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Background: Curcumin, a dietary polyphenol isolated from turmeric, is a potent phytochemical possessing intrinsic anticancer activities against various cancer types including prostate cancer. However, low water solubility and bioavailability of the compound are major challenges against its medical use. The objective of this study is to evaluate the therapeutic potential of curcumin-loaded emulsome nanoparticular system, i.e. CurcuEmulsomes, for the treatment of androgen dependent LNCaP prostate cancer cell line. Methods and results: The antiproliferative effect of both free curcumin and CurcuEmulsome were investigated comparatively on LNCaP and PNT1A cells. Cell viability data indicates that the inhibition in proliferation of LNCaP cells becomes more effective when curcumin is provided with its emulsome formulation rather than its free form. Corresponding to a therapeutic index of 2.25, Half maximal inhibitory (IC50) and cytotoxic (CC50) concentrations of CurcuEmulsomes for LNCaP and PNT1A cells were estimated as 17.1 µM and 38.6 µM, respectively. The fluorescence signal of autofluorescence curcumin was preserved within the CurcuEmulsomes at 72 h after the treatment. Thus, CurcuEmulsomes prolonged biological activity of curcumin. Induced apoptotic cell death and stimulated cell cycle arrest at G2/M phase were attributed to antiproliferative activity of CurcuEmulsomes. Treatment of LNCaP cells with CurcuEmulsomes increased expression of caspase-3 significantly by 11.76-fold, whereas decreased cyclin D1, Bcl-2 and AR expression levels significantly by of 0.18, 0.06 and 0.46-fold, respectively. Conclusions: Presented safety and anticancer activity of CurcuEmulsomes on LNCaP cell line highlights the potential of CurcuEmulsomes to benefit intrinsic anticancer activities of curcumin in androgen dependent prostate cancer therapy. Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey

Pathogenic microbes are the most common cause of chronic infections and mortality in mammals and loss of agricultural crops in the world. Antimicrobial agents including antibiotics and antifungals are often used in the treatment of infections due to their exceptional consequences faces various problems that limits the treatment by them. Therefore, herbal sources are attracting more attention due to lower side effects and in some cases better and faster effects. Plant essential oils (EOs) have many antimicrobial and pharmacological effects, but EOs are volatile, heat-sensitive and water-insoluble compounds that limit their use, encapsulating EOs can improve the properties of such compounds. Chitosan, a biodegradable nanopolymer, is very important in drug transfer due to better encapsulation, controlled release and low toxicity. Therefore, this research was conducted to investigate the encapsulation technique as a suitable method to preserve essential oils and increase their antimicrobial properties. First, the chitosan polymer was synthesized and used to encapsulate rosemary essential oil after examining its shape and size by spectroscopy (FTIR) and scanning electron microscopy (SEM). Then, the antibacterial effect of encapsulated EO and free EO was investigated by liquid microdilution method. The results showed that encapsulated EO had a greater antibacterial effect against gram-negative bacteria and fungi compared to free EO.

Background Acute lymphoblastic leukemia (ALL) is a cancer with high incidence rate in pediatrics and drug resistance is a major clinical concern for ALL treatment. The current study was designed to evaluate the role of exosomal miR-326 in diagnosis and treatment of children with B-ALL.Methods Exosomes were isolated from plasma samples of 30 patients and B-ALL cell lines through 2 different methods. Exosomes were then characterization, using nanoparticle tracking analysis, immunoblotting assay and electron microscopy. qRT-PCR was employed to measure the expression levels of miR-326. Exosome uptake was validated using transfection procedure. MTT assays were performed to investigate cells viability.Results qPCR showed significant increased levels of miR-326 in patients exosomes compared with non-cancer controls (P P Conclusions The novel introduced features of the exosomal miR-326 addresses a non-invasive, unique way of diagnosing primary drug resistance in pediatric ALL and establishes a novel therapeutic strategy for this cancer.

Objective Interaction of tumor cells with the surrounding environment is essential for tumor growth and progression that eventually leads to metastasis. Growing evidence shows that extracellular vesicles also known as exosomes play a crucial role in signaling between the tumor and its microenvironment. Tumor-derived exosomes have generally protumorigenic effects such as metastasis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. Methods In this study, exosomes were isolated from a chordoma cell line, MUG-Chor1, and characterized subsequently. The number of exosomes was determined and introduced into the healthy nucleus pulposus (NP) cells for 140 days. The protumorigenic effects of a chordoma cell line-derived exosomes that initiate the tumorigenesis on NP cells were investigated. The impact of tumor-derived exosomes on various cellular events including cell cycle, migration, proliferation, apoptosis, and viability has been studied by treating NP cells with chordoma cell-line-derived exosomes cells. Results Upon treatment with exosomes, the NP cells not only gained a chordoma-like morphology but also molecular characteristics such as alterations in the levels of certain gene expressions. The migratory and angiogenic capabilities of NP cells increased after treatment with chordoma-derived exosomes. Conclusion Based on our findings, we can conclude that exosomes carry information from tumor cells and may exert tumorigenic effects on nontumorous cells.

Extracellular vesicles (EVs) have lately emerged as crucial mediators in parasite infections. Recent research suggests that protozoan parasites, including Leishmania, employ EVs as transport vehicles to deliver biologically active effector molecules such as parasitic virulence factors to modulate the host immune system and their microenvironment. The immunomodulatory effects of EVs play an essential role in the formation and progression of parasitic diseases. The immunomodulatory strategies applied by EVs of protozoan origin have similarities to the development and progression of other infections or diseases such as cancer. In this chapter, we will provide recent insights into the role of EVs in host-pathogen interactions, intercellular-communication, immunomodulation and pathogenesis of Leishmania and other protozoan parasites, including Plasmodium spp., Toxoplasma spp. and Trypanosoma spp. In addition, biologically inspired by the immunomodulation strategies of protozoan parasites, new immunotherapeutic models are being currently investigated to implement EVs more intensively in both therapy and diagnostics. Therefore, besides highlighting the role of EVs in protozoan infections, this chapter sheds light briefly on new immunotherapeutic approaches utilizing the strategies of protozoan EVs in medicine.

Kaşıkcı E, Aydemir E, Bayrak ÖF, Şahin F. Onco Targets Ther. 2020;13:5763–5777. The authors have advised that errors were made during the selection of images used for Figure 3 and Figure 8 on pages 5769 and 5774, respectively. The corrected Figure 3 and 8 are shown in Download Article. The authors wish to explain that the new images were collected from another experimental repeat which occurred on a different day to those shown in the original publication. This does not change the results or calculations as the images are only representative of the groups described. Cells were counted from all the experimental and technical repeats and the statistical analysis was performed using cell numbers from the entire slide. Counting and imaging was not done at the same time. The authors wish to apologize for the error. Read the original article

Boron concentrations in 335 tap water samples collected from 75 cities in Turkey have been determined by inductively coupled plasma-mass spectrometry. Boron levels ranged between 0.001 and 5.5 mg/L...

Purpose: The boron and fluoride mainly accumulate in the bones and teeth of the human body. The purpose of this study is to determine boron or fluoride levels in the whole tooth, to evaluate the correlation between their levels and to compare these levels in primary/permanent, carious, and non-carious groups. Materials and Methods: The boron and fluoride levels of thirty-six teeth, separated such as primary carious (n=9) and non-carious (n=9), permanent carious (n=9) and non-carious (n=9), were determined by ICP-MS and ion-selective electrode, respectively. Results: While boron levels were between 0.001 and 5.88 ppm, the fluoride levels were between 21.24 and 449.22 ppm. The boron level of non-carious teeth was higher than those of carious teeth in primary and permanent tooth groups. However, this difference was not statistically significant (p>0.05). The fluoride level of non-carious teeth was higher than those of carious teeth in primary (p=0.062) and permanent teeth groups (p=0.046). Negative correlation, found between boron and fluoride in all groups, was significant only in non-carious teeth group (r=-0.488, p=0.040). Conclusion: The results of our study proved the importance of fluoride as a protective factor for dental caries once more. The boron levels in non-carious teeth were also higher than carious teeth. However, it was not significant. Moreover, there was negative correlation between teeth boron and fluoride levels. Therefore, it is necessary to conduct more detailed studies on the tooth boron level and its relation with caries formation and with fluoride levels.

In this paper, we report the polymersome-mediated intracellular delivery of pro-apoptotic BikDDA gene using two different peptide–copolymer covalent conjugation strategies specific for prostate cancer targeting. The BikDDA gene was used as a therapeutic agent on prostate cancer cells. The transfection efficiency of BikDDA-loaded poly[oligo(ethyleneglycol) methacrylate]-co-poly[2-(diisopropylamino) ethyl methacrylate] (P(OEG10MA)20-PDPA100) polymersomes revealed that they could serve as a suitable non-viral gene transfection tool. The targeted delivery of BikDDA into prostate cancer cells (LNCaP) using polymersomes was successfully carried out by conjugating the PSMA-targeting moiety (peptide 563) to P(OEG10MA)20-PDPA100 copolymer using either succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) as a bifunctional linker between the thiol-bearing targeting peptide and amino-bearing P(OEG10MA)20-PDPA100 copolymer or attaching a maleimide-modified targeting peptide onto a thiol-terminated P(OEG10MA)20-PDPA100 copolymer. The pH-responsive and biocompatible polymersomes, conjugated with peptide 563, exhibited an enhanced cellular uptake by LNCaP cells in comparison to the healthy prostate epithelial cell line PNT1A, thus indicating the cell-specific delivery. The increased Bik mRNA expression and cell death in these LNCaP cells indicates high effectiveness of the targeting polymersomes. According to these results, we believe more efficient gene delivery systems via specifically targeted pH-sensitive polymersomes can be a promising approach and promote the development of novel therapies against prostate cancer.

Calcium carbonate (CaCO3) is found in different polymorph structures such as aragonite, vaterite, and calcite. The most common and stable form of CaCO3, calcite, which is abundant in sedimentary rocks as magnesite ore. Magnesite has application areas in many industrial fields including paper, pharmaceutical and refractory materials. Magnesite is theoretically formulated MgCO3, but contains many impurities (silicium, iron, and also calcite), that limits its usability and applicability. In this research, we aimed to investigate the decalcification possibility of the raw magnesite material through application of Enterococcus feacelis (EF) with CaCO3 dissolution ability. The exact mechanism of CaCO3 dissolution was investigated by carbonic anhydrase enzyme assay and HPLC analysis of organic acids produced by EF. Consequently, EF reduced the amount of CaCO3 from 2.94% to 0.49% which means a reduction (?83.33%) in the rate of CaCO3 percentage. As a result of the experiments, it was observed that different organic acids produced by bacteria reacted with CaCO3 and removed the lime of magnesite ore. The bacteria used in the study did not show any pathogenic properties in rats, thus, it can be used safely for the industrial applications. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Hepatocelular carcinoma is one of the leading cancer types with no effective cure as poor prognosis is still a challenging aspect. Thus, alternative therapeutics are necessary to control hepatocelular carcinoma. Boron derivatives such as boric acid (BA), sodium perborate tetrahydrate (SPT) and sodium pentaborate pentahydrate (NaB) have been discovered to have anti-cancer effect. This study investigated the anti-proliferative effects of SPT against hepatocelular carcinoma (HCC) using in vitro and transcriptome approaches.Cytotoxic level of SPT on cell survival were detected using MTS assay. The apoptotic cell death and cell cycle arrest was determined using Annexin V/PI and cell cycle assay, respectively. Transcriptome analysis was performed using RNA-seq, followed by functional and KEGG pathway enrichment analysis. qPCR was used to validate the different genes.SPT treated HepG2 and Hep3B cells induced cytotoxicity having ICIn vitro experiments and RNA-seq analysis show anti-proliferative and apoptotic effect of SPT in HCC cells. Further studies might help in understanding the molecular mechanisms of SPT.

Phragmites communis L. is a halophytic plant that can withstand harsh environmental conditions such as salinity. In the present study, we isolated a bacterium associated with the rhizosphere of Phragmites communis L. Based on morphological and biochemical as well as MALDI-TOF and 16S rRNA sequencing results, the strain S6 was identified as Klebsiella aerogenes with a score of 2.34 for MALDI-TOF and a similarity of 99.86% with type strain Klebsiella aerogenes KCTC 2190T. Furthermore, we demonstrated that strain S6 tolerated up to 2.5 M of NaCl and exhibited resistance to only three antibiotics that are frequently used for Enterobacteriaceae. Plant growth-promoting (PGP) results showed that the strain S6 had multiple traits, it was able to fix atmospheric nitrogen, solubilized inorganic phosphate (Ca3(PO4)2 and potassium in addition to the production of siderophores, ammonia, cellulase, protease and amylase. Indole acetic acid (IAA) production was also detected, and the strain S6 showed a positive ACC deaminase activity. Moreover, when the strain S6 was used as an inoculum for pepper seeds, increases in different parameters including shoot and root lengths and fresh and dry weights were shown under normal and saline conditions. We reported in this study, that the inoculation of pepper (Capsicum annuum L.) seeds with the Klebsiella sp. strain S6 was efficient for pepper growth in normal and salt stress conditions. The results of this study thus indicate that natural plants from saline habitats present a good source for isolating beneficial PGPR to grow crops like pepper under saline conditions.

Mesenchymal Stem Cells (MSCs), as an adult stem cell type, are used to treat various disorders in clinics. However, derivation of homogenous and adequate amount of MSCs limits the regenerative treatment potential. Although mesoderm is the main source of mesenchymal progenitors during embryonic development, neuromesodermal progenitors (NMPs), reside in the primitive streak during development, is known to differentiate into paraxial mesoderm. In the current study, we generated NMPs from human embryonic stem cells (hESC), subsequently derived MSCs and characterized this cell population in vitro and in vivo. Using a bFGF and CHIR induced NMP formation protocol followed by serum containing culture conditions; here we show that MSCs can be generated from NMPs identified by not only the expression of T/Bra and Sox 2 but also FLK-1/PDGFRα in our study. NMP-derived MSCs were plastic adherent fibroblast like cells with colony forming capacity and trilineage (osteo-, chondro- and adipo-genic) differentiation potential. In the present study, we demonstrate that NMP-derived MSCs have an endothelial tendency which might be related to their FLK-1+/PDGFRα + NMP origin. NMP-derived MSCs displayed a protein expression profile of characterized MSCs. Growth factor and angiogenesis related pathway proteins were similarly expressed in NMP-derived MSCs and characterized MSCs. NMP-derived MSCs keep characteristics after short-term and long-term freeze-thaw cycles and localized into bone marrow followed by tail vein injection into NOD/SCID mice. Together, these data showed that hESC-derived NMPs might be used as a precursor cell population for MSC derivation and could be used for in vitro and in vivo research.

Parathyroid-like cells were aimed to be developed using cells isolated from thyroid since their embryological origins are the same.Activin A and sonic hedgehog (Shh) are the proteins used in differentiation (dif) medium. Parathyroid and thyroid cells were cultured in a 3-dimensional environment and divided into five groups: thyroid standard (st) medium, thyroid dif medium, parathyroid st medium, thyroid-parathyroid co-culture st medium, and thyroid-parathyroid co-culture dif medium. Throughout 28 days of incubation, groups were investigated by carrying out the live dead assay, confocal microscopy, real-time PCR, immunohistochemistry and biochemical assays.Thyroid-parathyroid co-culture cells grown in dif medium exhibited upregulated expressions of parathormone (PTH) (5.1-fold), PTH1R (3.6-fold), calcium sensing receptor (CaSR) (8.8-fold), and loss of thyroid-specific thyroid transcription factor 1 (TTF1) expression when compared to the thyroid st medium group. PTH secretion decreased by 35% in the parathyroid st medium group and 99.9% in the thyroid-parathyroid co-culture st medium group but decreased only 3.5% in the thyroid-parathyroid co-culture dif medium group on day 28.Using Activin A and Shh proteins, thyroid stem/progenitor cells were differentiated to parathyroid-like cells successfully in a co-culture environment. A potentially effective novel method for cell differenatiation is co-culture of cells having the same embryological origin.

Flow cytometry analysis emerges as an alternative methodology to microscopy for determination of the Leishmania-infection rates of macrophages. Various flow cytometric approaches have been established for the quantification of Leishmania parasites within host cells, labelled either directly fluorescent dyes or indirectly with fluorescently conjugated antibodies. Although these techniques allow accurate quantification of infection, they fail at detection of non-infected macrophages specifically. This study introduces a new flow cytometric approach for the determination of infection rates of macrophages infected by Leishmania infantum parasites. Prior to infection, J774A.1 macrophages and L. infantum promastigotes were stained separately with PKH26 and PKH67 dyes, respectively. Dual staining enabled detection of each cell type, where non-infected macrophages were also recorded for the quantification. Dual-PKH staining achieved high success in selective staining of promastigotes (99.71%) and macrophages (99.57%). The percentages of parasite-infected macrophages were determined for initial 1:2.5 and 1:10 infection ratios as 15.68 and 61.70%, respectively; indicating significant increase in infection rate parallel to the initial treatment ratio. These results demonstrated that the introduced dual-fluorescence flow cytometric approach can be successfully used as an accurate and rapid quantification method for L. infantum-infected macrophages and strengthens the hypothesis that flow cytometric approaches could replace conventional microscopic methodologies.

Boron (B) is an element involved in many physiological processes in humans and accelerates wound healing and increases angiogenesis. This study aimed to evaluate the possible effects of sodium pentaborate pentahydrate (NaB) on hair growth and reveal its effects on Wnt-1, β-catenin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and transforming growth factor-β1 (TGF-β1) signaling pathways, which are important molecular mechanisms involved in hair growth.Thirty-five Sprague-Dawley/Wistar albino rats were randomly divided into five groups: non-shaved control, shaved control, NaB 1 mg (shaved + NaB 1 mg elemental B/kg CA), NaB 2 mg (shaved + NaB 2 mg elemental B/kg CA), and NaB 4 mg (shaved + NaB 4 mg elemental B/kg CA). Hair density was measured using the trichoscopy method. Dorsal skin samples were examined histopathologically at the end of the 42nd day, and follicle count, follicle diameter, and subcutaneous tissue thickness were recorded. Wnt-1, β-catenin, PDGF, VEGF, TGF-βIn trichoscopy measurements, hair density increased in the NaB 4 mg group (90.9%). In histopathological examination, anagen follicles were observed to increase in the NaB 1 mg and 2 mg groups (p 0.05). Follicle diameter increased in all NaB groups (p 0.05). The Wnt-1, β-catenin, PDGF, VEGF, TGF-βNaB 1 and 2 mg B/kg supplementation induces the anagen phase in rats via Wnt-1, β-catenin, VEGF, PDGF, and TGF-β1 signaling pathways. NaB 4 mg B/kg suppresses these pathways and adversely affects hair growth.

Introduction: Radiation dermatitis (RD) is a side effect of radiation therapy (RT) which is experienced by over 90% of patients being treated for breast cancer. The current clinical trial was conducted to measure the preventative effects of a boron-based gel on several different clinical outcomes (dermatitis, erythema, dry desquamation, and moist desquamation) after 25 radiotherapy sessions. Methods: This research used a double-blind parallel-group design with a placebo control (n = 76) and randomized group (n = 181), with all participants being between 18 and 75 years old. Fifteen minutes before each radiotherapy, participants in the intervention group were given a gel containing 3% sodium pentaborate pentahydrate, while those in the placebo group received a gel with no chemical substance. Dermatitis, erythema, dry desquamation, and moist desquamation were compared between the 2 groups. Results: At baseline, there were no significant differences between the groups (p > 0.05), except for body mass index. After 14 days of treatment, dermatitis (98.7% vs. 9.9%; p < 0.001), erythema (96.1% vs. 12.2%; p < 0.001), dry desquamation (50% vs. 3.9%; p < 0.001), and moist desquamation (18.4% vs. 0.6%; p < 0.001) were much more common in the placebo group than the intervention group. To prevent dermatitis, erythema, dry desquamation, and moist desquamation in 1 patient, on average, 1.1 (95% confidence interval [CI]: 1.1–1.2), 1.2 (95% CI: 1.1–1.3), 2.2 (95% CI: 1.7–2.9), and 5.6 (95% CI: 3.8–11.0) patients need to be treated, respectively. Conclusion: The boron-based gel has a significant preventive effect on several categories of RD which might be used by clinicians in breast cancer.

Chordomas are highly therapy-resistant primary bone tumors that exhibit high relapse rates and may induce local destruction. Here, we evaluated the effects of tumor necrosis factor-alpha (TNF-α) on chordoma progression and clinical outcome. Chordoma cells were treated with TNF-α after which its short- and long-term effects were evaluated. Functional assays, qRT-PCR and microarray-based expression analyses were carried out to assess the effect of TNF-α on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, invasion and cancer stem cell-like properties. Finally, relationships between TNF-α expression and clinicopathological features were assessed in a chordoma patient cohort. We found that TNF-α treatment increased the migration and invasion of chordoma cells. Also, NF-κB activation was observed along with increased EMT marker expression. In addition, enhanced tumor sphere formation and soft agar colony formation were observed, concomitantly with increased chemo-resistance and CD338 marker expression. The TNF-α and TNFR1 expression levels were found to be significantly correlated with LIF, PD-L1 and Ki67 expression levels, tumor volume and a short survival time in patients. In addition, a high neutrophil to lymphocyte ratio was found to be associated with recurrence and a decreased overall survival. From our data we conclude that TNF-α may serve as a prognostic marker for chordoma progression and that tumor-promoting inflammation may be a major factor in chordoma tumor progression.

Obesity is a major public health problem worldwide and a risk factor for certain diseases, including cardiovascular disease, diabetes, cancer, and depression. Unfortunately, currently available anti-obesity drugs have failed in the long-term maintenance of weight control. It has been a challenge to design novel drugs that could potentially treat obesity or prevent uncontrolled weight-gain which lies underneath the pathology of obesity. Since obesity in a way is a consequence of the accumulating new mature adipocytes from undifferentiated precursors which is a process also termed as adipogenesis, drugs that might control adipogenesis could be beneficial for the treatment of obesity. In the current study, combined effect of sodium pentaborate pentahydrate (NaB) and pluronic F68 on adipogenic differentiation was examined by administering various combinations of the two agents to human adipose-derived stem cells (hADSCs) in in vitro. Immunocytochemistry and quantitative RT-PCR were performed to evaluate the levels of adipogenesis-promoting genes such as peroxisome proliferator-activated receptor-γ (PPARγ), fatty acid binding protein (FABP4), and adiponectin. Results indicated that expressions of all these three genes were restrained. Furthermore, Oil Red O staining revealed that lipid vesicle formation was reduced in hADSCs treated with differentiation medium containing NaB/F68 combination. Finally, expression levels of Hippo pathway kinases Lats2, MST1, and scaffold protein Sav1 were reduced in these cells, suggesting a possible link between Hippo pathway-dependent downregulation of PPARγ and the NaB/F68 treatment. Herein, we showed that combination of NaB and F68 curtails adipocyte differentiation by inhibiting the adipogenic transcriptional program leading to a decrease in lipid accumulation in adipocytes even at very low doses, thereby uncovered a striking opportunity to use this combination in obesity treatment.

The transmission of the SARS-CoV-2 coronavirus has been shown through droplets generated by infected people when coughing, sneezing, or talking in close contact. These droplets either reach the next person directly or land on nearby surfaces. The objective of this study is to develop a novel, durable, and effective disinfecting antimicrobial (antiviral, antibacterial, and antifungal) styrene-ethylene/butylene-styrene (SEBS) based thermoplastic elastomers (TPE). TPE incorporated with six different formulations was investigated for mechanical and antiviral performance. The formulations consist of a combination of zinc pyrithione (ZnPT), sodium pentaborate pentahydrate (NaB), disodium octaborate tetrahydrate (DOT), and chlorhexidine (CHX). ZnPT and DOT incorporated TPE showed a reduction of microbes such as bacteria by up to 99.99%, deactivated Adenovirus, Poliovirus, Norovirus, and reduced a strain of the coronavirus family by 99.95% in 60 min on TPE samples. Control samples had higher tensile strengths among all formulations and tensile strength decreased by around 14%, 21% and 27% for ZnPT and DOT combinations compared to control samples. The elongation at break decreased by around 7%, 9% and 12% with ZnPT and DOT combinations, where it reached minimum values of 720%, 702% and 684%, respectively. The 100% Modulus and 300% Modulus slightly increased with ZnPT and NaB combination (reaching values from 1.6 to 1.9 MPa and 2.6-2.9 MPa respectively) in comparison with control samples. The MFI also decreased with antimicrobial and antiviral additives (decreasing values from 64.8 to 43.3 g/10 min). ZnPT and NaB combination showed the lowest MFI (43.3 g/10 min) and reduced the MFI of control sample by around 33%. TPE samples containing ZnPT and DOT combination showed biocidal activity against the microorganisms tested and can be used to develop antimicrobial products for multiple touchpoints within a vehicle and micro-mobility.

Here we present self-assembled polymeric micelles as potential delivery systems for therapeutic agents with highly tunable properties. The major goal of this study is to design breast and prostate cancer specific targeting peptide modified PEtOx-co-PEI-b-PCL block copolymer based micelles as a targetable carrier system in cancer treatment. For this, a series of micelles based on poly(2-ethyl-2-oxazoline)-co-polyethyleneimine-block-poly(epsilon-caprolactone) [P(EtOx-co-EI)-b-PCL] copolymers with two different proportions of PEI (30% and 60% hydrolysis degrees of PEtOx) were successfully prepared. The block copolymers were synthesized using a combination of living cationic ring-opening polymerization and a copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Then, peptide 18 and peptide 563 were conjugated to P(EtOx-co-EI)-b-PCL through a thiol-ene click-type reaction to obtain the desired tumor-targeting. The structural properties of the copolymers were confirmed by H-1 NMR, FT-IR, UV-Vis spectrometry and GPC. Peptide and non-peptide-conjugated micelles with particle sizes between 82 +/- 0.6 and 170 +/- 10.7 nm were obtained by self-assembly with two different chain lengths of PEI blocks. The micelles containing the 60% PEI block showed increased zeta potential values. The cytotoxicity of the copolymers was evaluated under in vitro conditions. Overall, our results indicate that the micelles prepared with peptide-conjugated block copolymers can be used as potential nanocarriers for targeted therapeutic delivery systems. Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213M725] The authors would like to thank the Scientific and Technological Research Council of Turkey (TUBITAK) for financial support with grant number 213M725. WOS:000678167300001 2-s2.0-85113149945

Improvements in stem cell-based research and genetic modification tools enable stem cell-based tissue regeneration applications in clinical therapies. Although inadequate cell numbers in culture, invasive isolation procedures, and poor survival rates after transplantation remain as major challenges, cell-based therapies are useful tools for tissue regeneration.Organoids hold a great promise for tissue regeneration, organ and disease modeling, drug testing, development, and genetic profiling studies. Establishment of 3D cell culture systems eliminates the disadvantages of 2D models in terms of cell adaptation and tissue structure and function. Organoids possess the capacity to mimic the specific features of tissue architecture, cell-type composition, and the functionality of real organs while preserving the advantages of simplified and easily accessible cell culture models. Thus, organoid technology might emerge as an alternative to cell and tissue transplantation. Although transplantation of various organoids in animal models has been demonstrated, lioitations related to vascularized structure formation, cell viability and functionality remain as obstacles in organoid-based transplantation therapies. Clinical applications of organoid-based transplantations might be possible in the near future, when limitations related to cell viability and tissue integration are solved. In this review, the literature was analyzed and discussed to explore the current status of organoid-based transplantation studies.

The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A, oral polio vaccine, and smallpox proved to be reliable approaches for immunization for prolonged periods. During the pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate, having the advantages of being manufactured rapidly and tested easily in comparison with recombinant vaccines. In this study, an inactivated virus vaccine that includes a gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required has been optimized. The vaccine candidate (OZG-38.61.3) was then applied in mice by employing the intradermal route, which decreased the requirement of a higher concentration of inactivated virus for proper immunization, unlike most of the classical inactivated vaccine treatments. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 1013 or 1014 viral copy per dose) of OZG-38.61.3 was initially determined in Balb/c mice. This was followed by testing the immunogenicity and protective efficacy of OZG-38.61.3. Human ACE2-encoding transgenic mice were immunized and then infected with a dose of infective SARS-CoV-2 virus for the challenge test. Findings of this study show that vaccinated mice have lower SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

Because breast cancer is complicated at the pathological, histological, clinical, and molecular levels, identification of new genetic targets against carcinogenic pathways is required to generate clinically relevant treatment options. In the current study, ubiquitin-specific protease 7 (USP7), which regulates various cellular pathways including Mdm2, p53, and NF-kappa B, was selected as a potential gene editing strategy for breast cancer in vitro. Anticancer activity of USP7 gene suppression has been evaluated through cell proliferation, gene expression, cell cycle, sphere dissemination, and cell migration analysis. Here, siRNA and shRNA strategies and an allosteric small-molecule inhibitor of USP7 were used to define potential anticancer activity against MCF7 and T47D human breast cancer cell lines. Both blockage of deubiquitination by p5091 and knockdown of USP7 reduced cell proliferation, cell migration, colony formation, and sphere dissemination for both MCF7 and T47D breast cancer cell lines. Restriction of USP7 activity strongly enhanced apoptotic gene expression and reduced metastatic ability of breast cancer cell lines. This study describes one potential molecular target for the suppression of breast cancer proliferation and metastasis. Identification of USP7 as a promising gene editing candidate might open up the possibility of new molecular drug research in targeting the ubiquitination pathway in cancer.

Aim To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia. Methods Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status-matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-gamma, TNF-alpha, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit. Results In comparison with HC, Treg percentages in schizophrenia were higher (1.17 +/- 0.63 vs 0.81 +/- 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 +/- 0.69 vs 0.97 +/- 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 +/- 0.78 vs 1.64 +/- 0.89, P = 0.001) and stimulated (2.25 +/- 1.01 vs 1.72 +/- 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 +/- 5170.07 vs 1787.81 +/- 1363.32, P < 0.001), IL-17A (191.73 +/- 212.49 vs 46.43 +/- 23.99, P < 0.001), TNF-alpha (1557 +/- 1059.69 vs 426.57 +/- 174.62, P = 0.023), and IFN-gamma (3204.13 +/- 1397.06 vs 447.79 +/- 270.13, P < 0.001); and plasma levels of IL-6 (3.83 +/- 3.41vs 1.89 +/- 1.14, P = 0.003) and IL-17A (1.20 +/- 0.84 vs 0.83 +/- 0.53, P = 0.033) were higher in patients with schizophrenia than HC. Conclusion Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.

In the present study, three entomopathogenic strains of Bacillus sphaericus (MBI5, MBI6, and MBI7) were isolated from greenhouse pest and larval habitat of Istanbul, Turkey. All of the MBI groups tested in laboratory bioassays were able to kill larvae, but not pupae and adults of Culex spp. in water. The most efficient larvicidal activity of the strains was found in the presence of two toxin genes, binA and binB for MBI5, MBI6, and MBI7 strains. Each B. sphaericus strains identified in this study were characterized as unique and novel in terms of fatty acid methyl ester (FAME) profiles and 16S rRNA sequencing data. The results of this study suggest that the three strains of B. sphaericus may be new sources of potential biocontrol agent of mosquito.

Background. Postoperative peritoneal adhesions (PPA) are a serious problem for abdominal surgery. An effective remedy has not been found yet. New formulation of glycerol and sodium pentaborate may be able to solve the problem. Method. Female Wistar albino rats were randomly assigned into four equal groups. The adhesion model was created on the caecum anterior wall and covered with 2 ml 0.9% NaCl, 3% glycerol, 3% sodium pentaborate, and 3% glycerol plus 3% sodium pentaborate solutions in the groups, respectively. Two weeks later, the rats were sacrificed. PPA were graded macroscopically and microscopically. Results. Total adhesion scores of the 3% glycerol + 3% sodium pentaborate group were statistically different from the other groups for macroscopic and also microscopic evaluations (p<0.001). Conclusion. 3% glycerol plus 3% sodium pentaborate as a new formulation has preventive effects on PPA with a synergistic mechanism.

Karaman, Adem/0000-0002-3091-0609; Yayla, Muhammed/0000-0002-0659-3084, WOS: 000484777500004, PubMed: 31383063, BN has important roles in several physiological events, including bone growth and immune system. New infection-free cranioplasty and has an osteogenic activities material that are compatible with tissue are being developed. We aimed in our study to examine whether different combinations of Boron-nitride/Hydroxyapatite are embedded into the scaffold in the treatment of calvarial defects. 200 adult female Sprague-Dawley rats divided into 10 equal groups. Osteotomy was made by trepan drill in 8 mm diameter. the scaffolds were placed in the rats and were left to recovery for 2 months. During the experiment, CT scans were taken from the calvarial areas of the rats in the 2nd, 4th and 8th weeks. Significant healing was observed in defect diameters in 2.5% BN + 10% HA, 2.5% BN and 5% BN + 10% HA, respectively. After 8 weeks, it was seen that the amounts of OPN, BMP-2, RunX2 and ALP mRNA expression significantly decreased in 2.5% BN + 10% HA, 2.5% BN, 5% BN + 10% HA and 5% BN groups. It was shown that bone recovery was at the best grade in the groups, which contained 2.5% BN and 2.5% BN + 10% HA when compared to the other groups. BN is a very promising agent that will be used in reconstructive surgery for the treatment of calvarial bone defects., scientific and technological research council of turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112M495], This work was supported by [scientific and technological research council of turkey (TUBITAK)] under Grant [number 112M495].