Geographical Origin Authentication-A Mandatory Step in the Efficient Involvement of Honey in Medical Treatment.

Nowadays, in people's perceptions, the return to roots in all aspects of life is an increasing temptation. This tendency has also been observed in the medical field, despite the availability of high-level medical services with many years of research, expertise, and trials. Equilibrium is found in the combination of the two tendencies through the inclusion of the scientific experience with the advantages and benefits provided by nature. It is well accepted that the nutritional and medicinal properties of honey are closely related to the botanical origin of the plants at the base of honey production. Despite this, people perceive honey as a natural and subsequently a simple product from a chemical point of view. In reality, honey is a very complex matrix containing more than 200 compounds having a high degree of compositional variability as function of its origin. Therefore, when discussing the nutritional and medicinal properties of honey, the importance of the geographical origin and its link to the honey's composition, due to potential emerging contaminants such as Rare Earth Elements (REEs), should also be considered. This work offers a critical view on the use of honey as a natural superfood, in a direct relationship with its botanical and geographical origin.

The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.

This study delves into the critical role of alarmins in chronic spontaneous urticaria (CSU), focusing on their impact on disease severity and the quality of life (QoL) of patients. We investigated the alterations in alarmin levels in CSU patients and their correlations with the Urticaria Activity Score (UAS7) and the Dermatology Life Quality Index (DLQI). We analyzed serum levels of interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP) in 50 CSU patients, comparing these to 38 healthy controls. The study examined the relationship between alarmin levels and clinical outcomes, including disease severity and QoL. Elevated levels of IL-33 and TSLP in CSU patients (p < 0.0001) highlight their potential role in CSU pathogenesis. Although IL-25 showed higher levels in CSU patients, this did not reach statistical significance (p = 0.0823). Crucially, IL-33's correlation with both UAS7 and DLQI scores underscores its potential as a biomarker for CSU diagnosis and severity assessment. Of the alarmins analyzed, IL-33 emerges as particularly significant for further exploration as a diagnostic and prognostic biomarker in CSU. Its substantial correlation with disease severity and impact on QoL makes it a compelling candidate for future research, potentially serving as a target for therapeutic interventions. Given these findings, IL-33 deserves additional investigation to confirm its role and effectiveness as a biomarker and therapeutic target in CSU.

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.

Lactobacillus rhamnosus probiotic treatment modulates gut and liver inflammatory pathways in a hepatocellular carcinoma murine model. A preliminary study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a growing global concern with an increasing incidence rate. The intestinal microbiota has been identified as a potential culprit in modulating the effects of antitumoral drugs. We aimed to assess the impact of adding Lactobacillus rhamnosus probiotic to regorafenib in mice with HCC. METHODS: Cirrhosis and HCCs were induced in 56 male Swiss mice via diethylnitrosamine injection and carbon tetrachloride administration. Mice were divided into four groups: treated with vehicle (VC), regorafenib (Rego), L. rhamnosus probiotic, and a combination of regorafenib and probiotic (Rego-Pro). After 3 weeks of treatment, liver and intestinal fragments were collected for analysis. RESULTS: Regorafenib elevated gut permeability, an effect mitigated by probiotic intervention, which exhibited a notable correlation with reduced inflammation (p < 0.01). iNOS levels were also reduced by adding the probiotic with respect to the mice treated with regorafenib only (p < 0.001). Notably, regorafenib substantially increased IL-6, TNF-a and TLR4 in intestinal fragments (p < 0.01). The administration of the probiotic effectively restored IL-6 to its initial levels (p < 0.001). CONCLUSION: Reducing systemic and intestinal inflammation by administering L. rhamnosus probiotic may alleviate tumoral resistance and systemic adverse effects.

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-tumorigenic attributes, such as its role in immune response activation, cellular senescence induction, and tumor surveillance. Through a comprehensive exploration of the intricate interactions between IL-6 and the tumor microenvironment, this review highlights the need for a nuanced comprehension of IL-6 signaling in HCC. It underscores the importance of tailored therapeutic strategies that consider the dynamic stages and diverse surroundings within the tumor microenvironment. Future research directions aimed at unraveling the multifaceted mechanisms of IL-6 in HCC hold promise for developing more effective treatment strategies and improving patient outcomes.

Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review.

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts); the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoprotegerin, osterix, RANKL, Runx2); and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/ß, Notch, BMP, SMAD). Some phytochemical compounds-such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others-presented a beneficial and stimulating effect in the bone regeneration process due to the pro-estrogenic activity, the antioxidant and the anti-inflammatory effect and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone-related pathologies envisaged through the incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

IL-31-Pruritus Interleukin: Serum Values and Clinical Impact in Chronic Spontaneous Urticaria-A Romanian Retrospective Study.

(1) Background: This study aimed to evaluate the implications of interleukin-31 (IL-31) in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters that were identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the accepted international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Significantly elevated serum IL-31 levels were observed in CSU patients compared to the controls (p < 0.0001). Although no direct correlations were found between IL-31 and inflammatory markers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)), eosinophils, or total immunoglobulins E (IgE), significant differences in IL-31 levels were identified based on CSU severity, quality of life impact, itch intensity, and response to histamine H1 receptor antagonists (H1 antihistamines) (p < 0.05 for all). (4) Conclusions: Our findings underscore that IL-31 is not directly associated with general inflammation, eosinophilic response, or atopy in CSU. Nevertheless, its expression is influenced by key disease characteristics: severity, pruritus, and H1 antihistamine response. This investigation provides essential insights into CSU pathogenesis, potentially leading to novel therapeutic interventions. An enhanced understanding of these mechanisms is crucial due to the limitations of current treatment modalities in terms of fully managing CSU symptoms.

Goji-Berry-Mediated Green Synthesis of Gold Nanoparticles and Their Promising Effect on Reducing Oxidative Stress and Inflammation in Experimental Hyperglycemia.

The present report focuses on a rapid and convenient method applicable in the green synthesis of gold nanoparticles (AuNPs) using goji berry (Lycium barbarum-LB) extracts rich in antioxidant compounds, as well as on the structural analysis and evaluation of the induced antioxidant protection and anti-inflammatory effects of the synthesized gold nanoparticles upon endothelial cells (HUVECs) exposed to hyperglycemia. The synthesized AuNPs were characterized using ultraviolet-visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM), whereas the presence of bioactive compounds from the L. barbarum fruit extract on the surface of the nanoparticles was confirmed using Fourier transform infrared spectroscopy (FTIR). The antioxidant activity of the biosynthesized gold nanoparticles was evaluated on the HUVEC cell line. The results reveal that AuNPs with a predominantly spherical shape and an average size of 30 nm were obtained. The UV-Vis spectrum showed a characteristic absorption band at λmax = 536 nm of AuNPs. FTIR analysis revealed the presence of phenolic acids, flavonoids and carotenoids acting as capping and stabilizing agents of AuNPs. Both the L. barbarum extract and AuNPs were well tolerated by HUVECs, increased the antioxidant defense and decreased the production of inflammatory cytokines induced via hyperglycemia-mediated oxidative damage.

Effects of Gold Nanoparticles Phytoreduced with Rutin in an Early Rat Model of Diabetic Retinopathy and Cataracts.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycaemia. Plant-based therapies are characterised by low tissue bioavailability. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Eye fundus of retinal arterioles, transmission electron microscopy (TEM) of lenses, and histopathology of retinas were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fibre disorganisation. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately oedematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA and increased antioxidant capacity. Retinal edema and disorganisation in lens fibres were still present.

Sweeteners' Influence on In Vitro α-Glucosidase Inhibitory Activity, Cytotoxicity, Stability and In Vivo Bioavailability of the Anthocyanins from Lingonberry Jams.

Several lines of evidence demonstrate the multiple health-promoting properties of anthocyanins, but little is known regarding the bioavailability of these phytochemicals. Therefore, the stability during storage and bioavailability of anthocyanins from lingonberries jams were determined by HPLC, together with the impact of used sweeteners on their adsorption. Further, the in vitro α-glucosidase inhibition using spectrophotometric methods and cytotoxicity determined on normal and colon cancer cells were communicated. The content of anthocyanins was significantly decreased during storage in coconut sugar-based jam, but was best preserved in jam with fructose and stevia. Fructose and stevia-based jams showed the highest inhibition activity upon α-glucosidase. Lingonberry jams showed no cytotoxic effects on normal cells, but at low concentration reduced the tumor cells viability. Anthocyanins were still detectable in rats' blood streams after 24 h, showing a prolonged bioavailability in rats. This study brings important results that will enable the development of functional food products.

The effect of curcumin on reserpine-induced depression-like behaviour in rats.

The aim of this study was to construct an animal model of depression that reproduces the human clinical manifestation, to evaluate the possible benefits of curcumin (CUR) in the treatment of depression and to compare its effect with the effect of a classic antidepressant, escitalopram (ESC). The behavior of depressive-like animals induced by administration of 1.5 mg/kg i. p. reserpine (R), during 10 days (n = 24) was evaluated via the open field test (OFT) and elevated plus maze (EPM) compared to control animals (n = 24) treated with carboxymethylcellulose (CMC) used as a vehicle. On the 11th day, each group was divided into 3 subgroups (n = 8): control (CMC), CMC+CUR, CMC+ESC for group without depression and CMC+R, CMC+R+CUR, CMC+R+ESC for group with depression. CUR (150 mg/kg i.p.) and ESC (20 mg/kg i.p.) were intraperitoneally administrated for 21 days. The improvement in depressive behaviour was assessed by OFT, EPM and biochemical analysis on the 32nd day. The results demonstrated that R induced hypomotility and increased oxidative stress in the brain, but also in the serum of rats. CUR had an antioxidant effect in the brain without significant effect on depressive-like behaviour while ESC improved the hypomotility of the depressive rats.

Effects of Phytochemicals from Fermented Food Sources in Alzheimer's Disease In Vivo Experimental Models: A Systematic Review.

The socioeconomic burden of Alzheimer's Disease (AD) stems from its characteristic multifactorial etiology and, implicitly, the difficulties associated with its treatment. With the increase in life expectancy and health awareness, nutraceuticals and functional foods are filling in the gaps left by the limitation of classical medical treatment in chronic conditions associated with lifestyle factors, such as neurological disorders. Processes, such as fermentation that enhance food phytochemical content are garnering increased attention due to their functional and health-related properties. This systematic review aims to provide an overview of the evidence of phytochemicals from fermented food sources inducing therapeutic outcomes and cognitive benefits from in vivo experimental models of Alzheimer's Disease. The present systematic review was conducted in accordance with PRISMA guidelines. Searches were performed in the following databases: MEDLINE, Embase, Cochrane, Scopus, Google Scholar, and Science Citation Index Expanded (Web of Science) by two independent reviewers. Titles and abstracts yielded by the search were screened for eligibility against the inclusion criteria. The search strategy yielded 1899 titles, encompassing studies from 1948 to 2022. After the removal of duplicates, and screening of titles, abstracts, and full texts, thirty three studies obtained from the original search strategy and seven studies from references satisfied the inclusion criteria and were included in the present systematic review. Several studies have emphasized the potential of fermentation to yield small-molecule phytochemicals that are not present in raw products. When these phytochemicals are combined, their collective strength has demonstrated the ability to exceed the antioxidant, anti-inflammatory, and neuroprotective benefits of individual phytochemicals when given in their pure form. Among the various fermented foods that have been studied, soy isoflavones obtained through fermentation have shown the most substantial evidence of altering phytochemical content and improving outcomes in animal models of AD. While promising in initial results, other fermented foods and traditional medicines require more detailed research in order to establish their effectiveness and proper utilization. As is, many of the experimental designs lacked phytochemical analysis of the used fermented product or comparison with the non-fermented counterpart. This, coupled with proper reporting in animal studies, will significantly raise the quality of performed studies as well as the weight of obtained results.

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.

In Vivo Study of the Effects of Propranolol, Timolol, and Minoxidil on Burn Wound Healing in Wistar Rats.

Propranolol, timolol, and minoxidil have all shown benefits in treatment of burn injury and other skin wounds. The study evaluated their effects on full-thickness thermal skin burns in a Wistar rat model. Performed on 50 female rats; two dorsal skin burns were created on each animal. On the next day, the rats were divided into 5 groups (n = 10); each has received a specific treatment daily for 14 days: group I-topical vehicle (control), group II-topical silver sulfadiazine (SSD), group III-oral propranolol (5.5 mg) associated with topical vehicle, group IV-topical timolol 1% cream, and group V-topical minoxidil 5% cream. Wound contraction rates, malondialdehyde (MDA), glutathione (GSH, GSSG), and catalase activity in skin and/or serum were evaluated, and histopathological analyses were performed. Propranolol did not show advantages in necrosis prevention and wound contraction and healing, and did not reduce oxidative stress. It impaired keratinocyte migration, and promoted ulceration, chronic inflammation, and fibrosis, yet reducing the necrotic zone. Timolol prevented necrosis and promoted contraction and healing, increased antioxidant capacity and promoted keratinocyte migration and neo capillarization in comparison to the other treatments. Minoxidil reduced necrosis and enhanced contraction, resulting in positive outcomes after 1 week of treatment regarding local antioxidant defense, keratinocyte migration, neo capillarization, chronic inflammation, and fibrosis rates. However, after 2 weeks, it resulted in contrasting outcomes. In conclusion, topical timolol promoted wound contraction and healing, reducing local oxidative stress and improving keratinocyte migration, bringing arguments for potential benefits in skin epithelization.

The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings.

A growing body of evidence suggests that the gut microbiota affects the cardiovascular system directly and indirectly via biologically active molecules. TMAO, a key metabolite produced by gut bacteria is implicated in atherosclerosis and chronic endothelial dysfunction, but with an unclear effect on vascular tone, oxidative stress, and inflammation. Our study aimed to evaluate the acute effects of TMAO on vascular contractility in relation with oxidative stress markers and inflammation. Aortic rings were harvested from laboratory rats and placed in a tissue bath system containing TMAO in concentrations of 300, 100, 10 µM, and control. Vascular tone under the influence of vasoconstrictor phenylephrine and non-endothelial-dependent vasodilator sodium nitroprusside was assessed using force transducers connected to a computer-based acquisition system. Oxidative stress and inflammation were quantified by vascular assessment of the activity of NF-κB, NRF2, SOD1, and iNOS by western-blotting and MDA by spectrofluorimetry. After the incubation of the aortic rings in TMAO solutions for 1 h, there was no difference in vasoconstrictor and non-endothelial vasodilator response between the studied doses. TMAO acutely induced oxidative stress and inflammation, significantly increasing levels of MDA and the expression of NF-κB, NRF2, SOD1, and iNOS, mostly in a dose-dependent manner. Our study showed the lack of a short-term effect of studied TMAO doses on vascular contractility, but demonstrated an acute prooxidative effect and activation of major inflammatory pathways, which can partially explain the detrimental effects of TMAO in cardiovascular disease.

Green Synthesized Gold and Silver Nanoparticles Increased Oxidative Stress and Induced Cell Death in Colorectal Adenocarcinoma Cells.

The research investigated the effect of gold (Au-CM) and silver nanoparticles (Ag-CM) phytoreduced with Cornus mas fruit extract (CM) on a human colorectal adenocarcinoma (DLD-1) cell line. The impact of nanoparticles on the viability of DLD-1 tumor cells and normal cells was evaluated. Oxidative stress and cell death mechanisms (annexin/propidium iodide analysis, caspase-3 and caspase-8 levels, p53, BCL-2, BAX, NFkB expressions) as well as proliferation markers (Ki-67, PCNA and MAPK) were evaluated in tumor cells. The nanoparticles were characterized using UV-Vis spectroscopy and transmission electron microscopy (TEM) and by measuring zeta potential, hydrodynamic diameter and polydispersity index (PDI). Energy dispersive X-ray (EDX) and X-ray powder diffraction (XRD) analyses were also performed. The nanoparticles induced apoptosis and necrosis of DLD-1 cells and reduced cell proliferation, especially Ag-CM, while on normal cells, both nanoparticles maintained their viability up to 80%. Ag-CM and Au-CM increased the expressions of p53 and NFkB in parallel with the downregulation of BCL-2 protein and induced the activation of caspase-8, suggesting the involvement of apoptosis in cell death. Lipid peroxidation triggered by Ag-CM was correlated with tumor cell necrosis rate. Both nanoparticles obtained with phytocompounds from the CM extract protected normal cells and induced the death of DLD-1 tumor cells, especially by apoptosis.

Magnetic Nanoclusters Stabilized with Poly[3,4-Dihydroxybenzhydrazide] as Efficient Therapeutic Agents for Cancer Cells Destruction.

Magnetic structures exhibiting large magnetic moments are sought after in theranostic approaches that combine magnetic hyperthermia treatment (MH) and diagnostic magnetic resonance imaging in oncology, since they offer an enhanced magnetic response to an external magnetic field. We report on the synthesized production of a core-shell magnetic structure using two types of magnetite nanoclusters (MNC) based on a magnetite core and polymer shell. This was achieved through an in situ solvothermal process, using, for the first time, 3,4-dihydroxybenzhydrazide (DHBH) and poly[3,4-dihydroxybenzhydrazide] (PDHBH) as stabilizers. Transmission electron microscopy (TEM) analysis showed the formation of spherical MNC, X-ray photoelectronic spectroscopy (XPS) and Fourier transformed infrared (FT-IR) analysis proved the existence of the polymer shell. Magnetization measurement showed saturation magnetization values of 50 emu/g for PDHBH@MNC and 60 emu/g for DHBH@MNC with very low coercive field and remanence, indicating that the MNC are in a superparamagnetic state at room temperature and are thus suitable for biomedical applications. MNCs were investigated in vitro, on human normal (dermal fibroblasts-BJ) and tumor (colon adenocarcinoma-CACO2, and melanoma-A375) cell lines, in view of toxicity, antitumor effectiveness and selectivity upon magnetic hyperthermia. MNCs exhibited good biocompatibility and were internalized by all cell lines (TEM), with minimal ultrastructural changes. By means of flowcytometry apoptosis detection, fluorimetry, spectrophotometry for mitochondrial membrane potential, oxidative stress, ELISA-caspases, and Western blot-p53 pathway, we show that MH efficiently induced apoptosis mostly via the membrane pathway and to a lower extent by the mitochondrial pathway, the latter mainly observed in melanoma. Contrarily, the apoptosis rate was above the toxicity limit in fibroblasts. Due to its coating, PDHBH@MNC showed selective antitumor efficacy and can be further used in theranostics since the PDHBH polymer provides multiple reaction sites for the attachment of therapeutic molecules.

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.

Iron chelation alleviates multiple pathophysiological pathways in a rat model of cardiac pressure overload.

Iron dysmetabolism affects a great proportion of heart failure patients, while chronic hypertension is one of the most common risk factors for heart failure and death in industrialized countries. Serum data from reduced ejection fraction heart failure patients show a relative or absolute iron deficiency, whereas cellular myocardial analyses field equivocal data. An observed increase in organellar iron deposits was incriminated to cause reactive oxygen species formation, lipid peroxidation, and cell death. Therefore, we studied the effects of iron chelation on a rat model of cardiac hypertrophy. Suprarenal abdominal aortic constriction was achieved surgically, with a period of nine weeks to accommodate the development of chronic pressure overload. Next, deferiprone (100 mg/kg/day), a lipid-permeable iron chelator, was administered for two weeks. Pressure overload resulted in increased inflammation, fibrotic remodeling, lipid peroxidation, left ventricular hypertrophy and mitochondrial iron derangements. Deferiprone reduced cardiac inflammation, lipid peroxidation, mitochondrial iron levels, and hypertrophy, without affecting circulating iron levels or ejection fraction. In conclusion, metallic molecules may pose ambivalent effects within the cardiovascular system, with beneficial effects of iron redistribution, chiefly in the mitochondria.

Characterization and In Vitro Biocompatibility of Two New Bioglasses for Application in Dental Medicine-A Preliminary Study.

Bioactive glasses (BGs), also known as bioglasses, are very attractive and versatile materials that are increasingly being used in dentistry. For this study, two new bioglasses-one with boron (BG1) and another with boron and vanadium (BG2)-were synthesized, characterized, and tested on human dysplastic keratinocytes. The in vitro biological properties were evaluated through pH and zeta potential measurement, weight loss, Ca2+ ions released after immersion in phosphate-buffered saline (PBS), and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS) analysis. Furthermore, biocompatibility was evaluated through quantification of lactate dehydrogenase activity, oxidative stress, transcription factors, and DNA lesions. The results indicate that both BGs presented the same behavior in simulated fluids, characterized by high degradation, fast release of calcium and boron in the environment (especially from BG1), and increased pH and zeta potential. Both BGs reacted with the fluid, particularly BG2, with irregular deposits covering the glass surface. In vitro studies demonstrated that normal doses of the BGs were not cytotoxic to DOK, while high doses reduced cell viability. Both BGs induced oxidative stress and cell membrane damage and enhanced NFkB activation, especially BG1. The BGs down-regulated the expression of NFkB and diminished the DNA damage, suggesting the protective effects of the BGs on cell death and efficacy of DNA repair mechanisms.