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The physicochemical properties (size, shape, zeta potential, porosity, elasticity, etc.) of nanocarriers influence their biological behavior directly, which may result in alterations of the therapeutic outcome. Understanding the effect of shape on the cellular interaction and biodistribution of intravenously injected particles could have fundamental importance for the rational design of drug delivery systems. In the present study, spherical, rod and elliptical disk-shaped PLGA nanoparticles were developed for examining systematically their behavior in vitro and in vivo. An important finding is that the release of the encapsulated human serum albumin (HSA) was significantly higher in spherical particles compared to rod and elliptical disks, indicating that the shape can make a difference. Safety studies showed that the toxicity of PLGA nanoparticles is not shape dependent in the studied concentration range. This study has pioneering findings on comparing spherical, rod and elliptical disk-shaped PLGA nanoparticles in terms of particle size, particle size distribution, colloidal stability, morphology, drug encapsulation, drug release, safety of nanoparticles, cellular uptake and biodistribution. Nude mice bearing non-small cell lung cancer were treated with 3 differently shaped nanoparticles, and the accumulation of nanoparticles in tumor tissue and other organs was not statistically different (p > 0.05). It was found that PLGA nanoparticles with 1.00, 4.0 ± 0.5, 7.5 ± 0.5 aspect ratios did not differ on total tumor accumulation in non-small cell lung cancer.

The uniqueness of paclitaxel’s antimitotic action mechanism has fueled research toward its application in more effective and safer cancer treatments. However, the low water solubility, recrystallization, and side effects hinder the clinical success of classic paclitaxel chemotherapy. The aim of this study was to evaluate the in vivo efficacy and biodistribution of paclitaxel encapsulated in injectable amphiphilic cyclodextrin nanoparticles of different surface charges. It was found that paclitaxel-loaded amphiphilic cyclodextrin nanoparticles showed an antitumoral effect earlier than the drug solution. Moreover, the blank nanoparticles reduced the tumor growth with a similar trend to the paclitaxel solution. At 24 h, the nanoparticles had not accumulated in the heart and lungs according to the biodistribution assessed by in vivo imaging. Therefore, our results indicated that the amphiphilic cyclodextrin nanoparticles are potentially devoid of cardiac toxicity, which limits the clinical use and commercialization of certain polymeric nanoparticles. In conclusion, the amphiphilic cyclodextrin nanoparticles with different surface charge increased the efficiency of paclitaxel in vitro and in vivo. Cyclodextrin nanoparticles could be a good candidate vehicle for intravenous paclitaxel delivery.

Background and Objectives: Berberine is a promising phytochemical for obesity prevention due to its effects on adipogenesis and adipose tissue browning. Despite the benefits shown in cell studies, the clinical use of berberine is limited because of its low stability and bioavailability. Materials and Methods: Our study aimed to investigate the effects of intravenous liposomal and free berberine on body weight and adipose tissue browning in C57BL/6J mice. The mice were divided into two main groups for obesity prevention and treatment: the prevention group received treatment with a high-fat diet for 10 weeks; the recovery group received treatment after 10 weeks on a high-fat diet. Treatments included liposomal berberine (10 mcM), free berberine (10 mcM), and void nano-encapsule, and PBS was used as a control. Results: Berberine did not affect body weight in the prevention group. In the treatment group, nano-berberine reduced weight gain, while free berberine caused weight loss (p < 0.05). PRDM16 and CIDEA expressions in white and brown adipose tissues were higher in the berberine-treated groups (p < 0.05). No changes were observed in UCP1, PGC1α, C/EBPβ, and FABP4 expressions. The protein concentrations of UCP1, PGC1α, and PPARγ did not change. Conclusions: The effects of liposomal berberine on gene expression and protein concentrations were not different from the free form, but the nano form had higher stability.

European hazelnut (Corylus avellana) is a diploid tree species and is widely used in confections. Hazelnuts are, to a large part, produced in Turkey with the cultivar “Tombul” widely grown in the Black Sea region. In this work, the “Tombul” genome was partially sequenced by next-generation sequencing technology yielding 29.2% (111.85 Mb) of the ~ 385 Mb (1C). This sequence information was used to develop genetic markers in order to enable differentiation of material before the long maturation process and to facilitate future breeding strategies. A total of 90,142 simple sequence repeats (SSRs) were identified in the contigs giving a frequency of 1 SSR per 1240 nt in the assembly. Mononucleotides were the most abundant SSR marker type (60.9%) followed by di- and trinucleotides. Primer pairs were designed for 75,139 (83.3%) of the SSRs. Fifty SSR primers were applied to 47 hazelnut accessions from nine countries to test their effectiveness and polymorphism. The markers amplified an average of 3.2 fragments. The highest polymorphism information content value was for cavSSR11062 (0.97) and the lowest (0.04) was for cavSSR13386. Two markers were monomorphic: cavSSR12855 and cavSSR13267. Single-copy SSR primers were also assessed for their ability to discriminate 19 Turkish cultivars, and it was found that seven primer pairs (Cav4217, Cav14875, Cav14418, Cav2704, Cav12862, Cav3909, Cav1361) were sufficient for this task. Thus, this study developed new SSR markers for use in hazelnut breeding and genetic studies and also provide a method to distinguish and identify true-type Turkish cultivars.

More than half of European hazelnut (Corylus avellana) production occurs in Turkey. Despite this dominance, the yield of Turkish cultivars has remained stagnant over the past 10 years with Italian yield nearly double that in Turkey. This difference is due to Turkey’s unique cultivation system; hazelnuts are grown in bushy clusters (“ocak” system), not as single trees. Current hazelnut breeding efforts are shifting toward the development of materials for single plant orchards which are much higher yielding; thus, there is a need to explore germplasm for relevant agro-morphological traits and to determine their genetic control. The objectives of this study were to examine data for 44 such traits in 390 hazelnut accessions: 16 cultivars, 232 landraces and 142 wild individuals from nine provinces in Turkey and to map the loci associated with these characteristics using simple sequence repeat markers. Comparison of cultivars, landraces and wild hazelnut accessions revealed the effects of domestication and selection on the crop and indicated that useful alleles for traits such as cropping and reduced alternate bearing may exist in the wild germplasm. A total of 145 quantitative trait loci (QTL) were detected with the largest proportions identified for involucre (26%) and inflorescence (14%) morphology. Several markers co-localized with more than one trait including markers for male catkin abundance which were shared with plant vigor and height. Similarly, markers for female flower abundance co-localized with suckering and alternate bearing. Such markers and their linked QTL should be studied in more detail as they might help breeders select for plant vigor, decreased suckering and increased flower production: traits which will be extremely useful for Turkey’s transition to single plant orchards.

Background and Objectives: Hypocalcemia due to hypoparathyroidism (HypoPTH) is the most common complication following thyroid surgery, typically resulting from iatrogenic removal, tissue damage, or compromised vascularization of the parathyroid glands. Patients with persistent HypoPTH are at risk for long-term complications such as osteoporosis, cardiac dysfunction, and renal impairment. Lifelong regulation of calcium levels is therefore essential to prevent morbidity and mortality associated with these complications. In this study, we aimed to evaluate the functional engraftment efficacy of 3D bioprinted human parathyroid tissue constructs in a xenograft model in vivo. Materials and Methods: Primary cells obtained from freshly excised human parathyroid tissue specimens were isolated and 3D bioprinted using alginate-based bioink. The bioprinted tissue constructs were implanted into CD1 athymic mice. Histopathological evaluation of the grafted constructs was performed at different time points. In addition, surface calcium-sensing receptor (CaSR) expression was assessed by immunofluorescence as an indicator of functional parathyroid tissue engraftment. Results: The presence of CaSR on parathyroid cells within the 3D-printed scaffolds confirmed the persistence of functional parathyroid cells following implantation. In tissue samples obtained during the first, second, and third weeks after implantation, CaSR positivity was consistently observed in the parathyroid cells. However, at the three-month follow-up, the pores within the scaffolds were found to be filled with calcified material and replaced by fibrotic tissue. At this stage, the absence of parathyroid hormone (PTH) expression indicated a loss of functional activity in the grafted biomaterial. Conclusions: Human primary parathyroid cells were successfully isolated, and a functional, hormone-active parathyroid tissue substitute was developed ex vivo using 3D-bioprinted hydrogel scaffolds combined with autologous cells. Although short-term functional engraftment was achieved, long-term graft viability and hormonal activity were limited due to scaffold degradation and fibrosis. These findings indicate the necessity for further improvement in scaffold biocompatibility to enhance the therapeutic potential of 3D-bioprinted parathyroid tissue constructs for in vivo applications.

Inflammatory alterations of the extracellular matrix shape the tumor microenvironment and promote all stages of carcinogenesis. This study aims to determine the impact of cellular fibronectin on inflammatory facets of tumor-associated macrophages (TAMs) in breast cancer. Cellular fibronectin (FN) harboring the alternatively spliced extra domain A (FN-EDA) was determined to be a matrix component produced by the triple-negative breast cancer (TNBC) cells. High levels of FN-EDA correlated with poor survival in breast cancer patients. The proinflammatory cytokine IL-1β enhanced the expression of cellular fibronectin including FN-EDA. TAMs were frequently observed in the tumor areas rich in FN-EDA. Conditioned media from TNBC cells induced the differentiation of CD206 + CD163 + macrophages and stimulated the STAT3 pathway, ex vivo. In the macrophages, the STAT3 pathway enhanced FN-EDA-induced IL-1β secretion and NF-κB signaling. In conclusion, our data indicate a self-reinforcing mechanism sustained by FN-EDA and IL-1β through NF-κB and STAT3 signaling in TAMs which fosters an inflammatory environment in TNBC.

European hazelnut ( Corylus avellana L.), cultivated in several areas of the world including Europe, Anatolia, and the USA, is an economically important nut crop due to its high mineral, oleic acid, amino acid, and phenolic compound content and pleasant flavor. This study examined molecular genetic diversity and population structure of 54 wild accessions and 48 cultivars from the Slovenian national hazelnut collection using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. Eleven AFLP primer combinations and 49 SSR markers yielded 532 and 504 polymorphic fragments, respectively. As expected for a wind-pollinated, self-incompatible species, levels of genetic diversity were high with cultivars and wild accessions having mean dissimilarity values of 0.50 and 0.60, respectively. In general, cultivars and wild accessions clustered separately in dendrogram, principal coordinate, and population structure analyses with regional clustering of the wild material. The accessions were also characterized for ten nut and seven kernel traits and some wild accessions were shown to have breeding potential. Morphological principal component analysis showed distinct clustering of cultivars and wild accessions. An association mapping panel composed of 64 hazelnut cultivars and wild accessions had considerable variation for the nut and kernel quality traits. Morphological and molecular data were associated to identify markers controlling the traits. In all, 49 SSR markers were significantly associated with nut and kernel traits [ P  < 0.0001 and LD value ( r 2 ) = 0.15–0.50]. This work is the first use of association mapping in hazelnut and has identified molecular markers associated with important quality parameters in this important nut crop.

European hazelnut (Corylus avellana L.), cultivated in several areas of the world including Europe, Anatolia, and the USA, is an economically important nut crop due to its high mineral, oleic acid, amino acid, and phenolic compound content and pleasant flavor. This study examined molecular genetic diversity and population structure of both Slovenian and Turkish hazelnuts. In the first part of the work, genetic diversity of 54 wild accessions and 48 cultivars from the Slovenian national hazelnut collection was determined using amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers. The accessions were also characterized for ten nut and seven kernel traits and some wild accessions were shown to have breeding potential. An association mapping panel composed of 64 hazelnut cultivars and wild accessions had considerable variation for the nut and kernel quality traits. Morphological and molecular data were associated to identify markers controlling the traits. In all, 49 SSR markers were significantly associated with nut and kernel traits [P < 0.0001 and LD value (r2) = 0.15–0.50]. This work is the first use of association mapping in hazelnut and has identified molecular markers associated with important quality parameters in this important nut crop. In the second part of the work, 402 Turkish hazelnut accessions were screened with 30 SSR markers. The data obtained from this screen allowed selection of a national core collection of hazelnut. This core collection represents a maximum of genetic diversity in a minimum number of individuals. Turkish cultivar ‘Tombul’ was sequenced using next generation sequencing technology and new SSR markers were developed. It was found that seven SSR markers were sufficient to discriminate Turkish hazelnut cultivars from each other. This study provides molecular information for marker-assisted selection in hazelnut and gives new insight to discover the genetic potential of hazelnut germplasm.

European hazelnut ( Corylus avellana L.) is an economically and nutritionally important nut crop with wild and cultivated populations found throughout Europe and in parts of Asia. This study examined the molecular genetic diversity and population structure of 402 genotypes including 143 wild individuals, 239 landraces, and 20 cultivars from the Turkish national hazelnut collection using simple sequence repeat (SSR) markers. A total of 30 SSR markers yielded 407 polymorphic fragments. Diversity analysis of the Turkish hazelnut genotypes indicated that they fell into three subpopulations according to ad hoc statistics and neighbor-joining algorithm. Although all cultivars clustered together, they overlapped with the wild accessions and landraces. Thus, the dendrogram, principal coordinate, and population structure analyses suggest that they share the same gene pool. A total of 78 accessions were selected as a core set to encompass the molecular genetic and morphological diversity present in the national collection. This core set should have priority in preservation efforts and in trait characterization.