Nano-Based Approaches in Surface Modifications of Dental Implants: A Literature Review.

Rehabilitation of fully or partially edentulous patients with dental implants represents one of the most frequently used surgical procedures. The work of Branemark, who observed that a piece of titanium embedded in rabbit bone became firmly attached and difficult to remove, introduced the concept of osseointegration and revolutionized modern dentistry. Since then, an ever-growing need for improved implant materials towards enhanced material-tissue integration has emerged. There is a strong belief that nanoscale materials will produce a superior generation of implants with high efficiency, low cost, and high volume. The aim of this review is to explore the contribution of nanomaterials in implantology. A variety of nanomaterials have been proposed as potential candidates for implant surface customization. They can have inherent antibacterial properties, provide enhanced conditions for osseointegration, or act as reservoirs for biomolecules and drugs. Titania nanotubes alone or in combination with biological agents or drugs are used for enhanced tissue integration in dental implants. Regarding immunomodulation and in order to avoid implant rejection, titania nanotubes, graphene, and biopolymers have successfully been utilized, sometimes loaded with anti-inflammatory agents and extracellular vesicles. Peri-implantitis prevention can be achieved through the inherent antibacterial properties of metal nanoparticles and chitosan or hybrid coatings bearing antibiotic substances. For improved corrosion resistance various materials have been explored. However, even though these modifications have shown promising results, future research is necessary to assess their clinical behavior in humans and proceed to widespread commercialization.

Incorporation of PEGylated δ-decalactone into lipid bilayers: thermodynamic study and chimeric liposomes development.

Liposomes have been on the market as drug delivery systems for over 25 years. Their success comes from the ability to carry toxic drug molecules to the appropriate site of action through passive accumulation, thus reducing their severe side effects. However, the need for enhanced circulation time and site and time-specific drug delivery turned research focus on other systems, such as polymers. In this context, novel composites that combine the flexibility of polymeric nanosystems with the properties of liposomes gained a lot of interest. In the present work a mixed/chimeric liposomal system, composed of phospholipids and block copolymers, was developed and evaluated in regards with its feasibility as a drug delivery system. These innovative nano-platforms combine advantages from both classes of biomaterials. Thermal analysis was performed in order to offers an insight into the interactions between these materials and consequently into their physicochemical characteristics. In addition, colloidal stability was assessed by monitoring z-potential and size distribution over time. Finally, their suitability as carriers for biomedical applications was evaluated by carrying out in vitro toxicity studies.

ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries: A case-control study.

BACKGROUND: Dental caries represents one of the most common human diseases which can lead to pulpitis, pain, and tooth loss and can negatively affect growth and well-being. Although dietary and environmental factors have been extensively studied towards their contribution of the disease, genetic factors that contribute one's susceptibility over caries development remain rather clouded. AIM: To investigate the possible contribution of ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries. DESIGN: Samples from children (5-12 years old) were collected and genotyped for ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms. With regard to dmfs index and socio-economic status, an association between these polymorphisms and primary dentition caries was investigated. RESULTS: ACTN2 (rs6655267) and MPPED2 (rs536007) are not associated with primary dentition caries. MPPED2 (rs11031093, G Allele) is marginally associated. CONCLUSIONS: MPPED2 (rs11031093, G Allele) is marginally associated with caries susceptibility on primary dentition.

Recent Advances in Scaffolds for Guided Bone Regeneration.

The rehabilitation of alveolar bone defects of moderate to severe size is often challenging. Currently, the therapeutic approaches used include, among others, the guided bone regeneration technique combined with various bone grafts. Although these techniques are widely applied, several limitations and complications have been reported such as morbidity, suboptimal graft/membrane resorption rate, low structural integrity, and dimensional stability. Thus, the development of biomimetic scaffolds with tailor-made characteristics that can modulate cell and tissue interaction may be a promising tool. This article presents a critical consideration in scaffold's design and development while also providing information on various fabrication methods of these nanosystems. Their utilization as delivery systems will also be mentioned.

Dysbiosis Signature of Fecal Microbiota in Patients with Pancreatic Adenocarcinoma and Pancreatic Intraductal Papillary Mucinous Neoplasms.

Pancreatic cancer (PC) ranks as the seventh leading cause of cancer-related deaths, with approximately 500,000 new cases reported in 2020. Existing strategies for early PC detection primarily target individuals at high risk of developing the disease. Nevertheless, there is a pressing need to identify innovative clinical approaches and personalized treatments for effective PC management. This study aimed to explore the dysbiosis signature of the fecal microbiota in PC and potential distinctions between its Intraductal papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC) phenotypes, which could carry diagnostic significance. The study enrolled 33 participants, including 22 diagnosed with PDAC, 11 with IPMN, and 24 healthy controls. Fecal samples were collected and subjected to microbial diversity analysis across various taxonomic levels. The findings revealed elevated abundances of Firmicutes and Proteobacteria in PC patients, whereas healthy controls exhibited higher proportions of Bacteroidota. Both LEfSe and Random Forest analyses indicated the microbiome's potential to effectively distinguish between PC and healthy control samples but fell short of differentiating between IPMN and PDAC samples. These results contribute to the current understanding of this challenging cancer type and highlight the applications of microbiome research. In essence, the study provides clear evidence of the gut microbiome's capability to serve as a biomarker for PC detection, emphasizing the steps required for further differentiation among its diverse phenotypes.

Fe3O4 and Fe3O4core Aushell-based Hyperthermia Reduces Expression of Proliferation Markers Ki-67, TOP2A and TPX2 in a Human Breast Cancer Cell Line.

BACKGROUND/AIM: Hyperthermia represents an adjuvant local anticancer strategy which relies on the increase of temperature beyond the physiological level. In this study, we investigated the anticancer potential of Fe3O4 and Fe3O4core Aushell nanoparticles as hyperthermic agents in terms of cytotoxicity and studied the expression of cellular markers of proliferation (changes in mRNA levels via real-time polymerase chain reaction). MATERIALS AND METHODS: The human breast cancer cell line SK-BR-1 was incubated with either Fe3O4 or Fe3O4core Aushell nanoparticles stabilized with tryptophan, prior to hyperthermia treatment. The normal HEK293 cell line was used as a control. Toxicity was determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to estimate possible toxic effects of the tested nanoparticles. After RNA extraction and cDNA synthesis, mRNA expression of three indicators of proliferation, namely marker of proliferation Ki-67, DNA topoisomerase II alpha (TOP2A) and TPX2 microtubule nucleation factor (TPX2), was investigated. RESULTS: At each concentration tested, Fe3O4core Aushell nanoparticles showed greater toxicity compared to Fe3O4, while SK-BR-3 cells were more susceptible to their cytotoxic effects compared to the HEK293 cell line. The expression of Ki-67, TOP2A and TPX2 was reduced in SK-BR-3 cells by both Fe3O4 or Fe3O4core Aushell nanoparticles compared to untreated cells, while the only observed change in HEK293 cells was the up-regulation of TOP2A. CONCLUSION: Both Fe3O4core Aushell and Fe3O4 NPs exhibit increased cytotoxicity to the cancer cell line tested (SK-BR-3) compared to HEK293 cells. The down-regulation in SK-BR-3 cells of the three proliferative markers studied, Ki-67, TOP2A and TPX2, after incubation with NPs suggests that cells that survived thermal destruction were not actively proliferating.

Novel Multi-Responsive Hyperbranched Polyelectrolyte Polyplexes as Potential Gene Delivery Vectors.

In this work, we investigate the complexation behavior of poly(oligo(ethylene glycol)methyl methacrylate)-co-poly(2-(diisopropylamino)ethyl methacrylate), P(OEGMA-co-DIPAEMA), hyperbranched polyelectrolyte copolymers, synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization, with short-linear DNA molecules. The synthesized hyperbranched copolymers (HBC), having a different chemical composition, are prepared in order to study their ability to bind with a linear nucleic acid at various N/P ratios (amine over phosphate groups). Specifically, the three pH and thermo-responsive P(OEGMA-co-DIPAEMA) hyperbranched copolymers were able to form polyplexes with DNA, with dimensions in the nanoscale. Using several physicochemical methods, such as dynamic and electrophoretic light scattering (DLS, ELS), as well as fluorescence spectroscopy (FS), the complexation process and the properties of formed polyplexes were explored in response to physical and chemical stimuli such as temperature, pH, and ionic strength. The mass and the size of polyplexes are shown to be affected by the hydrophobicity of the copolymer utilized each time, as well as the N/P ratio. Additionally, the stability of polyplexes in the presence of serum proteins is found to be excellent. Finally, the multi-responsive hyperbranched copolymers were evaluated regarding their cytotoxicity via in vitro experiments on HEK 293 non-cancerous cell lines and found to be sufficiently non-toxic. Based on our results, these polyplexes could be useful candidates for gene delivery and related biomedical applications.

Association of BAFF and BAFF-R polymorphisms with sarcoidosis in a Greek patient cohort.

Introduction: Sarcoidosis is a disease that results from a combination of environmental and genetic factors. Its genetic basis however, is yet to be clarified. The purpose of this study is to determine whether single nucleotide polymorphisms (SNPs) of the B-cell activating factor (BAFF) and its receptor (BAFF-R) are associated with sarcoidosis. Material and methods: Blood samples from one hundred and seventy-three sarcoidosis patients and one hundred and sixty-four controls were collected. All samples were genotyped for BAFF rs2893321, rs1041569 and rs9514828, and for BAFF-R rs61756766. Results: Out of the three BAFF polymorphisms, none genotype had any significant association with sarcoidosis, although the T allele in rs1041569 and rs9514828 was overrepresented in sarcoidosis patients. A marginally significant association with sarcoidosis was found in the case of the CT genotype and T allele of BAFF-R rs61756766. Haplotype analysis of the BAFF polymorphisms was also performed, revealing an overrepresentation of the ATT, GTA and GTT haplotypes in the group of patients with cardiac involvement. Conclusions: Taken together, the results of this study suggest a possible relationship between BAFF SNPs, rs1041569 and rs9514828, and BAFF-R SNP rs61756766 with sarcoidosis susceptibility and their potential as biomarkers for the disease.

The Role of HIF1-related Genes and Non-coding RNAs Expression in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Renal cell carcinoma is one of the three most common malignant urologic tumors, with clear cell renal cell carcinoma (ccRCC) representing its most common subtype. Although nephrectomy can radically cure the disease, a large percentage of patients is diagnosed when metastatic sites are present and thus alternative, pharmaceutical approaches need to be sought. Since HIF1 up-regulates the transcription of genes that range from metabolic enzymes to non-coding RNAs, and is a key molecule of ccRCC pathogenesis, this study aimed to investigate the expression ALDOA, SOX-6, and non-coding RNAs (mir-122, mir-1271, and MALAT-1) in samples from ccRCC patients. PATIENTS AND METHODS: Tumor and adjacent normal tissue samples from 14 patients with ccRCC were harvested. Expression of ALDOA, mir-122, mir-1271, and MALAT-1 mRNA was estimated using real time PCR, whereas the expression of SOX-6 protein was investigated using immunohistochemistry. RESULTS: Up-regulation of HIF1 was observed, accompanied with up-regulation of ALDOA, MALAT-1, and mir-122. On the contrary, the expression of mir-1271 was found to be reduced, a finding that can be attributed to a potential MALAT-1 sponge function. Furthermore, SOX-6 protein levels (a transcription factor with tumor suppressing properties) were also reduced. CONCLUSION: The observed dysregulated expression levels highlight the importance of ALDOA, MALAT-1, mir-122, mir-1271, and SOX-6, which remain less studied than the known and well-studied HIF1 pathways of VEGF, TGF-α, and EPO. Furthermore, inhibition of the up-regulated ALDOA, mir-122, and MALAT-1 could be of therapeutic interest for selected ccRCC patients.

An Overview of Epigenetics in Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents a heterogenous group of cancers with complex genetic background and histological varieties, which require various clinical therapies. Clear cell RCC represents the most common form of RCC that accounts for 3 out of 4 RCC cases. Screening methods for RCC lack sensitivity and specificity, and thus biomarkers that will allow early diagnosis are crucial. The impact of epigenetics in the development and progression of cancer, including RCC, is significant. Noncoding RNAs, histone modifications and DNA methylation represent fundamental epigenetic mechanisms and have been proved to be promising biomarkers. MicroRNAs have advantageous properties that facilitate early diagnosis of RCC, while their expression profiles have been assessed in renal cancer samples (tissue, blood, and urine). Current literature reports the up-regulation of mir122, mir1271 and mir15b in RCC specimens, which induces cell proliferation via FOXP-1 and PTEN genes. However, it should be noted that conflicting results are found in urine and serum patient samples. Moreover, promoters of at least 200 genes are methylated in renal cancers leading to epigenetic dysregulation. In this review, we analyze the vast plethora of studies that have evaluated the role of epigenetic mechanisms in RCC patients and their clinical importance.

Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the various novel agents has not been fully clarified. With the different treatment options, there is an essential need to identify biomarkers to predict therapeutic efficacy and thus optimize therapeutic approaches. This study seeks to explore the diversity in mRNA expression profiles of inflammation and immunity-related circulating genes for the development of biomarkers that could predict the effectiveness of immunotherapy-based treatments using ICIs for individuals with mccRCC. Gene mRNA expression was tested by the RT2 profiler PCR Array on a human cancer inflammation and immunity crosstalk kit and analyzed for differential gene expression along with a machine learning approach for sample classification. A number of mRNAs were found to be differentially expressed in mccRCC with a clinical benefit from treatment compared to those who progressed. Our results indicate that gene expression can classify these samples with high accuracy and specificity.

Gut microbiome: Linking together obesity, bariatric surgery and associated clinical outcomes under a single focus.

Obesity is increasingly prevalent in the post-industrial era, with increased mortality rates. The gut microbiota has a central role in immunological, nutritional and metabolism mediated functions, and due to its multiplexity, it is considered an independent organ. Modern high-throughput sequencing techniques have allowed phylogenetic exploration and quantitative analyses of gut microbiome and improved our current understanding of the gut microbiota in health and disease. Its role in obesity and its changes following bariatric surgery have been highlighted in several studies. According to current literature, obesity is linked to a particular microbiota profile that grants the host an augmented potential for calorie release, while limited diversity of gut microbiome has also been observed. Moreover, bariatric surgery procedures represent effective interventions for sustained weight loss and restore a healthier microbiota, contributing to the observed fat mass reduction and lean mass increase. However, newer evidence has shown that gut microbiota is only partially recovered following bariatric surgery. Moreover, several targets including FGF15/19 (a gut-derived peptide), could be responsible for the favorable metabolic changes of bariatric surgery. More randomized controlled trials and larger prospective studies that include well-defined cohorts are required to better identify associations between gut microbiota, obesity, and bariatric surgery.

Hydrophilic Random Cationic Copolymers as Polyplex-Formation Vectors for DNA.

Research on the improvement and fabrication of polymeric systems as non-viral gene delivery carriers is required for their implementation in gene therapy. Random copolymers have not been extensively utilized for these purposes. In this regard, double hydrophilic poly[(2-(dimethylamino) ethyl methacrylate)-co-(oligo(ethylene glycol) methyl ether methacrylate] [P(DMAEMA-co-OEGMA)] random copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The copolymers were further modified by quaternization of DMAEMA tertiary amine, producing the cationic P(QDMAEMA-co-OEGMA) derivatives. Fluorescence and ultraviolet-visible (UV-vis) spectroscopy revealed the efficient interaction of copolymers aggregates with linear DNAs of different lengths, forming polyplexes, with the quaternized copolymer aggregates exhibiting stronger binding affinity. Light scattering techniques evidenced the formation of polyplexes whose size, molar mass, and surface charge strongly depend on the N/P ratio (nitrogen (N) of the amine group of DMAEMA/QDMAEMA over phosphate (P) groups of DNA), DNA length, and length of the OEGMA chain. Polyplexes presented colloidal stability under physiological ionic strength as shown by dynamic light scattering. In vitro cytotoxicity of the empty nanocarriers was evaluated on HEK293 as a control cell line. P(DMAEMA-co-OEGMA) copolymer aggregates were further assessed for their biocompatibility on 4T1, MDA-MB-231, MCF-7, and T47D breast cancer cell lines presenting high cell viability rates.

Amniotic Fluid-Derived Mesenchymal Stem/Stromal Cell-Derived Secretome and Exosomes Improve Inflammation in Human Intestinal Subepithelial Myofibroblasts.

Inflammatory Bowel Diseases (IBDs) are characterized by chronic relapsing inflammation of the gastrointestinal tract. The mesenchymal stem/stromal cell-derived secretome and secreted extracellular vesicles may offer novel therapeutic opportunities in patients with IBD. Thus, exosomes may be utilized as a novel cell-free approach for IBD therapy. The aim of our study was to examine the possible anti-inflammatory effects of secretome/exosomes on an IBD-relevant, in vitro model of LPS-induced inflammation in human intestinal SubEpithelial MyoFibroblasts (SEMFs). The tested CM (Conditioned Media)/exosomes derived from a specific population of second-trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped amniotic fluid MSCs (SS-AF-MSCs), and specifically, their secreted exosomes could be utilized as a novel cell-free approach for IBD therapy. Therefore, we studied the effect of SS-AF-MSCs CM and exosomes on LPS-induced inflammation in SEMF cells. SS-AF-MSCs CM and exosomes were collected, concentrated, and then delivered into the cell cultures. Administration of both secretome and exosomes derived from SS-AF-MSCs reduced the severity of LPS-induced inflammation. Specifically, IL-1ß, IL-6, TNF-α, and TLR-4 mRNA expression was decreased, while the anti-inflammatory IL-10 was elevated. Our results were also verified at the protein level, as secretion of IL-1ß was significantly reduced. Overall, our results highlight a cell-free and anti-inflammatory therapeutic agent for potential use in IBD therapy.

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines.

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 µg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1ß and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1ß were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1ß release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

BACKGROUND: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. PATIENTS AND METHODS: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. RESULTS: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. CONCLUSIONS: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Regulation of Hippo, TGFß/SMAD, Wnt/ß-Catenin, JAK/STAT, and NOTCH by Long Non-Coding RNAs in Pancreatic Cancer.

Rapidly evolving and ever-increasing knowledge of the molecular pathophysiology of pancreatic cancer has leveraged our understanding altogether to a next level. Compared to the exciting ground-breaking discoveries related to underlying mechanisms of pancreatic cancer onset and progression, however, there had been relatively few advances in the therapeutic options available for the treatment. Since the discovery of the DNA structure as a helix which replicates semi-conservatively to pass the genetic material to the progeny, there has been conceptual refinement and continuous addition of missing pieces to complete the landscape of central dogma. Starting from transcription to translation, modern era has witnessed non-coding RNA discovery and central role of these versatile regulators in onset and progression of pancreatic cancer. Long non-coding RNAs (lncRNAs) have been shown to act as competitive endogenous RNAs through sequestration and competitive binding to myriad of microRNAs in different cancers. In this article, we set spotlight on emerging evidence of regulation of different signaling pathways (Hippo, TGFß/SMAD, Wnt/ß-Catenin, JAK/STAT and NOTCH) by lncRNAs. Conceptual refinements have enabled us to understand how lncRNAs play central role in post-translational modifications of various proteins and how lncRNAs work with epigenetic-associated machinery to transcriptionally regulate gene network in pancreatic cancer.

The Effect of MicroRNA-126 Mimic Administration on Vascular Perfusion Recovery in an Animal Model of Hind Limb Ischemia.

Background: MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases. Methods: Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, n = 10) or 5 mg/kg microRNA mimic negative control (Group B, n = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR. Results: Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, p = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, p = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p < 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p < 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population. Conclusion: MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.

Histone Mark Profiling in Pediatric Astrocytomas Reveals Prognostic Significance of H3K9 Trimethylation and Histone Methyltransferase SUV39H1.

Alterations in global histone methylation regulate gene expression and participate in cancer onset and progression. The profile of histone methylation marks in pediatric astrocytomas is currently understudied with limited data on their distribution among grades. The global expression patterns of repressive histone marks H3K9me3, H3K27me3, and H4K20me3 and active H3K4me3 and H3K36me3 along with their writers SUV39H1, SETDB1, EZH2, MLL2, and SETD2 were investigated in 46 pediatric astrocytomas and normal brain tissues. Associations between histone marks and modifying enzymes with clinicopathological characteristics and disease-specific survival were studied along with their functional impact in proliferation and migration of pediatric astrocytoma cell lines using selective inhibitors in vitro. Upregulation of histone methyltransferase gene expression and deregulation of histone code were detected in astrocytomas compared to normal brain tissues, with higher levels of SUV39H1, SETDB1, and SETD2 as well as H4K20me3 and H3K4me3 histone marks. Pilocytic astrocytomas exhibited lower MLL2 levels compared to diffusely infiltrating tumors indicating a differential pattern of epigenetic regulator expression between the two types of astrocytic neoplasms. Moreover, higher H3K9me3, H3K36me3, and SETDB1 expression was detected in grade IIΙ/IV compared to grade II astrocytomas. In univariate analysis, elevated H3K9me3 and MLL2 and diminished SUV39H1 expression adversely affected survival. Upon multivariate survival analysis, only SUV39H1 expression was revealed as an independent prognostic factor of adverse significance. Treatment of pediatric astrocytoma cell lines with SUV39H1 inhibitor reduced proliferation and cell migration. Our data implicate H3K9me3 and SUV39H1 in the pathobiology of pediatric astrocytomas, with SUV39H1 yielding prognostic information independent of other clinicopathologic variables.

In vitro effect of hyperthermic Ag and Au Fe3O4 nanoparticles in cancer cells.

PURPOSE: To investigate the anti-cancer efficacy of hyperthermic Ag and Au Fe3O4 core nanoparticles via cytotoxicity study (MTT assay) and the underlying molecular mechanism of action (changes in gene expression via quantitive real time PCR (qRT-PCR). METHODS: HEK293, HCT116, 4T1 and HUH7 human cell lines and 4T1 musculus mammary gland cell line were incubated with Fe3O4 core Ag(Au) shell nanoparticles (NPs) prior to a hyperthermia session. MTT assay was performed to estimate the cytotoxic effects of these NPs. RNA extraction and cDNA synthesis followed so as to quantify mRNA fold change of hsp-70, p53, bcl-2 and casp-3 via qRT-PCR. RESULTS: Fe3O4 core Au shell (concentrations of 400 and 600µg/mL) produced the greatest reduction of viability on HCT116 and 4T1 cells while Fe3O4 core Ag shell (200, 400 and 600µg/mL) reduce viability on HUH7 cells. Hsp-70, p53 and casp-3 were up-regulated while bcl-2 was downregulated in most cases. CONCLUSIONS: Fe3O4 core Ag (Au) shell induced apoptosis on cancer cells (HCT116 and HUH7) via the p53/bcl-2/casp-3 pathway. 4T1 cells also underwent apoptosis via a p53-independent pathway.