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Silibinin (SIL), the most active phytocompound from Silybum marianum (L.), exerts many biological effects but has low stability and bioavailability. To overcome these drawbacks, the current research proposed the synthesis of silibilin oleate (SIL-O) and silibilin linoleate (SIL-L) derivatives as prodrugs with potentially optimized properties for biomedical applications, and the establishment of their in vitro-in ovo safety profiles. The physicochemical characterization of the obtained compounds using density functional theory (DFT) calculations, and Raman and 1H liquid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the formation of SIL-O and SIL-L complexes. Computational predictions revealed that these lipophilic derivatives present a lower drug-likeness score (-29.96 for SIL-O and -23.55 for SIL-L) compared to SIL, but an overall positive drug score (0.07) and no risk for severe adverse effects. SIL-O and SIL-L showed no cytotoxicity or impairment in cell migration at low concentrations, but at the highest concentration (100 µM), they displayed distinct toxicological profiles. SIL-L was more cytotoxic (on cardiomyoblasts - H9c2(2-1), hepatocytes - HepaRG, and keratinocytes - HaCaT) than SIL-O or SIL, significantly inhibiting cell viability (< 60%), altering cellular morphology, reducing cell confluence (< 70%), and inducing prominent apoptotic-like nuclear features. At the concentration of 100 µM, SIL-O presented an irritation score (IS) of 0.61, indicating a lack of irritant effect on the chorioallantoic membrane (CAM), while SIL-L was classified as a slight irritant with an IS of 1.99. These findings outline a more favorable in vitro and in ovo biocompatibility for SIL-O compared to SIL-L, whose applications are dosage-limited due to potential toxicity.

Over the past several decades, dental health products containing fluoride have been widely employed to mitigate tooth decay and promote oral hygiene. However, concerns regarding the potential toxicological repercussions of fluoride exposure have incited continuous scientific inquiry. The current study investigated the cytotoxicity of sodium fluoride (NaF) and xylitol (Xyl), both individually and in combination, utilizing human keratinocyte (HaCaT) and osteosarcoma (SAOS-2) cell lines. In HaCaT cells, NaF decreased proliferation in a concentration-dependent manner and induced apoptosis-related morphological changes at low concentrations, whereas Xyl exhibited dose-dependent cytotoxic effects. The combination of NaF and Xyl reduced cell viability, particularly at higher concentrations, accompanied by apoptosis-like morphological alterations. Sub-cytotoxic NaF concentrations (0.2%) significantly affected caspase activity and the expression of pro-apoptotic genes. Conversely, Xyl demonstrated no discernible effect on these biological parameters. In SAOS-2 cells, NaF increased proliferation at high concentrations, contrasting with Xyl's concentration-dependent cytotoxic effects. The combination of NaF and Xyl had a minimal impact on cell viability. Sub-cytotoxic NaF concentrations did not influence caspase activity or gene expression, while Xyl induced dose-dependent morphological alterations, increased caspase activity, and upregulated pro-apoptotic gene expression. In ovo experiments on the chorioallantoic membrane (CAM) revealed that only NaF induced irritant effects, suggesting potential vascular adverse outcomes. This study advocates for the combined use of NaF and Xyl, highlighting their cytotoxicity benefits in healthy cells while maintaining safety considerations for tumor cells.

Although remarkable progress has been made, colorectal cancer remains a significant global health issue. One of the most challenging aspects of cancer treatment is the resistance of tumor cells to classical chemotherapy. Conventional therapy for colorectal cancer often involves the use of 5-fluorouracil as a chemotherapeutic agent. Aspirin, a drug used primarily to prevent cardiovascular complications, became a focus of attention due to its potential use as an antitumor agent. The purpose of the study was to evaluate the potential synergistic cytotoxic effects of aspirin and 5-fluorouracil on colorectal adenocarcinoma cells. The viability of cells, the impact on the morphology and nuclei of cells, the potential antimigratory effect, and the impact on the expression of the major genes associated with cell apoptosis (Bcl-2, Bax, Bad), as well as caspases 3 and 8, were evaluated. The results indicated that the two compounds exerted a synergistic effect, causing a reduction in cell viability accompanied by changes characteristic of the apoptosis process—the condensation of nuclei and the reorganization of actin filaments in cells, the reduction in the expression of the Bcl-2 gene, and the increase in the expression of Bax and Bad genes, along with caspases 3 and 8. Considering all these findings, it appears that aspirin may be investigated in depth in order to be used in conjunction with 5-fluorouracil to increase antitumor activity.

Colorectal cancer (CRC) is a heterogenous pathology with high incidence and mortality rates globally, but it is also preventable so finding the most promising candidates (natural compounds or repurposed drugs) to be chemopreventive alternatives has become a topic of interest in recent years. The present work aims to elucidate the potential effects of a combination between genistein (GEN), an isoflavone of natural origin, and aspirin (ASA) in CRC prevention/treatment by performing an in vitro evaluation in human colorectal cancer cells (HCT-116) and an in ovo analysis using the chick embryo chorioallantoic membrane (CAM) model. Cell viability was verified by an MTT (migratory potential by scratch) assay, and the expressions of MMP-2 and MMP-9 were analyzed using RT-qPCR. Our results indicated a dose-dependent cytotoxic effect of ASA (2.5 mM) + GEN (10–75 µM) combination characterized by reduced cell viability and morphological changes (actin skeleton reorganization and nuclei deterioration), an inhibition of HCT-116 cells’ migratory potential by down-regulating MMP-2 and MMP-9 mRNA expressions, and an antiangiogenic effect by modifying the vascular network. These promising results raise the possibility of future in-depth investigations regarding the chemopreventive/therapeutical potential of ASA+GEN combination.

Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.

Cancer is a significant health problem worldwide; consequently, new therapeutic alternatives are being investigated, including those found in the vegetable kingdom. Eugenol (Eug) has attracted attention for its therapeutic properties, especially in stomatology. The purpose of this study was to investigate the cytotoxicity of Eug, in vitro, on osteosarcoma (SAOS-2) and oropharyngeal squamous cancer (Detroit-562) cells, as well as its potential irritant effect in ovo at the level of the chorioallantoic membrane (CAM). The data obtained following a 72 h Eug treatment highlighted the reduction in cell viability up to 41% in SAOS-2 cells and up to 37% in Detroit-562 cells, respectively. The apoptotic-like effect of Eug was indicated by the changes in cell morphology and nuclear aspect; the increase in caspase-3/7, -8 and -9 activity; the elevated expression of Bax and Bad genes; and the increase in luminescence signal (indicating phosphatidylserine externalization) that preceded the increase in fluorescence signal (indicating the compromise of membrane integrity). Regarding the vascular effects, slight signs of coagulation and vascular lysis were observed, with an irritation score of 1.69 for Eug 1 mM. Based on these results, the efficiency of Eug in cancer treatment is yet to be clarified.

Melanoma, the tumor arising from the malignant transformation of pigment-producing cells—the melanocytes—represents one of the most severe cancer types. Despite their rarity compared to cutaneous melanoma, the extracutaneous subtypes such as uveal melanoma (UM), acral lentiginous melanoma (ALM), and mucosal melanoma (MM) stand out due to their increased aggressiveness and mortality rate, demanding continuous research to elucidate their specific pathological features and develop efficient therapies. Driven by the emerging progresses made in the preclinical modeling of melanoma, the current paper covers the most relevant in vitro, in vivo, and in ovo systems, providing a deeper understanding of these rare melanoma subtypes. However, the preclinical models for UM, ALM, and MM that were developed so far remain scarce, and none of them is able to completely simulate the complexity that is characteristic to these melanomas; thus, a continuous expansion of the existing library of experimental models is pivotal for driving advancements in this research field. An overview of the applicability of precision medicine in the management of rare melanoma subtypes is also provided.

Antibiotics are considered the cornerstone of modern medicine; however, currently, antibiotic resistance has become a global health issue. Antibiotics also find new uses in the treatment of other pathologies as well as cancer. The present study aimed to verify the impact of tetracycline and ampicillin in a colorectal adenocarcinoma cell line, HT-29. The effects of the two antibiotics on cell viability and nucleus were evaluated by the means of MTT assay and the Hoechst staining method, respectively. The irritant potential at vascular level of the chorioallantoic membrane was tested by the HET-CAM assay. Treatment of HT-29 cells with the two antibiotics determined different effects: (i) tetracycline induced a dose- and time-dependent cytotoxic effect characterized by decreased cell viability, changes in cells morphology, apoptotic features (nuclear fragmentation), and inhibition of cellular migration, whereas (ii) ampicillin exerted a biphasic response—cytotoxic at low doses and proliferative at high concentrations. In terms of effect on blood vessels, both antibiotics exerted a mild irritant effect. These results are promising and could be considered as starting point for further in vitro studies to define the molecular mechanisms involved in the cytotoxic/proliferative effects.

Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacokinetic/pharmacological profile. Betulinic acid is a pentacyclic triterpenic compound that was identified as an anticancer agent whose main advantage consists in its selective activity, which ensures the almost total lack of cytotoxic side effects. Conjugates of betulinic acid with substituted triazoles, scaffolds with significant pharmacological properties, were synthesized and tested as anticancer agents in order to achieve new therapeutic alternatives. The current paper aims to obtain a C30-1,2,4-triazole derivative of betulinic acid simultaneously acetylated at C3 whose biological activity was tested against RPMI melanoma cells. The compound revealed significant cytotoxic effects at the tested concentrations (2, 10 and 50 μΜ) by significantly decreasing the cell viability to 88.3%, 54.7% and 24.5%, respectively, as compared to the control. The compound’s testing in normal HaCaT cells showed a lack of toxicity, which indicates its selective dose-dependent anticancer activity. The investigation of its underlying molecular mechanism revealed an apoptotic effect induced at the mitochondrial level, which was validated through high-resolution respirometry studies.

Implementing metallic nanoparticles as research instruments for the transport of therapeutically active compounds remains a fundamentally vital work direction that can still potentially generate novelties in the field of drug formulation development. Gold nanoparticles (GNP) are easily tunable carriers for active phytocompounds like pentacyclic triterpenes. These formulations can boost the bioavailability of a lipophilic structure and, in some instances, can also enhance its therapeutic efficacy. In our work, we proposed a biological in vitro assessment of betulinic acid (BA)-functionalized GNP. BA-GNP were obtained by grafting BA onto previously synthesized citrate-capped GNP through the use of cysteamine as a linker. The nanoformulation was tested in HaCaT human keratinocytes and RPMI-7951 human melanoma cells, revealing selective cytotoxic properties and stronger antiproliferative effects compared to free BA. Further examinations revealed a pro-apoptotic effect, as evidenced by morphological changes in melanoma cells and supported by western blot data showing the downregulation of anti-apoptotic Bcl-2 expression coupled with the upregulation of pro-apoptotic Bax. GNP also significantly inhibited mitochondrial respiration, confirming its mitochondrial-targeted activity.

Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the screening and structural investigations by ESI Orbitrap MS in the negative ion mode and CID MS/MS of phase I and phase II metabolites detected in mouse plasma after the intraperitoneal administration of a nanoemulsion containing BA in SKH 1 female mice. Obtained results indicate that the main phase I metabolic reactions that BA undergoes are monohydroxylation, dihydroxylation, oxidation and hydrogenation, while phase II reactions involved sulfation, glucuronidation and methylation. The fragmentation pathway for BA and its plasma metabolites were elucidated by sequencing of the precursor ions by CID MS MS experiments.

Pentacyclic triterpenes, such as betulinic, ursolic, and oleanolic acids are efficient and selective anticancer agents whose underlying mechanisms of action have been widely investigated. The introduction of N-bearing heterocycles (e.g., triazoles) into the structures of natural compounds (particularly pentacyclic triterpenes) has yielded semisynthetic derivatives with increased antiproliferative potential as opposed to unmodified starting compounds. In this work, we report the synthesis and biological assessment of benzotriazole esters of betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) (compounds 1–3). The esters were obtained in moderate yields (28–42%). All three compounds showed dose-dependent reductions in cell viability against A375 melanoma cells and no cytotoxic effects against healthy human keratinocytes. The morphology analysis of treated cells showed characteristic apoptotic changes consisting of nuclear shrinkage, condensation, fragmentation, and cellular membrane disruption. rtPCR analysis reinforced the proapoptotic evidence, showing a reduction in anti-apoptotic Bcl-2 expression and upregulation of the pro-apoptotic Bax. High-resolution respirometry studies showed that all three compounds were able to significantly inhibit mitochondrial function. Molecular docking showed that compounds 1–3 showed an increase in binding affinity against Bcl-2 as opposed to BA, OA, and UA and similar binding patterns compared to known Bcl-2 inhibitors.

Cancer remains a leading cause of death worldwide and, even though several advances have been made in terms of specific treatment, the late-stage detection and the associated side effects of the conventional drugs sustain the search for better treatment alternatives. Probiotics are live microorganisms that have been proven to possess numerous health benefits for human hosts, including anticancer effects. In the present study, the in vitro effect of the association of two probiotic strains (PBT), Lactobacillus sporogenes and Clostridium butyricum, were tested against colon (HT-29 and HCT 116), lung (A549), and liver (HepG2) cancer cell lines, alone or in combination with 5-fluorouracil (5FU). Moreover, the underlying mechanism of PBT and PBT-5FU against the HT-29 cell line was evaluated using the Hoechst 33342 staining, revealing characteristic apoptotic modifications, such as chromatin condensation, nuclear fragmentation, and membrane blebbing. Furthermore, the increase in the expression of pro-apoptotic Bax, Bid, Bad, and Bak proteins and the inhibition of the anti-apoptotic Bcl-2 and Bcl-XL proteins were recorded. Collectively, these findings suggest that the two strains of probiotic bacteria, alone or in association with 5FU, induce apoptosis in colon cancer cells and may serve as a potential anticancer treatment.

Introduction Many experimental and clinical trials have suggested that flaxseed might be a potent antihypertensive, but the evidence concerning the effects of flaxseed supplements on plasma C-reactive protein (CRP) concentrations has not been fully conclusive. We assessed the impact of the effects of flaxseed supplementation on plasma CRP concentrations through a systematic review of literature and meta-analysis of available randomised controlled trials (RCTs). Material and methods The literature search included EMBASE, ProQuest, CINAHL, and PUBMED databases up to 1st February 2016 to identify RCTs investigating the effect of flaxseed supplements on plasma CRP concentrations. Meta-analysis was performed using a random-effects model, and effect size was expressed as weighed mean difference (WMD) and 95% confidence interval (CI). Results Meta-analysis of 17 selected RCTs with 1256 individuals did not suggest a significant change in plasma CRP concentrations following supplementation with flaxseed-containing products (WMD: –0.25 mg/l, 95% CI: –0.53, 0.02, p = 0.074). The effect size was robust in the leave-one-out sensitivity analysis. Subgroup analysis did not suggest any significant difference in terms of changing plasma CRP concentrations among different types of flaxseed supplements used in the included studies, i.e. flaxseed oil (WMD: –0.67 mg/l, 95% CI: –2.00, 0.65, p = 0.320), lignan extract (WMD: –0.32 mg/l, 95% CI: –0.71, 0.06, p = 0.103) and ground powder (WMD: –0.18 mg/l, 95% CI: –0.42, 0.06, p = 0.142). Conclusions The meta-analysis of RCTs did not show a significant change in plasma CRP concentrations following supplementation with various flaxseed products. Large, well-designed studies should be still performed to validate the current results.

The smoketree (Cotinus coggygria) is a historically known medicinal plant from Southeast Europe. Its ethnomedicinal use in skin and mucosal lesions is commonly accepted across countries. Other utilizations reported locally include fever reduction, cardiac diseases, hypertension, urinary diseases, cough, asthma, hemorrhoids, diabetes, numbness of arm, liver disease, and cancer. Departing from the smoketree’s traditional uses, this review summarizes investigations on the phytochemistry and bioactivity of the plant. In vitro and in vivo experiments supporting wound-healing, anti-inflammatory, antibacterial, cytotoxic, antioxidative, hepatoprotective, and antidiabetic effects are presented. Metabolites from smoketree that are responsible for the main pharmacological effects of smoketree are pointed out. Furthermore, the review performs a comparison between C. coggygria and the lacquer tree (Toxicodendron vernicifluum). The latter is a comprehensively studied species used in Asian phytotherapy, with whom the European smoketree shares a consistent pool of secondary metabolites. The comparative approach aims to open new perspectives in the research of smoketree and anticipates an optimized use of C. coggygria in therapy. It also points out the relevance of a chemosystematic approach in the field of medicinal plants research.

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

A new class of magnetite (Fe3O4) particles, coined as “Single Crystalline Micrometric Iron Oxide Particles” (SCMIOPs), were obtained by hydrothermal synthesis. Both the single Fe3O4 phase content and the particle sizes range, from 1 µm to 30 µm, can be controlled by synthesis. The notable finding states that these particles exhibit vanishing remanent magnetization (σr=0.28 emu/g) and coercive force (Hc=1.5 Oe), which indicate a superparamagnetic-like behavior (unexpected at micrometric particles size), and remarkably high saturation magnetization (σs=95.5 emu/g), what ensures strong magnetic response, and the lack of agglomeration after the magnetic field removal. These qualities make such particles candidates for biomedical applications, to be used instead of magnetic nanoparticles which inevitably involve some drawbacks like aglommeration and insufficient magnetic response. In this sense, cytocompatibility/cytotoxicity tests were performed on human cells, and the results have clearly indicated that SCMIOPs are cytocompatible for healthy cell lines HaCaT (human keratinocytes) and HEMa (primary epidermal melanocytes) and cytotoxic for neoplastic cell lines A375 (human melanoma) and B164A5 (murine melanoma) in a dose-dependent manner.

Malocclusion is a global health problem, mainly affecting children and adolescents. For this reason, orthodontic treatment must be, on the one hand, safe, non-toxic, and effective and, on the other hand, it must have the best possible esthetic profile. Thus, the use of orthodontic appliances is addressed to all age groups, including young children, for a long period of time, which is why their safety profile is a matter of real interest. For this reason, the purpose of the present study was to evaluate the safety and biocompatibility of an acrylic removable orthodontic appliance made of polymethylmethacrylate and stainless steel alloy made by our team of researchers. To verify the biocompatibility of the medical device, it was immersed in artificial saliva with three different pHs (3, 7, and 10) for a period of ten days. Subsequently, the three types of saliva were tested on human keratinocytes (HaCaT cell line) in terms of viability and modification of cell morphology. Finally, the use of 3D reconstructed human epidermis verified the cytotoxic and irritating potential of the medical device, thus providing relevant information regarding its biocompatibility. The results revealed that by maintaining the orthodontic device in the saliva there is no release of substances with a toxic effect on the human keratinocytes and on the 3D reconstructed human epidermis. There were also no significant changes in cell morphology. In conclusion, it is suggested that the acrylic removable appliance has a safety profile recommended for in vivo use.

In the field of oncology, the plant kingdom has an inexhaustible supply of bioactive compounds. Phytochemical compounds isolated from Helleborus species have been found to be useful in various chronic diseases. This has brought Helleborus to the attention of medical researchers. H. purpurascens is a plant characteristic of the Carpathian area, known since ancient times for its beneficial effects. The aim of the study was to evaluate the flavonoids composition of a hydroalcoholic extract of H. purpurascens, as well as to assess its antioxidant activity and antitumor potential at the level of two healthy cell lines and four tumor cell lines. In addition, the expression of the genes involved in the apoptotic process (Bcl-2, Bad, and Bax) were evaluated. The results indicated that the extract has a high concentration of flavonoids, such as epicatechin, quercetin, and kaempferol. The extract has an increased antioxidant activity, very similar to that of the standard, ascorbic acid and cytotoxic effects predominantly in the breast cancer cell line, being free of cytotoxic effects in healthy cell lines. Underlying the cytotoxic effect is the induction of the process of apoptosis, which in the present study was highlighted by decreasing the expression of anti-apoptotic genes (Bcl-2) and increasing the expression of pro-apoptotic genes (Bad and Bax). In conclusion, the hydroalcoholic extract of H. purpurascens can be considered an important source for future medical applications in cancer therapy.

Introduction Lupinus spp. are herbaceous perennial flowering plants included in the Fabaceae family. Among the approximately 200 species belonging to this genre, Lupinus albus L., also known as white lupin, Lupinus angustifolius L., and narrow-leafed lupin or blue lupin, represent two of the most studied species due to their intense culinary use and potential biological activity. The intention of the study was to characterize total phenolic content, perform FTIR analysis, and antiproliferative effects against A375 human melanoma cells extracts obtained from germinated and ungerminated seeds from Lupinus albus L. and Lupinus angustifolius L. Material and methods Total phenolic content was assessed using the Folin-Ciocalteu colorimetric method. FTIR spectra were carried out by a Shimadzu Prestige-21 spectrometer in the range 400–4000 cm-1, using KBr pellets and resolution of 4 cm-1. Antiproliferative capacity was screened by employing the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and scratch assay methods. Results The study showed increased values corresponding to total phenolic content for the germinated extracts. FTIR spectra confirmed the presence of genistein and main cinnamic acids derivatives (ferulic, caffeic, rosmarinic, and coumaric acids). All tested extracts showed weak antiproliferative potential against A375 human melanoma cells. Conclusions Germination increased the amount of bioactive compounds in the seeds of the two studied species of lupin. FTIR analyses provided an important fingerprint of the chemical composition.

Cancer persists as a global challenge due to the extent to which conventional anticancer therapies pose high risks counterbalanced with their therapeutic benefit. Naturally occurring substances stand as an important safer alternative source for anticancer drug development. In the current study, a series of modified lupane and ursane derivatives was subjected to in vitro screening on the NCI-60 cancer cell line panel. Compounds 6 and 7 have been identified as highly active with GI50 values ranging from 0.03 µM to 5.9 µM (compound 6) and 0.18–1.53 µM (compound 7). Thus, these two compounds were further assessed in detail in order to identify a possible antiproliferative mechanism of action. DAPI (4′,6-diamidino-2-phenylindole) staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that both compounds induced upregulation of proapoptotic Bak and Bad genes while downregulating Bcl-XL and Bcl-2 antiapoptotic genes. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, while compound 7 showed higher in silico Bcl-XL inhibition potential as compared to the native inhibitor ATB-737, suggesting that compounds may induce apoptotic cell death through targeted antiapoptotic protein inhibition, as well.

A series of novel hybrid chalcone N-ethyl-piperazinyl amide derivatives of oleanonic and ursonic acids were synthesized, and their cytotoxic potential was evaluated in vitro against the NCI-60 cancer cell line panel. Compounds 4 and 6 exhibited the highest overall anticancer activity, with GI50 values in some cases reaching nanomolar values. Thus, the two compounds were further assessed in detail in order to identify a possible apoptosis- and antiangiogenic-based mechanism of action induced by the assessed compounds. DAPI staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that up-regulation of pro-apoptotic Bak gene combined with the down-regulation of the pro-survival Bcl-XL and Bcl-2 genes caused altered ratios between the pro-apoptotic and anti-apoptotic proteins’ levels, leading to overall induced apoptosis. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, suggesting that compounds may induce apoptotic cell death through targeted anti-apoptotic protein inhibition, as well. Ex vivo determinations showed that both compounds did not significantly alter the angiogenesis process on the tested cell lines.

Dental pathology remains a global health problem affecting both children and adults. The most important dental diseases are dental caries and periodontal pathologies. The main cause of oral health problems is overpopulation with pathogenic bacteria and for this reason, conventional therapy can often be ineffective due to bacterial resistance or may have unpleasant side effects. For that reason, studies in the field have focused on finding new therapeutic alternatives. Special attention is paid to the plant kingdom, which offers a wide range of plants and active compounds in various pathologies. This review focused on the most used plants in the dental field, especially on active phytocompounds, both in terms of chemical structure and in terms of mechanism of action. It also approached the in vitro study of active compounds and the main types of cell lines used to elucidate the effect and mechanism of action. Thus, medicinal plants and their compounds represent a promising and interesting alternative to conventional therapy.

Malignant melanoma represents the deadliest type of skin cancer with narrow treatment options in advanced stages. Herbal constituents possessing anticancer properties occupy a particular spot in melanoma research as potential chemotherapeutics. Rutin (RUT) is a natural compound exerting antioxidant, antimicrobial, anti-inflammatory, UV-filtering, and SPF-enhancing activities that are beneficial to the skin; however, its effect as an anti-melanoma agent is less investigated. The current study is focused on assessing the cytotoxic potential of RUT against two different human melanoma cell lines: RPMI-7951 and SK-MEL-28 by evaluating its impact in terms of cell viability, cells’ morphology, and nuclear aspect assessment, and senescence-inducing properties. The results indicate a dose-dependent decrease in the viability of both cell lines, with calculated IC50 values of 64.49 ± 13.27 µM for RPMI-7951 cells and 47.44 ± 2.41 µM for SK-MEL-28, respectively, accompanied by a visible reduction in the cell confluency and apoptotic features within the cell nuclei. RUT exerted a senescence-inducing property highlighted by the elevated expression of senescent-associated beta-galactosidase (SA-β-gal) in SK-MEL-28 cells. Despite the in vitro anti-melanoma effect revealed by our results, further studies are required to elucidate the mechanisms of RUT-induced cytotoxicity and senescence in melanoma cells.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models—hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.

Increased sugar consumption and unhealthy dietary patterns are key drivers of many preventable diseases that result in disability and death worldwide. However, health awareness has increased over the past decades creating a massive on-going demand for new low/non-caloric natural sweeteners that have a high potential and are safer for consumption than artificial ones. The current study aims to investigate the nutritional properties, in vitro toxicological profile, total/individual polyphenols content, and the antioxidant, anti-cariogenic, and antimicrobial activity of two newly obtained vegan and sugar-free chocolate (VHC1 and VHC2). The energy values for the two finished products were very similar, 408.04 kcal/100 g for VHC1 and 404.68 kcal/100 g for VHC2. Both products, VHC1 and VHC2 present strong antioxidant activities, whereas antimicrobial results show an increased activity for VHC1 compared to VHC2, because of a higher phenolic content. In vitro toxicological evaluation revealed that both samples present a safe toxicological profile, while VHC2 increased cellular turnover of dermal cell lines, highlighting its potential use in skin treatments. The current work underlines the potential use of these vegetal mixtures as sugar-free substitutes for conventional products, as nutraceuticals, as well as topic application in skin care due to antimicrobial and antioxidant effects.

Betulonic acid belongs to the pentacyclic triterpenic derivative class and can be obtained through the selective oxidation of betulin. In this study we set obtaining several functionalized derivatives of this compound by its condensation with several amino compounds such as aminoguanidine, hydroxylamine, n-butylamine and thiosemicarbazide as our goal. The functionalization of the parent compound led to several molecules with antiproliferative potential, the most promising being 3–2-carbamothioylhydrazonolup-20(29)-en-28-oic acid.

Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.

Albendazole is a benzimidazole derivative with documented antitumor activity and low toxicity to healthy cells. The major disadvantage in terms of clinical use is its low aqueous solubility which limits its bioavailability. Albendazole was incorporated into stable and homogeneous polyurethane structures with the aim of obtaining an improved drug delivery system model. Spectral and thermal analysis was used to investigate the encapsulation process and confirmed the presence of albendazole inside the nanoparticles. The in vitro anticancer properties of albendazole encapsulated in polyurethane structures versus the un-encapsulated compound were tested on two breast cancer cell lines, MCF-7 and MDA-MB-231, in terms of cellular viability and apoptosis induction. The study showed that the encapsulation process enhanced the antitumor activity of albendazole on the MCF-7 and MDA-MB-23 breast cancer lines. The cytotoxic activity manifested in a concentration-dependent manner and was accompanied by changes in cell morphology and nuclear fragmentation.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves’ extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Background: Orthodontic mini-implant failure is a debatable subject in clinical practice. However, the most important parameter to evaluate the success rate of mini-implant is the primary stability, which is mainly influenced by cortical bone thickness (CBT) and insertion angle. Materials and methods: Three-dimensional finite element models of the maxilla were created and a custom-made, self-drilling, tapered mini-implant was designed. For the pull-out test, 12 simulations were performed, sequentially increasing the thickness of the cortical bone (1, 1.5 and 2 mm) and the insertion angle (30°, 60°, 90°, 120°). For the force analysis, 24 simulations were performed using an experimental orthodontic traction force of 2 N both in the horizontal and vertical axis. Results: Insertion angle and CBT have significant impact on force reaction values (p < 0.05). Cortical bone stress had the lowest value when the mini-implant had a 30° insertion angle and the highest value when the implant had a 120° insertion angle, while the CBT was 1 mm. Cortical bone stress had the lowest value with an insertion angle of 90° and the highest value when the implant was inserted at an angle of 30°, while the CBT was 2 mm independent of the force direction. Regarding the biosafety profile of the mini-implant alloy, the present results reveal that the custom-made mini-implant presents good biocompatibility. Conclusions: When the CBT is reduced, we recommend inclined insertion while, when the CBT is appropriate, perpendicular insertion is advised.

A facile sol-gel route has been applied to synthesize hybrid silica-PVA-iron oxide nanocomposite materials. A step-by-step calcination (processing temperatures up to 400 °C) was applied in order to oxidize the organics together with the iron precursor. Transmission electron microscopy, X-ray diffraction, small angle neutron scattering, and nitrogen porosimetry were used to determine the temperature-induced morpho-textural modifications. In vitro cytotoxicity assay was conducted by monitoring the cell viability by the means of MTT assay to qualify the materials as MRI contrast agents or as drug carriers. Two cell lines were considered: the HaCaT (human keratinocyte cell line) and the A375 tumour cell line of human melanoma. Five concentrations of 10 µg/mL, 30 µg/mL, 50 µg/mL, 100 µg/mL, and 200 µg/mL were tested, while using DMSO (dimethylsulfoxid) and PBS (phosphate saline buffer) as solvents. The HaCaT and A375 cell lines were exposed to the prepared agent suspensions for 24 h. In the case of DMSO (dimethyl sulfoxide) suspensions, the effect on human keratinocytes migration and proliferation were also evaluated. The results indicate that only the concentrations of 100 μg/mL and 200 μg/mL of the nanocomposite in DMSO induced a slight decrease in the HaCaT cell viability. The PBS based in vitro assay showed that the nanocomposite did not present toxicity on the HaCaT cells, even at high doses (200 μg/mL agent).

Colon cancer is a widespread pathology with complex biochemical etiology based on a significant number of intracellular signaling pathways that play important roles in carcinogenesis, tumor proliferation and metastasis. These pathways function due to the action of key enzymes that can be used as targets for new anticancer drug development. Herein we report the synthesis and biological antiproliferative evaluation of a series of novel S-substituted 1H-3-R-5-mercapto-1,2,4-triazoles, on a colorectal cancer cell line, HT-29. Synthesized compounds were designed by docking based virtual screening (DBVS) of a previous constructed compound library against protein targets, known for their important role in colorectal cancer signaling: MEK1, ERK2, PDK1, VEGFR2. Among all synthesized structures, TZ55.7, which was retained as a possible PDK1 (phospholipid-dependent kinase 1) inhibitor, exhibited the most significant cytotoxic activity against HT-29 tumor cell line. The same compound alongside other two, TZ53.7 and TZ3a.7, led to a significant cell cycle arrest in both sub G0/G1 and G0/G1 phase. This study provides future perspectives for the development of new agents containing the 1,2,4-mercapto triazole scaffold with antiproliferative activities in colorectal cancer.

A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin–eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.

The metallic elements concentrations of medicinal plants (coriander, dill, Echinacea, lavender, chamomile, mint, and plantain, used for phytopharmaceutical products), cultivated in unpolluted region, were analyzed by neutron activation analysis. The essential nutrients, macro-, micro-, and trace elements (K, Ca, Mg, Na, Fe, Mn, Rb, Sr, and Zn), potentially toxic elements (Al, As, Ba, Co, Sb, Cr, and V), and rare earth elements were monitored and were compared with those presented in the literature. An estimation of their contributions to intake and toxicity for a person was made, which revealed that (a) teas prepared from the examined plants represent useful contribution to the food provided intake of three essential macronutrients (K, Ca, and Mg); (b) the Cu, Mn, Rb, Sr, Zn, and rare earths levels are normal or low; (c) the quantities of As, Ba, Co, Sb, Cr, and V do not represent toxicological concerns; (d) the examination of the estimated Al and Fe quantities recovered in infusions in the conditions of usual daily tea consumption is below the Tolerable Daily Intake values. The strategy of cultivation of medicinal plants in unpolluted areas is efficient and beneficial. However, individual plants ability to concentrate preferentially certain elements suggests controlling the contamination level of raw materials.

Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental results showed that the measured effectiveness Mlog(1/MRC50) does not depend on the number of azo groups or the ones corresponding to metobolites, but it is influenced by the number of anilide groups, as well as by the substituents’ positions within molecules. The conformational analysis pointed out the intramolecular hydrogen bonds, especially the simple tautomerization of quinoidic (STOH) or aminoidic (STNH2) type. The effectiveness is strongly influenced by the “push-pull” electronic effect, specific to two hydroxy or amino groups separated by an azo moiety (double alternate tautomery, (DAT), to the –COOH or –SO3H groups which are located in ortho or para position with respect to the azo group. The levels of the lipophylic/hydrophilic, electronic and steric equilibriums, pointed out by the Mlog(1/MRC50) values, enabled the calculation of their average values Clog(1/MRC50) (“Köln model”), characteristic to one derivative class (class isotoxicity). The azo group reduction and the hydrolysis of the amido/peptidic group are two concurrent enzymatic reactions, which occur with different reaction rates and mechanisms. The products of the partial biodegradation are aromatic amines. No additive or synergic effects are noticed among them.

Given the present high incidence of melanoma and skin cancer, interest in potential drugs of plant origin has increased significantly. Pentacyclic lupane-type triterpenes are widely distributed in plants, offering numerous pharmacological benefits. Betulin is an important compound in the bark of Betula pendula Roth and has important therapeutic properties, including antitumor activities. Its biological effect is limited by its poor water solubility, which can be improved by cyclodextrin complexation. The best results have been obtained by using a novel cyclodextrin derivative, octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonate)]-γ-CD. The complexes between betulin and the previously mentioned cyclodextrin were analyzed by scanning electron microscopy (SEM)and differential scanning calorimetry (DSC) and pharmacologically evaluated in vitro (MTT and immunocytochemistry tests) and in vivo in C57BL/6J mice. The solubility of betulin is improved by cyclodextrin complexation, which creates a stable complex that improves the in vitro and in vivo properties of the active compound.

Cutaneous melanoma is a complex disorder characterized by an elevated degree of heterogeneity, features that place it among the most aggressive types of cancer. Although significant progress was recorded in both the understanding of melanoma biology and genetics, and in therapeutic approaches, this malignancy still represents a major problem worldwide due to its high incidence and the lack of a curative treatment for advanced stages. This review offers a survey of the most recent information available regarding the melanoma epidemiology, etiology, and genetic profile. Also discussed was the topic of cutaneous melanoma murine models outlining the role of these models in understanding the molecular pathways involved in melanoma initiation, progression, and metastasis.

The current study aimed to investigate the chemical composition and the synergistic potential of two essential oils (EOs), as obtained from Salvia officinalis L. (SEO), and Thymus vulgaris L. (TEO). The antifungal potential was tested in vitro against Fusarium graminearum (Fg 06_17), the herbicidal effect was studied using weed seeds of Amaranthus retroflexus (ARET), Chenopodium album (CALB), Echinochloa crus-galli (EGAL), but also wheat seeds (WS) of the Lovrin variety and tomato seeds Saint-Pierre of the variety. The GC-MS profile highlights that the mains compounds identified in SEO were: caryophyllene (25.364%), camphene (14.139%), eucalyptol (13.902%), and β-pinene (11.230%), while in TEO, the predominant phytochemicals were: γ-terpinene (68.415%) and p-thymol (24.721%). The results indicated that the tested EOs alone as well as in combination have allelopathic effect against investigated seeds, while the synergistic effect of TEO and SEO in terms of fungal growth was demonstrated at a level of 0.06%. Thyme and sage EOs exhibited in vitro anti-proliferative activity on two melanoma cell lines, namely A375 human melanoma and B164A5 mouse melanoma alone, as well as in combination. SEO was most effective in terms of decreasing the cell viability of murine and human melanoma cell lines when compared to TEO.

The present study focuses on the synthesis and analysis of a genistein ester derivative with myristic acid followed by beta cyclodextrin encapsulation; physicochemical analysis using consecrated techniques such as FTIR, MS, DSC, and SEM revealed both a successful esterification and inclusion inside the cyclodextrin cavity. Cytotoxic effects were measured in vitro on three human cell lines: HeLa (cervix adenocarcinoma), A2780 (ovary carcinoma), and A431 (skin epidermoid carcinoma). The in vitro biological analysis exhibited rather poor antiproliferative results on all three tested cancer cell lines, behavior that may be due to the high stability of the complex within the in vitro environment.

Conventional cytostatic cancer treatments rarely result in the complete eradication of tumor cells. Therefore, new therapeutic strategies focus on antagonizing the immunosuppressive activity of established tumors. In particular, recent studies of antigen-loaded dendritic cells (DCs) eliciting a specific antitumor immune response has raised the hopes of achieving the complete elimination of tumor tissue. Genistein, fingolimod and betulin have already been described as active compounds in different types of cancer. Herein, we applied an integrated screening approach to characterize both their cytostatic and their immune-modulating properties side-by-side. As will be described in detail, our data confirmed that all three compounds exerted proapoptotic and antiproliferative activity in different B16 melanoma cell lines to a given extent, as revealed by an MTT assay, CFSE and DAPI staining. However, while genistein and fingolimod also affected the survival of primary bone marrow (BM) derived DCs of C57BL/6 mice, betulin exhibited a lower cytotoxicity for BMDCs in comparison to the melanoma cells. Moreover, we could show for the first time, that only betulin caused a simultaneous, highly specific immune-stimulating activity, as measured by the IL-12p70 release of Toll-like receptor 4-stimulated BMDCs by ELISA, which was due to increased IL-12p35 mRNA expression. Interestingly, the activation of DCs resulted in enhanced T lymphocyte stimulation, indicated by increased IL-2 and IFN-γ production of cytotoxic T cells in spleen cell co-culture assays which led to a decreased viability of B16 cells in an antigen specific model system. This may overcome the immunosuppressive environment of a tumor and destroy tumor cells more effectively in vivo if the immune response is specific targeted against the tumor tissue by antigen-loaded dendritic cells. In summary, cytostatic agents, such as betulin, that simultaneously exhibit immune stimulatory activity may serve as lead compounds and hold great promise as a novel approach for an integrated cancer therapy.

Background. Both 1,2,3- and 1,2,4-triazoles are nowadays incorporated in numerous antibacterial pharmaceutical formulations. Aim. Our study aimed to prepare three substituted 1,2,4-triazoles and to evaluate their antibacterial properties. Materials and Methods. One disubstituted and two trisubstituted 1,2,4-triazoles were prepared and characterised by physical and spectroscopic properties (melting point, FTIR, NMR, and GC-MS). The antibacterial properties were studied against three bacterial strains: Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853), by the agar disk diffusion method and the dilution method with MIC (minimal inhibitory concentration) determination. Results. The spectroscopic characterization of compounds and the working protocol for the synthesis of the triazolic derivatives are described. The compounds were obtained with 15–43% yields and with high purities, confirmed by the NMR analysis. The evaluation of biological activities showed that the compounds act as antibacterial agents against Staphylococcus aureus (ATCC 25923), while being inactive against Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). Conclusions. Our results indicate that compounds containing 1,2,4-triazolic moiety have great potential in developing a wide variety of new antibacterial formulations.

ABSTRACT Introduction: the majority of studies of acute gastrointestinal bleeding in children are retrospective, focusing on therapeutic endoscopy. Previous studies performed in adult patients have demonstrated that both scheduled second look endoscopy and high dose continuous omeprazole infusion are effective in the prevention of peptic ulcer rebleeding. The aim of this study was to compare the efficacy of these two strategies using esomeprazole for the prevention of rebleeding following primary endoscopic hemostasis in children with peptic ulcers. The main outcome was to assess the rebleeding rate within 30 days after the initial hemostasis. Methods: consecutive pediatric cases who underwent endoscopic treatment for bleeding peptic ulcers were randomized into two treatment groups following hemostasis. The first group received esomeprazole as an intravenous bolus every 12 hours for 72 hours and a routine second look endoscopy within 12-24 hours with endotherapy retreatment in the case of a persistent stigmata of bleeding. The second group received a continuous high dose esomeprazole infusion for 72 hours without endoscopic reassessment unless required due to rebleeding. Results: a total of 63 children were randomized to the second look endoscopy group and 64 to the esomeprazole infusion group. Rebleeding occurred within 30 days in four patients (6.3%) in the first group and in three patients (4.6%) in the second group (p = 0.7). Conclusions: a pharmaceutical approach using a high dose continuous esomeprazole infusion in children after an initial endoscopic hemostasis has a similar efficacy compared to second look endoscopy and bolus esomeprazole administration for the prevention of peptic ulcer rebleeding. Thus, the discomfort of a second endoscopy in children can be avoided and is only recommended for selected high risk cases.