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

Cancer-Targeted Nanotheranostics: Recent Advances and Future Perspectives

The term nanotheranostics refers to the applications of various nanoparticles that serve the purposes of diagnosis and treatment simultaneously. Their versatile nature holds a promising potential towards their use in cancer management, making them an intriguing field of research. Current nanotechnology methods allow the formulation of a nanostructure that consists of a pharmaceutical molecule and a contrast agent which permits the monitoring of the nanoplatform’s biodistribution and accumulation at the tumour site. The contrast agent can be detected in real time by using non-invasive imaging techniques which include computed tomography, ultrasounds and positron emission tomography. Surface modifications of the nanoparticle are also possible providing greater targeting efficacy (mainly through the use of antibodies) and enhancing the effectiveness of both the imaging agent and the therapeutic substance. Another approach involves constructing a nanoparticle that detects differences in tumour microenvironment and consequently releases its cargo (e.g. a chemotherapeutic agent). This targeted drug release is a highly desirable attribute, resulting in reduced toxicity. Hopefully, these features combined in a single nanoplatform will offer novel clinical tools for personalized anti-cancer theranostics. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

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. © 2020 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Lt

Regulation of Hippo, TGFβ/SMAD, Wnt/β-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, TGFβ/SMAD, Wnt/β-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

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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity

Objective The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity. Methods This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples. Results The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels Conclusion Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity. © 2020 Lippincott Williams and Wilkins. All rights reserved

Design and development of DSPC:DAP:PDMAEMA-b-PLMA nanostructures: from the adumbration of their morphological characteristics to in vitro evaluation

In this study, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-3-dimethylammonium-propane (DAP) and amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PLMA-b-PDMAEMA) in the weight ratios: 1:0:0.03, 1:0.1:0.03, 1:0.3:0.03, 1:0.5:0.03, 1:0.7:0.03, and1:1:0.03, were used for the design and development of hybrid polymer-lipid nanostructures. The polymer-lipid nanostructures were prepared using the aqueous heat method. The pure lipid systems were used as reference systems. Differential Scanning Calorimetry (DSC) was utilized to investigate the interactions between the components. The presence of the polymeric guest caused different orientation of the polar groups of phospholipids, as the DSC thermotropic values revealed. The changes of the physicochemical characteristics of the systems with the increase of the weight ratio of DAP are more intense in comparison to those without this lipid due to the presence of the block copolymer, which contributes significantly to the repulsive interactions between the vesicles as a result of its positive charge. The only exception is the DSPC:DAP:PLMA-b-PDMAEMA nanosystem at 1:0.5:0.03 wt ratio, where the size of the polymer/lipid structures (Dh≈320 nm) increased and the ζ-potential decreased in absolute values in comparison with the systems with lower weight ratio of the DAP lipid. Cryogenic Transmission Electron Microscopy (cryo-TEM) images showed different structures which strongly depend on the composition of the system, ranging from lamella structures, disc forms, and “spaghetti” morphologies. Based on toxicity studies, it was found all samples are biocompatible and show a dose-dependent cytotoxicity on HEK293 (Human Embryonic Kidney 293 cell line). In conclusion, we developed polymer/lipid nanostructures with knowledge of their structural and physicochemical characteristics, useful as drug or antigen delivery platforms. © 202

Association between genetic polymorphisms in long non-coding RNAs and pancreatic cancer risk

BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as candidate biomarkers of cancer, having regulatory functions in both oncogenic and tumor-suppressive pathways. Concerning pancreatic cancer (PC), deregulation of lncRNAs involved in tumor initiation, invasion, and metastasis seem to play a key role. However, data is scarce about regulatory mechanism of lncRNA expression. OBJECTIVE: The aim of our study was to investigate the contribution of two lncRNAs polymorphisms (rs1561927 and rs4759313 of PVT1 and HOTAIR, respectively) in PC susceptibility. METHODS: A case-control study was conducted analysing rs1561927 and rs4759313 polymorphisms using DNA collected in a population-based case-control study of pancreatic cancer (111 pancreatic ductal adenocarcinoma cases (PDAC), 56 pancreatic neuroendocrine tumor (PNET), and 125 healthy controls). RESULTS: Regarding the PVT1 rs1561927 polymorphism the G allele was significantly overrepresented in both PDAC and PNET patients compared to the controls, while the presence of the HOTAIR rs4759314 G allele was found to be overrepresented in the PNET patients only compared to the controls. The PVT1 rs1561927 AG/GG genotypes were associated with poor overall survival in PDAC patients. CONCLUSIONS: Our results suggested that polymorphisms of these two lncRNA polymorphisms implicated in pancreatic carcinogenesis. Further large-scale and functional studies are needed to confirm our results. © 2019-IOS Press and the authors. All rights reserved