The critical role and functional mechanism of microRNA-146a in doxorubicin-induced apoptosis in breast cancer cells.

BACKGROUND: Breast cancer among women is the most frequently diagnosed cancer and the leading cause of death worldwide. There many advances in diagnosing and treating this disease, early diagnosis and treatment are still a significant challenge in the early stages. In recent years, microRNAs have attracted much attention in cancer diagnosis and treatment. However, the role of miR-146a in breast cancer is still controversial. We aimed to investigate the roles of miR-146a in apoptosis in breast cancer cells. METHODS: A microarray dataset from the GEO database was selected, and using the GEO2R tool, the gene expression profile of this dataset was extracted. Then, the target scan database was used to explore the miR-146a target genes. The link between the signaling pathways was collected. We used miR-146a mimic, which was transfected to the MCF-7 cells to investigate the miR-146a roles in the apoptosis. The expression levels of miR-146a and BAX, BCL-2, and p-21(most essential genes in the apoptosis) were quantified by qPCR and western blot analysis. RESULTS: Our findings indicated that doxorubicin induces miR-146a expression. In addition, overexpression of miR-146a affected MCF-7 cell viability, induced apoptosis, and led to reduced expression levels of BCL-2 and P-21, as well as increased BAX expression levels. CONCLUSION: Considering the role of doxorubicin in inducing apoptosis and increasing the expression of miR-146a, it can be suggested that this miR is involved in inducing apoptosis in BC cells. In addition, miR-146a can be considered a therapeutic candidate.

Correction: Zare et al. Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics. Pharmaceutics 2022, 14, 1620.

In the original publication [...].

D-allose: Molecular Pathways and Therapeutic Capacity in Cancer.

BACKGROUND: Despite the implementation of various cancer therapies, adequate therapeutic efficacy has not been achieved. A growing number of studies have been dedicated to the discovery of new molecules to combat refractory cancer cells efficiently. Recently, the use of a rare type of sugar, D-allose, has attracted the attention of research communities. In combination with the first-line treatment of cancers, including different types of radiotherapies and chemotherapies, D-allose has been detected with favorable complementary effects. Understanding the mechanism of therapeutic target molecules will enable us to develop new strategies for cancer patients that do not currently respond to the present therapies. OBJECTIVE: We aimed to provide a review of the effects of D-allose in cancer treatment, its mechanisms of action, and gaps in this field that require more investigations. DISCUSSION: With rare exceptions, in many cancer types, including head and neck, lung, liver, bladder, blood, and breast, D-allose consistently has exhibited anticancer activity in vitro and/or in vivo. Most of the D-allose functions are mediated through thioredoxin-interacting protein molecules. D-allose exerts its effects via reactive oxygen species regulation, cell cycle arrest, metabolic reprogramming, autophagy, apoptosis induction, and sensitizing tumors to radiotherapy and chemotherapy. CONCLUSION: D-allose has shown great promise for combating tumor cells with no side effects, especially in combination with first-line drugs; however, its potential for cancer therapy has not been comprehensively investigated in vitro or in vivo.

Modification of magnetic mesoporous N-doped silica nanospheres by CuO NPs: a highly efficient catalyst for the multicomponent synthesis of some propellane indeno indole derivatives.

Herein, magnetic mesoporous N-doped silica nanospheres decorated by CuO nanoparticles (M-MNS/CuO) were prepared and used for the green and efficient synthesis of some [3.3.3] propellane indeno[1,2-b] indole derivatives. In order to prepare N-doped silica nanoparticles, tetraethyl orthosilicate (TEOS) was used as the silica source, and diethanolamine (DEA) as a nitrogen precursor. Immobilization of CuO nanoparticles on the mesoporous N-doped silica nanosphere surfaces increases the surface area of catalyst and provides Lewis acidic sites in addition to nitrogen atoms as active basic sites. The presence of nitrogen atoms and copper oxide nanoparticles in the catalyst structure, give dual acidic and basic properties. The synthesized catalyst was characterized by FESEM, EDS, HRTEM, XRD, VSM, FTIR, and BET techniques which proved its magnetic core shell structure.

Nitinol: From historical milestones to functional properties and biomedical applications.

Isoatomic NiTi alloy (Nitinol) has become an important biomaterial due to its unique characteristics, including shape memory effect, superelasticity, and high damping. Nitinol has been widely used in the biomedical field, including orthopedics, vascular stents, orthodontics, and other medical devices. However, there have been convicting views about the biocompatibility of Nitinol. Some studies have shown that Nitinol has extremely low cytotoxicity, indicating Nitinol has good biocompatibility. However, some studies have shown that the in-vivo corrosion resistance of Nitinol significantly decreases. This comprehensive paper discusses the historical developments of Nitinol, its biomedical applications, and its specific functional property. These render the suitability of Nitinol for such biomedical applications and provide insights into its in vivo and in vitro biocompatibility in the physiological environment and the antimicrobial strategies that can be applied to enhance its biocompatibility. Although 3D metal printing is still immature and Nitinol medical materials are difficult to be processed, Nitinol biomaterials have excellent potential and commercial value for 3D printing. However, there are still significant problems in the processing of Nitinol and improving its biocompatibility. With the deepening of research and continuous progress in surface modification and coating technology, a series of medical devices made from Nitinol are expected to be released soon.

Encapsulation of miRNA and siRNA into Nanomaterials for Cancer Therapeutics.

Globally, cancer is amongst the most deadly diseases due to the low efficiency of the conventional and obsolete chemotherapeutic methodologies and their many downsides. The poor aqueous solubility of most anticancer medications and their low biocompatibility make them ineligible candidates for the design of delivery systems. A significant drawback associated with chemotherapy is that there are no advanced solutions to multidrug resistance, which poses a major obstacle in cancer management. Since RNA interference (RNAi) can repress the expression of genes, it is viewed as a novel tool for advanced drug delivery. this is being explored as a promising drug targeting strategy for the treatment of multiple diseases, including cancer. However, there are many obstructions that hinder the clinical uses of siRNA drugs due to their low permeation into cells, off-target impacts, and possible unwanted immune responses under physiological circumstances. Thus, in this article, we review the design measures for siRNA conveyance frameworks and potential siRNA and miRNA drug delivery systems for malignant growth treatment, including the use of liposomes, dendrimers, and micelle-based nanovectors and functional polymer-drug delivery systems. This article sums up the advancements and challenges in the use of nanocarriers for siRNA delivery and remarkably centers around the most critical modification strategies for nanocarriers to build multifunctional siRNA and miRNA delivery vectors. In short, we hope this review will throw light on the dark areas of RNA interference, which will further open novel research arenas in the development of RNAi drugs for cancer.

Association between the Expression Levels of MicroRNA-101, -103, and -29a with Autotaxin and Lysophosphatidic Acid Receptor 2 Expression in Gastric Cancer Patients.

Background: Gastric cancer (GC) is regarded as the most prevalent malignancy with the high mortality rate, worldwide. However, gastroscopy, a biopsy of suspected sample, and detecting CEA, CA19-9, and CA72-4 are presently used, but these diagnostic approaches have several limitations. Recently, microRNAs as the most important member of noncoding RNAs (ncRNAs) have received attention; recent evidence demonstrates that they can be used as the promising candidate biomarkers for GC diagnosis. We aimed to investigate the association between the microRNA-29a, -101, and -103 expression and autotaxin (ATX) and lysophosphatidic acid receptor 2 (LPA2) expression in GC patients. Material and Methods. The present study was conducted on 40 paired samples of primary GC tissue and adjacent noncancerous tissue. The gene expression levels of miR-101, -103, -29, ATX, and LPA2 were analyzed by quantitative reverse-transcription PCR (qRT-PCR). Besides, the protein levels of ATX and LPA2 were evaluated using western blot. Results: The expression levels of miR-29 and miR-101 were significantly lower (p value < 0.0001), but the miR-103 and LPA2 were significantly higher in gastric tumor samples compared to the corresponding nontumor tissues (p value < 0.0001). Moreover, the diagnostic accuracy of miRs to discrimine the GC patients from noncancerous controls was reliable (miR-101, sensitivity: 82.5% and specificity: 85%; miR-103, sensitivity: 72.5% and specificity: 90%; miR-29, sensitivity: 77.5% and specificity: 70%). Conclusion: It seems that determining the expression level of miR-101, -103, and -29, as the novel diagnostic biomarkers, has diagnostic value to distinguish GC patients from healthy individuals.

Strategies to Enhance ZnO Photocatalyst's Performance for Water Treatment: A Comprehensive Review.

Despite the photocatalytic organic pollutant degradation using ZnO started in 1910-1911, many challenges are still ahead, and several critical issues have to be addressed. Large band gap, and short life-time of photogenerated electrons and holes are critical issues negatively affect the photocatalytic activity of ZnO. Various approaches have been introduced to overcome these issues including intrinsic doping, extrinsic doping, and heterostructure. This review introduces unique and deep insights into tuning of the photocatalytic activity of ZnO. It starts by description of how to tune the photocatalytic activity of pristine ZnO through tuning its morphology, surface area, exposed face, and intrinsic defects. Afterward, the review explains how the Z-scheme approach succeed to address the redox weakened issue of heterojunction approach. In general, this review provides a clear image that helps the researcher to tune the photocatalytic activity of pristine ZnO and its heterostructure.

Metformin reduces lipid accumulation in HepG2 cells via downregulation of miR-33b.

INTRODUCTION: Here, we aimed to investigate whether the beneficial effects of metformin on lipid accumulation is mediated through regulation of miR-33b. METHODS: The expression of the genes and miRNAs and protein levels were evaluated using real-time PCR and western blot, respectively. To investigate the potential role of miR-33b in lipid accumulation, the mimic of the miR-33b was transfected into HepG2 cells. RESULTS: We found that metformin reduces high glucose-induced lipid accumulation in HepG2 cells through inhibiting of SREBP1c and FAS and increasing the expression of CPT1 and CROT. Overexpression of miR-33b significantly prevented the decreasing effect of metformin on lipid content and intra and extra triglyceride levels. Importantly, miR-33b mimic inhibited the increasing effects of metformin on the expression of CPT1 and CROT. CONCLUSION: These findings suggest that metformin attenuates high glucose-induced lipid accumulation in HepG2 cell by downregulating the expression of miR-33b.

Surface Engineering Strategies to Enhance the In Situ Performance of Medical Devices Including Atomic Scale Engineering.

Decades of intense scientific research investigations clearly suggest that only a subset of a large number of metals, ceramics, polymers, composites, and nanomaterials are suitable as biomaterials for a growing number of biomedical devices and biomedical uses. However, biomaterials are prone to microbial infection due to Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), hepatitis, tuberculosis, human immunodeficiency virus (HIV), and many more. Hence, a range of surface engineering strategies are devised in order to achieve desired biocompatibility and antimicrobial performance in situ. Surface engineering strategies are a group of techniques that alter or modify the surface properties of the material in order to obtain a product with desired functionalities. There are two categories of surface engineering methods: conventional surface engineering methods (such as coating, bioactive coating, plasma spray coating, hydrothermal, lithography, shot peening, and electrophoretic deposition) and emerging surface engineering methods (laser treatment, robot laser treatment, electrospinning, electrospray, additive manufacturing, and radio frequency magnetron sputtering technique). Atomic-scale engineering, such as chemical vapor deposition, atomic layer etching, plasma immersion ion deposition, and atomic layer deposition, is a subsection of emerging technology that has demonstrated improved control and flexibility at finer length scales than compared to the conventional methods. With the advancements in technologies and the demand for even better control of biomaterial surfaces, research efforts in recent years are aimed at the atomic scale and molecular scale while incorporating functional agents in order to elicit optimal in situ performance. The functional agents include synthetic materials (monolithic ZnO, quaternary ammonium salts, silver nano-clusters, titanium dioxide, and graphene) and natural materials (chitosan, totarol, botanical extracts, and nisin). This review highlights the various strategies of surface engineering of biomaterial including their functional mechanism, applications, and shortcomings. Additionally, this review article emphasizes atomic scale engineering of biomaterials for fabricating antimicrobial biomaterials and explores their challenges.

Nanoscience and quantum science-led biocidal and antiviral strategies.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) caused the COVID-19 pandemic. According to the World Health Organization, this pandemic continues to be a serious threat to public health due to the worldwide spread of variants and their higher rate of transmissibility. A range of measures are necessary to slow the pandemic and save lives, which include constant evaluation and the careful adjustment of public-health responses augmented by medical treatments, vaccines and protective gear. It is hypothesized that nanostructured particulates underpinned by nanoscience and quantum science yield high-performing antiviral strategies, which can be applied in preventive, diagnostic, and therapeutic applications such as face masks, respirators, COVID test kits, vaccines, and drugs. This review is aimed at providing comprehensive and cohesive perspectives on various nanostructures that are suited to intensifying and amplifying the effectiveness of antiviral strategies. Growing scientific literature over the past eighteen months indicates that quantum dots, iron oxide, silicon oxide, polymeric and metallic nanoparticles have been employed in COVID-19 diagnostic assays, vaccines, and personal protective equipment (PPE). Quantum dots have displayed their suitability as more sensitive imaging probes in diagnostics and prognostics, and as controlled drug-release carriers that target the virus. Nanoscience and quantum science have assisted the design of advanced vaccine delivery since nanostructured materials are suited for antigen delivery, as mimics of viral structures and as adjuvants. Furthermore, the quantum science- and nanoscience-supported tailored functionalization of nanostructured materials offers insight and pathways to deal with future pandemics. This review seeks to illustrate several examples, and to explain the underpinning quantum science and nanoscience phenomena, which include wave functions, electrostatic interactions, van der Waals forces, thermal and electrodynamic fluctuations, dispersion forces, local field-enhancement effects, and the generation of reactive oxygen species (ROS). This review discusses how nanostructured materials are helpful in the detection, prevention, and treatment of the SARS-CoV-2 infection, other known viral infection diseases, and future pandemics.

Encapsulation of Pharmaceutical and Nutraceutical Active Ingredients Using Electrospinning Processes.

Electrospinning is an inexpensive and powerful method that employs a polymer solution and strong electric field to produce nanofibers. These can be applied in diverse biological and medical applications. Due to their large surface area, controllable surface functionalization and properties, and typically high biocompatibility electrospun nanofibers are recognized as promising materials for the manufacturing of drug delivery systems. Electrospinning offers the potential to formulate poorly soluble drugs as amorphous solid dispersions to improve solubility, bioavailability and targeting of drug release. It is also a successful strategy for the encapsulation of nutraceuticals. This review aims to briefly discuss the concept of electrospinning and recent progress in manufacturing electrospun drug delivery systems. It will further consider in detail the encapsulation of nutraceuticals, particularly probiotics.

pHEMA: An Overview for Biomedical Applications.

Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications.

Collagen-based biomaterials for biomedical applications.

Collagen is an insoluble fibrous protein that composes the extracellular matrix in animals. Although collagen has been used as a biomaterial since 1881, the properties and the complex structure of collagen are still extensive study subjects worldwide. In this article, several topics of importance for understanding collagen research are reviewed starting from its historical milestones, followed by the description of the collagen superfamily and its complex structures, with a focus on type I collagen. Subsequently, some of the superior properties of collagen-based biomaterials, such as biocompatibility, biodegradability, mechanical properties, and cell activities, are pinpointed. These properties make collagen applicable in biomedicine, such as wound healing, tissue engineering, surface coating of medical devices, and skin supplementation. Moreover, some antimicrobial strategies and the general host tissue responses regarding collagen as a biomaterial are presented. Finally, the current status and clinical application of the three-dimensional (3D) printing techniques for the fabrication of collagen-based scaffolds and the reconstruction of the human heart's constituents, such as capillary structures or even the entire organ, are discussed. Besides, an overall outlook for the future of this unique biomaterial is provided.

Cartilage Tissue and Therapeutic Strategies for Cartilage Repair.

High incidence of articular cartilage defects is still a major challenge in orthopedic and trauma surgery worldwide. It also has great socioeconomic effects as it is the major cause of disability in industrialized countries. This highlights the essential need for new treatments. Knowledge about the factors that have been implicated in the pathogenesis of cartilage diseases, including changes in the composition and structure of cartilaginous extracellular matrix (ECM), molecular factors and environmental signaling pathways could help the development of innovative therapeutic strategies. It is consensuses that the success of any technology aiming to repair chondral defects will be dependent upon its ability to produce tissues that most closely replicate the mechanical and biochemical properties of native cartilage. Increasing the knowledge about cartilage tissue and its molecular biomarkers could help find new and useful therapeutic approaches in cartilage damage. This review tries to describe cartilage tissue biology in detail and discuss different available therapeutic modalities with their pros and cons. New cartilage regeneration strategies and therapies, focusing on cellbased therapy and tissue engineering, and their underlying molecular and cellular bases will be pointed out as well.

Resveratrol Reduces Lipid Accumulation through Upregulating the Expression of MicroRNAs Regulating Fatty Acid Bet Oxidation in Liver Cells: Evidence from In-vivo and In-vitro Studies.

MicroRNAs have been shown to regulate lipogenesis in liver. The aim of the present study was to investigate whether the effects of resveratrol (RSV) on lipogenesis are associated with the changes in the expression of two miRNAs (miR-107 and miR-10b) that regulate lipogenic pathways. 30 wild type C57BL/6j male mice were randomly fed three diets: a standard chow diet (ND), a high fat diet (HFD, 60% fat) and the high fat diet supplemented with 0.4% RSV (HFD-RSV) for 16 weeks. HepG2 cells were treated with high glucose (33 mM) and RSV (20 µM) for 24 h. The expression of the genes and miRNAs were measured by real-time PCR. Triglyceride level was increased in the liver of mice and HepG2 cells. In both animal and In-vitro experiments, triglyceride level was significantly decreased in groups treated with RSV. The expression of the miR-107 and miR-10b was significantly upregulated in the liver of HFD mice, whereas HFD-RSV group demonstrated a significant lower expression of both miRNAs compared to HFD group. In addition, RSV treatment significantly upregulated the expression of CPT-1a and PPARα genes in the liver of HFD mice. Moreover, treatment with RSV could reduce the expression of miR-107 and miR-10b and increase the expression of CPT-1a and PPARα in HG-treated HepG2 cells. These evidence, as a whole, suggest that RSV could exert its anti-lipogenic effect partially through alterations in the expression of miR-107 and miR-10b in liver cells.

Smart Fortified PHBV-CS Biopolymer with ZnO-Ag Nanocomposites for Enhanced Shelf Life of Food Packaging.

Thymus vulgaris leaf extract was used as a stabilizer and reducing agent in the green, facile, and biomimetic hydrothermal decomposition reaction for the fabrication of zinc oxide-silver nanocomposites (ZnO-Ag NCs). The nanocomposite (NC) as an active agent was integrated into poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-chitosan (PHBV-CS) in a highly precise ratio of solvent mixture by ultrasonication without the aid of any coupling agent to fabricate the novel degradable biopolymer (BP) nanocomposite via solvent casting method to enhance the mechanical properties and antimicrobial activity and with the lowest immigration rate to improve the shelf life of poultry items. The ZnO-Ag NCs as a nanoactive agent in the food packaging preserved food safety by controlling its spoilage. The morphology, physical, mechanical, barrier, antibacterial, and migration properties of the nanocrystals were assessed via several characterization methods to show the enhancement of the prepared polymer in various aspects of properties. The NCs BP were used for potential sensory evaluation of chicken breast refrigerated over a period of 15 days. The data demonstrated that these bio-based nanocomposites show great antimicrobial activity that offers perspectives for the replacement of traditional petrochemical-based polymers currently used for food packaging of poultry items.

Novel Green Biomimetic Approach for Synthesis of ZnO-Ag Nanocomposite; Antimicrobial Activity against Food-borne Pathogen, Biocompatibility and Solar Photocatalysis.

A simple, eco-friendly, and biomimetic approach using Thymus vulgaris (T. vulgaris) leaf extract was developed for the formation of ZnO-Ag nanocomposites (NCs) without employing any stabilizer and a chemical surfactant. T. vulgaris leaf extract was used for the first time, in a novel approach, for green fabrication of ZnO-Ag NCs as a size based reducing agent via the hydrothermal method in a single step. Presence of phenols in T. vulgaris leaf extract has served as both reducing and capping agents that play a critical role in the production of ZnO-Ag NCs. The effect of silver nitrate concentration in the formation of ZnO-Ag NCs was studied. The in-vitro Antimicrobial activity of NCs displayed high antimicrobial potency on selective gram negative and positive foodborne pathogens. Antioxidant activity of ZnO-Ag NCs was evaluated via (2,2-diphenyl-1-picrylhydrazyl) DPPH method. Photocatalytic performance of ZnO-Ag NCs was appraised by degradation of phenol under natural sunlight, which exhibited efficient photocatalytic activity on phenol. Cytotoxicity of the NCs was evaluated using the haemolysis assay. Results of this study reveal that T. vulgaris leaf extract, containing phytochemicals, possess reducing property for ZnO-Ag NCs fabrication and the obtained ZnO-Ag NCs could be employed effectively for biological applications in food science. Therefore, the present study offers a promising way to achieve high-efficiency photocatalysis based on the hybrid structure of semiconductor/metal.

MCU-knockdown attenuates high glucose-induced inflammation through regulating MAPKs/NF-κB pathways and ROS production in HepG2 cells.

Mitochondrial Ca2+ is a key regulator of organelle physiology and the excessive increase in mitochondrial calcium is associated with the oxidative stress. In the present study, we investigated the molecular mechanisms linking mitochondrial calcium to inflammatory and coagulative responses in hepatocytes exposed to high glucose (HG) (33mM glucose). Treatment of HepG2 cells with HG for 24 h induced insulin resistance, as demonstrated by an impairment of insulin-stimulated Akt phosphorylation. HepG2 treatment with HG led to an increase in mitochondrial Ca2+ uptake, while cytosolic calcium remained unchanged. Inhibition of MCU by lentiviral-mediated shRNA prevented mitochondrial calcium uptake and downregulated the inflammatory (TNF-α, IL-6) and coagulative (PAI-1 and FGA) mRNA expression in HepG2 cells exposed to HG. The protection from HG-induced inflammation by MCU inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). Importantly, MCU inhibition in HepG2 cells abrogated the phosphorylation of p38, JNK and IKKα/IKKß in HG treated cells. Taken together, these data suggest that MCU inhibition may represent a promising therapy for prevention of deleterious effects of obesity and metabolic diseases.

High glucose induces inflammatory responses in HepG2 cells via the oxidative stress-mediated activation of NF-κB, and MAPK pathways in HepG2 cells.

OBJECTIVE: The aim of this study was to investigate the effects of high glucose (HG) on inflammation in HepG2 cells. METHODS: The molecular mechanisms linking HG to inflammation was assessed in HepG2 cells exposed to HG (33 mM). RESULTS: The results showed that HG significantly enhanced TNF-α, IL-6 and PAI-1 expression in HepG2 cells. Increased expression of cytokines was accompanied by enhanced phosphorylation of JNK, P38, ERK and IKKα/IKKß. In addition, JNK, ERK, P38 and NF-kB inhibitors could significantly attenuate HG-induced expression of TNF-α, IL-6 and PAI-1. Furthermore, HG could promote the generation of reactive oxygen species (ROS), while N-acetyl cysteine, a ROS scavenger, had an inhibitory effect on the expression of TNF-α, IL-6 and PAI-1 in HG-treated cells. CONCLUSIONS: Our results indicated that HG-induced inflammation is mediated through the generation of ROS and activation of the MAPKs and NF-kB signalling pathways in HepG2 cells.