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Daniel Oltean-Dan,1 Gabriela-Bombonica Dogaru,2 Maria Tomoaia-Cotisel,3,4 Dragos Apostu,1 Alexandru Mester,5 Horea-Rares-Ciprian Benea,1 Mihai-Gheorghe Paiusan,1 Elena-Mihaela Jianu,6 Aurora Mocanu,3 Reka Balint,3 Catalin-Ovidiu Popa,7 Cristian Berce,8 Gyorgy-Istvan Bodizs,9 Alina-Mihaela Toader,10 Gheorghe Tomoaia1,41Iuliu Hatieganu University of Medicine and Pharmacy, Department of Orthopedics and Traumatology, 400132 Cluj-Napoca, Romania; 2Iuliu Hatieganu University of Medicine and Pharmacy, Department of Medical Rehabilitation, 400347 Cluj-Napoca, Romania; 3Babes Bolyai University, Faculty of Chemistry and Chemical Engineering, Department of Chemical Engineering, Research Center of Physical Chemistry, 400028 Cluj-Napoca, Romania; 4Academy of Romanian Scientists, 050085 Bucharest, Romania; 5Iuliu Hatieganu University of Medicine and Pharmacy, Department of Oral Rehabilitation, Oral Health and Management, 400012 Cluj-Napoca, Romania; 6Iuliu Hatieganu University of Medicine and Pharmacy, Department of Histology, 400349 Cluj-Napoca, Romania; 7Technical University of Cluj-Napoca, Department of Materials Science and Engineering, 400641 Cluj-Napoca, Romania; 8Iuliu Hatieganu University of Medicine and Pharmacy, Center for Experimental Medicine, 400349 Cluj-Napoca, Romania; 9Rehabilitation Clinic, 400347 Cluj-Napoca, Romania; 10Iuliu Hatieganu University of Medicine and Pharmacy, Department of Physiology, 400006 Cluj-Napoca, RomaniaPurpose: Bone consolidation after severe trauma is the most challenging task in orthopedic surgery. This study aimed to develop biomimetic composite for coating Ti implants. Afterwards, these implants were tested in vivo to assess bone consolidation in the absence or the presence of high-frequency pulsed electromagnetic short-waves (HF-PESW).Materials: Biomimetic coating was successfully developed using multi-substituted hydroxyapatite (ms-HAP) functionalized with collagen (ms-HAP/COL), embedded into poly-lactic acid (PLA) matrix (ms-HAP/COL@PLA), and subsequently covered with self-assembled COL layer (ms-HAP/COL@PLA/COL, named HAPc).Methods: For in vivo evaluation, 32 Wistar albino rats were used in four groups: control group (CG) with Ti implant; PESW group with Ti implant+HF-PESW; HAPc group with Ti implant coated with HAPc; HAPc+PESW group with Ti implant coated with HAPc+HF-PESW. Left femoral diaphysis was fractured and fixed intramedullary. From the first post-operative day, PESW and HAPc+PESW groups underwent HF-PESW stimulation for 14 consecutive days. Biomimetic coating was characterized by XRD, HR-TEM, SEM, EDX and AFM.Results: Osteogenic markers (ALP and osteocalcin) and micro-computed tomography (CT) analysis (especially bone volume/tissue volume ratio results) indicated at 2 weeks the following group order: HAPc+PESW>HAPc≈PESW (P>0.05) and HAPc+PESW>control (P

Chemotherapy is a known treatment modality that improves the long-term survival of breast cancer patients. However, due to the resistance to numerous anticancer drugs, alternative chemotherapeutic strategies are required. Regarding antimetabolic drugs, several compounds have proven anticancer properties, such as statins. The present study aimed to investigate the in vitro effects of V9302, a competitive antagonist of glutamine flux, on different subtypes of breast cancers (estrogen, progesterone, and HER2 receptor-positive or negative, and Pgp-negative and Pgp-overexpressing). The interactions of V9302 with standard chemotherapeutic drugs (doxorubicin and cisplatin) were also determined by MTT staining on breast cancer cell lines. Furthermore, the influence of V9302 on the cell cycle of MCF-7 and its Pgp-overexpressing counterpart KCR was monitored by flow cytometry. It was shown that V9302 exerted synergistic interactions with doxorubicin in all breast cancer cell lines. In cell cycle analysis, the KCR cell line was more sensitive to V9302. After 48 h, cell proliferation was completely blocked, and elevated G1, suppressed S, and decreased G2/M could be detected. Inhibition of glutamate transport can be assumed to block resistance related to Pgp.

Context Ambrosia artemisiifolia L. (Asteraceae) contains sesquiterpene lactones as characteristic secondary metabolites. Many of these compounds exert antiproliferative and cytotoxic effects.Objective To isolate the sesquiterpene lactones from the aerial part of A. artemisiifolia and to elucidate their cytotoxic, antiproliferative and antibacterial effects.Materials and methods The compounds were identified by one-dimensional (1D) and 2D NMR, HR-MS spectroscopy from the methanol extract. Isolated compounds were investigated for their cytotoxic and antiproliferative effects on human colonic adenocarcinoma cell lines and human embryonal lung fibroblast cell line using MTT assay. The selectivity of the sesquiterpenes was calculated towards the normal cell line. To check the effect of drug interactions between compounds and doxorubicin, multidrug-resistant Colo 320 cells were used.Results A new seco-psilostachyinolide derivative, 1,10-dihydro-1′-noraltamisin, and seven known compounds were isolated from the methanol extract. Acetoxydihydrodamsin had the most potent cytotoxic effect on sensitive (Colo205) cell line (IC50 = 7.64 µM), also the strongest antiproliferative effect on Colo205 (IC50 = 5.14 µM) and Colo320 (IC50 = 3.67 µM) cell lines. 1′-Noraltamisin (IC50 = 8.78 µM) and psilostachyin (IC50 = 5.29 µM) showed significant antiproliferative effects on the multidrug-resistant Colo320 cell line and had moderate selectivity against human embryonal lung fibroblast cell line. Psilostachyin C exhibited cytotoxic effects on Colo205 cells (IC50 = 26.60 µM). None of the isolated compounds inhibited ABCB1 efflux pump (EP; P-glycoprotein) or the bacterial EPs.Discussion and conclusions Acetoxydihydrodamsin, 1′-noraltamisin, and psilostachyin showed the most remarkable cytotoxic and antiproliferative activity on tumour cell lines and exerted selectivity towards MRC-5 cell line.

Polyporenic acids N-R (1–5), five novel 24-methylene lanostane triterpenes along with seven known polyporenic acids (6–12), were identified from the fruiting bodies of Buglossoporus quercinus. The isolation of compounds 1–12 was performed by a combination of multistep flash chromatography and reversed-phase high-performance liquid chromatography (HPLC). The structure determination was carried out by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments. The isolated fungal metabolites were investigated for their antiproliferative activity in vitro by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the resistant Colo 320 human colon adenocarcinoma cell line expressing P-glycoprotein (ABCB1). The lanostane triterpenes exerted moderate antiproliferative activity with IC50 values in the range of 20.7–106.2 μM. A P-glycoprotein efflux pump modulatory test on resistant Colo 320 cells highlighted that fungal metabolites 3, 5, 8, and 10–12 have the ability to inhibit the efflux pump activity of cancer cells. Moreover, the drug interactions of triterpenes with doxorubicin were studied by the checkerboard method. Compounds 3–4, and 7–12 interacted in a synergistic manner, while an outstanding potency was detected for compound 9, which was defined as strong synergism (CI = 0.276). The current study reveals that B. quercinus is a remarkable source of fungal steroids with considerable chemosensitizing activity on cancer cells.

Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups.

Multidrug resistance (MDR) is a major obstacle in the therapy of infectious diseases and cancer. One of the major mechanisms of MDR is the overexpression of efflux pumps (EPs) that are responsible for extruding antimicrobial and anticancer agents. EPs have additional roles of detoxification that may aid the development of bacterial infection and the progression of cancer. Therefore, targeting EPs may be an attractive strategy to treat bacterial infections and cancer. The development and discovery of a new drug require a long timeline and may come with high development costs. A potential alternative to reduce the time and costs of drug development is to repurpose already existing drugs. Antidepressants and antipsychotic agents are widely used in clinical practice in the treatment of psychiatric disorders and some somatic diseases. Antidepressants and antipsychotics have demonstrated various beneficial activities that may be utilized in the treatment of infections and cancer. This review aims to provide a brief overview of antibacterial and anticancer effects of selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and phenothiazine antipsychotics, while focusing on EPs. However, it should be noted that the antimicrobial activity of a traditionally non-antibiotic drug may have clinical implications regarding dysbiosis and bacterial MDR.

Abstract Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10. Curiously, the expression of the well-characterized UVB-inducible MMP9, which is located outside of the cluster, remains unchanged. In accordance with the increased expression of the MMP gene cluster upon UVB irradiation, RNA polymerase II showed increased occupancy at their promoters following UVB irradiation. The results also demonstrate increased acetylated histone H3K9 levels at the promoters of the MMP13, MMP12, MMP3, MMP1 and MMP10 genes. These findings suggest a coordinated transcriptional activation of genes in the MMP cluster at 11q22.3 and that acetylation of histone H3 at lysine 9 has an important role in the UVB-dependent enhancement of transcription of MMP genes in this region.

Urinary tract infections (UTIs) are common bacterial infections caused mainly by enteric bacteria. Numerous virulence factors assist bacteria in the colonization of the bladder. Bacterial efflux pumps also contribute to bacterial communication and to biofilm formation. In this study, the phenotypic and genetic antibiotic resistance of clinical UTI pathogens such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were determined by disk diffusion method and polymerase chain reaction (PCR). Following this, different classes of antibiotics were evaluated for their antibacterial activity at pH 5, 6, 7 and 8 by a microdilution method. Gentamicin (GEN) was the most potent antibacterial agent against E. coli strains. The effect of GEN on the relative expression of marR and sdiA genes was evaluated by quantitative PCR. The slightly acidic pH (pH 6) and GEN treatment induced the upregulation of marR antibiotic resistance and sdiA QS activator genes in both E. coli strains. Consequently, bacteria had become more susceptible to GEN. It can be concluded that antibiotic activity is pH dependent and so the artificial manipulation of urinary pH can contribute to a more effective therapy of multidrug resistant bacterial infections.

The cost optimal scheduling of a household refrigerator is presented in this work. The fundamental approach is the model predictive control methodology applied to the piecewise affine model of the refrigerator.

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.

Bacteria often show resistance against antibiotics due to various mechanisms such as the expression of efflux pumps, biofilm formation, or bacterial quorum sensing (QS) controls. For successful therapy, the discovery of alternative agents is crucial. The objective of this study was to evaluate the efflux pump, anti-biofilm, and QS inhibiting, as well as antibacterial effects of 2-trifluoroacetonylbenzoxazole ligands (1–3) and their metal complexes (4–12) in bacteria. The ligand 2 and its Zn(II) complex 5, and furthermore the Cu(II) complex 7 of ligand 1, exerted remarkable antibacterial activity on the Staphylococcus aureus 272123 (MRSA) strain. In the minimum inhibitory concentration (MIC) reduction assay the ligand 3, the Zn(II) complex 5 of ligand 2, and the Cu(II), Ni(II), Mg(II), Fe(III) complexes (7, 8, 9, 12) of ligand 1 enhanced the antibacterial activity of ciprofloxacin in MRSA. An increased ethidium bromide accumulation was detected for ligand 3 in MRSA while the Fe(III) complex 12 of ligand 1 decreased the biofilm formation of the reference S. aureus ATCC 25923 strain. The Zn(II) and Ag(II) complexes (3 and 4) of ligand 1 and ligand 3 inhibited the QS. Based on our results, the ligands and their metal complexes could be potential alternative drugs in the treatment of infectious diseases.

Infections caused by Salmonella species and Staphylococcus aureus represent major health and food industry problems. Bacteria have developed many strategies to resist the antibacterial activity of antibiotics, leading to multidrug resistance (MDR). The over-expression of drug efflux pumps and the formation of biofilms based on quorum sensing (QS) can contribute the emergence of MDR. For this reason, the development of novel effective compounds to overcome resistance is urgently needed. This study focused on the antibacterial activity of nine symmetrical selenoesters (Se-esters) containing additional functional groups including oxygen esters, ketones, and nitriles against Gram-positive and Gram-negative bacteria. Firstly, the minimum inhibitory concentrations of the compounds were determined. Secondly, the interaction of compounds with reference antibiotics was examined. The efflux pump (EP) inhibitory properties of the compounds were assessed using real-time fluorimetry. Finally, the anti-biofilm and quorum sensing inhibiting effects of selenocompounds were determined. The methylketone and methyloxycarbonyl selenoesters were the more effective antibacterials compared to cyano selenoesters. The methyloxycarbonyl selenoesters (Se-E2 and Se-E3) showed significant biofilm and efflux pump inhibition, and a methyloxycarbonyl selenoester (Se-E1) exerted strong QS inhibiting effect. Based on results selenoesters could be promising compounds to overcome bacterial MDR.

ABSTRACT: Adenosine receptors are expressed in various mammalian tissues where they mediate the effects of adenosine on cellular functions through a number of signalling mechanisms. 18F-NECA is the positron-emitting derivative of the A2-receptor agonist NECA (5'-n-ethyl-carboxamidoadenosine) and is a radioligand for PET imaging of adenosine receptors. Contractility and relaxation studies were performed on guinea pig atrial myocardium, pulmonary artery, and thoracic aorta to compare the pharmacological effects of NECA and F-NECA (a non-emitting derivative) on tissues. Furthermore, the effect of NECA and F-NECA on the potassium conductance was investigated in DDT1 MF-2 smooth muscle cells with the patch-clamp technique. Both NECA and F-NECA reduced the contractile force in atrial myocardium and evoked phasic contraction in pulmonary artery (A1 adenosine-receptor-mediated actions) in a dose dependent manner; however, the apparent affinity was lower for F-NECA. No difference was found in relaxation induced by these compounds in 1 μM noradrenaline-precontracted aorta and pulmonary artery (in the presence of DPCPX, an A1 adenosine receptor antagonist, tissue containing A2B adenosine receptors). NECA (5 μM) and F-NECA (5 μM) also decreased the peak current and accelerated activation and inactivation properties of the potassium channels, but F-NECA was less effective. These results suggest that while NECA and F-NECA are equivalent agonists of vascular A2B receptors, they mediate different changes of some parameters. When evaluating the data obtained by the use of radiolabelled ligands, one has to take into consideration the possible physiological effects of the ligands besides its binding properties to tissues.

Introduction Recurrent depressive disorder is heterogeneous in respect to its etiology (predominantly exogenous or endogenous). Patients with recurrent depressive disorder (RDD) may change diagnosis to bipolar disorder (BD). Regarding the “true” RDD there is the possibility that in most cases it is exogenous, and the prevalence of endogenous RDD might be similar to BD. There is still debate regarding useful criteria for distinguishing between bipolar and monopolar depression especially at the first episode. Objectives The purpose of the study is to identify useful phenotypes that could help distinguishing between endogenous monopolar and bipolar depression. Methods The study was carried out on patients diagnosed with RDD and BD according to ICD 10 criteria. The following data was analyzed: socio-demographic parameters, family psychiatric history, seasonality, suicidal attempts, and behavioral phenotypes such as nicotine, alcohol, or illicit drug use. Results The study included 105 RDD and 74 BD patients. In the RDD sample the mean age at disorder onset was 45.93 years, while in the BD sample, was 32.45 years. Significant differences between the samples were found in: family psychiatric history (BD patients having more relatives with schizophrenia, P = 0.01), smoking habits (BD patients smoking more cigarettes than RDD patients, P = 0.001), and seasonal depression (mainly summer and winter in RDD, and mainly summer and autumn in BD). No differences were found regarding suicidal attempts, alcohol or illicit drug use. Conclusions Onset age, family psychiatric history, smoking habits, and seasonality may reflect endogenous depression (BD or RDD) or different subtypes of BD or RDD. [ABSTRACT FROM AUTHOR]

Soil contamination is a significant environmental issue that poses a threat to human health and the ecosystems. Conventional remediation techniques, such as excavation and landfilling, are often expensive, disruptive, and unsustainable. As a result, there has been growing interest in developing sustainable remediation strategies that are cost-effective, environmentally friendly, and socially acceptable. One such solution is phytoextraction: a nature-based approach that uses the abilities of hyperaccumulator plants to uptake and accumulate metals and metalloids (potentially toxic elements [PTE]) without signs of toxicity. Once harvested, plant biomass can be treated to reduce its volume and weight by combustion, thus obtaining bioenergy, and the ashes can be used for the recovery of metals or in the construction industry. However, phytoextraction has shown variable effectiveness due to soil conditions and plant species specificity, which has led researchers to develop additional approaches known as assisted phytoextraction to enhance its success. Assisted phytoextraction is a remediation strategy based on modifying certain plant traits or using different materials to increase metal uptake or bioavailability. This review article provides a practical and up-to-date overview of established strategies and the latest scientific advancements in assisted phytoextraction. Our focus is on improving plant performance and optimizing the uptake, tolerance, and accumulation of PTE, as well as the accessibility of these contaminants. While we highlight the advantages of using hyperaccumulator plants for assisted phytoextraction, we also address the challenges and limitations associated with this approach. Factors such as soil pH, nutrient availability, and the presence of other contaminants can affect its efficiency. Furthermore, the real-world challenges of implementing phytoextraction on a large scale are discussed and strategies to modify plant traits for successful phytoremediation are presented. By exploring established strategies and the latest scientific developments in assisted phytoextraction, this review provides valuable guidance for optimizing a sustainable, nature-based technology. Integr Environ Assess Manag 2024;00:1-20. © 2024 SETAC., (© 2024 SETAC.)

This work aimed to compare the effect of four new toothpastes (P1-P4) based on pure and biomimetic substituted nano-hydroxyapatites (HAPs) on remineralization of human enamel. Artificially demineralized enamel slices were daily treated for ten days with different toothpastes according to the experimental design. Tooth enamel surfaces were investigated using atomic force microscope (AFM) images and surface roughness (Ra) determined before and after treatment. The surface roughness of enamel slices was statistically analyzed by one-way ANOVA and Bonferroni's multiple comparison test. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) data revealed the HAP structure with crystal sizes between 28 and 33 nm and crystallinity between 29 and 37%. The average size of HAP particles was found to be between 30 and 40 nm. The Ra values indicated that P3 (HAP-Mg-Zn-Sr-Si) toothpaste was the most effective after 10 days of treatment, leading to the lowest mean roughness. The P3 and P2 (HAP) toothpastes were found to be effective in promoting remineralization. Specifically, their effectiveness can be ranked as follows: P3 = P2 > P4 (HAP-Mg-Zn-Si) > P1 (HAP-Zn), considering both the chemical composition and the size of their constitutive nanoparticles. The proposed toothpastes might be used successfully to treat early tooth decay.

In this work, we report solid-state synthetized defective Bi 2 O 3 containing Bi(V) sites as effective and recyclable arsenic adsorbent materials. Bi 2 O 3 was extensively characterized, and structure-related adsorption processes are reported. Both As(V) and As(III) species-adsorption processes were investigated in a wide range of concentrations, pH values, and times. The effect of several competing ions was also tested together with the adsorbent recyclability.

This study assesses the empathy level, cognitive performance and emotion recognition skills of remitted patients with schizophrenia, schizoaffective disorder and bipolar disorder, and also explores the relationship between impairments in the mentioned domains. The study was performed on 77 subjects divided into two groups: PAT sample (N = 37) included remitted patients with either schizophrenia, schizoaffective or bipolar disorder who were compared with healthy control subjects from the HC sample (N = 40). Along with sociodemographic and clinical data, empathy levels (using EQ (Empathy Quotient) scale), the ability to recognize another person's emotional state (using RMET (Reading the Mind in the Eyes Test)), and cognitive performance (using MoCA (Montreal Cognitive Assessment) Scale) were investigated. The intensity of the psychiatric symptoms was measured with BPRS-E (Brief Psychiatric Rating Scale-Expanded). The remitted patients had lower EQ ( p = 0.02) and RMET ( p < 0.0001) scores than the healthy subjects. In the PAT group, RMET scores were positively correlated with MoCA total scores. Both EQ and RMET scores were negatively correlated with BPRS-E total scores. Psychiatric disorder was a significant predictor for deficits in emotion recognition. There were no significant differences in RMET, EQ and MoCA scores between patients with respect to diagnosis, the type of antipsychotic or the associated medication. In both samples, females had higher empathy levels ( p = 0.04) and better emotion recognition abilities ( p = 0.04) than males. Patients with schizophrenia, schizoaffective or bipolar disorder, currently in remission, displayed lower empathy levels and poorer emotion recognition skills than healthy subjects. Poor emotion recognition skills were associated with symptom severity and impairments in global cognition.

The Fe(II)-catalyzed transformation of ferrihydrite into highly crystalline forms may represent an important pathway for soil organic matter (SOM) destabilization under moderately reducing conditions. However, the link between redox-driven changes in soil Fe mineral composition and crystallinity and SOM chemical properties in the field remains elusive. We evaluated abiotic Fe(II)-catalyzed mineralogical transformation of Fe (oxyhydr)oxides in bulk soils and two particle-size SOM fractions, namely the fine silt plus clay (<20 μm, FSi + Cl) and fine sand (50-200 μm, FSa) fractions of an agricultural soil unamended or amended with biochar, compost, or the combination of both. After spiking with Fe(II) and incubating for 7 days under anoxic and sterile conditions at neutral pH, the FSa fractions (Fe(II):Fe (III) molar ratios ≈ 3.3) showed more significant ferrihydrite transformations with respect to FSi + Cl fractions (Fe(II):Fe (III) molar ratios ≈ 0.7), with the consequent production of well-ordered Fe oxides in most soils, particularly those unamended or amended with biochar alone. Nonetheless, poorly crystalline ferrihydrite still constituted about 45% of the FSi + Cl fractions of amended soils after reaction with Fe(II), which confirms that the higher SOM and clay mineral content in this fraction may possibly inhibit atom exchange between aqueous Fe(II) and the solid phase. Building on our knowledge of abiotic Fe(II)-catalyzed mineralogical changes, the suppression of ferrihydrite transformation in FSi + Cl fractions in amended soils could ultimately lead to a slower turnover of ferrihydrite, possibly preserving the carbon sequestration potential associated with this mineral. Conversely, in both bulk soils and FSa fractions, the extent to which mineral transformation occur seemed to be contingent on the quality of the amendment used., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Electrical stimulation for delivery of biochemical agents such as genes, proteins and RNA molecules amongst others, holds great potential for controlled therapeutic delivery and in promoting tissue regeneration. Electroactive biomaterials have the capability of delivering these agents in a localized, controlled, responsive and efficient manner. These systems have also been combined for the delivery of both physical and biochemical cues and can be programmed to achieve enhanced effects on healing by establishing control over the microenvironment. This review focuses on current state-of-the-art research in electroactive-based materials towards the delivery of drugs and other therapeutic signalling agents for wound care treatment. Future directions and current challenges for developing effective electroactive approach based therapies for wound care are discussed., (Copyright © 2017. Published by Elsevier B.V.)

Objective: The aim of this review article was to evaluate the long-term technical success rates of the known endovenous ablation procedures in the treatment of the incompetence of the great saphenous vein., Methods: A literature search was conducted in the PubMed-database until the 5 January 2016. All publications with four to five years follow-up were eligible. Meta-analysis was performed by the IVhet-model., Results: Eight hundred and sixty-two unique publications were found; 17 of them were appropriate for meta-analysis. Overall, 1420 limbs were included in the trial, 939 for endovenous laser ablation, 353 for radiofrequency ablation and 128 for ultrasound guided foam sclerotherapy. Overall, technical success rates were 84.8% for endovenous laser ablation, 88.7% for radiofrequency ablation and 32.8% for ultrasound guided foam sclerotherapy. There were no significant differences between endovenous laser ablation, radiofrequency ablation and ultrasound guided foam sclerotherapy regarding the great saphenous vein reopening (p = 0.66; OR: 0.22; 95% of CI: 0.08-0.62 for radiofrequency ablation vs. endovenous laser ablation; p = 0.96; OR: 0.11; 95% of CI: 0.06-0.20 for endovenous laser ablation vs. ultrasound guided foam sclerotherapy; p = 0.93; OR: 3.20; 95% of CI: 0.54-18.90 for ultrasound guided foam sclerotherapy vs. radiofrequency ablation)., Conclusion: Both endovenous laser ablation and radiofrequency ablation are efficient in great saphenous vein occlusion on the long term. Lacking long-conducted large trials, the efficacy and reliability of ultrasound guided foam sclerotherapy to treat great saphenous vein-reflux is not affirmed., (© The Author(s) 2016.)

X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents--iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid--are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented.

Our aim was to determine the place of cryosurgery in the treatment of the incompetence of the great saphenous vein. Primary end-point of this study was to evaluate the clinical effectiveness of cryostripping and cryosclerosis. Complications frequently related to saphenous vein stripping were analyzed secondary. A literature search was conducted in the PubMed-database until September 2014. Randomized controlled trials with at least 6 months follow-up were eligible. Meta-analysis was performed by the IVhet-model. Forty-two unique publications were found- Five of them (3 trials), comparing cryostripping to stripping and endovenous LASER ablation, were eligible for meta-analysis. There were no significant differences between cryostripping and conventional stripping regarding the clinical effectiveness (P=0.06; RR:1.12; 95% of CI: 0.99-1.27) and saphenous neuralgia related to surgery (P=0.48; RR:0.94; 95% of CI: 0.89-0.99). The records of bruising were not uniform and comparable. No randomized controlled trials were found to perform a meta-analysis on cryosclerosis, therefore a short literature review is presented. The study has limitations and weak conclusions because of imprecision (small number of involved trials and limbs) and short term follow-up. Low quality evidences suggest that cryostripping is a reliable, efficient method with better cosmetic results than conventional stripping, however, long term comparisons are not available so far. Cryosclerosis could be an alternate to the known endovenous minimal invasive ablation procedures, but there are no exact strong evidences, especially on the long term.

Numerous scientific studies and clinical trials are carried out each year exploring the use of mesenchymal stromal cells in regenerative medicine and tissue engineering. However, the effective and reliable expansion of this very important cell type remains a challenge. In this study the importance of cell-to-cell contact during expansion has been explored on the proliferation and differentiation potential of the produced cells. Cells were cultured up to passage 5 under conditions where cell-to-cell contact was either probable (40-70% confluence; see supporting information, Protocol A) or where it was unlikely (10-50% confluence; see supporting information, Protocol B). The effect of the two different conditions on expansion efficiency; proliferation rate and tri-lineage differentiation potential was assessed. Differences in immunophenotype, cell size and senescence were also investigated. Protocol B cultures expanded twice as fast as those cultured with Protocol A. In passage 5 experiments low confluence expanded cells displayed a 10% higher overall proliferation rate, and produced 23% more cells in growth, 12% more in osteogenic, 77% more in adipogenic, but 27% less in chondrogenic medium. Differentiation potential wasn't decisively affected at the mRNA level. However, Protocol B favoured bone and cartilage differentiation at the secretional level. Protocol A populations showed reduced purity, expressing CD105 in only 76% compared to the 96.7% in Protocol B cultures. Protocol A populations also contained significantly more (+4.2%) senescent cells, however, no difference was found in cell size between the two protocols. The findings of this study suggest that cell-to-cell contact, and therefore high confluence levels, is detrimental to MSC quality., (© 2015 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.)