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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 poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform.

Ozone is an allotropic form of oxygen, so in the medical field ozone therapy has special effects. Starting from the premise that bio-oxidative ozone therapy reduces the number of bacteria, in the present study two approaches were proposed: to evaluate the biological effects of ozone gas on the tooth enamel remineralization process and to demonstrate its impact on the morphology and confluence of human primary gingival cells, namely keratinocytes (PGK) and fibroblasts (HGF). The ozone produced by HealOzone was applied in vivo to 68 M1s (first permanent molars), both maxillary and mandibular, on the occlusal surfaces at pit and fissure. The molars included in the study recorded values between 13 and 24 according to the DIAGNOdent Pen 2190 scale, this being the main inclusion/exclusion criterion for the investigated molars. Because the gas can make contact with primary gingival cells during the ozonation process, both human gingival fibroblasts and keratinocytes were exposed to different doses of ozone (20 s, 40 s, 60 s), and its effects were observed with the Olympus IX73 inverted microscope. The contact of ozone with the human primary gingival cells demonstrates cell sensitivity to the action of ozone, this being higher in fibroblasts compared to keratinocytes, but it is not considered toxic because all the changes are reversible at 48 h after exposure.

Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget�s disease and tumours that cause osteolysis. A major concern related to bisphosphonates therapy is represented by osteonecrosis of jaw, a serious, debilitating, and mostly, a therapy-resistant disease, reported as a frequent side effect of bisphosphonates. The present study was aimed to assess and compare the effect of four commercially available bisphosphonates, very frequently used as oral (Fosamax - F and Actonel - A) and injectable (Ossica - O and Zoledronic acid - Z) therapy on primary human gingival fibroblasts - HGF viability. Alamar blue cell viability assay was performed to assess the effect of test compounds (1.5; 2.5; 5 and 10 mM) on gingival fibroblasts viability after a 24 h interval. In these experimental conditions, injectable bisphosphonates (O and Z) proved to be safe for HGF cells, whereas oral compounds (F and A) were cytotoxic even at low concentrations.

Background Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension. Materials and methods Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties). Results After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction. Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage. Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p

The aim of this study was to characterize the interaction between the binary systems of albendazole (ABZ)—cyclodextrins (CDs) with pharmaceutical excipients. Hydroxyl-propyl-beta-cyclodextrin (HPBCD) and random methyl-beta-cyclodextrin (RAMEB) were used as cyclodextrins and magnesium stearate, mannitol, polyvinylpyrrolidone K30 (PVP K30), colloidal silica, starch, and talc were used as excipients. The utilized investigation techniques were attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffractometry (PXRD) and thermoanalytical techniques: thermogravimetry (TG)/derivative thermogravimetry (DTG)/heat flow (HF) and differential scanning calorimetry (DSC). The ATR-FTIR analysis clearly suggested interactions under ambient conditions between ABZ-HPBCD with PVP K30 and SiO2 and between ABZ-RAMEB with SiO2 and talc. The PXRD patterns indicated the formation of less crystalline mixtures but with no clear indication of interactions, since no peaks appeared nor disappeared. The modifications on the DSC curves suggested an interaction between ABZ-HPBCD and PVP K30 and SiO2 respectively, and in case of ABZ-RAMEB was observed an interaction with talc. Thermal analysis (TG/DTG/HF) carried out in open crucibles in dynamic air atmosphere suggested that at temperatures over 40 °C dehydration of samples occurred, later followed by thermolysis and appearance of interactions in all studied cases. Our study concludes by recommending precautionary measures in elaborating new solid formulations containing ABZ, HPBCD and PVP K30/SiO2 and for the ones containing ABZ, RAMEB and Talc/SiO2, due to the present interactions under ambient conditions.

Magnetic iron oxide nanoparticles (MIONPs) were placed in the spotlight lately due to their excellent biocompatibility and the possibility to tailor their magnetic properties making them useful in a plethora of bioapplications, including magnetic resonance imaging and targeted nanoplatforms for anticancer drugs delivery. The aim of the present study consisted in achieving a toxicological profile of the biocompatible colloidal suspension of iron oxide nanoparticles coated with a double layer of oleic acid (Fe₃O₄ @OA) obtained by combustion method by performing in vitro (on human keratinocytes-HaCaT and human and murine melanoma cells) and in ovo studies on chick chorioallantoic membrane (HET-CAM assay). The colloidal suspension obtained proved to be stable in phosphate buffer saline and the size of the nanoparticles were in the range of 30 nm, an optimum size for biomedical applications. Fe₃O₄ @OA colloidal suspension reduced viability of human keratinocytes only at concentrations higher than 25 μg/mL, whereas in the case of melanoma cells the effect was observed at lower doses (starting with 10 μg/mL). An interesting phenomena was detected at the highest concentration tested (50 μg/mL) to all cell lines, more precisely, a particular enucleation process associated only with Fe₃O₄ @OA colloidal suspension stimulation. The irritant potential data evaluated by HET-CAM assay indicated the following hierarchy: Fe₃O₄ < Fe₃O₄ @OA < OA. Our results provide relevant information regarding the mechanism of action of Fe₃O₄ @OA that needs elucidation by future in vitro and in vivo studies.

Satureja hortensis L. presents an increased interest due to its chemical composition, abundant in monoterpenes, aglyconic and glycosylates flavonoids, and phenolic acids, leading to important biological activity. The present study compared the biological activity of volatile oil (VO) and total hydro-alcoholic extract (TE) of Satureja hortensis L. in terms of: i) antioxidant activity; ii) antimicrobial activity; and iii) viability, migration and proliferation on two healthy cell lines (keratinocytes-HaCaT and fibroblasts-1BR3) and two melanoma cell lines (human-A375 and murine-B164A5). Antioxidant activity of VO and TE showed maximal values around 72%. Antimicrobial screening highlighted the inhibitory capacity of VO against all seven tested bacteria strains, with the most pronounced effect against S. aureus and C. albicans, while TE exerted only a slight activity against three bacteria strains. VO showed greater efficacy than TE on both tumor cell lines (A375 and B164A5), the activity of the compounds was higher when low concentrations were used (5, 10 and 25 µM) while at high concentrations (50 and 100 µM) the percentages of viability were increased.

The current study was purported to assess the: (i) in vitro toxicity of betulin silver nanoparticles (AgNPs-B), bare and capped with polyethylene glycol (PEG), on two murine melanoma cell lines (B164A5 and B16Ova) and on healthy cell lines (keratinocytes and melanocytes), and (ii) in vivo antitumor efficacy of PEGylated AgNPs-B in an experimental melanoma model. Bare and PEG-capped AgNPs-B were synthesized by a chemical reduction method resulting in stable and non-aggregated spherical AgNPs-B and PEG-AgNPs-B, of narrow size distributions and mean hydrodynamic diameters of 25 nm and 75 nm, respectively. In vitro assessments were achieved by MTT and Annexin V-FITC assays and in vivo evaluation involved non-invasive techniques for the surveillance of the physiological skin parameters changes and histopathological examination of the harvested organs. The in vitro results revealed selective cytotoxicity against melanoma cells, at low doses that are nontoxic to normal cells; higher doses were associated with the loss of selectivity and toxicity for healthy cells. PEGylated formulation of betulin exerted a dose-dependent pro-apoptotic effect, more obvious in the case of B164A5 cells. Histopathological analysis suggested that PEGylated AgNPs-B developed relevant in vivo effects as antimelanoma agents by decreasing the tumor volume and inhibiting the development of secondary tumors.

The available information on the interplay between low-dose cadmium intake and copper, manganese, and iron homeostasis in invertebrates is limited. We have currently studied the accumulation of these trace metals in the hepatopancreas of adult snails, Cantareus aspersus, following 14 and 28 days of exposure to low doses of dietary cadmium, up to 1 mg/kg dw (dry weight). The cadmium dose, but not the duration of exposure, had a significant effect on hepatopancreas copper deposition, the values being significantly elevated compared to controls. A significant peak in manganese levels at 14 days was found in snails administered the lowest cadmium dose. These increases occurred even in the absence of cadmium increase in the hepatopancreas. Our data suggest that low dose cadmium feeding can produce a transient disturbance in hepatopancreas copper and manganese homeostasis. Such responses may serve as early biomarkers of physiological changes occurring during the initial stages of cadmium intoxication.

Simple Summary Hepatocellular carcinoma (HCC) is characterized by a broad molecular and genetic heterogeneity, which makes it a challenging subject in terms of the underlying mechanisms, response and resistance to treatment, and finding novel therapeutic options. Nowadays, new experimental models (3D in vitro models, in vivo mouse and non-mouse models, and computational studies) allow more detailed studies of hepatocellular carcinoma pathogenesis and treatment. Here, we provide insights into the current preclinical models frequently applied for the study of hepatocellular carcinoma. Abstract Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Oral contraceptives (OCs) are widely used due to their efficiency in preventing unplanned pregnancies and treating several human illnesses. Despite their medical value, the toxicity of OCs remains a public concern. Previous studies indicate the carcinogenic potential of synthetic sex hormones and their link to the development and progression of hormone-dependent malignancies such as breast cancer. However, little is known about their influence on the evolution of triple-negative breast carcinoma (TNBC), a malignancy defined by the absence of estrogen, progesterone, and HER2 receptors. This study reveals that the active ingredients of modern OCs, 17β-Ethinylestradiol, Levonorgestrel, and their combination induce differential effects in MDA-MB-231 TNBC cells. The most relevant behavioral changes occurred after the 24 h treatment with 17β-Ethinylestradiol, summarized as follows: (i) decreased cell viability (64.32% at 10 µM), (ii) cell roundness and loss of confluence, (iii) apoptotic aspect of cell nuclei (fragmentation, membrane blebbing), and (iv) inhibited cell migration, suggesting a potential anticancer effect. Conversely, Levonorgestrel was generally associated with a proliferative activity. The association of the two OCs exerted similar effects as 17β-Ethinylestradiol but was less effective. Further studies are necessary to elucidate the hormones’ cytotoxic mechanism of action on TNBC cells.

Background and Objectives: Breast cancer (BC) remains one of the major causes of cancer death in women worldwide. The difficulties in assessing the deep molecular mechanisms involved in this pathology arise from its high complexity and diverse tissue subtypes. Long non-coding RNAs (lncRNAs) were shown to have great tissue specificity, being differentially expressed within the BC tissue subtypes. Materials and Methods: Herein, we performed lncRNA profiling by PCR array in triple negative breast cancer (TNBC) and luminal A tissue samples from 18 BC patients (nine TNBC and nine luminal A), followed by individual validation in BC tissue and cell lines. Tissue samples were previously archived in formalin-fixed paraffin-embedded (FFPE) samples, and the areas of interest were dissected using laser capture microdissection (LCM) technology. Results: Two lncRNAs (OTX2-AS1 and SOX2OT) were differentially expressed in the profiling analysis (fold change of 205.22 and 0.02, respectively, p &lt, 0.05 in both cases), however, they did not reach statistical significance in the individual validation measurement (p &gt, 0.05) when analyzed with specific individual assays. In addition, GAS5 and NEAT1 lncRNAs were individually assessed as they were previously described in the literature as being associated with BC. GAS5 was significantly downregulated in both TNBC tissues and cell lines compared to luminal A samples, while NEAT1 was significantly downregulated only in TNBC cells vs. luminal A. Conclusions: Therefore, we identified GAS5 lncRNA as having a differential expression in TNBC tissues and cells compared to luminal A, with possible implications in the molecular mechanisms of the TNBC subtype. This proof of principle study also suggests that LCM could be a useful technique for limiting the sample heterogeneity for lncRNA gene expression analysis in BC FFPE tissues. Future studies of larger cohort sizes are needed in order to assess the biomarker potential of lncRNA GAS5 in BC.

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin’s (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment

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&mdash, 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%) &lt, PEG_SilCo_BA (72.05%) &lt, BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) &lt, PEG_SilCo_BA (86.80%) &lt, BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

Recent scientific evidence suggests a link between epigenetic changes (DNA methylation) and tumorigenesis. Moreover, a potential carcinogenic mechanism of cadmium was associated with changes in DNA methylation. In this study we investigated the impact of CdCl2 and CuSO4 aqueous solutions on DNA methylation in HT-29 cells by quantifying DNA methyltransferase (DNMT1, DNMT3A and DNMT3B) mRNA expression. Furthermore, we also studied the cytotoxic and anti-migratory potential of these substances. The results showed a dose-dependent decrease of viable cell percentage following 24 h of exposure (at concentrations of 0.05; 0.2; 1; 10 and 100 µg/ml), and an inhibitory effect on HT-29 cell migration capacity. In addition, RT-qPCR results showed that cadmium acts as a hypomethylating agent by suppressing DNMT expression, whereas copper acts as a hypermethylating compound by increasing DNMT expression. These findings suggest a cytotoxic potential of both cadmium and copper on HT-29 cells and their capacity to induce epigenetic changes.

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame&rsquo, s role in colorectal cancer.

Claudia Geanina Farcas,1,2,* Cristina Dehelean,2,* Iulia Andreea Pinzaru,2 Marius Mioc,2 Vlad Socoliuc,3,4 Elena-Alina Moaca,2 Stefana Avram,2 Roxana Ghiulai,2 Dorina Coricovac,2 Ioana Pavel,5 Praveen Kumar Alla,5 Octavian Marius Cretu,6 Codruta Soica,2 Felicia Loghin1 1Faculty of Pharmacy, Department of Toxicology, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj Napoca, Cluj Napoca, Romania; 2Faculty of Pharmacy, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 3Laboratory of Magnetic Fluids, Center for Fundamental and Advanced Technical Research, Romanian Academy – Timisoara Branch, Timisoara, Romania; 4Research Center for Complex Fluids Systems Engineering, Politehnica University of Timisoara, Timisoara, Romania; 5Department of Chemistry, Wright State University, Dayton, OH, USA; 6Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timisoara, Romania*These authors contributed equally to this workCorrespondence: Iulia Andreea Pinzaru; Marius Mioc Email iuliapinzaru@umft.ro; marius.mioc@umft.roPurpose: Breast cancer presents one of the highest rates of prevalence around the world. Despite this, the current breast cancer therapy is characterized by significant side effects and high risk of recurrence. The present work aimed to develop a new therapeutic strategy that may improve the current breast cancer therapy by developing a heat-sensitive liposomal nano-platform suitable to incorporate both anti-tumor betulinic acid (BA) compound and magnetic iron nanoparticles (MIONPs), in order to address both remote drug release and hyperthermia-inducing features. To address the above-mentioned biomedical purposes, the nanocarrier must possess specific features such as specific phase transition temperature, diameter below 200 nm, superparamagnetic properties and heating capacity. Moreover, the anti-tumor activity of the developed nanocarrier should significantly affect human breast adenocarcinoma cells.Methods: BA-loaded magnetoliposomes and corresponding controls (BA-free liposomes and liposomes containing no magnetic payload) were obtained through the thin-layer hydration method. The quality and stability of the multifunctional platforms were physico-chemically analysed by the means of RAMAN, scanning electron microscopy-EDAX, dynamic light scattering, zeta potential and DSC analysis. Besides this, the magnetic characterization of magnetoliposomes was performed in terms of superparamagnetic behaviour and heating capacity. The biological profile of the platforms and controls was screened through multiple in vitro methods, such as MTT, LDH and scratch assays, together with immunofluorescence staining. In addition, CAM assay was performed in order to assess a possible anti-angiogenic activity induced by the test samples.Results: The physico-chemical analysis revealed that BA-loaded magnetoliposomes present suitable characteristics for the purpose of this study, showing biocompatible phase transition temperature, a diameter of 198 nm, superparamagnetic features and heating capacity. In vitro results showed that hyperthermia induces enhanced anti-tumor activity when breast adenocarcinoma MDA-MB-231 cells were exposed to BA-loaded magnetoliposomes, while a low cytotoxic rate was exhibited by the non-tumorigenic breast epithelial MCF 10A cells. Moreover, the in ovo angiogenesis assay endorsed the efficacy of this multifunctional platform as a good strategy for breast cancer therapy, under hyperthermal conditions. Regarding the possible mechanism of action of this multifunctional nano-platform, the immunocytochemistry of the MCF7 and MDA-MB-231 breast carcinoma cells revealed a microtubule assembly modulatory activity, under hyperthermal conditions.Conclusion: Collectively, these findings indicate that BA-loaded magnetoliposomes, under hyperthermal conditions, might serve as a promising strategy for breast adenocarcinoma treatment.Keywords: magnetoliposomes, hyperthermia, betulinic acid, breast adenocarcinoma

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic represents the primary public health concern nowadays, and great efforts are made worldwide for efficient management of this crisis. Considerable scientific progress was recorded regarding SARS-CoV-2 infection in terms of genomic structure, diagnostic tools, viral transmission, mechanism of viral infection, symptomatology, clinical impact, and complications, but these data evolve constantly. Up to date, neither an effective vaccine nor SARS-CoV-2 specific antiviral agents have been approved, but significant advances were enlisted in this direction by investigating repurposed approved drugs (ongoing clinical trials) or developing innovative antiviral drugs (preclinical and clinical studies). This review presents a thorough analysis of repurposed drug admitted for compassionate use from a chemical structure—biological activity perspective highlighting the ADME (absorption, distribution, metabolism, and excretion) properties and the toxicophore groups linked to potential adverse effects. A detailed pharmacological description of the novel potential anti-COVID-19 therapeutics was also included. In addition, a comprehensible overview of SARS-CoV-2 infection in terms of general description and structure, mechanism of viral infection, and clinical impact was portrayed.

Cancer remains a major health problem worldwide due to its high mortality rate. New therapeutic options highlight the importance of discovering new compounds that target the tumor microenvironment, interrupt angiogenesis and act selectively. The present study assessed the antitumor effect and investigated the mechanism of action of a rhodamine B‑conjugated oleanolic acid derivative (RhodOA). Consequently, the compound was tested on different human tumor cell lines (A375 melanoma, A549 lung adenocarcinoma and MDA‑MB‑231 breast adenocarcinoma) and on a non‑tumor cell line HaCaT human keratinocyte. RhodOA produced a dose‑dependent decrease in tumor cell viability especially in the melanoma cells while affecting the keratinocytes less. In melanoma cells, RhodOA reduced cell migration and produced condensation of cell nuclei and of actin fibers. Furthermore, an impairment in melanoma cell mitochondrial function was observed, while the mitochondrial function of keratinocytes was left intact. In the in ovo chorioallantoic membrane model, RhodOA elicited antiangiogenic effect, without showing irritation effect on the membrane. The study provides information on the selective antitumor effect of the derivative and its ability to inhibit cellular respiration, therefore RhodOA can be classified as 'MITOCAN'.

Breast cancer is the most frequently diagnosed malignant pathology, representing the primary cause of cancer death in women. Natural products are an appealing strategy to limit the progression of the disease. Targeting angiogenesis in breast cancer may positively impact on poor prognosis of breast cancer. As source of natural compounds, we investigated the leaves of Melissa officinalis L. (MO), known as lemon balm, an aromatic plant that spontaneously grows in the South and Western areas of Romania, being traditionally recommended as anxiolytic, antispasmodic, or as digestive remedy. Our aim was to investigate the phytochemical profiling and the antiangiogenic and chemopreventive bioactivity of MO from Banat region, on breast cancer. Two ethanolic extracts of MO (MOE96 and MOE70) and one methanolic extract (MOM80) were subjected to polyphenol and triterpene profiling by HPLC-MS, and the antioxidant capacity was evaluated. The antiangiogenic potential was investigated using the chorioallantoic membrane assay (CAM). The MTT(3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide) assay was used to investigate the cytotoxic effects on MCF-7 and MDA-MB-231breast cancer cells, as well as on MCF-10A normal breast epithelial cells, while apoptosis was performed by DAPI staining. Rosmarinic acid (RA) and ursolic acid (UA) were revealed as dominant phytocompounds. The highest concentration in phytochemicals were found in MOM80; MOE96 was more concentrated in UA, while MOE70 extracted more RA. MOE96 inhibited cancer progression and angiogenesis in the in ovo CAM model using MDA-MB-231 cells, inhibiting breast cancer progression and angiogenesis for the MDA-MB-231 breast cancer cell line; no secondary tumoral areas were registered, indicative for a preventive effect against breast tumor cell invasiveness. The highest cell inhibitory activity was also exhibited by MOE96, in particular against the estrogen receptor positive MCF7 breast cancer cell line, with no cytotoxic effect on healthy cells. The estrogen receptor positive MCF7 cell line proved to be more sensitive to the extract antiproliferative activity than the triple negative MDA-MB-231 breast cancer cell line. Nevertheless, the chemopreventive potential of MOE96 extract is phenotype-dependent and is rather related to the apoptosis and antiangiogenic effects suggesting a multitargeted mechanism of action due to its multiple compound composition next to a concentration ratio of RA : UA in favor of UA.

Superparamagnetic hyperthermia, obtained by increasing the temperature to 42–43 °C in tumor tissue where magnetic nanoparticles are found, as a result of superparamagnetic relaxation, following the application of an external alternating magnetic field at a frequency of hundreds of kiloherz, is an alternative method that is noninvasive and apparently lacking toxicity and that has real potential as a cancer therapy. However, magnetic nanoparticles used as thermal mediators play a very important role in the efficacy of the method in the irreversible destruction of tumors. The NPs must meet a number of physical and magnetic characteristics in order to obtain the maximum hyperthermal effect, but also a reduced or even lack of toxicity on healthy cells. This chapter presents just this aspect of biocompatibility/cytotoxicity and nanoformulations of magnetic nanoparticles for their use in superparamagnetic hyperthermia. We will consider the recent nanoformulations that could be used successfully in superparamagnetic hyperthermia, tested in vitro and in vivo, as well as current trends in dual therapy, thermochemotherapy, or thermo-radiotherapy.

Artemisinin is one of the most important naturally occurring compound found in Artemisia annua, being highly active against Plasmodium falciparum, the malaria causing parasite, and currently studied in the oncological field. The aim of this study was to obtain and characterize the host–guest inclusion complexes formed between artemisinin and three functionalized cyclodextrins, namely Randomly methylated-β-cyclodextrin (CD1), Heptakis(2,6-di-O-methyl)-β-cyclodextrin (CD2) and Heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (CD3). As instrumental tools, thermal analysis (TG/DTG/HF) and UATR-FTIR spectroscopy were used. Later on, the inclusion complexes were tested as to evaluate their antioxidant (AOA) and in vitro activity on both healthy keratinocytes and a human melanoma cell line, A375. Both instrumental techniques suggested the formation of inclusion complexes and the increase of thermal stability of artemisinin in complexes versus pure compound. Regarding the antioxidant activity evaluation of all samples, it was shown that this is significantly inferior in comparison to ascorbic acid, while the in vitro biological activity showed that inclusion complexes (CPX2 and CPX3) exerted an inhibitory effect on human melanoma cells growth, similar to the effect induced by artemisinin.

The present study was aimed to evaluate total phenols, flavonoid and flavonols content and to assess relative cytotoxicity of Medicago sativa hydro-alcoholic and alcoholic leaves and stems extracts on human lung carcinoma (A549) and human breast carcinoma (MDA-MB-231). All extracts tested have proven to be rich in hydroxylated compounds, larger amounts of phenolic compounds were found in extracts obtained using 70% ethanol, a proper polar solvent for this molecule types. Evaluation of antioxidant activity reveals values all most comparable with the ones of ascorbic acid. The extracts induced a cytotoxic effect on both tumor cell lines in a concentration-depend manner.

The lymphatic system is considered to be the second circulatory system within the body, responsible for the maintenance of fluid homeostasis and immune protection. Among the aforementioned roles, it was proved that lymphatics are involved in dissemination of cancer and infections. This review offers a short description of the physiological features of lymphatic network, the lymphatic transport and the main drug delivery systems for lymphatic uptake.

The present study was purported to assess the toxicological profile of bare and polyethylene glycol (PEG) coated spherical silver nanoparticles (AgNPs) by means of in vitro (on human keratinocytes - HaCat cells) and in vivo non-invasive tests (after intraperitoneal - i.p. administration to mice). Bare and PEG-coated AgNPs were synthesized by applying Turkevich's method slightly modified. The physico-chemical characterization revealed the formation of stable, spherical AgNPs and PEG-AgNPs, with narrow size distributions and mean hydrodynamic sizes in the range of 19 nm and 50 nm, respectively. Toxicity data revealed a dose-dependent safe profile for low concentrations of test compounds (

The extensive biochemical research of multiple types of cancer has revealed important enzymatic signaling pathways responsible for tumor occurrence and progression, thus compelling the need for the discovery of new means with which to block these signaling cascades. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) pathway, which plays an important role in maintaining relevant cellular functions, exhibits various alterations in common human cancers, thus representing a suitable target in cancer treatment. Molecules bearing the 1,2,4-triazole moiety are known to possess multiple biological activities, including anticancer activity. The current study used molecular docking in the design of 5-mercapto-1,2,4-triazole derivatives with antiproliferative activity targeting the PI3K/AKT pathway. Three structures emerged as the result of this method, which indicated for these a highly favorable accommodation within the active binding site of PI3K protein, thus acting as potential PI3K inhibitors, and hence interfering with the above-mentioned pathway. The molecules were synthesized and their chemical structure was confirmed. The antiproliferative activity of these compounds was tested on 4 cancer cell lines (A375, B164A5, MDA-MB-231 and A549) and on normal human keratinocytes (HaCaT) by in vitro alamarBlue assay. The 3 compounds revealed antitumor activity against the breast cancer cell line (MDA-MB-231) and reduced toxicity on the normal cell line. The antibacterial activity of the compounds was also tested in vitro on Gram-positive and Gram-negative bacterial strains, revealing moderate activity.

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).

Background Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget’s disease and tumours that cause osteolysis. A major concern related to bisphosphonates therapy is represented by osteonecrosis of jaw, a serious, debilitating, and mostly, a therapy-resistant disease, reported as a frequent side effect of bisphosphonates. In the present study were proposed two approaches: 1) to verify the impact of four commercially available bisphosphonates, very frequently used as oral (Fosamax - F and Actonel - A) and injectable (Ossica - O and Zoledronic acid - Z) therapy on primary human gingival fibroblasts - HGF viability and 2) to evaluate the protective effect of an ozone saline solution on HGF cells pretreated with bisphosphonates. Methods Alamar blue cell viability assay was performed to assess the effect of test compounds (1.5; 2.5; 5 and 10 μM) on gingival fibroblasts viability after a 24 h interval. An ozone - O3 saline solution – 80 µg/mL was added to bisphosphonates pretreated fibroblasts for 24 h and cell viability and cell morphology changes were determined by the means of Alamar blue test and microscopic images. Results Fosamax and Actonel induced a significant reduction of HGF cells viability even at concentrations as low as 2.5 μM (82 and 79.33%) and changes in cells morphology (round and floating cells), effects that were reversed by O3 saline solution administration: an increased cell viability after F and A at 2.5 μM: 147.54 and 120.11%), no changes in cells morphology and an improved confluence. Ossica and Zoledronic acid exerted no cytotoxic effect. Conclusions In conclusion, in these experimental conditions, injectable bisphosphonates (O and Z) proved to be safe for HGF cells, whereas oral compounds (F and A) were cytotoxic even at low concentrations, effects that were counteracted by O3 saline solution administration. Based on these data, ozone saline solution might represent a therapeutic alternative for bisphosphonates noxious effects on oral mucosa cells.

Magnetic iron oxide nanoparticles (MIONPs) were placed in the spotlight lately due to their excellent biocompatibility and the possibility to tailor their magnetic properties making them useful in a plethora of bioapplications, including magnetic resonance imaging and targeted nanoplatforms for anticancer drugs delivery. The aim of the present study consisted in achieving a toxicological profile of the biocompatible colloidal suspension of iron oxide nanoparticles coated with a double layer of oleic acid (Fe₃O₄ @OA) obtained by combustion method by performing

Melissa officinalis is a medicinal herb with an extensive pharmacological profile that has been proven to have beneficial effects in oral and gastrointestinal disorders. However, the effects of this plant in oral, pharyngeal, and colorectal malignancies, types of cancer with an increased incidence in recent years, are less investigated. The present study aims to evaluate the pharmacological profile of a Melissa officinalis total extract for potential benefits in oral, pharynx and colorectal carcinoma. The LC-MS profile of MO total extract (MOte) indicated a rich content in polyphenols, data that support the potent antioxidant capacity exhibited and the antimicrobial activity against both Gram-negative and Gram-positive bacteria. In addition, MOte triggered a dose-dependent and selective decrease in the viability of tumor cells (tongue and pharynx squamous cell carcinomas, and colorectal adenocarcinoma), with the most significant effect being recorded at 100 μg/mL. At the same concentration, MOte exhibited an antiangiogenic effect by inhibiting the process of angiogenesis in ovo. Overall, our findings support the potential benefits of Melissa officinalis leaf total extract as a valuable candidate for the prophylaxis of oral, pharyngeal and colorectal neoplasms.