Synthesis, In Vivo Anticonvulsant Activity Evaluation and In Silico Studies of Some Quinazolin-4(3H)-One Derivatives.

Two series, "a" and "b", each consisting of nine chemical compounds, with 2,3-disubstituted quinazolin-4(3H)-one scaffold, were synthesized and evaluated for their anticonvulsant activity. They were investigated as dual potential positive allosteric modulators of the GABAA receptor at the benzodiazepine binding site and inhibitors of carbonic anhydrase II. Quinazolin-4(3H)-one derivatives were evaluated in vivo (D1-3 = 50, 100, 150 mg/kg, administered intraperitoneally) using the pentylenetetrazole (PTZ)-induced seizure model in mice, with phenobarbital and diazepam, as reference anticonvulsant agents. The in silico studies suggested the compounds act as anticonvulsants by binding on the allosteric site of GABAA receptor and not by inhibiting the carbonic anhydrase II, because the ligands-carbonic anhydrase II predicted complexes were unstable in the molecular dynamics simulations. The mechanism targeting GABAA receptor was confirmed through the in vivo flumazenil antagonism assay. The pentylenetetrazole experimental anticonvulsant model indicated that the tested compounds, 1a-9a and 1b-9b, present a potential anticonvulsant activity. The evaluation, considering the percentage of protection against PTZ, latency until the onset of the first seizure, and reduction in the number of seizures, revealed more favorable results for the "b" series, particularly for compound 8b.

Discovery of A Novel Series of Quinazoline-Thiazole Hybrids as Potential Antiproliferative and Anti-Angiogenic Agents.

Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series of quinazoline-thiazole hybrids (SA01-SA07) as antiproliferative and anti-angiogenic agents. Four out of the seven compounds displayed superior antiproliferative activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib (IC50 = 6.28 µM). The affinity towards the VEGFR2 kinase domain was assessed through in silico prediction by molecular docking, molecular dynamics studies, and MM-PBSA. The series displayed a high degree of similarity to sorafenib regarding the binding pose within the active site of VEGFR2, with a different orientation of the 4-substituted-thiazole moieties in the allosteric pocket. Molecular dynamics and MM-PBSA evaluations identified SA05 as the hybrid forming the most stable complex with VEGFR2 compared to sorafenib. The impact of the compounds on vascular cell proliferation was assessed on EA.hy926 cells. Six compounds (SA01-SA05, SA07) displayed superior anti-proliferative activity (IC50 = 0.79-5.85 µM) compared to sorafenib (IC50 = 6.62 µM). The toxicity was evaluated on BJ cells. Further studies of the anti-angiogenic effect of the most promising compounds, SA04 and SA05, through the assessment of impact on EA.hy296 motility using a wound healing assay and in ovo potential in a CAM assay compared to sorafenib, led to the confirmation of the anti-angiogenic potential.

The impact of chronic Trimethylamine N-oxide administration on liver oxidative stress, inflammation, and fibrosis.

TMAO, a gut microbiota derived byproduct, has been associated with various cardiometabolic diseases by promoting oxidative stress and inflammation. The liver is the main organ for TMAO production and chronic exposure to high doses of TMAO could alter its function. In this study, we evaluated the effect of chronic exposure of high TMAO doses on liver oxidative stress, inflammation, and fibrosis. TMAO was administered daily via gastric gavage to laboratory rats for 3 months. Blood was drawn for the quantification of TMAO, and liver tissues were harvested for the assessment of oxidative stress (MDA, GSH, GSSG, GPx, CAT, and 8-oxo-dG) and inflammation by quantification of IL-1α, TNF-α, IL-10, TGF-ß, NOS and COX-2 expression. The evaluation of fibrosis was made by Western blot analysis of α-SMA and Collagen-3 protein expression. Histological investigation and immunohistochemical staining of iNOS were performed in order to assess the liver damage. After 3 months of TMAO exposure, TMAO serum levels enhanced in parallel with increases in MDA and GSSG levels in liver tissue and lower values of GSH and GSH/GSSG ratio as well as a decrease in GPx and CAT activities. Inflammation was also highlighted, with enhanced iNOS, COX-2, and IL-10 expression, without structural changes and without induction of liver fibrosis.

Selection of a Digitalis purpurea Cell Line with Improved Bioconversion Capacity of Hydroquinone into Arbutin.

This study aimed to investigate the biotransformation capabilities of a hydroquinone-tolerant Digitalis purpurea cell line (DpHQ) for bioconverting hydroquinone (HQ) into arbutin, a compound with significant therapeutic and cosmetic applications. The research evaluated the influence of various HQ concentrations, feeding protocols, and carbon sources on arbutin bioconversion yield. By using HPLC-MS for the quantification of arbutin in biomass and medium, the study revealed that higher precursor (HQ) concentration led to a more pronounced growth inhibition under single dosing than sequential dosing. At lower sugar (3%) and precursor (4 mM HQ) levels, arbutin predominantly remained within the cells, whereas higher sugar (6%) and HQ (5-6 mM) levels promoted its release into the medium. Arbutin production ranged from 591 mg/L under single dosing to 3049 mg/L with sequential dosing, with the highest yield being achieved with 5 mM HQ in divided doses and 6% glucose. This study holds novelty for being the first to demonstrate the DpHQ's tolerance to high concentrations of HQ and its efficient capabilities to bioconvert HQ to arbutin, indicating that D. purpurea is equipped with the enzymes required for this process. These aspects highlight its potential as a biotechnological source for arbutin synthesis.

Recent Updates Regarding the Antiproliferative Activity of Galium verum Extracts on A375 Human Malignant Melanoma Cell Line.

The biological activity of Galium verum herba was exerted on various tumor cell lines with incredible results, but their potential effect on malignant melanoma has not been established yet. Therefore, the current study was structured in two directions: (i) the investigation of the phytochemical profile of diethyl ether (GvDEE) and butanol (GvBuOH) extracts of G. verum L. and (ii) the evaluation of their biological profile on A375 human malignant melanoma cell line. The GvDEE extract showed an FT-IR profile different from the butanol one, with high antioxidant capacity (EC50 of GvDEE = 0.12 ± 0.03 mg/mL > EC50 of GvBuOH = 0.18 ± 0.05 mg/mL). The GvDEE extract also showed antimicrobial potential, especially against Gram-positive bacteria strains, compared to the butanol extract, which has no antimicrobial activity against any bacterial strain tested. The results regarding the antitumor potential showed that both extracts decreased A375 cell viability largely (69% at a dose of 55 µg/mL of the GvDEE extract). Moreover, both extracts induce nuclear fragmentation by forming apoptotic bodies and slight chromatin condensation, which is more intense for GvDEE. Considering the results, one can state that the Galium verum herba possesses antitumor effects on the A375 human malignant melanoma cell line, a promising phytocompound for the antitumor approach to skin cancer.

Investigation of Epilobium hirsutum L. Optimized Extract's Anti-Inflammatory and Antitumor Potential.

Epilobium hirsutum L., commonly known as hairy willowherb, is a perennial herbaceous plant native to Europe and Asia. In Romania, the Epilobium genus includes 17 species that are used in folk medicine for various purposes. This study aimed to investigate the anti-inflammatory and antitumor potential of the optimized extract of Epilobium hirsutum (EH) in animal models. The first study investigated the anti-inflammatory properties of EH optimized extract and the model used was carrageenan-induced paw inflammation. Wistar rats were divided into three groups: negative control, positive control treated with indomethacin, and a group treated with the extract. Oxidative stress markers, cytokine levels, and protein expressions were assessed. The extract demonstrated anti-inflammatory properties comparable to those of the control group. In the second study, the antitumor effects of the extract were assessed using the tumor model of Ehrlich ascites carcinoma. Swiss albino mice with Ehrlich ascites were divided into four groups: negative, positive treated with cyclophosphamide (Cph), Group 3 treated with Cph and EH optimized extract, and Group 4 treated with extract alone. Samples from the ascites fluid, liver, and heart were analyzed to evaluate oxidative stress, inflammation, and cancer markers. The extract showed a reduction in tumor-associated inflammation and oxidative stress. Overall, the EH optimized extract exhibited promising anti-inflammatory and antitumor effects in the animal models studied. These findings suggest its potential as a natural adjuvant therapeutic agent for addressing inflammation and oxidative stress induced by different pathologies.

Phytochemical and Nutraceutical Screening of Ethanol and Ethyl Acetate Phases of Romanian Galium verum Herba (Rubiaceae).

Galium species are used worldwide for their antioxidant, antibacterial, antifungal, and antiparasitic properties. Although this plant has demonstrated its antitumor properties on various types of cancer, its biological activity on cutaneous melanoma has not been established so far. Therefore, the present study was designed to investigate the phytochemical profile of two extracts of G. verum L. herba (ethanolic and ethyl acetate) as well as the biological profile (antioxidant, antimicrobial, and antitumor effects) on human skin cancer. The extracts showed similar FT-IR phenolic profiles (high chlorogenic acid, isoquercitrin, quercitrin, and rutin), with high antioxidant capacity (EC50 of ethyl acetate phase (0.074 ± 0.01 mg/mL) > ethanol phase (0.136 ± 0.03 mg/mL)). Both extracts showed antimicrobial activity, especially against Gram-positive Streptococcus pyogenes and Staphylococcus aureus bacilli strains, the ethyl acetate phase being more active. Regarding the in vitro antitumor test, the results revealed a dose-dependent cytotoxic effect against A375 melanoma cell lines, more pronounced in the case of the ethyl acetate phase. In addition, the ethyl acetate phase stimulated the proliferation of human keratinocytes (HaCaT), while this effect was not evident in the case of the ethanolic phase at 24 h post-stimulation. Consequently, G. verum l. could be considered a promising phytocompound for the antitumor approach of cutaneous melanoma.

Stachys Species: Comparative Evaluation of Phenolic Profile and Antimicrobial and Antioxidant Potential.

This study aimed to investigate the polyphenolic composition and antioxidant and antimicrobial potential of six Romanian Stachys species: S. officinalis, S. germanica, S. byzantina, S. sylvatica, S. palustris, and S. recta. The LC-MS/MS method was used to analyze the polyphenolic profile, while the phenolic contents were spectrophotometrically determined. The antioxidant activity was evaluated using the following methods: DPPH, FRAP, nitrite-induced autooxidation of hemoglobin, inhibition of cytochrome c-catalyzed lipid peroxidation, and electron paramagnetic resonance spectroscopy. The in vitro antimicrobial properties were assessed using agar-well diffusion, broth microdilution, and antibiofilm assays. Fifteen polyphenols were identified using LC-MS and chlorogenic acid was the major component in all the samples (1131.8-6761.4 µg/g). S. germanica, S. palustris, and S. byzantina extracts each displayed an intense antiradical action in relation to high contents of TPC (6.40 mg GAE/mL), flavonoids (3.90 mg RE/mL), and caffeic acid derivatives (0.89 mg CAE/mL). In vitro antimicrobial and antibiofilm properties were exhibited towards Candida albicans, Gram-positive and Gram-negative strains, with the most intense efficacy recorded for S. germanica and S. byzantina when tested against S. aureus. These results highlighted Stachys extracts as rich sources of bioactive compounds with promising antioxidant and antimicrobial efficacies and important perspectives for developing phytopharmaceuticals.

Discovery of New Hydrazone-Thiazole Polyphenolic Antioxidants through Computer-Aided Design and In Vitro Experimental Validation.

Oxidative stress is linked to a series of diseases; therefore, the development of efficient antioxidants might be beneficial in preventing or ameliorating these conditions. Based on the structure of a previously reported compound with good antioxidant properties and on computational studies, we designed several catechol derivatives with enhanced antioxidant potential. The compounds were synthesized and physicochemically characterized, and their antioxidant activity was assessed through different antiradical, electron transfer and metal ions chelation assays, their electrochemical behavior and cytotoxicity were studied. The results obtained in the in vitro experiments correlated very well with the in silico studies; all final compounds presented very good antioxidant properties, generally superior to those of the reference compounds used. Similarly, the results obtained from studying the compounds' electrochemical behavior were in good agreement with the results of the antioxidant activity evaluation assays. Regarding the compounds' cytotoxicity, compound 7b had a dose-dependent inhibitory effect against all cell lines. In conclusion, through computer-aided design, we developed several catechol thiazolyl-hydrazones with excellent antioxidant properties, of which compound 7b, with two catechol moieties in its structure, exhibited the best antioxidant activity.

Formulation and Characterization of Mucoadhesive Polymeric Films Containing Extracts of Taraxaci Folium and Matricariae Flos.

Taraxaci folium and Matricariae flos plant extracts contain a wide range of bioactive compounds with antioxidant and anti-inflammatory effects. The aim of the study was to evaluate the phytochemical and antioxidant profile of the two plant extracts to obtain a mucoadhesive polymeric film with beneficial properties in acute gingivitis. The chemical composition of the two plant extracts was determined by high-performance liquid chromatography coupled with mass spectrometry. To establish a favourable ratio in the combination of the two extracts, the antioxidant capacity was determined by the method of reduction of copper ions Cu2+ from neocuprein and by reduction of the compound 1.1-diphenyl-2-2picril-hydrazyl. Following preliminary analysis, we selected the plant mixture Taraxaci folium/matricariae flos in the ratio of 1:2 (m/m), having an antioxidant capacity of 83.92% ± 0.02 reduction of free nitrogen radical of 1.1-diphenyl-2-2picril-hydrazyl reagent. Subsequently, bioadhesive films of 0.2 mm thickness were obtained using various concentrations of polymer and plant extract. The mucoadhesive films obtained were homogeneous and flexible, with pH ranging from 6.634 to 7.016 and active ingredient release capacity ranging from 85.94-89.52%. Based on in vitro analysis, the film containing 5% polymer and 10% plant extract was selected for in vivo study. The study involved 50 patients undergoing professional oral hygiene followed by a 7-day treatment with the chosen mucoadhesive polymeric film. The study showed that the film used helped accelerate the healing of acute gingivitis after treatment, with anti-inflammatory and protective action.

An In Vitro and In Vivo Assessment of Antitumor Activity of Extracts Derived from Three Well-Known Plant Species.

One of the objectives of this study consists of the assessment of the antitumor activity of several extracts from three selected plant species: Xanthium spinosum L., Trifolium pratense L., and Coffea arabica L. and also a comparative study of this biological activity, with the aim of establishing a superior herbal extract for antitumor benefits. The phytochemical profile of the extracts was established by HPLC-MS analysis. Further, the selected extracts were screened in vitro for their antitumor activity and antioxidant potential on two cancer cell lines: A549-human lung adenocarcinoma and T47D-KBluc-human breast carcinoma and on normal cells. One extract per plant was selected for in vivo assessment of antitumor activity in an Ehrlich ascites mouse model. The extracts presented high content of antitumor compounds such as caffeoylquinic acids in the case of X. spinosum L. (7.22 µg/mL-xanthatin, 4.611 µg/mL-4-O-caffeoylquinic acid) and green coffee beans (10.008 µg/mL-cafestol, 265.507 µg/mL-4-O-caffeoylquinic acid), as well as isoflavones in the case of T. pratense L. (6806.60 ng/mL-ononin, 102.78 µg/mL-biochanin A). Concerning the in vitro results, the X. spinosum L. extracts presented the strongest anticancerous and antioxidant effects. In vivo, ascites cell viability decreased after T. pratense L. and green coffee bean extracts administration, whereas the oxidative stress reduction potential was important in tumor samples after T. pratense L. Cell viability was also decreased after administration of cyclophosphamide associated with X. spinosum L. and T. pratense L. extracts, respectively. These results suggested that T. pratense L. or X. spinosum L. extracts in combination with chemotherapy can induce lipid peroxidation in tumor cells and decrease the tumor viability especially, T. pratense L. extract.

New Approaches on the Anti-Inflammatory and Cardioprotective Properties of Taraxacum officinale Tincture.

The present research investigated the in vivo anti-inflammatory and cardioprotective activities, as well as the antioxidant potential of Taraxacum officinale tincture (TOT), in relation to the polyphenolic composition. Chromatographic and spectrophotometric techniques were used to determine the polyphenolic profile of TOT and the antioxidant activity was preliminarily assessed in vitro by DPPH• and FRAP spectrophotometric methods. The in vivo anti-inflammatory and cardioprotective activities were studied in rat turpentine-induced inflammation and in rat isoprenaline-induced myocardial infarction (MI) models. The main polyphenolic compound identified in TOT was cichoric acid. The oxidative stress determinations showed the capacity of the dandelion tincture not only to decrease the total oxidative stress (TOS), the oxidative stress index (OSI), and the total antioxidant capacity (TAC), but also the malondialdehide (MDA), thiols (SH), and nitrites/nitrates (NOx) levels both in inflammation and MI models. In addition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatin kinase-MB (CK-MB), and nuclear factor kappa B (NF-κB) parameters were decreased by the administration of the tincture. The results show that T. officinale could be considered a valuable source of natural compounds with important benefits in pathologies linked to oxidative stress.

The In Vitro Anticoccidial Activity of Some Herbal Extracts against Eimeria spp. Oocysts Isolated from Piglets.

Coccidiosis in pigs seldom results in important economic losses. However, it can influence growth rates in weaners and it is an important hygiene indicator in swine farms. Certain herbs, along with their extracts, have been used over the course of history in traditional medicine. The aim of this study was to evaluate the in vitro anticoccidial effects of Allium sativum L. (garlic), Artemisia absinthium L. (wormwood), Coriandrum sativum L. (coriander), Cucurbita pepo L. (pumpkin), Satureja hortensis L. (summer savory), and Calendula officinalis L. (marigold) against Eimeria suis and Eimeria debliecki oocysts. The stock solution of oocysts (58% E. suis + 42% E. debliecki) was incubated for three days, before adding the tested solutions. The unsporulated Eimeria spp. oocysts were then placed in a 3 mL well plate and incubated for 96 h at 27 °C, in a suspension containing serial dilutions of alcoholic plant extracts (5%, 2.5%, 1.25%, 0.625%, and 0.312%). The percentage of sporulated and destroyed oocysts was recorded every 24 h for 96 h. All extracts had a good in vitro anticoccidial effect against oocysts of Eimeria spp. compared with the control groups. Oocyst sporulation was significantly (p = 0.05) inhibited by the 5% marigold extract (3.6% sporulated oocysts). The same extract had the highest lytic effect on oocysts (65.2% destroyed oocysts). Our results prove that the most effective alcoholic plant extract is the marigold extract, followed, in order of efficiency, by the wormwood, coriander, garlic, pumpkin, and summer savory extracts. This study represents a preliminary contribution for establishing a new generation of natural disinfectants aimed at destroying Eimeria oocysts in the context of swine contamination.

The Effect of Extraction Methods on Phytochemicals and Biological Activities of Green Coffee Beans Extracts.

The objectives of the present study consisted of identifying the impact of extraction methods and parameters held over the phytochemistry and biological activities of green coffee beans. Extraction processes belonging to two categories were performed: classical methods-maceration, Soxhlet extraction, and such innovative methods as turboextraction, ultrasound-assisted extraction, and a combination of the latter two. Total polyphenolic and flavonoid content, as well as in vitro antioxidant activity of the resulted extracts were spectrophotometrically determined. Extracts displaying the highest yields of bioactive compounds were subjected to High Performance Liquid Chromatography-Mass Spectrometry analysis. The extracts with the best phytochemical profiles were selected for biological activity assessment. In vivo, a model of plantar inflammation in Wistar rats was used to determine antioxidant activity, by evaluating the oxidative stress reduction potential, and anti-inflammatory activity. In vitro antimicrobial activity was also determined. The Soxhlet extraction and ultrasound-assisted extraction gave the highest bioactive compound yields. The highest total polyphenolic content was 2.691 mg/mL gallic acid equivalents and total flavonoid content was 0.487 mM quercetin equivalents for the Soxhlet extract subjected to 60 min extraction time. Regarding the antioxidant activity, ultrasound-assisted extraction reached the highest levels, i.e., 9.160 mg/mL Trolox equivalents in the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and 26.676 mM Trolox equivalents in the FRAP (Ferric Reducing Antioxidant Power) assay, at a 30 min extraction time and 50 °C extraction temperature. The 60 min Soxhlet extract reached the highest level for the ABTS+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, 16.136 mM Trolox equivalents, respectively. Chlorogenic acid was present in the highest concentration in the same Soxhlet extract, 1657.179 µg/mL extract, respectively. Sterolic compounds were found in high concentrations throughout all the analyzed extracts. A proportional increase between yields and extraction parameter values was observed. Increased inhibition of Gram-negative bacteria was observed. The finally selected Soxhlet extract, that of 60 min extraction time, presented a significant in vivo antioxidant activity, with a slight anti-inflammatory activity. Antioxidant levels were elevated after 2 h of extract administration. Pro-inflammatory cytokine secretion was not influenced by the administration of the extract.

Antioxidants in Age-Related Diseases and Anti-Aging Strategies.

Aging is an intricate process and an important risk factor in the development and advancement of many disorders [...].

Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients.

Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients' survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller-Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs and tissue samples, indicating that the mechanisms of miRNA sorting into sEVs still needs to be elucidated. Functional analysis of miRNA target genes and drug interactions revealed that candidate miRNAs and their targets, can be regulated by different NAT regimens. This evidence supports their role in governing the patients' therapy response and highlights their potential use as prediction biomarkers.

The Effects of Allium sativum L., Artemisia absinthium L., Cucurbita pepo L., Coriandrum sativum L., Satureja hortensis L. and Calendula officinalis L. on the Embryogenesis of Ascaris suum Eggs during an In Vitro Experimental Study.

Ascaris suum is present in traditionally managed indoor pig herds and in industrialized farms, especially in older fatteners and sows. The increasing resistance to common antihelminthic drugs redirected research towards alternative and traditional therapies, which also include medicinal plants. This study comparatively evaluated the in vitro antiparasitic effects of Allium sativum L., Artemisia absinthium L., Cucurbita pepo L., Coriandrum sativum L., Satureja hortensis L. and Calendula officinalis L. against A. suum egg hatching and larval development. A. suum eggs were sampled from randomized fecal specimens collected from traditionally raised swine. The egg suspension (ES, 12 × 103/mL) was divided into two controls (C) (1C-1 mL ES + 1 mL distilled water, 2C-five plates of 1 mL ES + 1 mL ethanol of 70%, 35%, 17.5%, 8.75%, and 4.375%, respectively) and six experimental groups, and placed in 3 mL cell plates. The experimental groups (EG, 1-6) included ES + each alcoholic plant extract (10%, 5%, 2.5%, 1.25%, 0.625%). Both C and EG were performed in quintuplicate. All variants were incubated at 27 °C for a total of 21 days. A. suum eggs were examined after 2, 14 (L1), and 21 (L2/L3) days of incubation. The efficacy of all tested plant extracts increased with concentration. Anti-embryogenic effects on A. suum eggs were expressed by all plants. A superior influence was observed in A. sativum L., A. absinthium L., C. pepo L. and S. hortensis L. extracts, at all concentrations tested. A. sativum L. and A. absinthium L. extracts showed the strongest antihelminthic activity, while C. sativum L. and C. officinalis L. were the weakest ascaricids. Future in-depth phytochemical studies are required to identify the compounds responsible for the anthelminthic properties of these plant species.

Breast Cancer-Delivered Exosomal miRNA as Liquid Biopsy Biomarkers for Metastasis Prediction: A Focus on Translational Research with Clinical Applicability.

Metastasis represents the most important cause of breast cancer-associated mortality. Even for early diagnosed stages, the risk of metastasis is significantly high and predicts a grim outcome for the patient. Nowadays, efforts are made for identifying blood-based biomarkers that could reliably distinguish patients with highly metastatic cancers in order to ensure a closer follow-up and a more personalized therapeutic method. Exosomes are nano vesicles secreted by cancer cells that can transport miRNAs, proteins, and other molecules and deliver them to recipient cells all over the body. Through this transfer, cancer cells modulate their microenvironment and facilitate the formation of the pre-metastatic niche, leading to sustained progression. Exosomal miRNAs have been extensively studied due to their promising potential as prognosis biomarkers for metastatic breast cancer. In this review, we tried to depict an overview of the existing literature regarding exosomal miRNAs that are already validated as potential biomarkers, and which could be immediately available for the clinic. Moreover, in the last section, we highlighted several miRNAs that have proven their function in preclinical studies and could be considered for clinical validation. Considering the lack of standard methods for evaluating exosomal miRNA, we also discussed the challenges and the technical aspects underlying this issue.

Antioxidant Activity Evaluation and Assessment of the Binding Affinity to HSA of a New Catechol Hydrazinyl-Thiazole Derivative.

Polyphenols have attained pronounced attention due to their ability to provide numerous health benefits and prevent several chronic diseases. In this study, we designed, synthesized and analyzed a water-soluble molecule presenting a good antioxidant activity, namely catechol hydrazinyl-thiazole (CHT). This molecule contains 3',4'-dihydroxyphenyl and 2-hydrazinyl-4-methyl-thiazole moieties linked through a hydrazone group with very good antioxidant activity in the in vitro evaluations performed. A preliminary validation of the CHT developing hypothesis was performed evaluating in silico the bond dissociation enthalpy (BDE) of the phenol O-H bonds, compared to our previous findings in the compounds previously reported by our group. In this paper, we report the binding mechanism of CHT to human serum albumin (HSA) using biophysical methods in combination with computational studies. ITC experiments reveal that the dominant forces in the binding mechanism are involved in the hydrogen bond or van der Waals interactions and that the binding was an enthalpy-driven process. NMR relaxation measurements were applied to study the CHT-protein interaction by changing the drug concentration in the solution. A molecular docking study added an additional insight to the experimental ITC and NMR analysis regarding the binding conformation of CHT to HSA.

Polyphenolic Profile, Anti-Inflammatory and Anti-Nociceptive Activities of Some African Medicinal Plants.

The aim of the present study was to investigate the polyphenolic profile and the anti-inflammatory and anti-nociceptive activities of four traditionally used medicinal plants from Burkina Faso: Parkia biglobosa, Detarium microcarpum, Vitellaria paradoxa and Sclerocarya birrea. The analysis of the main phenolic compounds was performed by the HPLC-UV-MS method. The anti-inflammatory effect of the aqueous bark extracts was investigated by the λ-carrageenan-induced rat paw edema test. The anti-nociceptive activity was evaluated by the Randall−Selitto test under inflammatory conditions. Seven phenolic acids (gallic, protocatechuic, gentisic, vanillic, p-coumaric, ferulic, and syringic acids), and three flavonoids (catechin, epicatechin, and quercitrin) were identified in the plant samples. High contents of gallic acid were determined in the D. microcarpum, P. biglobosa and S. birrea extracts (190−300 mg/100 g), and V. paradoxa extract was the richest in epicatechin (173.86 mg/100 g). The λ-carrageenan-induced inflammation was significantly reduced (p < 0.001) by the P. biglobosa and D. microcarpum extracts (400 mg/kg p.o.). Under the inflammatory conditions, a significant anti-nociceptive activity (p < 0.001) was obtained after 2−3 h from the induction of inflammation. The effects of the tested extracts could be related to the presence of polyphenols and could be useful in the management of certain inflammatory diseases.