among the most commonly used drugs in medical practice, the main indications for their application are: inflammatory joint disease, degenerative diseases and the like. Side effects of NSAIDs - those of the digestive tract (GIT), dyspepsia (nausea, vomiting), development of gastritis, ulcers or similar complications (bleeding, perforation, malignant degeneration).Given the accumulating evidence of adverse effects associated with chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are the gold standard for the treatment of chronic inflammatory joint disease, it is necessary to develop safer therapeutic strategies for these patients.Medicines of natural origin are the first choice for prevention. They slow down the progressive nature of the disease, favorably affect the activity of the musculoskeletal system, and contribute to the strengthening and development of cartilage
Microphones as Airspeed Sensors for Unmanned Aerial Vehicles
No full textThis paper puts forward a novel design for an airspeed instrument aimed at small fixed-wing tail-sitter unmanned aerial vehicles. The working principle is to relate the power spectra of the wall-pressure fluctuations beneath the turbulent boundary layer present over the vehicle’s body in flight to its airspeed. The instrument consists of two microphones; one flush-mounted on the vehicle’s nose cone, which captures the pseudo-sound caused by the turbulent boundary layer, and a micro-controller that processes the signals and computes the airspeed. A feed-forward single-layer neural network is used to predict the airspeed based on the power spectra of the microphones’ signals. The neural network is trained using data obtained from wind tunnel and flight experiments. Several neural networks were trained and validated using only flight data, with the best one achieving a mean approximation error of 0.043 m/s and having a standard deviation of 1.039 m/s. The angle of attack has a significant impact on the measurement, but if the angle of attack is known, the airspeed could still be successfully predicted for a wide range of angles of attack.<br/
Review on the pharmacological activities of lactoferricin and lactoferricin analogues
Get PDFINTRODUCTION: Antimicrobial peptides (AMPs) are a growing class of natural and synthetic compounds with a wide spectrum of targets including viruses, bacteria, fungi, and parasites.AIM: The aim of the present review was to make an overview of the available literature on the pharmacological activities of these peptides, focusing on lactoferricin and lactoferricin analogues.MATERIALS AND METHODS: To achieve this aim, information from databases, such as PubMed, Google Scholar and ResearchGate was searched and summarized.RESULTS: Antimicrobial peptides (AMPs) are considered a promising alternative to the antibiotics used nowadays. They have drawn a special attention in the fight against infections caused by antibiotic-resistant bacterial strains. Lactoferricin is the most studied AMP derived from milk protein. Lactoferricin (Lfcin) is a fragment of the ferro-chelate complex of the bovine protein lactoferrin (Lf). The amphipathic and cationic properties of Lfcin account for its broad spectrum antimicrobial activity. Lfcin also manifests potential antiviral, immunomodulatory, antitumor and anti-inflammatory properties. Shorter analogues of Lfcins have been synthesized with a broad spectrum of activities and enhanced pharmacokinetic properties.CONCLUSION: Lactoferricin and its analogues are a good demonstration that it is possible to design and obtain synthetic peptides with enhanced pharmacological activities
Use of medicinal plants in cardiovascular diseases
Get PDFСърдечно-съдовите заболявания са група болести, засягащи сърцето и кръвоносните съдове (артерии и вени). Причините за сърдечно-съдовите заболявания са различни, но най-честите са атеросклерозата и артериалната хипертония. Те са най-значимата причина за смъртността в световен мащаб. Над 17,6 милиона души в света умират всяка година в резултат на сърдечно-съдови заболявания.Проблемът е особено актуален за нашата страна, като данните сочат, че в България на всеки 3 човека 2 умират от сърдечно-съдови заболявания. Разходите за здравеопазването в България за 2013 са 3,3 млрд. лв. Около 18% от бюджета на НЗОК отива за лечение на сърдечно-съдови заболявания.Днес антихипертензивното лечение най-общо може да се раздели на лечение с класически медикаменти и лекарства от нови генерации. Трябва да бъдем наясно, че невинаги монотерапията ще постигне желания ефект, средният брой лекарства, необходими за достигане и трайно поддържане на желаните нива на артериалното налягане, е около и над 3. Следователно много често се използва комбинираната терапия за избор на медикаменти с изявена органна протекция, при която да се достигнат прицелните нива на артериалното налягане. Оптималният контрол на налягането спомага за намаляване на сърдечно-съдовата болест и смъртност.Поддържането на здравословно и балансирано хранене, както и здравословен начин на живот може да помогне да се избегне рискът от високо кръвно налягане.Главното действие на билките, които прила гаме при сърдечно-съдовите заболявания, е да подобрят кръвоснабдяването на сърдечния мускул и крайниците, както и да заздравят стените на кръвоносните съдове.На билколечение и профилактика подлежат неусложнените случаи с коронарна недостатъчност и с ритъмни и проводни нарушения. За целта се използват дроги, чиито съставки разширяват коронарните съдове и имат диуретично действие. Такъв ефект имат цвета от глог - Fl.Crataegi ; стръкове от горицвет - Hb.Adonidis vernalis; чесънът - Allium sativum; момина сълза - Convallaria majalis f.Liliaceae.Cardiovascular diseases are a group of conditions affecting the heart and the blood vessels (arteries and veins). The reasons for the cardiovascular diseases are different, but the most frequent ones are atherosclerosis and arterial hypertonia. They are the most significant reasons for mortality on an international scale. Over 17.6 million of people in the world die each year as a result of cardiovascular diseases. The problem is especially pressing in our country, where the data shows that in Bulgaria of every 3 persons, 2 die from cardiovascular illnesses. The health care costs in Bulgaria for 2013 are 3.3 billion BGN. Around 18% of the budget of the National Fund for Health Insurance go for treatment of cardiovascular diseases.Today the treatment for hypertension in general can be divided into treatment with classical medications and such with new generation medications. We must be aware that monotherapy will not always achieve the desired effect. The average number of medications, required for achieving and sustaining longterm levels of arterial pressure is around and above 3. Therefore, combined therapy is used very often for choosing medications with obvious organ protection, which reach the target levels of arterial pressure. The optimal control of pressure helps decrease the amount cardiovascular diseases and their mortality. Maintaining a healthy and balanced diet, as well as healthy lifestyle can help avoid the risk of high blood pressure.The main effect of herbs, which we use in cardiovascular diseases, is improving the blood supply to the hearth muscle and limbs, as well as strengthening of the blodd vessel walls.Subject to herb treatment and prevention are non-complicated cases of coronary insufficiency and rhythm and conduction disorders. For that purpose we use drugs, whose ingredients widen the coronary vessels and act as diuretics. Such effect have the flower of hawthorn - Fl.Crataegi; sprigs of pheasant‘s eye - Hb.Adonidisvernalis; garlic - Alliumsativum; lily-ofthe- valley - Convallariamajalis f.Liliaceae
