Normal Human Fibroblast Cells Research Articles

First iron(II) organometallic compound acting as ABCB1 inhibitor

Five new iron (II) complexes bearing imidazole-based (Imi-R) ligands with the general formula [Fe(η5-C5H5)(CO)(PPh3)(Imi-R)][CF3SO3] were synthesized and fully characterized by several spectroscopic and analytical techniques. All compounds crystallize in centrosymmetric space groups in a typical “piano stool” distribution. Given the growing importance of finding alternatives to overcome different forms of multidrug resistance, all compounds were tested against cancer cell lines with different ABCB1 efflux pump expression, namely, the doxorubicin-sensitive (Colo205) and doxorubicin-resistant (Colo320) human colon adenocarcinoma cell lines. Compound 3 bearing 1-benzylimidazole was the most active in both cell lines with IC50 values of 1.26 ± 0.11 and 2.21 ± 0.26 μM, respectively, being also slightly selective against the cancer cells (vs. MRC5 normal human embryonic fibroblast cell lines). This compound, together with compound 2 bearing 1H-1,3-benzodiazole, were found to display very potent ABCB1 inhibitory effect. Compound 3 also showed the ability to induce cell apoptosis. Iron cellular accumulation studies by ICP-MS and ICP-OES methods revealed that the compounds’ cytotoxicity is not related to the extent of iron accumulation. Yet, it is worth mentioning that, from the compounds tested, 3 was the only one where iron accumulation was greater in the resistant cell line than in the sensitive one, validating the possible role of ABCB1 inhibition in its mechanism of action.

Evaluation of Recovery Methods for Fragaria vesca L. Oil: Characteristics, Stability and Bioactive Potential.

Wild strawberry (Fragaria vesca L.) seed oil (WSO) recovered by two methods-cold pressing (CP) and extraction with supercritical carbon dioxide (SCO2E)-taking into account the different extraction times, was characterized for its composition and quality. The cytotoxicity assessment of WSOs was also carried out using the normal human dermal fibroblast (NHDF) cell line. Tocopherol and total polyphenol contents were significantly higher in WSO recovered by SCO2E, up to 1901.0 and 58.5 mg/kg, respectively, in comparison with CP oil. In CP oil, the highest content of carotenoids and squalene was determined (123.8 and 31.4 mg/kg, respectively). Phytosterol summed up to 5396 mg/kg in WSO collected in 30 min of SCO2E. Moreover, the highest oxidative stability was found for this oil. All studied WSOs were non-cytotoxic in lactate dehydrogenase (LDH) leaching and sulforhodamine B (SRB) assays; however, oils collected by SCO2E in 15 and 30 min were found to be cytotoxic in the tetrazolium salt (MTT) test, with the CC50 at a concentration of 3.4 and 5.5%, respectively. In conclusion, the composition of WSO indicates that, depending on the method of its recovery, seeds can have different bio-potencies and various applications.

Assessing the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica on AMJ13 and SK-GT-4 human cancer cell lines

Background: Breast and esophageal cancer are the most aggressive and prominent causes of death worldwide. In addition, these cancers showed resistance to current chemotherapy regimens with limited success rates and fatal outcomes. Recently many studies reported the significant cytotoxic effects of phenolic and terpene fractions extracted from various Prunus species against different cancer cell lines. As a result, it has a good chance to be tested as a complement or replacement for standard chemotherapies. Methods: The study aimed to evaluate the cytotoxicity of phenolic and terpene fractions extracted from Iraqi Prunus arabica on breast (AMJ13) and esophageal (SK-GT-4) cancer cell lines by using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide). Analysis using the Chou-Talalay method was performed to assess the synergistic effect between the extracted fractions and chemotherapeutic agent (docetaxel). Moreover, high-performance liquid chromatography (HPLC) analysis was conducted for the quantitative determination of different bioactive molecules of both phenolic and terpene fractions in the extract. Results: According to the findings, the treatment modalities significantly decreased cancer cell viability of AMJ13 and SK-GT-4 and had insignificant cytotoxicity on the normal cells (normal human fibroblast cell line) (all less than 50% cytotoxicity). Analysis with Chou-Talalay showed a strong synergism with docetaxel on both cancer cell lines (higher cytotoxicity even in low concentrations) and failed to induce cytotoxicity on the normal cells. Important flavonoid glycosides and terpenoids were detected by HPLC, in particularly, ferulic acid, catechin, chlorogenic acid, β-sitosterol, and campesterol. Conclusions: In conclusion, the extracted fractions selectively inhibited the proliferation of both cancer cell lines and showed minimal cytotoxicity on normal cells. These fractions could be naturally derived drugs for treating breast and esophageal cancers.

Design, Synthesis, and Investigation of Cytotoxic Effects of 5-Hydroxyindole-3-Carboxylic Acid and Ester Derivatives as Potential Anti-breast Cancer Agents.

Breast cancer is a deadly disease with a high prevalence rate among females. Despite several treatments, scientists are still engaged in finding less invasive treatments for this disease. The cellular proliferation rate and cell viability survey are critical to assess the drug's effect on both normal and malignant cell populations. Indole derivatives are promising candidates for their cytotoxic effect causing on breast cancer cells; however, they are less toxic on normal cells. This study synthesized 23 novel 5-hydroxyindole-3-carboxylic acids and related esters featuring various linear, cyclic, and primary aromatic amines. The MTT assay indicated the cytotoxicity of all acid and ester derivatives against the MCF-7 cells with no significant cytotoxicity on normal human dermal fibroblasts cells. Compound 5d, an ester derivative possessing a 4-methoxy group, was the most potent compound, with a half-maximal effective concentration of 4.7 µM. Compounds 5a, 5d, and 5l bearing ester group in their structure demonstrated cytotoxicity values < 10 µM against the MCF-7 cell line and were safe for advanced screening.

Possible implementation of salicylate anions in lead detoxification

The water-soluble coordination polymer of formula {[Pb(Sal)2(H2O)]n} (SaLead), was obtained from the reaction between Pb(NO3)2 and the potassium salt of salicylic acid (SalH), an anti-inflammatory drug, which is also use as food preservation, in cosmetics etc. The compound was characterized by melting point, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray diffraction crystallography (XRD) in solid state and in solution by Ultra Violet (UV) and 1H NMR spectroscopies. The binding affinity of SalK to Pb(II) ions towards SaLead was determined in order to examine its possible implementation in lead detoxification. The in vitro non-toxic behaviour of SalK and its complex SaLead was evaluated against normal human fetal lung fibroblast cells (MRC-5). The corresponding IC50 values are 260 ± 13 and > 1600 μM respectively. The non-genotoxic in vitro activity of SaLead was confirmed with the micronucleus (MN) assay, while its in vivo non-toxicity behaviour was evaluated with Allium cepa and Artemia salina assays.

The Apoptotic Activity of Curcumin Against Oral Cancer Cells Without Affecting Normal Cells in Comparison to Paclitaxel Activity.

Until now, chemotherapy, which has a series of side effects, has been the most widely employed treatment for different types of cancer. However, bioactive products have been utilized as alternative medicines for tumors due to their bioactivities with low or no side effects in normal cells. This research reported for the first time that curcumin (CUR) and paclitaxel (PTX) have significant anti-cancer activity against normal human gingival fibroblast (HGF) and tongue squamous cell carcinoma fibroblast (TSCCF) cell lines. The results showed that CUR (13.85µgmL-1) and PTX (8.17µgmL-1) significantly inhibited TSCCF cell viability, with no significant effect on normal HGF cells. SEM showed morphological changes in cells treated with CUR and PTX, especially with TSCCF cells, compared to HGF normal cells. For TSCCF, the results showed the highest necrosis was achieved with CUR (58.8%) and PTX (39%) as compared to the control (2.99%). For normal HGF cells, the highest early and late apoptosis was achieved with PTX. Further, DCFH-DA analyses showed no significant ROS stimulation in TSCCF and HGF cell lines treated with CUR and PTX. The 1H NMR analysis results show the presence of methoxy and hydroxyl groups and aromatic hydrogens in the CUR structure. In conclusion, the results confirmed that CUR is more specific to the oral cancer cells but not normal cells by inducing apoptosis in a dose- and time-dependent manner, with decreased TSCCF cell viability, and the cytotoxicity of CUR and PTX is not through the ROS pathway.

In Vitro Pro-Apoptotic and Anti-Migratory Effects of Marantodes pumilum (syn. Labisia pumila) Extracts on Human Prostate Cancer Cell Lines: Bioguided Isolation of 5-Henicosene-1-yl-resorcinol.

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Marantodes pumilum Blume Kuntze plant extracts on prostate cancer cells, identify the active compound/s, and characterize their mechanism of action. The crude methanolic extract was partitioned into n-hexane (MPh), chloroform (MPc), and aqueous (MPa) extracts. Antiproliferative fractions (IC50 < 30 μg/mL based on SRB staining of LNCaP and PC3 cell lines) were further fractionated. Active compound/s were identified using spectroscopic methods. In vitro mechanistic studies on PC3 cells included: annexin V-FITC staining, mitochondrial membrane potential (MMP) depolarization measurements, the activity of caspases 3 and 7, nuclear DNA fragmentation, cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, Alox-5, VEGF-A, CXCR4, and CXCL12 mRNA gene expression via RT-PCR, 2D migration (scratch assay), and 3D invasion (Boyden chamber). MPc extract was the most active, inducing cell death (p < 0.05) via apoptosis, as evidenced by nuclear DNA fragmentation and an increase in MMP depolarization (p < 0.05) as well as the activation of caspases 3/7 (MPc p < 0.01) in both PC3 and LNCaP cell lines. In addition, MPc upregulated Bax and Smac/DIABLO, downregulated Bcl-2 (p < 0.05), and inhibited ALOX-5 mRNA gene expression (p < 0.001). MPc was not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Moreover, MPc inhibited migration and invasion of PC3 cells (p < 0.01). These effects were accompanied by the downregulation of both VEGF-A and CXCL-12 gene expressions (p < 0.001). A monounsaturated 5-alkyl resorcinol was isolated as the active compound in the MPc extract and identified as 5-henicosene-1-yl-resorcinol.

Concurrent Tissue Engineering for Wound Healing in Diabetic Rats Utilizing Dual Actions of Green Synthesized CuO NPs Prepared from Two Plants Grown in Egypt.

Diabetes mellitus is among the disrupting factors of orchestrated events in wound healing. This necessitates the urge for tailored medications, which are continually offered by nano-sized materials. Herein, we present greenly synthesized copper oxide nanoparticles (CuO NPs), obtained from either Punica granatum L. (PG) or Pisidium guajava L. (GV) extract, to function as potent bactericidal and fungicidal materials that promote regeneration and healing of the targeted diabetic wounded tissues. PG or GV plant extracts were compared as source of reducing agents for CuO NPs synthesis process. The yield and photocatalytic degradation potential were compared. NPs obtained from the superior extract, PG, were characterized using particles size, zeta potential, XRD, TEM, SEM, and EDX. The antimicrobial effects were evaluated on multidrug-resistant human pathogens and then the percentage biofilm inhibitory concentration was determined. The cytotoxicity and wound scratch study were conducted on a normal human skin cell line. In-vivo wound healing activity in diabetic rats was assessed along with histopathological and immunohistochemical examination of CD45 and α-SMA. The greenly synthesized CuO NPs are spherical in shape having a diameter of 233nm. CuO NPs (250µg/mL) acted as promising biocontrol agent against a variety of multidrug-resistant human pathogens. They significantly exhibited 29.460±0.811% healing of the scratched wound compared to only 2.001±0.155% for the control. Wound healing experiments revealed the safety of a low CuO NPs concentration in a diabetic animal model as well as on human normal skin fibroblast cell line. The treated group with a dose of 2mg/cm2 showed superior results with a WC50 value of 7.2 days, and 92% wound contraction after 13-days. Immunohistochemical investigation of the same group demonstrated well-established fibrous tissue (5.7±3.7/HPF), and an amplified granulation tissue of recently developed blood vessels (70±1.5/HPF). Green synthesized CuO NPs could overcome drug resistance and promote wound healing process effectively.

Antibiotic-Lysobacter enzymogenes proteases combination as a novel virulence attenuating therapy.

Minimizing antibiotic resistance is a key motivation strategy in designing and developing new and combination therapy. In this study, a combination of the antibiotics (cefixime, levofloxacin and gentamicin) with Lysobacter enzymogenes (L. enzymogenes) bioactive proteases present in the cell- free supernatant (CFS) have been investigated against the Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and the Gram-negative Escherichia coli (E. coli O157:H7). Results indicated that L. enzymogenes CFS had maximum proteolytic activity after 11 days of incubation and higher growth inhibitory properties against MSSA and MRSA compared to E. coli (O157:H7). The combination of L. enzymogenes CFS with cefixime, gentamicin and levofloxacin at sub-MIC levels, has potentiated their bacterial inhibition capacity. Interestingly, combining cefixime with L. enzymogenes CFS restored its antibacterial activity against MRSA. The MTT assay revealed that L. enzymogenes CFS has no significant reduction in human normal skin fibroblast (CCD-1064SK) cell viability. In conclusion, L. enzymogenes bioactive proteases are natural potentiators for antimicrobials with different bacterial targets including cefixime, gentamicin and levofloxacin representing the beginning of a modern and efficient era in the battle against multidrug-resistant pathogens.

Antioxidant, Antimicrobial and Cytotoxic Activities of Amides and Aristolactams from Piper wallichii (Miq.) Hand.-Mazz. Stems

Four amides, namely, piperine (1), pellitorine (2), piperiline (5) and N-trans-p-coumaroyltyramine (7), and three aristolactams, i.e., piperolactams D (3), B (4) and A (6), were isolated from the methanol extract of Piper wallichii stems. Piperiline, piperolactams B and D were obtained from this plant for the first time. Compounds 1, 3, 5, 6 and 7 were evaluated for their antioxidant, antimicrobial and cytotoxic activities. Piperine (1) displayed the highest antioxidant activity in scavenging DPPH radicals with an IC50 value of 94.51 ± 11.91 μM. Piperolactams D (3) and A (6) showed antibacterial activity against Gram-positive bacteria (B. subtilis and S. aureus) with MICs of between 500-1000 μM. All test compounds were cytotoxic to breast cancer (MCF-7) cells, while the aristolactams were more toxic to colon cancer (Caco-2) cells than the amides. Compounds 1, 3, 6 and 7 were moderately cytotoxic to the doxorubicin-resistant MCF-7 subline (MCF-7/DOX). All compounds were non-toxic to normal human fibroblast (NIH/3T3) cells.

Anticancer potential of fermented milk with autochthonous lactic acid bacteria.

The purpose of this study was to investigate the effect of fermented milk supernatants of autochthonous lactic acid bacteria, including Lactobacillus helveticus KMCH1 (ON561781), Lactococcus lactis KMCM3 (ON561782), and Lactiplantibacillus plantarum KMJC4 (ON615217), on human colon cancer (HT-29) and normal mouse fibroblast (L929) cells in vitro. Proteolytic activity, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test, evaluation of apoptosis induction, and cell cycle arrest by flow cytometry were the assays performed in this study. The measurement of proteolytic activity of three types of fermented milk supernatant using an orthophthalaldehyde reagent showed that the fermented milk supernatant of L. helveticus KMCH1 included the highest proteolysis. Three types of fermented milk supernatant showed anticancer effects on HT-29 cell in a time- and concentration-based manner (at a concentration of 16 mg ml-1 for 72 h of incubation), while the effect of three types of supernatant on inhibition of L929 cell was 3%-10%. Besides, three types of supernatant inhibited HT-29 cell proliferation by inducing apoptosis and cell cycle arrest in the S phase. Autochthonous lactic acid bacteria strains were able to produce bioactive peptides with anticancer effects in fermented milk. Inhibition of HT-29 cell proliferation was dependent on peptide concentration.

Expression Strategy of Soluble Recombinant Human TGF-β3 in Escherichia coli: sfGFP -Fusion Tag

Transforming growth factor-beta 3 (TGF-β3) is an important cytokine involved in various biological processes. TGF-β3 is used as a scar-reducing antifibrotic agent for acute and chronic wounds and fibrosing disorders. TGF-β3, a valuable therapeutic protein, is produced recombinantly in different expression systems. TGF-β3, produced in the Escherichia coli (E. coli) expression system, widely used due to its various advantages in recombinant production, is commercially available. However, the main problem encountered in protein expression in E. coli cells is the formation of an inclusion body. Various approaches have been developed to solve this problem. The use of a fusion tag is one of the most powerful strategies used to obtain protein in the soluble active form in the E. coli expression system. Superfolder GFP (sfGFP) is one of the fusion tags used to increase the solubility of the fusion partner in E. coli. In this study, TGF-β3 with sfGFP fusion tag (sfGFP-TGFβ3) was successfully produced in soluble form in E. coli BL21 (DE3) in high yield and purity for the first time. Purified protein was identified by western blot and SDS-PAGE. 20 mg of protein with 98% purity was obtained from 1 L of bacterial culture. It was determined that the obtained high purity protein did not have a cytotoxic effect on BJ normal human skin fibroblast cells. The impact of sfGFP-TGFβ3 fusion protein on wound healing was evaluated with in vitro scratch wound healing assay. The results showed that the sfGFP-TGFβ3 fusion protein produced in soluble form in the E. coli expression system has the potential to support the wound healing process.

GLUT-Targeting Phototherapeutic Nanoparticles for Synergistic Triple Combination Cancer Therapy.

The combination of multimodal therapies into one nanocarrier system is promising for its potential to enhance treatment performance by overcoming the efficacy problems encountered in conventional monomodal therapy. In this study, targeted and multimodal therapeutic hybrid nanocarriers are fabricated for breast cancer treatments. In this context, the synthesized gold nanorods (AuNRd), photothermal therapy (PTT) agent, are coated with doxorubicin (DOX) conjugated, targeted, and biocompatible tetrablock glycopeptide (P(DMAEMA-b-HMBAMA-b-FrucMA)-b-P(Lys)/DOX, P-DOX) polymer. Here, fructose-based (Fruc) glycopeptide polymer enhances cellular uptake into breast cancer through GLUT5. A photosensitizer molecule, indocyanine green (ICG), was loaded into the particles to provide photodynamic therapy (PDT) upon NIR light at 808 nm. In the final step of the fabrication, the polymer-coated nanoparticles are integrated with antisense ISIS5132 oligonucleotides to prevent apoptotic resistance of cells against drug molecules. The biocompatibility and therapeutic efficacy of the nanoparticles are evaluated on both human normal skin fibroblast cell (CCD-1079Sk) and human breast cancer cell (MCF7) lines. These multimodal therapeutic AuNRd@P-DOX/ICG/ISIS5132 nanoparticles demonstrate an efficient triple synergistic effect of chemo-/PTT/PDT, which is desired for breast cancer treatment. We believe that this promising multimodal therapeutic nanoparticle system can promote the further clinical application in the treatment of breast cancer and can also be adapted to other types of cancer.

The effects of size and surface functionalization of polystyrene nanoplastics on stratum corneum model membranes: An experimental and computational study

Nanoplastics are mainly generated from the decomposition of plastic waste and artificial production and have attracted much attention due to their wide distribution in the environment and the potential risk for humans. As the largest organ of the human body, the skin is inevitably in contact with nanoplastics. Stratum corneum is the first barrier when the skin is exposed to nanoplastics. However, little is known about the interactions between nanoplastics and stratum corneum. Here, the effects of particle size and surface functionalization (amino-modified and carboxy-modified) of polystyrene nanoplastics on the stratum corneum models were studied by Langmuir monolayer and molecular dynamics simulations. An equimolar mixture of ceramide/cholesterol/free fatty acid was used to mimic stratum corneum intercellular lipids. The Langmuir monolayer studies demonstrated that the larger size and surface functionalization of polystyrene nanoplastics significantly reduced the stability of stratum corneum lipid monolayer in a concentration-dependent fashion. Simulation results elucidated that functionalized polystyrene oligomers had a stronger interaction with lipid components of the stratum corneum model membrane. The cell experiments also indicated that functionalized polystyrene nanoplastics, especially for amino-modified polystyrene nanoplastics, had significant cytotoxicity on normal human dermal fibroblast cells. Our results provide fundamental information and the basis for a deeper understanding of the health risks of nanoplastics to humans.

Ferritin-Coated SPIONs as New Cancer Cell Targeted Magnetic Nanocarrier.

Superparamagnetic iron oxide nanoparticles (SPIONs) may act as an excellent theragnostic tool if properly coated and stabilized in a biological environment, even more, if they have targeting properties towards a specific cellular target. Humanized Archaeoglobus fulgidus Ferritin (HumAfFt) is an engineered ferritin characterized by the peculiar salt-triggered assembly-disassembly of the hyperthermophile Archaeoglobus fulgidus ferritin and is successfully endowed with the human H homopolymer recognition sequence by the transferrin receptor (TfR1 or CD71), overexpressed in many cancer cells in response to the increased demand of iron. For this reason, HumAfFt was successfully used in this study as a coating material for 10 nm SPIONs, in order to produce a new magnetic nanocarrier able to discriminate cancer cells from normal cells and maintain the potential theragnostic properties of SPIONs. HumAfFt-SPIONs were exhaustively characterized in terms of size, morphology, composition, and cytotoxicity. The preferential uptake capacity of cancer cells toward HumAfFt-SPIONs was demonstrated in vitro on human breast adenocarcinoma (MCF7) versus normal human dermal fibroblast (NHDF) cell lines.

Nanostructured γ-Al2O3 Synthesis Using an Arc Discharge Method and its Application as an Antibacterial Agent against XDR Bacteria

In the last few years, many efforts have been devoted to investigating the antibacterial activity of metal nanoparticles, especially against multidrug-resistant bacteria. Recently extensively drug-resistant (XDR) bacteria have emerged and caused a global threat. The purpose of this manuscript was to synthesize nanostructured γ-Al2O3 as an antibacterial agent against some XDRs. The results showed that Al2O3 was a mix of rod and spherical shapes in the nano range with diameters of less than 30 nm. The zeta potential was determined to estimate the surface charge for the synthesized γ-Al2O3, which was recorded as −34 ± 1.8 mV, indicating good stability. The synthesized nanostructured γ-Al2O3 showed a potent antibacterial activity against extensively drug-resistant Acinetobacter baumanii, with an inhibition zone diameter that reached 19 mm and a minimum inhibitory concentration (MIC) value that reached 2 µg/mL. The observed antibacterial activity of the prepared Al2O3 nanoparticles confirmed that the main mechanistic actions include bacterial cells apoptosis, ROS increment, cellular membrane disruption, and DNA damage. The cytotoxic effect (CC50) of the prepared γ-Al2O3-NPs was 1250 µg/mL in a normal human lung fibroblast cell line (WI-38 cells). It can be concluded that the synthesized γ-Al2O3 had an acceptable toxicity, which may pave the way for its use as a potent agent in the fight against XDR bacteria.

Green Synthesis of Highly Fluorescent Carbon Dots from Bovine Serum Albumin for Linezolid Drug Delivery as Potential Wound Healing Biomaterial: Bio-Synergistic Approach, Antibacterial Activity, and In Vitro and Ex Vivo Evaluation

A simple and green approach was developed to produce novel highly fluorescent bovine serum albumin carbon dots (BCDs) via facile one-step hydrothermal treatment, using bovine serum albumin as a precursor carbon source. Inherent blue photoluminescence of the synthesized BCDs provided a maximum photostability of 90.5 ± 1.2% and was characterized via TEM, FT-IR, XPS, XRD, UV-visible, and zeta potential analyses. By virtue of their extremely small size, intrinsic optical and photoluminescence properties, superior photostability, and useful non-covalent interactions with the synthetic oxazolidinone antibiotic linezolid (LNZ), BCDs were investigated as fluorescent nano-biocarriers for LNZ drug delivery. The release profile of LNZ from the drug delivery system (LNZ-BCDs) revealed a distinct biphasic release, which is beneficial for mollifying the lethal incidents associated with wound infection. The effective wound healing performance of the developed LNZ-BCDs were evaluated through various in vitro and ex vivo assays such as MTT, ex vivo hemolysis, in vitro antibacterial activity, in vitro skin-related enzyme inhibition, and scratch wound healing assays. The examination of LNZ-BCDs as an efficient wound healing biomaterial illustrated excellent biocompatibility and low cytotoxicity against normal human skin fibroblast (HSF) cell line, indicating distinct antibacterial activity against the most common wound infectious pathogens including Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus, robust anti-elastase, anti-collagenase, and anti-tyrosinase activities, and enhanced cell proliferation and migration effect. The obtained results confirmed the feasibility of using the newly designed fluorescent LNZ-BCDs nano-bioconjugate as a unique antibacterial biomaterial for effective wound healing and tissue regeneration. Besides, the greenly synthesized BCDs could be considered as a great potential substitute for toxic nanoparticles in biomedical applications due to their biocompatibility and intense fluorescence characteristics and in pharmaceutical industries as promising drug delivery nano-biocarriers for effective wound healing applications.

Dosimetric quantities and cell survival for spatially fractionated radiation therapy

Purpose: Spatially Fractionated Radiation Therapy (SFRT) is characterized by large differences in peak and valley doses. Preclinical and clinical studies suggest that differences in biological mechanisms lead to differential normal tissue and tumor response compared to uniform irradiation. We hypothesize that to evaluate clinical effectiveness and understand fundamental biological mechanisms, radiobiological rather than physical dose quantities should be utilized for comparisons. The aim of this work is to determine whether Equivalent Uniform Dose (EUD) is a superior predictor of cell survival than absorbed dose.Methods: Absorbed dose parameters were compared to the Equivalent Uniform Dose to assess their predictive value for the relative effectiveness of uniform and SFRT with X-rays. A Bayesian bootstrap technique was utilized to model uncertainties in the biological fit parameters for a human fibroblast (MRC5) and two human tumor cell lines (LN18 and A549). Dose uncertainties were evaluated through measurements and error modeling of SFRT profiles. A dimensionless Relative Effectiveness Factor (REF) is proposed to quantify differences between uniform and SFRT irradiation.Results: For all cell lines, cell survival after SFRT matched uniform irradiation within the estimated uncertainties at equal values of the EUD. Average and peak dose showed poor correlation with in vitro cell survival. The proposed REF factor is dose dependent and suggests enhanced cell killing for both tumor cell lines (1.14 ± .08 for LN18, 1.32 ± .13 for A549 at 8 Gy EUD) for SFRT. Normal human fibroblasts showed reduced cell killing relative to uniform irradiation (.58 ± .06 for MRC5). Synthetically generated SFRT dose profiles revealed that EUD uncertainties are dominated by valley dose uncertainties, especially at high doses.Discussion: EUD is more predictive of cell survival than average or valley dose. Valley dose is close to equal to the EUD for values &gt;10 Gy and has the advantage of being independent of uncertainties in biological parameters. The REF is a novel and useful metric to compare quantitative differences in SFRT and uniform irradiation.Conclusion: EUD is recommended for comparisons of SFRT and uniform irradiation. The results suggest an increase in survival of normal-human fibroblast cells and reduced survival for both tumor cell lines after SFRT relative to uniform irradiation.

Latonduine-1-Amino-Hydantoin Hybrid, Triazole-Fused Latonduine Schiff Bases and Their Metal Complexes: Synthesis, X-ray and Electron Diffraction, Molecular Docking Studies and Antiproliferative Activity

A series of latonduine derivatives, namely 11-nitro-indolo[2,3-d]benzazepine-7-(1-amino-hydantoin) (B), triazole-fused indolo[2,3-d]benzazepine-based Schiff bases HL1 and HL2 and metal complexes [M(p-cymene)(HL1)Cl]Cl, where M = Ru (1), Os (2), and [Cu(HL2)Cl2] (3) were synthesized and characterized by spectroscopic techniques (UV–vis, 1H, 13C, 15N–1H HSQC NMR) and ESI mass spectrometry. The molecular structures of B and HL1 were confirmed by single-crystal X-ray diffraction, while that of 3 by electron diffraction of nanometer size crystalline sample. Molecular docking calculations of species B in the binding pocket of PIM-1 enzyme revealed that the 1-amino-hydantoin moiety is not involved in any hydrogen-bonding interactions, even though a good accommodation of the host molecule in the ATP binding pocket of the enzyme was found. The antiproliferative activity of organic compounds B, HL1 and HL2, as well as complexes 1–3 was investigated in lung adenocarcinoma A549, colon adenocarcinoma LS-174 and triple-negative breast adenocarcinoma MDA-MB-231 cells and normal human lung fibroblast cells MRC-5 by MTT assays; then, the results are discussed.

Effect of Nasturtium Extract on Oral Cancer.

Considering the global prevalence of cancers and the complications of common cancer treatments, there is growing interest in using medicinal herbs to complement cancer treatments and reduce treatment's side effects. Therefore, we investigate the effect of the extract of Nasturtium on the viability of oral cancer cells. In this experimental study, we prepared aqueous extract from Nasturtium leaves and human oral cancer cells (OCC-24) and normal fibroblast cells (HF2FF cell line) from a cell bank. Then the toxic effect of different concentrations of the extract on cell viability after 24-48 hours of exposure was investigated with the methylthiazol tetrazolium assay. Ultimately, the optical density was measured at 570 nm by an Elisa Reader. Analysis of inhibitory concentration 50 (IC50) was also performed. The data were analyzed by paired Student's t-test and one-way analysis of variance. Data showed that the extract had statistically significant anticancer effects in concentrations above 0.125 mg/ml for 24-hour exposure and in concentrations above 0.5 mg/ml for 48-hour exposure (p-value <0.05). Also, this extract had an adverse effect on the viability of normal cells; however, this effect occurred in high doses of the extract (p-value <0.05). Analysis of IC50 criteria indicates that with increasing time, a higher concentration of the extract is required to inhibit the viability of cancer cells. Because of the results, this aqueous extract can be suggested as a potential therapeutic agent in oral cancer. The best concentration of the extract was found to be 1 mg/ml.