Claudia Watz

Bio: Claudia Watz is an academic researcher. The author has contributed to research in topics: Medicine & HaCaT. The author has an hindex of 4, co-authored 8 publications receiving 37 citations.

Phytochemical and Biological Screening of Oenothera Biennis L. Hydroalcoholic Extract

Abstract: Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 μmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 μg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells.

Abstract: 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.

Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments

Abstract: Background Objectives: The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. Materials and Methods: The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). Results: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. Conclusions: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.

Solid Polymeric Nanoparticles of Albendazole: Synthesis, Physico-Chemical Characterization and Biological Activity

Abstract: 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.

A Custom-Made Orthodontic Mini-Implant—Effect of Insertion Angle and Cortical Bone Thickness on Stress Distribution with a Complex In Vitro and In Vivo Biosafety Profile

Abstract: 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.

Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.

Abstract: 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.

Food flavonols: Nutraceuticals with complex health benefits and functionalities

Abstract: Background Flavonols are one of the most promising class of bioactive compounds belonging to the broad family of the flavonoids, characterized by a unique set of features in their basic chemical skeleton and several specific substitutions in selected position of the rings A, B and C. This interesting class of phytochemicals includes compounds such as quercetin, kaempferol, myricetin, rhamnetin, morin, fisetin, galagin, azaleatin and their respective glycosyl derivatives. They have been identified in several foods and provide them great health benefits. Scope and approach This review updates and integrates, in a critical fashion, the current knowledge on flavonols as food sources, chemical features, structure-activity relationships, bioavailability and health benefits (from preclinical and clinical studies), focusing on both in vitro and in vivo reports. Key findings and conclusions Dietary flavonols are bioavailable molecules in human with impressive health benefits (such as antioxidation, cardioprotection, antibacterial, antiviral and anticancer activity) and the process of metabolization also produces compounds with remarkable bioactivities just like the corresponding precursors. Their inclusion into human diet is highly recommended for their unquestionable health promoting properties, being excellent nutraceuticals as well as ingredients for good functional food.

Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy.

Abstract: Rutin is a unique antioxidant flavonoid that is mainly found in fruit, vegetables, cereals, and many other plant-based human diets. This review aims to highlight the in vitro anticancer properties of rutin including combination therapeutic strategies. Literature resources were gathered through PubMed, Scopus, Web of Science, and Google Scholar databases that cover the period of 1995-2021. Rutin is demonstrated to inhibit the proliferation of breast, colon, lung, and prostate cancers and other tumors. Furthermore, rutin alone or in combination with other therapeutic agents has been shown to regulate several signalling pathways involving the Ras/Raf and PI3K/Akt, MAPK, and TGF-β2/Smad2/3Akt/PTEN, etc., which are related to the processes of carcinogenesis and induction of apoptosis. The combination of rutin with other chemotherapy drugs may benefit on prevention of tumor cells by decreasing drug resistance and chemotherapy side effects. Moreover, rutin induces apoptosis synergistically with the therapeutic agent. More in vivo and clinical data are however needed to evaluate the true potential of rutin as an anticancer agent as an adjuvant. The present review highlights the effects of rutin which can be a promising candidate in combination with other antitumor drugs or alone for cancer treatment in vitro. Also, rutin can lead to decrease in drug resistance and chemotherapeutic side effects.

Albendazole and Mebendazole as Anti-Parasitic and Anti-Cancer Agents: an Update

Abstract: The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

Thermosensitive Betulinic Acid-Loaded Magnetoliposomes: A Promising Antitumor Potential for Highly Aggressive Human Breast Adenocarcinoma Cells Under Hyperthermic Conditions.

Abstract: Purpose 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.