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This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery . EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, p  = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H 2 O 2 /g tisssue/h vs. 15.7 ± 1.55 nmol H 2 O 2 /g tisssue/h, p  < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery., Competing Interests: The authors declare no conflict of interest.

Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January-August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus , A. baumannii , Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia , and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.

Melatonin is commonly found in various fruits, juices, and some fermented beverages. Its concentration in wine is influenced by soil properties, climatic factors, and yeast activity. Even if it is found in fermented beverages in relatively low proportions, melatonin still holds significant nutritional value, giving anti-aging properties, anti-inflammatory actions, and antidepressant effects. In this context, this article focuses on evaluating the impact of different Saccharomyces and non-Saccharomyces yeast species on the formation of melatonin and its contribution to wines' total antioxidant capacity. Considering that the antioxidant activity of wine is usually related to the content of phenolic compounds, ten such compounds were analyzed. The evaluation of bioactive compounds was performed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry. The total antioxidant capacity of wine samples was evaluated by the ABTS + method. The administration of bâtonnage products increased the efficiency of non- Saccharomyces yeasts. The mixtures of Saccharomyces and non- Saccharomyces yeasts generated higher values for melatonin. The results confirm a significant impact from the grape variety and the specific yeast strains on the melatonin concentration. Also, a strong dependence between antioxidant activity and melatonin levels was observed. Given the limited existing studies on the presence of melatonin in wines, new perspectives are needed for future exploration and understanding.

Olea europaea L. is the most valuable species of the Olea type, and its products offer a wide range of therapeutical uses. The olive tree has been extensively studied for its nourishing qualities, and the "Mediterranean diet", which includes virgin olive oil as a key dietary component, is strongly associated with a reduced risk of cardiovascular disease and various malignancies. Olive leaves, a by-product in the olive harvesting process, are valued as a resource for developing novel phytomedicines. For this purpose, two ethanolic extracts obtained from Olivae folium from Spain (OFS) and Greece (OFG) were investigated. Our findings contribute to a wider characterization of olive leaves. Both extracts displayed important amounts of phenolic compounds and pentacyclic triterpenes, OFG having higher concentrations of both polyphenols, such as oleuropein and lutein, as well as triterpenes, such as oleanolic acid and maslinic acid. The antioxidant capacity is similar for the two extracts, albeit slightly higher for OFG, possibly due to metal polyphenol complexes with antioxidant activity. The extracts elicited an antimicrobial effect at higher doses, especially against Gram-positive bacteria, such as Streptococcus pyogenes . The extract with lower inorganic content and higher content of polyphenols and triterpenic acids induced a strong anti-radical capacity, a selective cytotoxic effect, as well as antimigratory potential on A375 melanoma cells and antiangiogenic potential on the CAM. No irritability and a good tolerability were noted after evaluating the extracts on the in vivo Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Therefore, the present data are suggestive for the possible use of the two types of olive leaf products as high-antioxidant extracts, potentially impacting the healthcare system through their use as antimicrobial agents and as anticancer and anti-invasion treatments for melanoma.

Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm formation on lenses raises significant problems, leading to various ocular complications and discomfort. The aim of this review is to develop safer and more effective strategies for preventing and managing microbial biofilms on CL, improving the eye health and comfort of wearers. Taking these into consideration, the present study investigates the intricate mechanisms of biofilm formation, by exploring the interplay between microbial adhesion, the production of extracellular polymeric substances, and the properties of the lens material itself. Moreover, it emphasizes the diverse range of microorganisms involved, encompassing bacteria, fungi, and other opportunistic pathogens, elucidating their implications within lenses and other medical device-related infections and inflammatory responses. Going beyond the challenges posed by biofilms on CL, this work explores the advancements in biofilm detection techniques and their clinical relevance. It discusses diagnostic tools like confocal microscopy, genetic assays, and emerging technologies, assessing their capacity to identify and quantify biofilm-related infections. Finally, the paper delves into contemporary strategies and innovative approaches for managing and preventing biofilms development on CL. In Conclusion, this review provides insights for eye care practitioners, lens manufacturers, and microbiology researchers. It highlights the intricate interactions between biofilms and CL, serving as a foundation for the development of effective preventive measures and innovative solutions to enhance CL safety, comfort, and overall ocular health. Research into microbial biofilms on CL is continuously evolving, with several future directions being explored to address challenges and improve eye health outcomes as far as CL wearers are concerned., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Voinescu et al.)

The need to develop advanced wastewater treatment techniques and their use has become a priority, the main goal being the efficient removal of pollutants, especially those of organic origin. This study presents the photo-degradation of a pharmaceutical wastewater containing Kabi cytarabine, using ultraviolet (UV) radiation, and a synthesized catalyst, a composite based on bismuth and iron oxides (BFO). The size of the bandgap was determined by UV spectroscopy, having a value of 2.27 eV. The specific surface was determined using the BET method, having a value of 0.7 m 2 g -1 . The material studied for the photo-degradation of cytarabine presents a remarkable photo-degradation efficiency of 97.9% for an initial concentration 0f 10 mg/L cytarabine Kabi when 0.15 g of material was used, during 120 min of interaction with UV radiation at 3 cm from the irradiation source. The material withstands five photo-degradation cycles with good results. At the same time, through this study, it was possible to establish that pyrimidine derivatives could be able to combat infections caused by Escherichia coli and Candida parapsilosis .

The emergence and spread of antimicrobial resistance have been significant global health challenges, exacerbated by the COVID-19 pandemic. As healthcare systems faced unprecedented pressures, the management of non-COVID conditions, including urinary tract infections (UTIs), also encountered obstacles due to changes in microbial flora and antibiotic usage patterns. This cross-sectional study aimed to characterize the antimicrobial resistance trends among bacterial uropathogens isolated from patients in the Western region of Romania, between January 2020 and December 2022. The objectives were to map the resistance patterns and observe the pandemic's influence on antimicrobial resistance, particularly among enterobacterial Gram-negative species, to guide treatment and infection control strategies. From a total of 2472 urine samples collected during the study period, 378 positive samples were analyzed. This study found that Escherichia coli was the most commonly isolated uropathogen, making up 46.3% of the cases (n = 175), with Klebsiella pneumoniae at 20.6% (n = 78). There was a high resistance of Klebsiella pneumoniae to several antibiotics, while carbapenemase production increased to 52.5% and extended-spectrum beta-lactamase (ESBL) present in 24.3% of the strains. Escherichia coli showed high resistance rates to amoxicillin-clavulanic acid (from 45.4% in 2020 to 53.8% in 2022) and trimethoprim/sulfamethoxazole (from 27.5% in 2020 to 47.2% in 2022). The increasing trend of antimicrobial resistance noted during the pandemic, especially in Gram-negative enterobacterial species, highlights the urgent need for robust infection control measures and rational antibiotic use. This study underscores the critical importance of continuous surveillance to adapt antibiotic therapies effectively and prevent the further spread of resistance, thereby ensuring effective management of UTIs in the evolving healthcare landscape influenced by the pandemic.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.

The intricate cooperation between cancer cells and nontumor stromal cells within melanoma microenvironment (MME) enables tumor progression and metastasis. We previously demonstrated that the interplay between tumor-associated macrophages (TAMs) and melanoma cells can be disrupted by using long-circulating liposomes (LCLs) encapsulating prednisolone phosphate (PLP) (LCL-PLP) that inhibited tumor angiogenesis coordinated by TAMs. In this study, our goal was to improve LCL specificity for protumor macrophages (M2-like (i.e., TAMs) macrophages) and to induce a more precise accumulation at tumor site by loading PLP into IL-13-conjugated liposomes (IL-13-LCL-PLP), since IL-13 receptor is overexpressed in this type of macrophages. The IL-13-LCL-PLP liposomal formulation was obtained by covalent attachment of thiolated IL-13 to maleimide-functionalized LCL-PLP. C57BL/6 mice bearing B16.F10  s.c melanoma tumors were used to investigate the antitumor action of LCL-PLP and IL-13-LCL-PLP. Our results showed that IL-13-LCL-PLP formulation remained stable in biological fluids after 24h and it was preferentially taken up by M2 polarized macrophages. IL-13-LCL-PLP induced strong tumor growth inhibition compared to nonfunctionalized LCL-PLP at the same dose, by altering TAMs-mediated angiogenesis and oxidative stress, limiting resistance to apoptosis and invasive features in MME. These findings suggest IL-13-LCL-PLP might become a promising delivery platform for chemotherapeutic agents in melanoma.

Background and Objectives : This cross-sectional study conducted at the Timișoara Institute of Cardiovascular Diseases, Romania, and the Centre for Translational Research and Systems Medicine from "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Romania, investigated the relationship between indexed epicardial adipose tissue thickness (EATTi) and oxidative stress in epicardial adipose tissue (EAT) adipocytes in the context of coronary artery disease (CAD) among open-heart surgery patients. The objective was to elucidate the contribution of EATTi as an additional marker for complexity prediction in patients with CAD, potentially influencing clinical decision-making in surgical settings. Materials and Methods : The study included 25 patients undergoing cardiac surgery, with a mean age of 65.16 years and a body mass index of 27.61 kg/m 2 . Oxidative stress in EAT was assessed using the ferrous iron xylenol orange oxidation spectrophotometric assay. The patients were divided into three groups: those with valvular heart disease without CAD, patients with CAD without diabetes mellitus (DM), and patients with both CAD and DM. The CAD complexity was evaluated using the SYNTAX score. Results : The EATTi showed statistically significant elevations in the patients with both CAD and DM (mean 5.27 ± 0.67 mm/m 2 ) compared to the CAD without DM group (mean 3.78 ± 1.05 mm/m 2 , p = 0.024) and the valvular disease without CAD group (mean 2.67 ± 0.83 mm/m 2 , p = 0.001). Patients with SYNTAX scores over 32 had significantly higher EATTi (5.27 ± 0.66 mm/m 2 ) compared to those with lower scores. An EATTi greater than 4.15 mm/m 2 predicted more complex CAD (SYNTAX score >22) with 80% sensitivity and 86% specificity. The intra- and interobserver reproducibility for the EATTi measurement were excellent (intra-class correlation coefficient 0.911, inter-class correlation coefficient 0.895). Conclusions : EATTi is significantly associated with CAD complexity in patients undergoing open-heart surgery. It serves as a reliable indicator of more intricate CAD forms, as reflected by higher SYNTAX scores. These findings highlight the clinical relevance of EATTi in pre-operative assessment, suggesting its potential utility as a prognostic marker in cardiac surgical patients.

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 (EC 50 of GvDEE = 0.12 ± 0.03 mg/mL > EC 50 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.

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.

Recent research has revealed the importance of miRNAs in the diagnosis and clinical evolution of papillary thyroid cancer (PTC). We aim to identify a specific miRNA profile that could differentiate between specific subtypes of PTC., Methods: In this cross-sectional study, total RNA was extracted from paraffin-embedded tissues of 43 patients, 17 with an infiltrative follicular variant of PTC (iFVPTC) and 26 with a conventional variant of PTC (cPTC). Nine miRNAs were evaluated using qRT-PCR technology and specific miRNA assays., Results: We found specific patterns for cPTC and iFVPTC, such as miRNA altered in both types of tumours (miR-146b-5p, miR-181a-5p, miR-221-3p, miR-21-5p and miR-222-3p) and two miRNAs significantly expressed only in cPTC (miR-20b-5p, miR-21-5p). The iFVPTC group presented strong and moderate correlations between miRNA expression and clinical data. miR-221-3p, miR-195-5p, miR-181-5p, miR-146b-5p and miR-222 were correlated with age, tumour size (TS) or lymph node metastases (N), while only miR-20b-5p, miR-195-5p and miR-181-5p were correlated with TS, N and age in the cPTC group., Conclusions: The present study allowed the identification of a signature of two miRNAs to confirm miRNA differences between the two histological subtypes of TC. Our results provide advances in the molecular diagnosis of TC and could help to improve the diagnostic performance of already existing molecular classifiers.

The emergency department (ED) represents an important setting for addressing inappropriate antimicrobial prescribing practices because of the time constraints and the duration of microbiological diagnosis. The purpose of this study is to evaluate the etiology and antimicrobial resistance (AMR) pattern of the community-acquired pathogens, as well as the epidemiological characteristics of patients admitted through the ED, in order to guide appropriate antibiotic therapy., Methods: A retrospective observational study was performed on 657 patients, from whom clinical samples (urine, purulent secretions, blood cultures, etc.) were collected for microbiological diagnosis in the first 3 days after presentation in the ED. The identification of pathogens and the antimicrobial susceptibility testing with minimum inhibitory concentration determination were carried out according to the laboratory protocols., Results: From the 767 biological samples analyzed, 903 microbial isolates were identified. E. coli was most frequently isolated (24.25%), followed by Klebsiella spp., S. aureus (SA), and non-fermentative Gram-negative bacilli. E. coli strains maintained their natural susceptibility to most antibiotics tested. In the case of Pseudomonas spp. and Acinetobacter spp., increased rates of AMR were identified. Also, 32.3% of SA strains were community-acquired MRSA., Conclusions: The introduction of rapid microbiological diagnostic methods in emergency medicine is imperative in order to timely identify AMR strains and improve therapeutic protocols.

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 (EC 50 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.

Bismuth oxides were synthesized from bismuth carbonate using the sol-gel method. Studies have described the formation of Bi 2 O 3 , as a precursor of HNO 3 dissolution, and intermediate oxides, such as Bi x O y when using H 2 SO 4 and H 3 PO 4 . The average size of the crystallite calculated from Scherrer's formula ranged from 9 to 19 nm, according to X-ray diffraction. The FTIR analysis showed the presence of specific Bi 2 O 3 bands when using HNO 3 and of crystalline phases of "bismuth oxide sulphate" when using H 2 SO 4 and "bismuth phosphate" when using H 3 PO 4 . The TG curves showed major mass losses and specific thermal effects, delimited in four temperature zones for materials synthesized with HNO 3 (with loss of mass between 24% and 50%) and H 2 SO 4 (with loss of mass between 45% and 76%), and in three temperature zones for materials synthesized with H 3 PO 4 (with loss of mass between 13% and 43%). Further, the thermal stability indicates that materials have been improved by the addition of a polymer or polymer and carbon. Confocal laser scanning microscopy showed decreased roughness in the series, [Bi x O y ] N > [Bi x O y -6% PVA] N > [Bi x O y -C-6% PVA] N , and increased roughness for materials [Bi x O y ] S , [Bi x O y -6% PVA] S , [Bi x O y -C-6% PVA] S , [Bi x O y ] P , [Bi x O y -6% PVA] P and [Bi x O y -C-6% PVA] P . The morphological analysis (electronic scanning microscopy) of the synthesized materials showed a wide variety of forms: overlapping nanoplates ([Bi x O y ] N or [Bi x O y ] S ), clusters of angular forms ([Bi x O y -6% PVA] N ), pillars ([Bi x O y -6% PVA] S -Au), needle particles ([Bi x O y -Au], [Bi x O y -6% PVA] S -Au, [Bi x O y -C-6% PVA] S -Au), spherical particles ([Bi x O y -C-6% PVA] P -Pt), 2D plates ([Bi x O y ] P -Pt) and 3D nanometric plates ([Bi x Oy-C-6% PVA] S -Au). For materials obtained in the first synthesis stage, antimicrobial activity increased in the series [Bi x O y ] N > [Bi x O y ] S > [Bi x O y ] P . For materials synthesized in the second synthesis stage, when polymer (polyvinyl alcohol, PVA) was added, maximum antimicrobial activity, regardless of the microbial species tested, was present in the material [Bi x O y -6% PVA] S . For the materials synthesized in the third stage, to which graphite and 6% PVA were added, the best antimicrobial activity was in the material [Bi x O y -C-6% PVA] P . Materials synthesized and doped with metal ions (gold or platinum) showed significant antimicrobial activity for the tested microbial species.

Skin tags, also known as fibroepithelial polyps (FPs) or acrochordons, are soft, pigmented excrescences, with a prevalence of 50-60% in the population, occurring especially in the fourth decade of life. To date, FPs have been efficiently eliminated using minimum invasive methods such as surgical removal, cauterization, laser irradiation, and cryosurgery. Over-the-counter treatments are also of interest for patients due to their non-invasive character, but their clinical efficiency has not been clearly demonstrated. This study was designed in order to evaluate the efficacy of a modern-pharmaceutical-formulation-type poloxamer-based binary hydrogel, having Origanum vulgare L. essential oil (OEO-PbH) as an active ingredient in the management of FPs. The formulation has been shown to possess good qualities in terms of stability and sterility. Non-invasive measurements revealed changes in some physiological skin parameters. An increase in transepidermal water loss (TEWL) and erythema index was noted, while skin surface water content (SWC) decreased during eight weeks of treatment. The macroscopic evaluation revealed that the FPs dried and shrunk after topical treatment with OEO-PbH. Clinically, patients presented a lowering of the number of lesions on the treated area of 20-30% after one month of treatment and around 50% after the second month. Histopathological examination suggests that topical treatment with OEO-PbH may induce histological changes in the epidermis, dermis, and fibrovascular cores of FPs, including a loss of thickness, reduced size and number of blood vessels, and low cellularity. These changes may contribute to the observed reduction in size of FPs after treatment with OEO-PbH.

Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs' in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required., Competing Interests: The authors declare no conflict of interest.

Background and Objectives: this study aimed to research links between C-reactive protein (CRP), lactate dehydrogenase (LDH), creatinekinase (CK), 25-OH vitamin D (25-OHD), ferritin (FER), high-density lipoprotein cholesterol (HDL)cholesterol and clinical severity in patients from the western part of Romania, and compare their potential use as biomarkers for intensive care units (ICU) admission and death in children, adults and elders. Materials and Methods: this study is a retrospective cohort study, performed on patients positively diagnosed with COVID-19. Available CRP, LDH, CK 25-OH vitamin D, ferritin, HDL cholesterol and clinical severity were recorded. The following were assessed: median group differences, association, correlation and receiver operating characteristic. Results: 381 children, 614 adults and 381 elders were studied between 1 March 2021 and 1 March 2022. Most children and adults presented mild symptomatology (53.28%, 35.02%, respectively), while most elders presented severe symptomatology (30.04%). ICU admission was 3.67% for children, 13.19% for adults and 46.09% for elders, while mortality was 0.79% for children, 8.63% for adults and 25.1% for elders. With the exception of CK, all other biomarkers showed some significant associations with clinical severity, ICU admission and death. Conclusions: CRP, LDH, 25-OH vitamin D, ferritin and HDL are important biomarkers for COVID-19 positive patients, especially in the pediatric population, while CK was mostly within normal ranges.

Malignant melanoma is one of the most pressing problems in the developing world. New therapeutic agents that might be effective in treating malignancies that have developed resistance to conventional medications are urgently required. Semisynthesis is an essential method for improving the biological activity and the therapeutic efficacy of natural product precursors. Semisynthetic derivatives of natural compounds are valuable sources of new drug candidates with a variety of pharmacological actions, including anticancer ones. Two novel semisynthetic derivatives of betulinic acid-N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) and N-(2,3-indolo-betulinoyl)glycylglycine (BA2)-were designed and their antiproliferative, cytotoxic, and anti-migratory activity against A375 human melanoma cells was determined in comparison with known N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic acid (BA4) and naturally occurring betulinic acid (BI). A dose-dependent antiproliferative effect with IC 50 values that ranged from 5.7 to 19.6 µM was observed in the series of all five compounds including betulinic acid. The novel compounds BA1 (IC 50 = 5.7 µM) and BA2 (IC 50 = 10.0 µM) were three times and two times more active than the parent cyclic structure B4 and natural BI. Additionally, compounds BA2, BA3, and BA4 possess antibacterial activity against Streptococcus pyogenes ATCC 19615 and Staphylococcus aureus ATCC 25923 with MIC values in the range of 13-16 µg/mL and 26-32 µg/mL, respectively. On the other hand, antifungal activity toward Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 was found for compound BA3 with MIC 29 µg/mL. This is the first report of antibacterial and antifungal activity of 2,3-indolo-betulinic acid derivatives and also the first extended report on their anti-melanoma activity, which among others includes data on anti-migratory activity and shows the significance of amino acid side chain on the observed activity. The obtained data justify further research on the anti-melanoma and antimicrobial activity of 2,3-indolo-betulinic acid derivatives.

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.

Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species ( E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus , while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities.

The aim of this study was to identify possible influences of extraction methods as well as extraction parameters on the phytochemical and biological profiles of Xanthium spinosum L. extracts. Extraction methods were chosen as follows: classical methods, maceration and Soxhlet extraction; innovative extraction methods, turboextraction, ultrasound-assisted extraction, and a combination of the latter two. Extracts were subjected to total polyphenolic and flavonoid content spectrophotometric analysis. The phytochemical profile was determined for the best-yielding extracts using HPLC-MS analysis. Following the newly acquired data, another sorting of the extracts was performed. Biological activities such as antimicrobial and anti-inflammatory actions were evaluated, as well as oxidative stress reduction potential, on a Wistar rats inflammation model. Comparable results were achieved with Soxhlet extraction and ultrasound-assisted extraction, both surpassing all other tested methods in terms of yields. Bioactive compound concentrations tended to increase with the increase in extraction time and temperature. These maximal values lowered once the degradation points of the bioactive compounds were reached. Extracts demonstrated good protection against Gram-negative bacteria. Additionally, they provided good cellular protection and increased the antioxidant defense in the analyzed rat plantar tissue.

The study was designed to analyze and evaluate the antioxidant and antibacterial properties of the essential oils of Thymus pulegioides L. grown in Western Romania. Thymus pulegioides L. essential oil (TPEO) was extracted by steam distillation (0.71% v/w) using a Craveiro-type apparatus. GC-MS investigation of the TPEO identified 39 different compounds, representing 98.46% of total oil. Findings revealed that thymol (22.89%) is the main compound of TPEO, followed by para-cymene (14.57%), thymol methyl ether (11.19%), isothymol methyl ether (10.45%), and beta-bisabolene (9.53%). The oil exhibits good antibacterial effects; C. parapsilosis, C. albicans, S. pyogenes, and S. aureus were the most sensitive strains. The antioxidant activity of TPEO was evaluated by peroxide and thiobarbituric acid value, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), [2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium] (ABTS) radical scavenging assay, and beta-carotene/linoleic acid bleaching testing. The antioxidative data recorded reveal, for the first time, that TPEO inhibits primary and secondary oxidation products, in some particular conditions, better than butylated hydroxyanisole (BHA) with significant statistical difference (p < 0.05). Moreover, TPEO antioxidant capabilities in DPPH and ABTS assays outperformed alpha-tocopherol (p < 0.001) and delta-tocopherol (p < 0.001). Molecular docking analysis revealed that one potential target correlated with the TPEO antimicrobial activity was d-alanine-d-alanine ligase (DDl). The best scoring ligand, linalyl anthranilate, shared highly similar binding patterns with the DDl native inhibitor. Furthermore, molecular docking analysis also showed that the main constituents of TPEO are good candidates for xanthine oxidase and lipoxygenase inhibition, making the essential oil a valuable source for protein-targeted antioxidant compounds. Consequently, TPEO may represent a new potential source of antioxidant and antibacterial agents with applicability in the food and pharmaceutic industries.

This study presents phytochemical characterization and biological evaluation of Origanum vulgare L. essential oil (OEO) formulated as polymeric micelles drug delivery systems as a possible non-invasive approach for the management of skin tags. GC-MS analysis of Romanian OEO revealed the identification and quantification of 43 volatile compounds (thymol and carvacrol being the main ones). The antioxidant activity was shown by four consecrated methods: CUPRAC, ABTS, ORAC and DPPH. OEO was incorporated by micellar solubilization into a binary hydrogel based on a Pluronic F 127/L 31 block-copolymers mixture. The pH, consistency, spreadability, particle size, polydispersity index and zeta potential of the OEO-loaded poloxamer-based binary hydrogel (OEO-PbH) were investigated. OEO-PbH was skin compatible in terms of pH and exhibited adequate spreadability and consistency. The minimal inhibitory concentrations of the tested OEO were similar to those obtained for the formulation, lower (2.5 µg/mL) for yeast and higher (40-80 µg/mL) for Gram-negative bacilli. As keratinocytes are among main components of skin tags, an in vitro evaluation was conducted in order to see the effect of the formulation against HaCaT human keratinocytes. OEO-PbH decreased HaCaT cells migration and proliferation and elicited a cytotoxic and pro-apoptotic effect in a dose- and time-dependent manner. No harmful effect on the viability of dendritic cells (DCs) was detected following the incubation with different concentrations (0-200 µg/mL) of the 5% formulation. Treatment in inflammatory DCs (+LPS) indicated a decrease in cytokine production of IL-6, TNF-α and IL-23 but no significant effect on IL-10 in any of the tested concentrations.

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.e., phospholipid, SIM and DOX concentration, which were assessed in an optimization experimental design with the purpose of designing an optimal formulation. The optimal formulation, meeting the established quality profile, was additionally characterized in terms of the release profile and antiproliferative effects. During dissolution studies, a novel chronoamperometric method was used for the simultaneous quantification of SIM and DOX. The obtained data confirmed the similarity of this method with a validated HPLC method. The anticancer potential of the optimal formulation was tested against two human cancerous cell lines, namely T47D-KBluc human mammary ductal carcinoma cell line and A549 human pulmonary cancer cell line. The results highlighted that the antiproliferative effect of the optimal formulation is concentration dependent and favors a synergistic effect of the two drugs.

The antibacterial activity of zinc oxide particles has received significant interest worldwide, especially through the implementation of technology to synthesize particles in the nanometer range. This study aimed to determine the antimicrobial efficacy of silica-based iron oxide matrix (SiO 2 Fe x O y ) synthesized with various amounts of ZnO (SiO 2 Fe x O y ZnO) against various pathogens. It is observed that, with the addition of ZnO to the system, the average size of the porosity of the material increases, showing increasingly effective antibacterial properties. Zinc-iron-silica oxide matrix composites were synthesized using the sol-gel method. The synthesized materials were investigated physicochemically to highlight their structural properties, through scanning electron microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FT-IR). At the same time, surface area, pore size and total pore volume were determined for materials synthesized using the Brunauer-Emmett-Teller (BET) method. Although the material with 0.0001 g ZnO (600 m 2 /g) has the highest specific surface area, the best antimicrobial activity was obtained for the material with 1.0 g ZnO, when the average pore volume is the largest (~8 nm) for a specific surface of 306 m 2 /g. This indicates that the main role in the antibacterial effect has reactive oxygen species (ROS) generated by the ZnO that are located in the pores of the composite materials. The point of zero charge (pH pZc ) is a very important parameter for the characterization of materials that indicate the acid-base behaviour. The pH pZc value varies between 4.9 and 6.3 and is influenced by the amount of ZnO with which the iron-silica oxide matrix is doped. From the antimicrobial studies carried out, it was found that for S. aureus the total antibacterial effect was obtained at the amount of 1.0 g ZnO. For Gram-negative bacteria, a total antibacterial effect was observed in S. flexneri (for the material with 0.1 g ZnO), followed by E. coli (for 1.0 g ZnO). For P. aeruginosa , the maximum inhibition rate obtained for the material with 1.0 g ZnO was approximately 49%.

Aims: Viscosity is an important mechanical property directly linked to the shear wave dispersion within tissues. The purpose of this study was to establish the normal viscosity value of the parotid gland (PG) and submandibular gland (SMG) in a group of healthy subjects, using the novel Viscosity Plane-wave UltraSound (ViPLUS) technique, and to assess its potential dependence on gender and age., Material and Methods: The study group included a total of 49 healthy volunteers (median age 31, 65% females) prospectively examined between February 2021 and March 2021. The viscosity of both PG and SMG was measured using the new Aixplorer MACH 30 ultrasound system (SuperSonic Imagine, Aix-en-Provence, France) equipped with a curvilinear C6-1X transducer. The mean value of three valid measurements was considered (quantified in Pa.s)., Results: The mean viscosity value for the PG was 2.13±0.23 Pa.s, significantly lower than the mean viscosity value of the SMG 2.44±0.35 Pa.s (p<0.0001). A negative low correlation between SMG viscosity and age was found (rho=-0.38, p=0.006). Viscosity values of the SMG were significantly lower in the age group between 35-77 years (2.12±0.35 Pa.s) than in the age groups 25-34 years (2.52±0.36 Pa.s), and 20-24 years (2.53±0.24 Pa.s), respectively (p<0.05). Viscosity values of both salivary glands did not differ significantly between gender groups., Conclusions: Supersonic ViPLUS represents an innovative and useful non-invasive method to assess the viscosity of the parotid and submandibular glands. Age is a potential confounding factor in the evaluation of normal SMG viscosity.

Green route is an economic, facile and eco-friendly method, employed for the synthesis of various types of nanoparticles, having it as a starting point biological entity, especially as a plant extract. The present study aims to obtain silver nanoparticles (AgNPs) starting from an ethanolic extract of Populi gemmae (Pg), by adjusting the reaction parameters. The morphological and structural characterization exhibited that both the reaction temperature and the concentration of metal salt, contributes to the obtaining of Pg-AgNPs with adjustable size and shape. The newly synthesized nanoparticles exhibited a good antibacterial activity on Gram-positive bacteria as well as antifungal activity. The in vitro antiproliferative activity of Pg-AgNPs was assessed on two different cancer cell lines (breast cancer cells-MCF7 and lung carcinoma epithelial cells-A549). Results have shown that the green-synthetized Pg-AgNPs&#95;S2 (obtained at 60 °C, using AgNO 3 of 5 M) induced a substantial decrease in tumor cell viability in a dose-dependent manner with an IC 50 ranging from 5.03 to 5.07 µg/mL on A549 cell line and 3.24 to 4.93 µg/mL on MCF7 cell line.

The goal of this research was to design novel chloro-substituted salicylanilide derivatives and their β-cyclodextrin complexes in order to obtain efficient antibacterial compounds and to demonstrate the beneficial role of complexation on the efficiency of these compounds. Thus, salicylanilide derivatives, esters, and hydrazides were obtained by microwave-assisted synthesis and their structure proven based on FTIR and NMR spectra. In order to improve water solubility, chemical and physical stability, and drug distribution through biological membranes, the inclusion complexes of the ethyl esters in β-cyclodextrin were also obtained using kneading. Inclusion-complex characterization was accomplished by modern analytical methods, X-ray diffraction, SEM, TGA, FTIR, and UV-vis spectroscopy. The newly synthesized compounds were tested against some Gram-positive and Gram-negative bacteria. Antimicrobial tests revealed good activity on Gram-positive bacteria and no inhibition against Gram-negative strains. The MIC and MBC values for compounds derived from N-(2-chlorophenyl)-2-hydroxybenzamide were 0.125-1.0 mg/mL. N-(4-chlorophenyl)-2-hydroxybenzamide derivatives were found to be less active. The inclusion complexes generally behaved similarly to the guest compounds, and antibacterial activity was not been altered by complexation.

The rise of multidrug-resistant (MDR) pathogens has become a global health threat and an economic burden in providing adequate and effective treatment for many infections. This large-scale concern has emerged mainly due to mishandling of antibiotics (ABs) and has resulted in the rapid expansion of antimicrobial resistance (AMR). Nowadays, there is an urgent need for more potent, non-toxic and effective antimicrobial agents against MDR strains. In this regard, clinicians, pharmacists, microbiologists and the entire scientific community are encouraged to find alternative solutions in treating infectious diseases cause by these strains. In its "10 global issues to track in 2021", the World Health Organization (WHO) has made fighting drug resistance a priority. It has also issued a list of bacteria that are in urgent need for new ABs. Despite all available resources, researchers are unable to keep the pace of finding novel ABs in the face of emerging MDR strains. Traditional methods are increasingly becoming ineffective, so new approaches need to be considered. In this regard, the general tendency of turning towards natural alternatives has reinforced the interest in essential oils (EOs) as potent antimicrobial agents. Our present article aims to first review the main pathogens classified by WHO as critical in terms of current AMR. The next objective is to summarize the most important and up-to-date aspects of resistance mechanisms to classical antibiotic therapy and to compare them with the latest findings regarding the efficacy of alternative essential oil therapy.

Due to the plethora of pharmacological activities reported in the literature, Origanum vulgare L. is a valuable aromatic plant for the medicine of the XXI century. Recent studies highlight that Origanum vulgare L. essential oil (OvEo) has gained attention in the dermatological field due to the cosmeceutical potential correlated with the presence of thymol and carvacrol. As a result of the fulminant expansion of bacterial resistance to antibiotics and the aggressiveness of skin infections, OvEo was extensively studied for its antimicrobial activity against Staphyloccocus spp. and Pseudomonas aeruginosa . Moreover, researchers have also assessed the anti-inflammatory activity of OvEo, suggesting its tissue remodeling and wound healing potential. Whereas OvEo comprises important biological activities that are used in a wide range of pathologies, recently, essential oils have shown great potential in the development of new therapeutic alternatives for skin disorders, such as acne, wounds or aging. Furthermore, substantial efforts have been committed to the development of modern formulations, such as microemulsions and nanoemulsions, in order to create the possibility for topical application. The review brings to the fore the most recent findings in the dermatological field regarding potential plant-based therapies involving OvEo, emphasizing the modern pharmaceutical formulation approaches and the cutaneous benefits in skin disorders.

Primary melanoma aggressiveness is determined by rapid selection and growth of cellular clones resistant to conventional treatments, resulting in metastasis and recurrence. In addition, a reprogrammed tumor-immune microenvironment supports melanoma progression and response to therapy. There is an urgent need to develop selective and specific drug delivery strategies for modulating the interaction between cancer cells and immune cells within the tumor microenvironment. This study proposes a novel combination therapy consisting of sequential administration of simvastatin incorporated in IL-13-functionalized long-circulating liposomes (IL-13-LCL-SIM) and doxorubicin encapsulated into PEG-coated extracellular vesicles (PEG-EV-DOX) to selectively target both tumor-associated macrophages and melanoma cells. To this end, IL-13 was conjugated to LCL-SIM which was obtained via the lipid film hydration method. EVs enriched from melanoma cells were passively loaded with doxorubicin. The cellular uptake of rhodamine-tagged nano-particles and the antiproliferative potential of the treatments by using the ELISA BrdU-colorimetric immunoassay were investigated in vitro . Subsequently, the therapeutic agents were administered i.v in B16.F10 melanoma-bearing mice, and tumor size was monitored during treatment. The molecular mechanisms of antitumor activity were investigated using angiogenic and inflammatory protein arrays and western blot analysis of invasion (HIF-1) and apoptosis markers (Bcl-xL and Bax). Quantification of oxidative stress marker malondialdehyde (MDA) was determined by HPLC. Immunohistochemical staining of angiogenic markers CD31 and VEGF and of pan-macrophage marker F4/80 was performed to validate our findings. The in vitro data showed that IL-13-functionalized LCL were preferentially taken up by tumor-associated macrophages and indicated that sequential administration of IL-13-LCL-SIM and PEG-EV-DOX had the strongest antiproliferative effect on tumor cells co-cultured with tumor-associated macrophages (TAMs). Accordingly, strong inhibition of tumor growth in the group treated with the sequential combination therapy was reported in vivo . Our data suggested that the antitumor action of the combined treatment was exerted through strong inhibition of several pro-angiogenic factors (VEGF, bFGF, and CD31) and oxidative stress-induced upregulation of pro-apoptotic protein Bax. This novel drug delivery strategy based on combined active targeting of both cancer cells and immune cells was able to induce a potent antitumor effect by disruption of the reciprocal interactions between TAMs and melanoma cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Negrea, Rauca, Meszaros, Patras, Luput, Licarete, Toma, Porfire, Muntean, Sesarman and Banciu.)

Purpose: The aim of this study was to evaluate the antioxidant potential, antimicrobial activity, the in vitro anticancer effect (tested on MCF-7 breast cancer cell line), as well as the antiangiogenic and immunomodulatory potential of Populus nigra L. bud (Pg) extract collected from the western part of Romania., Results: Populus nigra L. bud extract presents an important antioxidant activity, due to the rich phytochemical composition. Regarding the biological activity, results have shown that poplar bud extract presents a significant inhibitory activity against Gram-positive bacteria and a dose-dependent decrease of MCF-7 tumor cell viability with an IC 50 of 66.26 μg/mL, while not affecting healthy cells. Phenomena of early apoptotic events at the maximum concentration tested (150 μg/mL) were detected by Annexin V-PI double staining. The extract induced G0/G1 phase cell cycle arrest. In addition, Pg extract showed antiangiogenic potential on the chorioallantoic membrane. Also, at the highest concentration (150 μg/mL), good tolerability and no signs of toxicity upon vascular plexus were observed. Moreover, in low concentrations, the Pg extract had immunomodulatory activity on primary human dendritic cells by upregulating IL-12 and IL-23 subunits., Conclusion: The study concludes that poplar bud extract elicited antioxidant activity, antitumor properties on the breast cancer cell line, followed by an antiangiogenic effect and an immunomodulatory potential on human primary dendritic cells. The biological activity of Populus nigra L. buds extract may open new directions of research on the topic addressed., (© 2022. The Author(s).)

Biomaterials available for a wide range of applications are generally polysaccharides. They may have inherent antimicrobial activity in the case of chitosan. However, in order to have specific functionalities, bioactive compounds must be immobilized or incorporated into the polymer matrix, as in the case of cellulose. We studied materials obtained by functionalizing cellulose with quaternary ammonium salts: dodecyl-trimethyl-ammonium bromide (DDTMABr), tetradecyl-trimethyl-ammonium bromide (TDTMABr), hexadecyl-trimethyl ammonium chloride (HDTMACl), some phosphonium salts: dodecyl-triphenyl phosphonium bromide (DDTPPBr) and tri n-butyl-hexadecyl phosphonium bromide (HDTBPBr) and extractants containing sulphur: 2-mercaptobenzothiazole (MBT) and thiourea (THIO). Cel-TDTMABr material, whose alkyl substituent chain conformation was shortest, showed the best antimicrobial activity for which, even at the lowest functionalization ratio, 1:0.012 (w:w), the microbial inhibition rate is 100% for Staphylococcus aureus, Escherichia coli, and Candida albicans . Among the materials obtained by phosphonium salt functionalization, Cel-DDTPPBr showed a significant bactericidal effect compared to Cel-HDTBPBr. For instance, to the same functionalization ratio = 1:0.1, the inhibition microbial growth rate is maximum in the case of Cel-DDTPPBr for Staphylococcus aureus, Escherichia coli, and Candida albicans. At the same time, for the Cel-HDTBPBr material, the total bactericidal effect is not reached even at the functionalization ratio 1:0.5. This behavior is based on the hydrophobicity difference between the two extractants, DDTPPBr and HDTBPBr. Cel-MBT material has a maximum antimicrobial effect upon Staphylococcus aureus, Escherichia coli, and Candida albicans at functionalized ratio = 1:0.5. Cel-THIO material showed a bacteriostatic and fungistatic effect, the inhibition of microbial growth being a maximum of 76% for Staphylococcus aureus at the functionalized ratio = 1:0.5. From this perspective, biomaterials obtained by SIR impregnation of cellulose can be considered a benefit to be used to obtain biomass-derived materials having superior antimicrobial properties versus the non-functional support.

Background and Objectives : Proteus and Providencia are related genera of opportunistic pathogens belonging to the Morganellaceae family, often a cause of infections in the immunocompromised hosts, such as diabetic patients. Their clinical significance has increased due to their intrinsic resistance to polymyxins, which is often associated with acquired resistance mechanisms. In this study we evaluated the infections caused by Proteus mirabilis and Providencia stuartii in two groups of patients, with diabetes (group 1) and without diabetes (group 2) admitted to the intensive care unit and surgical wards. The infections were investigated in terms of infection type, risk factors, clinical course, predictive factors for unfavourable outcomes and antibiotic resistance profile. Materials and Methods : An observational, retrospective, cross-sectional study was conducted, comprising all patients infected with these pathogens. Bacterial identification and antibiotic sensitivity testing were performed using the Vitek2C automated system. Results : Comparison of the two groups showed that the statistically significant common infectious risk factors were found less frequently among diabetic patients when compared with non-diabetic patients, and that antimicrobial resistance was significantly lower in the diabetic patient group. However, survival rates did not differ between the two groups, drawing attention to the implications of diabetes as comorbidity. Additionally, with regard to the antibiotic resistance profile, 38.89% of P. stuartii strains isolated from diabetic patients belonged to the difficult-to-treat (DTR) phenotype, contributing to the severity of these infections compared with those caused by P. mirabilis , of which 32% were wild type strains and 0% were DTR phenotype. The DTR/extended spectrum beta-lactamase producing P. stuartii isolates more than doubled the risk of mortality, while the presence of nasogastric nutrition tripled the risk. Conclusions : P. stuartii infections that occurred in diabetic patients proved to be more difficult to treat, the majority of them being healthcare-associated bacteremias.

Considering the challenge created by the development of bacterial and fungal strains resistant to multiple therapeutic variants, new molecules and materials with specific properties against these microorganisms can be synthesized, like those synthesized from biopolymers such as chitosan with improved antimicrobial activities. Antimicrobial activities of seven obtained materials were tested on four reference strains belonging to American Type Culture Collection. The best antimicrobial activity was obtained by functionalization by impregnation of chitosan with quaternary ammonium salts, followed by that obtained by functionalization of chitosan with phosphonium. The lowest antibacterial and antifungal effects were expressed by Ch-THIO and Ch-MBT, but new materials obtained with these extractants may be precursors with a significant role in the direct control of active molecules, such as cell growth factors or cell signaling molecules.

An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.

This study was conducted to identify the volatile compounds of Mentha × smithiana essential oil (MSEO) and evaluate its antioxidant and antibacterial potential. The essential oil (EO) content was assessed by gas chromatography-mass spectrometry (GC-MS). Carvone (55.71%), limonene (18.83%), trans -carveol (3.54%), cis -carveol (2.72%), beta-bourbonene (1.94%), and caryophyllene oxide (1.59%) were the main identified compounds. The MSEO displayed broad-spectrum antibacterial effects and was also found to be the most effective antifungal agent against C andida albicans and Candida parapsilosis . The antioxidant activity of MSEO was tested against cold-pressed sunflower oil by peroxide, thiobarbituric acid, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), and β-carotene/linoleic acid bleaching methods. The EO showed strong antioxidant effects as reflected by IC 50 values of 0.83 ± 0.01 mg/mL and relative antioxidative activity of 87.32 ± 0.03% in DPPH and β-carotene/linoleic acid bleaching assays, respectively. Moreover, in the first 8 days of the incubation period, the inhibition of primary and secondary oxidation compounds induced by the MSEO (0.3 mg/mL) was significantly stronger (p < 0.05) than that of butylated hydroxyanisole. In silico molecular docking studies were conducted to highlight the underlying antimicrobial mechanism as well as the in vitro antioxidant potential. Recorded data showed that the antimicrobial activity of MSEO compounds could be exerted through the D-Alanine-d-alanine ligase (DDl) inhibition and may be attributed to a cumulative effect. The most active compounds are minor components of the MSEO. Docking results also revealed that several mint EO components could exert their in vitro antioxidant activity by employing xanthine oxidase inhibition. Consequently, MSEO could be a new natural source of antioxidants and antiseptics, with potential applications in the food and pharmaceutical industries as an alternative to the utilization of synthetic additives.

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.

Background: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells., Objective: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells., Methods: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays., Results: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60μg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate., Conclusion: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Carbapenem-resistant Proteeae (CRP) is a group of multidrug-resistant (MDR) microorganisms that raise special treatment problems due to their intrinsic resistance to colistin. In this study, our aim is to provide a phenotypic and molecular characterization of the carbapenemases secreted by CRP strains isolated from inpatients from an intensive care unit (ICU) and surgical wards, as well as the identification of the risk factors involved in their acquisition., Methods: An observational, cross-sectional study was performed which included all Proteeae strains isolated in samples from inpatients on high-risk wards of the largest university hospital in Western Romania, from July 2017 to April 2019. Meropenem-resistant strains (N=65) with MIC ≥16 µg/mL were subjected to a singleplex PCR assay for the detection of bla NDM, bla VIM and bla CTX-M genes. The analysis of risk factors was performed by logistic regression., Results: Out of 8317 samples that were processed, 400 Proteeae strains were isolated: 64% belonging to the genus Proteus , 26.75% to the genus Providencia and 9.25% to the genus Morganella . Most CRP strains (N=56) were of MBL type, and 55 had the bla NDM gene as the prevalent gene substrate. P. stuartii was the main species that provided the circulating MDR strains. Most CRP strains came from patients admitted to ICU, being isolated mainly from bronchial aspirates and blood cultures. Multivariate analysis revealed 3 independent risk factors - mechanical ventilation>96h (HR: 40.51 [13.65-120.25], p <0.001), tracheostomy (HR: 2.65 [1.14-6.17], p = 0.024) and prolonged antibiotic therapy (HR: 1.01 [1.00-1.02], p = 0.03)., Conclusion: There is a significant increase in the incidence of CR P. stuartii strains, the MBL- bla NDM type being predominant. These strains presented various other resistance mechanisms, being often extremely difficult to treat and led to an excess of lethality of 27.16%., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Rus et al.)

Purpose: Several mass spectrometry-based methods for antimicrobial sensitivity testing have been described in recent years. They offer an alternative to commercially available testing systems which were considered to have disadvantages in terms of cost- and time-efficiency. The aim of this study was to develop an LC-MS/MS-based antibiotic hydrolysis assay for evaluating antimicrobial resistance (AMR) of Gram-negative bacteria., Materials and Methods: Four species of Gram-negative bacilli ( Klebsiella pneumoniae, Escherichia coli, Providencia stuartii and Acinetobacter baumannii ) were tested against six antibiotics from three different classes: ampicillin, meropenem, imipenem, ceftazidime, ceftriaxone and cefepime. Bacterial suspensions from each species were incubated with a mixture of the six antibiotics. Any remaining antibiotic following incubation was measured using LC-MS/MS. The results were interpreted using measurements obtained for an E. coli strain sensitive to all antibiotics and expressed as percentage of hydrolyzed antibiotic. These were subsequently compared to commercially-available system for the bacteria identification and susceptibility testing., Results: Overall, LC-MS/MS assay and commercial antimicrobial susceptibility platform results showed good agreement in terms of an organism being resistant/sensitive to an antibiotic. The time required to complete the LC-MS/MS-based hydrolysis test was under 5 h, significantly shorter that commercially available susceptibility testing platforms., Conclusion: By using a sensitive strain for results interpretation and simultaneous use of multiple antibiotics, the proposed protocol offers improved robustness and multiplexing over previously described methods for antibiotic sensitivity testing. Nevertheless, further research is needed before routine assimilation of the method, especially for strains with intermediate resistance., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Serafim et al.)

Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA , qnrB , and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA ( E. coli ) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids' migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs ( p > 0.05). The presence of plasmids qnrA , qnrB , and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer.

Cannabidiol (CBD) is an alkaloid present in Cannabis sativa , along with tetrahydrocannabinol (THC) and more than 100 other substances belonging to a group of compounds called cannabinoids. Whereas the legal status and medical use of Cannabis is a controversial issue in many countries, inconsistent legislation makes CBD status even more complicated. Some CBD products are legal in some countries, while banned in other countries, further compounding the confusion. In 2018, the Food and Drug Administration (FDA) approved the first CBD containing medical product, Epidiolex ® , for the treatment of paediatric seizures. Currently, several clinical trials are in progress for the potential treatment of neurologic and behavioural disorders. CBD's current legal and regulatory status is a continuously evolving issue; the current review is presenting historical and present information regarding the use of CBD products worldwide.

Black chokeberry fruits possess a wide range of biological activities, among which the most important that are frequently mentioned in the literature are their antioxidant, anti-inflammatory, anti-proliferative, and antimicrobial properties. The present paper reports, for the first time, the encapsulation of the ethanolic extract of Aronia melanocarpa L. fruits into two mesoporous silica-type matrices (i.e., pristine MCM-41 and MCM-41 silica decorated with zinc oxide nanoparticles). The aim of this work was to evaluate the antiradicalic capacity, the antimicrobial potential, and the effects on the cell viability on a cancer cell line (i.e., A375 human melanoma cell line) versus normal cells (i.e., HaCaT human keratinocytes) of black chokeberry extract loaded on silica-type matrices in comparison to that of the extract alone. The ethanolic polyphenolic extract obtained by conventional extraction was characterized by high-performance liquid chromatography with a photodiode array detector (HPLC-PDA) and spectrophotometric methods. The extract was found to contain high amounts of polyphenols and flavonoids, as well as good radical scavenging activity. The extract-loaded materials were investigated by Fourier transform infrared spectroscopy, N 2 adsorption-desorption isotherms, thermal analysis, and radical scavenger activity on solid samples. The black chokeberry extract, both free and loaded onto mesoporous silica-type matrices, exhibited a significant antioxidant capacity. Antibacterial activity was recorded only for Gram-positive bacteria, with a more potent antibacterial effect being observed for the extract loaded onto the ZnO-modified MCM-41 silica-type support than for the free extract, probably due to the synergistic effect of the ZnO nanoparticles that decorate the pore walls of silica. The cellular viability test (i.e., MTT assay) showed dose- and time-dependent activity regarding the melanoma cell line. The healthy cells were less affected than the cancer cells, with all tested samples showing good cytocompatibility at doses of up to 100 µg/mL. Improved in vitro antiproliferative and antimigratory (i.e., scratch assay) potential was demonstrated through the loading of black chokeberry extract into mesoporous silica-type matrices, and the screened samples exhibited low selectivity against the tested non-tumor cell line. Based on presented results, one can conclude that mesoporous silica-type matrices are good hosts for black chokeberry extract, increasing its antioxidant, antibacterial (on the screened strains), and in vitro antitumor (on the screened cell line) properties.