Review of the Anticancer and Cytotoxic Activity of some Species from Genus Euphorbia

Euphorbiaceae is a widely spread family. To genus Euphorbia, from that family, belongs more than 2000 species. The plants of this genus have been used for a long time in traditional medicine. Their main active components: alkanes, triterpenes, phytosterols, tannins, polyphenols and flavanoids are supposed to be responsible for different types of activity. Euphorbia formosana Hayata is a medicinal plant used to treat rheumatism, liver cirrhosis, herpes zoster and it is used as tumor suppressor. Euphorbia tirucalli L. have been used to obtain methanolic extracts. Their cytotoxic activity have been examined against many different types of cancer cells, such as colon cancer cell line, liver cancer cell line, ovarian cancer cell line and prostate cancer cell line. Leukemic cell lines, THP-1 and HL-60, were inhibited after 24 h of treatment with 400 μg/mL E. formosana. In vitro anticancer activity assays of E. formosana suggest potent anticancer effects that cause both cell cycle arrest and apoptosis of leukemic cancer cells. The ethanolic extract of Euphorbia helioscopia L. inhibited the growth of only three cancer cell lines, Hep-2 (27%), T-47D (7%) and PC-5 (11%). Cell viability assays were conducted on the pancreatic cancer primary tumor cell line to assess the relative toxicity of the E. tirucalli extracts. The toxicity of both aqueous and methanolic extracts was found to be dose dependent, with cell viability decreasing with increasing extract concentration. Both extracts demonstrated similar activity at 50 μg/mL with a viability of 50%, while only the methanol extract exerted a significant decrease in cell viability at concentration of 25 μg/mL. The pronounced cytotoxic activity of these few species from the genus Euphorbia, suggests that it could be very interesting to investigate more deeply about their potent anticancer ability. So, the aim of this study was to make a review of the anticancer activity of some of the Euphorbia species that were examined experimentally, using different in vitro or in vivo assays

The role and importance of the decarboxylation process in the production of quality full-spectrum cannabis extract for medicinal purposes

Cannabis is now one of the most thoroughly studied and analyzed plant materials. More than 100 cannabinoids have been isolated and identified in cannabis along with the primary psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC). In addition to Δ9-THC, there are other components of cannabis that are medically beneficial. For example, cannabidiol (CBD) and cannabigerol (CBG) can moderate or influence the psychoactive effects of Δ9-THC. The raw cannabis plant consists of cannabinoids in their acidic form. When someone states that cannabinoids are in their “acidic form”, they are referring to the chemical structure of the compound itself. A cannabinoid in its acidic form has a carboxyl group (-COOH) attached. While tetrahydrocannabinolic acid (THCA) is the non-psychoactive precursor to THC, it does not bind to the CB1 and CB2 receptors. Instead, it binds with other cannabinoids receptors in the endocannabinoid system. When THC is not decarboxylated, it is THCA. Although THCA possesses therapeutic effects, like anti-inflammatory and neuroprotective qualities, it is not in its most beneficial or psychoactive form. Decarboxylation is a chemical reaction that removes a carboxyl group (-COOH) and releases carbon dioxide (CO2). The two main catalysts for decarboxylation to occur are heat and time. High CBD strains tend to decarboxylate a bit slower than those with high THC content. Decarboxylate high CBD strains by baking them for 15-20 minutes at 149°C and decarboxylate high THC strains by baking them for 10-18 minutes at the same temperature (149°C) in the oven. Full decarboxylation may require more time to occur. It is important to keep tight temperature control applying cannabis to various technological applications. While heat is needed to decarboxylate the acids into the active form of cannabinoids our bodies can use, extreme temperatures can destroy many of the important plant materials that contribute to positive health outcomes, like terpenes

Development of a technological method for microbiological decontamination of dry cannabis flowers

In the countries with a National medicinal cannabis program, pharmaceutical regulations specify that herbal cannabis products must adhere to strict safety standards regarding microbial contamination. Treatment using non-hazardous radio frequency (RF) is non-ionizing, meaning it won’t change the molecular structure of the cannabis flower (1). Our goal was to develop a technological method for the decontamination of a dry cannabis flower, with the aim of reducing the count of some microorganisms in the flower itself, thus ensuring the health safety of the herbal product. For this purpose, we used a dry flowers of the THC-variety Jack Кush, with its treatment in an APEX7 irradiation machine, on different programs. Before the treatments, dried flowers had the following microbiological analysis: Total aerobic microbial count (TAMC)=4.6*103CFU/g; Total yeast and mold count (TYMC)=2.3*104CFU/g; Bile-tolerant gram-negative bacteria (BTG-)10CFU/g; Escherichia coli (EC) and Salmonella (SA) are absent. Following the recommendation of the APEX7 manufacturer, we have developed three ways to irradiate the dried flower, namely: 1st program (90°C/1 min); 2nd program (95°C/1 min) and 3rd program (98°C/1 min). After treatment with 1st program the following results were obtained: TAMC=6*103CFU/g; TYMC<10CFU/g; BTG-<10CFU/g; EC and SA are absent. After treatment with 2nd and 3rd program, the same results were obtained: TAMC=4*103CFU/g; TYMC<10CFU/g; BTG-<10CFU/g; EC and SA are absent. Microbiological analyzes were performed in accordance with the Ph.Eur. monograph 04/2019:50108. We can conclude that the method used is effective in drastically reducing the count of pathogenic microorganisms and thus producing a safe final product

Ground Truth Spanish Automatic Extractive Text Summarization Bounds

The textual information has accelerated growth in the most spoken languages by native Internet users, such as Chinese, Spanish, English, Arabic, Hindi, Portuguese, Bengali, Russian, among others. It is necessary to innovate the methods of Automatic Text Summarization (ATS) that can extract essential information without reading the entire text. The most competent methods are Extractive ATS (EATS) that extract essential parts of the document (sentences, phrases, or paragraphs) to compose a summary. During the last 60 years of research of EATS, the creation of standard corpus with human-generated summaries and evaluation methods which are highly correlated with human judgments help to increase the number of new state-of-the-art methods. However, these methods are mainly supported for the English language, leaving aside other equally important languages such as Spanish, which is the second most spoken language by natives and the third most used on the Internet. A standard corpus for Spanish EATS (SAETS) is created to evaluate the state-of-the-art methods and systems for the Spanish language. The main contribution consists of a proposal for configuration and evaluation of 5 state-ofthe-art methods, five systems and four heuristics using three evaluation methods (ROUGE, ROUGE-C, and Jensen-Shannon divergence). It is the first time that Jensen-Shannon divergence is used to evaluate AETS. In this paper the ground truth bounds for the Spanish language are presented, which are the heuristics baseline:first, baseline:random, topline and concordance. In addition, the ranking of 30 evaluation tests of the state-of-the-art methods and systems is calculated that forms a benchmark for SAETS

Ефикасност при употребата на хербални препарати во третман на воспаленија на оралната лигавица

Оралните воспаленија (ОВ) можат да бидат предизвикани од најразлични општи или локални етиолошки фактори. Стоматитите, како чести и болни инфламаторни заболувања на оралната лигавица, се карактеризираат со: везикули, афти, ерозии и улцерации. Хербалните препарати (ХП), кои се користат за елиминирање на причината, имаат значајна улога во третманот на ОВ. Овие препарати поседуваат антиинфламаторни, антибактериски, антифунгални и аналгетски ефекти. Цел: Да се евалуираат клинички истражувања кои ја потврдуваат ефикасноста на ХП кај ОВ. Материјали и методи: Беше извршена евалуација на неколку хумани клинички студии, публикувани во последните пет години, во базата на податоци PubMed®. Резултати: Орални мукоадхезивни гелови и водички за испирање на уста, на база на: Aloe vera, Propolis, Matricaria chamomilla, Commiphora myrrha, Zataria multiflora, Curcuma longa се користат при третман кај ОВ. Во една студија, кај 65% од пациентите третирани со Propolis-водичка за испирање на уста, била целосно подобрена клиничката слика кај ОВ, во седумдневен третман. Друга студија покажала дека кај 76,6% од пациентите третирани со Aloe vera гел дошло до целосно исчезнување на улцерациите на мукозната лигавица, а кај 76,7% од пациентите третирани со гел од Commiphora myrrha, целосно исчезнала болката, после шестиот ден од третманот. Куркумата, користена како течност за испирање на уста, во едно истражување кај 80% од пациентите имало комплетно повлекување на промените после две-неделен третман. Употребата на водичка за испирање на уста со екстракт од Zataria multiflora (ZME), двојно ја намалила инциденцата на оралниот мукозитис, во однос на плацебо–групата. Интензитетот на болката и појавата на орален мукозитис биле 3,152 пати поретки кај групата која користела ZME. Заклучок: Хербалните препарати брзо и ефикасно можат да доведат до елиминација на симптомите и ублажување на болката. Затоа, нивната употреба кај вакви заболувања рапидно расте. Клучни зборови: мукозитис, стоматитис, третман, хербална медицина

Cyclic voltammetry as a sensitive approach in investigation of doxorubicin

Introduction and objective Doxorubicin is an anthracycline drug. Its chemotherapeutic effect is due to two possible mechanisms, 1)disruption of topoisomerase-II-mediated DNA repair due to its intercalation into DNA helix and 2)generation of free radicals and their damage to cellular membranes, DNA, and proteins. This can be a result of its planar aromatic chromophore which intercalates between two base pairs of DNA [1]. Therefore, its pharmacological/toxicological characteristics are largely dependent on its oxidative properties, and the aim of this study is to summarize the methods and data based on its еlectrochemical behavior of doxorubicin, obtained by the means of cyclic voltammetry (CV) [2]. Methods Cyclic voltammetry is a versatile electrochemical method where the redox reactions occurring at the working electrode result in a flow of current. The potentiostat measures this current and plots it as a function of the applied potential. Each successful forwards and backwards potential sweep produces a a cyclic voltammogram characterized by anodic and cathodic peak currents, peak potentials, and the oxidation and reduction onset potentials. Results Our research revealed several studies that feature the electrochemical behavior of doxorubicin. CV in pH~7.4 has shown that doxorubicin undergoes a reversible two-electron reduction with value E1/2 = -665 mV(versus Ag/AgCl, saturated KCl). This process was defined as quasi reversible, at low scan rates. Further, the interaction of doxorubicin hydrochloride with calf thymus DNA was studied by measuring cathodic peak current, which gradually decreased as more DNA was added into the cell [3]. The interaction of doxorubicin with calf thymus DNA, was mostly assessed by electrochemical sensors using surface modified working electrodes [4,5,6]. Electrochemical sensor based on multi-walled carbon nanotubes modified platinum electrode (Pt/MWCNTs) [4], electrodeposition of silver nanoparticles and electro-polymerization of alginate layers on the surface of a glassy carbon electrode have been also used in this purpose [5]. CV of doxorubicine on a screen-printed electrodes modified with single-wall carbon nanotubes (SPE/CNT) have shown linear dependence of the intensity of electro reduction/oxidation on the square root of the scan rate which proved that the process is a controlled by diffusion. Moreover, thay imployed differential pulse voltammetry to validate a sensitive method for doxorubicine quantification. The drug binding processes were examined by DPV via the registration of a decrease in peak current intensity of guanine, adenine, and thymine of DNA in the presence of doxorubicin [6]. Conclusion Cyclic voltammetry can be used as an efffective tool for quantification of doxorubicine and its interactions with DNA or other metals. Reverible oxidation of doxorubicin to semiquinone and back, releases reactive oxygen species that cause DNA damage and lipid peroxidation. The effectivness of the therapeutic effect of doxorubicine depends on its interaction with DNA. These interactions were mostly assessed by using an electrochemical surface modified sensor, in the presence of DNA. These data lead to a conclusion that electrochemical platforms represent a sensitive approach for the investigation of DNA–drug interaction in electrode systems. Examining the electrochemical signals doxorubicin or DNA–doxorubicin complex before and after binding establishes the interaction and helps in mechanism elucidation

Cannabidiol based borderline products – from development to registration processes

Cannabidiol (CBD) is the second most abundant phytocannabinoid structure in Cannabis sativa L., Cannabaceae family. It contains a bicyclic 21-carbon skeleton with a double bond in the terpene ring (Jacobs et al., 2016). Cannabidiol based products have been used mainly for additional treatment of pain, depression and anxiety in cancer suffering patients as well as immunostimulatory agents. They are used for treatment of nausea and vomiting, especially during chemotherapy or radiation therapy. Their effects are exerted through the endocannabinoid system through multiple receptors, including cannabinoid receptors (CBRs), opioid and serotonin receptors, adrenergic receptors, and G protein�coupled receptors (Pertwee & Cascio, 2014). At high doses can modulate the intoxicating effects of THC through CB1- dependent mechanisms despite having low CB1 binding affinity (Jacobs et al., 2016). In Republic of North Macedonia, the production, use and sale of registered cannabis products are regulated by the Law of Use of Narcotic Drugs and Psychotropic Substances (Official Gazette of R.M no. 37/2016). A borderline product is a product that contains: (1)probiotics; (2)active components of plant origin and it is classified as a food supplement in at least one member state of the European Union, and according to the special regulations applied in the Republic of Macedonia, it cannot be classified as a food supplement; (3)vitamins and minerals in quantities greater than the permitted prescribed in accordance with the special regulations applied in the Republic of Macedonia, if it is classified as a food supplement in at least one member state of the European Union and there is no registered product with the same strength in the Republic of Macedonia (Official Gazette of R.M no. 203/2015). According to the second term of this law CBD products are still registered as borderline products in our country

Технолошки пристап во производството на стандардизиран екстракт од канабис базиран на канабинол (CBN) за медицински цели

Канабинолот (CBN) се добива со деградација на тетрахидроканабинол (ТНС), кога производот од канабис е изложен на топлина или подлежи на стареење. CBN е благ психоактивен канабиноид кој делува како слаб парцијален агонист со афинитет кон CB1 рецепторите. Докажани се неговите седативни, антиинфламаторни и невропротективни својства. За да се произведе стандардизиран екстракт базиран на CBN, потребно е да се изврши присилна деградација или забрзано стареење на ТНС, со цел распаѓање до неговиот метаболит CBN. За таа цел беше применет процес на деградација на ТНС по забрзано стареење на етанолен екстракт со 32,8% (w/w) THC и 7,4% (w/w) CBN и последователно негова молекуларна дестилација, со цел концентрирање на CBN. Притоа, искористивме етанолен екстракт од Glueberry OG кој беше подлегнат на студија за забрзано стареење од една година. Опремата и методите опфаќаат процеси на деградација на висока температура и молекуларна дестилација. Примероците беа испитувани со помош на HPLC метод со UVдетектор. По студијата за забрзано стареење, екстрактот содржи 9,7% (w/w) ТНС и 36,2% (w/w) CBN. По деградација на екстрактот, не е детектиран ТНС, а CBN се зголемил до 43,1% (w/w). Финалниот производ по молекуларна дестилација содржи 55,8% (w/w) CBN. Резултатите укажуваат дека овој метод е погоден за добивање на екстракти со задоволителен принос на CBN. Примената на покачена температура врз екстрактот може лесно да го оксидира THC во CBN. Оваа технологија може да вклучи и употреба на гасови, кислород или азот, вклучувајќи опрема за барботирање со гасови

Безбедност на пациентите во клиничка пракса - програма за контролиран пристап до лекот леналидомид

Леналидомид е лек кој поседува антинеопластично, антиангиогено, проеритропоетско и имуномодулаторно дејство, но притоа поседува и изразено тератогено дејство. Клиничкиот фармацевт при ЈЗУ Универзитетска клиника за хематологија - Скопје е одговорен за спроведување на процесот на фармаковигиланца. Затоа, со цел подобрување на безбедноста на пациентите, на клиниката се спроведе контролирана дистрибуција на лекот таблети леналидомид од 5 mg. Kако мерка за минимализација на ризикот (ММР) за пациентите кои го примаат овој лек се спроведе програмата за контролиран пристап (CAP), според која пропишувањето на лекот го вршат исклучиво лекари кои се евидентирани во Регистарот на едуцирани лекари за спроведување на програмата за превенција на бременост (PPP). Со тоа се водеше грижа пациентот да го прими лекот само доколку се исполнети барањата од PPP. Бидејќи лекот се излачува и во спермата, во програмата покрај жени мораше да бидат вклучени и пациенти од машка популација. За лекот таблети леналидомид 5 mg, PPP е спроведена кај 36 пациенти (23 мажи и 13 жени), во тек на 18 месеци, започнувајќи од октомври 2021 година. Вo овој период лекот е издаден на 14 пациенти со мултипен миелом кои претходно примиле барем една линија на терапија (во комбинација со дексаметазон), 22 пациенти со терапија на одржување на новодијагностициран мултипен миелом кај кои е спроведена трансплантација на автологни матични клетки и 1 пациент со дијагноза Не-Хочкинов фоликуларен лимфом. Со едуцирање на пациентите и преземање на сите пропишани мерки од PPP, потенцијалниот ризик од тератогеното дејство на лекот беше сведен на минимум

Clinically significant drug interactions of Eltrombopag: a retrospective study from the clinical pharmacist perspective

Introduction: Thrombopoietin is the main cytokine regulating megakaryopoiesis and platelet production. Eltrombopag interacts with the transmembrane domain of thrombopoietin receptors and initiates signaling cascades inducing proliferation and differentiation from bone marrow progenitor cells. The aim of the study was to determine drug interaction at patients that are receiving Eltrombopag along with other medications. Materials and methods: A retrospective, longitudinal study was conducted at the Hematology Clinic in Skopje, N. Macedonia. A clinical pharmacist, focusing on Eltrombopag and concomitant medications interactions, reviewed a total number of 16 patient’s histories for the period of 6 months (January-June 2023). Anamnestic data on additional drugs, herbal supplements, vitamins, minerals were also taken. Potential drug interactions were identified using Stockley's interactions checker, categorized by severity and subclassified into co-administered drugs altering pharmacokinetics. Results: A total number of 73 interactions were identified, of which 23 (31.51%) were with moderate clinical relevance, 14 (19.18%) were with no clinical importance and required counseling about possible adverse effects and additional monitoring. The rest of 36 (49,32%) interactions were without clinical significance. Additionally, we determine that 7 (9.59%) of total interactions directly related to patients receiving Eltrombopag (ciclosporin, atorvastatin, rosuvastatin, dexamethasone, prednisolone, valsartan, and magnesium) and categorized as moderate and needs close monitoring. Conclusion: This study demonstrates toxicity potential of Eltrombopag at patients associated with concomitant medicines. Close collaboration of physicians and clinical pharmacists is necessary in all cases where patients are receiving Eltrombopag along with other medications in order all significant interactions to be identified, prevented and managed