BRL-3A Cells Research Articles

Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1.

Introduction: Paracetamol is a potent hepatotoxin and may cause severe acute hepatocellular injury. The present study was intended to assess the hepatoprotective potential of Caralluma umbellata Haw. (Asclepiadaceae) (C. umbellata ) against paracetamol-induced hepatotoxicity in vitro and in vivo experimental models. Methods: Preliminary analysis for antioxidant and hepatoprotective property was evaluated for methanolic (MCU), aqueous (ACU) and hydro methanolic (HCU) extracts of C. umbellata using in vitro cell-free antioxidant such as DPPH, ABTS, nitric oxide, lipid peroxidation models and cell-based hepatoprotective study using BRL3A cells. In vivo, hepatoprotective activity was studied in paracetamol treated male Wistar albino rats. Furthermore, molecular mechanism behind the protective effect of MCU was explored by RT PCR technique by utilizing cytochrome P450 (CYP) CYP2E1. Results: C. umbellata extracts especially, MCU showed a better antioxidant property. MCU offered significant dose-dependent protection against paracetamol-induced hepatic damage in both in vitro and in vivo assays by improving all the biochemical findings towards the normal range. In a mechanism-based study, MCU has offered significant down-regulation (p < 0.05) of CYP2E1. These findings were in line with the hepatoprotective activity findings where MCU showed significant protection. Conclusion: In conclusion, these findings suggest that MCU possess hepatoprotective activity. One of the possible mechanisms behind the protective effect of MCU is found to be inhibition of CYP2E1.

The novel protein C3orf43 accelerates hepatocyte proliferation

BackgroundOur previous study found that single-pass membrane protein with coiled-coil domains 1 (C3orf43; XM_006248472.3) was significantly upregulated in the proliferative phase during liver regeneration. This indicates that C3orf43 plays a vital role in liver cell proliferation. However, its physiological functions remains unclear.MethodsThe expressions of C3orf43 in BRL-3A cells transfected with C3orf43-siRNA (C3-siRNA) or overexpressing the vector plasmid pCDH-C3orf43 (pCDH-C3) were measured via RT-qPCR and western blot. Cell growth and proliferation were determined using MTT and flow cytometry. Cell proliferation-related gene expression was measured using RT-qPCR and western blot.ResultsIt was found that upregulation of C3orf43 by pCDH-C3 promoted hepatocyte proliferation, and inhibition of C3orf43 by C3-siRNA led to the reduction of cell proliferation. The results of qRT-PCR and western blot assay showed that the C3-siRNA group downregulated the expression of cell proliferation-related genes like JUN, MYC, CCND1 and CCNA2, and the pCDH-C3 group upregulated the expression of those genes.ConclusionThese findings reveal that C3orf43 may contribute to hepatocyte proliferation and may have the potential to promote liver repair and regeneration.

Serine peptidase inhibitor Kazal type I (SPINK1) promotes BRL-3A cell proliferation via p38, ERK, and JNK pathways.

Serine peptidase inhibitor Kazal type I (SPINK1) has the similar spatial structure as epidermal growth factor (EGF); EGF can interact with epidermal growth factor receptor (EGFR) to promote proliferation in different cell types. However, whether SPINK1 can interact with EGFR and further regulate the proliferation of hepatocytes in liver regeneration remains largely unknown. In this study, we investigated the role of SPINK1 in a rat liver hepatocyte line of BRL-3A in vitro. The results showed the upregulation of endogenous Spink1 (gene addition) significantly increased not only the cell viability, cell numbers in S and G2 /M phase, but also upregulated the genes/proteins expression related to cell proliferation and anti-apoptosis in BRL-3A. In contrast, the cell number in G1 phase and the expression of pro-apoptosis-related genes/proteins were significantly decreased. The similar results were observed when the cells were treated with exogenous rat recombinant SPINK1. Immunoblotting suggested SPINK1 can interact with EGFR. By Ingenuity Pathway Analysis software, the SPINK1 signalling pathway was built; the predicted read outs were validated by qRT-PCR and western blot; and the results showed that p38, ERK, and JNK pathways-related genes/proteins were involved in the cell proliferation upon the treatment of endogenous Spink1 and exogenous SPINK1. Collectively, SPINK1 can associate with EGFR to promote the expression of cell proliferation-related and anti-apoptosis-related genes/proteins; inhibit the expression of pro-apoptosis-related genes/proteins via p38, ERK, and JNK pathways; and consequently promote the proliferation of BRL-3A cells. For the first time, we demonstrated that SPINK1 can associate with EGFR to promote the proliferation of BRL-3A cells via p38, ERK, and JNK pathways. This work has direct implications on the underlying mechanism of SPINK1 in regulating hepatocytes proliferation in vivo and liver regeneration after partial hepatectomy.

Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups-its uptake, efflux, and location in a cell

Traditional amine terminated PAMAM dendrimers may be readily surface engineered by a facile one-pot conversion with dialkyl itaconate esters into 4-carbomethoxypyrrolidone terminated PAMAM (G=0-4) dendrimers. These terminated dendrimers are uniquely characterized by exhibiting blue fluorescence emissions (λexc=370nm, λmaxem=440nm). Thanks to this property they can be directly analyzed by confocal microscopy and flow cytometry without additional fluorescence labeling, treatment of dendrimers with chemicals or adjusting pH. These intrinsically fluorescent dendrimers were shown to be very effective for assessing important biological cell features such as cellular entry, intracellular trafficking/localization and efflux properties. For example, all tested cell lines (e.g., B14, BRL-3A, and mHippoE-18) rapidly accumulated PAMAM-pyrrolidone dendrimer. The BRL-3A cell line exhibited both cytoplasmic and nuclear localization patterns; whereas in B14 cells and mHippoE-18 cells, the blue dendrimer fluorescence could only be detected in intracellular endosome-like structures. The dendrimer was observed to be released from all three cell lines during the first 24h; however, efflux was substantially slower from the B-14 cell line. The highest efflux rate was observed for the mHippoE-18 cells. This first successful biological experiment opens a broad spectrum of using these dendrimers as new bioimaging agents for extensive biological cell characterizations.

The novel protein C9orf116 promotes rat liver cell line BRL-3A proliferation.

Our previous study has proved that the chromosome 9 open reading frame 116 (C9orf116) (NM_001106564.1) was significantly up-regulated in the proliferation phase of liver regeneration. To study its possible physiological function, we analyzed the effect of C9orf116 on BRL-3A cells via over-expression and interference technique. MTT results showed that the cell viability of the interference group was significantly lower than the control group at 48h after transfection (P<0.05), whereas it was significantly higher in the over-expression group (P<0.05). The flow cytometry results showed that C9orf116 knockdown or over-expression had little effect on BRL-3A cell apoptosis. However, the number of cells in division phase (G2/M) was significantly reduced in the interference group (P<0.05), but significantly increased in the over-expression group (P<0.01). Furthermore, the expressions of cell proliferation-related genes CCNA2, CCND1 and MYC both at mRNA and protein levels were down-regulated in the interference group and up-regulated in the over-expression group. Therefore, we concluded that C9orf116 may promote cell proliferation by modulating cell cycle transition and the expression of key genes CCNA2, CCND1 and MYC in BRL-3A cells.

Upregulation of NM23-E2 accelerates the liver regeneration after 40% decreased-size liver transplantation in rats

BackgroundPotential of liver regeneration after living-donor liver transplantation is closely associated with the recipient's prognosis, whereas exogenous gene might regulate the liver regeneration progress. NM23 is a multifunctional gene, which inhibits tumor metastasis and regulates cell proliferation, differentiation, development, and apoptosis; however, there is little research about NM23 in promoting liver cell proliferation. MethodsTo investigate the effect of NM23-E2 on the liver cell proliferation, the NM23-E2 overexpression vector or negative control vector was transfected into BRL-3A cells and donor liver, respectively. NM23-E2, Cyclin D1, and PCNA expression levels in BRL-3A cells and liver tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Cell Counting Kit-8 was used to detect cell proliferation and flow cytometry for investigating cell cycle. The liver regeneration rate was determined by calculating (regenerated-liver weight of recipient − liver weight of donor/liver weight of donor) × 100%. ResultsNM23-E2 overexpression increased the NM23-E2, Cyclin D1, and PCNA levels significantly in BRL-3A cells and liver tissues (P < 0.05). The number of S phase cells was more than that of negative control group, and cell proliferation rate was higher than that of the control group in BRL-3A cells markedly (P < 0.05). Moreover, the liver regeneration rate in the NM23-E2 overexpression group was also higher than that in negative control group on postoperative day 1, day 3, day 5, and day 7. ConclusionsOverexpression of NM23-E2 can increase Cyclin D1 and PCNA expression, shorten cell cycle, and thereby promoting the proliferation of liver cells and accelerating the regeneration of liver after 40% decreased-size rat liver transplantation.

Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway

The TLR4/NF-κB pathway had important roles in hepatic ischemia/reperfusion (I/R) injury. In this study, we reported a protective effect of curcumin against hepatic I/R injury via TLR4/NF-κB pathway. Curcumin significantly inhibited cell apoptosis, and decreased levels of LDH and production of TNF-a, IL-1b, and IL-6 in the cell supernatant. In addition, curcumin ameliorated elevated TLR4 and NF-κB caused by hypoxia/reoxygenation stimulation in BRL-3A cells. In vivo assays revealed that curcumin reduce levels of ALT and AST, and reversed TLR4/NF-κB signaling pathway caused by hepatic I/R stimulation in liver tissues. These results suggested that curcumin ameliorates hepatic I/R injury, which may be mediated in part via the TLR4/NF-κB signaling pathway.

Magnesium isoglycyrrhizinate blocks fructose-induced hepatic NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder

Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels. Furthermore, magnesium isoglycyrrhizinate modulated lipid metabolism-related genes characterized by up-regulating peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase-1 (CPT-1), and down-regulating sensor for fatty acids to control-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of fructose-fed rats, resulting in the reduction of triglyceride and total cholesterol levels. These effective actions were further confirmed in fructose-exposed BRL-3A and HepG2 cells. The molecular mechanisms underpinning these observations suggest that magnesium isoglycyrrhizinate may inhibit NF-κB/NLRP3 inflammasome activation to reduce immunological-inflammatory response, which in turn may prevent liver lipid metabolic disorder and accumulation under high fructose condition. Thus, blockade of NF-κB/NLRP3 inflammasome activation and lipid metabolism disorder by magnesium isoglycyrrhizinate may be the potential therapeutic approach for improving fructose-induced liver injury with metabolic syndrome in clinic.

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway.

Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats.

Valorization of Dacryodes rostrata fruit through the characterization of its oil

Dacryodes rostrata (kembayau) is an important food and oil resource for local communities in Borneo, but it is not commonly known to wider community. The objective of this work is to valorize kembayau fruit by evaluating the characteristics of the oil from the fruit. In this study, the physicochemical characteristics and the lipophilic essential nutrient; the fatty acid composition, vitamin E and beta-carotene content of oils obtained from the peel, pulp and seeds of kembayau fruits were studied. The pulp of the kembayau fruit contained highest proportion of oil, followed by peel and seed. Kembayau fruit contained vitamin E and had trace amount of beta-carotene. Besides, kembayau fruit oils were not toxic to BRL3A cells, provided hepatoprotection and reversed lipid peroxidation in paracetamol-induced toxicity. Our results suggest that kembayau can be a potential source for cooking oil as the physicochemical characteristics are comparable with commercial source such as oil palm.

Effects of Lonicera caerulea berry extract on lipopolysaccharide-induced toxicity in rat liver cells: Antioxidant, anti-inflammatory, and anti-apoptotic activities

Lonicera caerulea L. berry extract has antioxidant and anti-inflammatory properties. The mechanism underlying the inhibitory effect of L. caerulea berry extract on lipopolysaccharide (LPS)-induced toxicity in BRL-3A cells was investigated in this study. It was observed that post-treatment with L. caerulea berry extract inhibited LPS-elicited decreases in catalase and superoxide dismutase activities, total antioxidant capacity, acetylcholinesterase activity, the mRNA expression levels of interleukin-10, and the protein expressions of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma-2. Furthermore, the extract significantly reduced LPS-induced increases in the activities of aspartate aminotransferase and alanine aminotransferase, the mRNA expressions of nuclear factor-kappa B and tumour necrosis factor-alpha, and the protein expressions of caspase-3, cleaved caspase-3, cleaved PARP, and Bax. Moreover, the extract suppressed LPS-induced apoptosis of BRL-3A cells. Taken together, the L. caerulea berry extract attenuates LPS-induced liver toxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways. Additionally, cyanidin-3-glucoside contributes more to these activities of the extract.

Methamphetamine induces hepatotoxicity via inhibiting cell division, arresting cell cycle and activating apoptosis: In vivo and in vitro studies

Methamphetamine (METH) resulted in acute hepatic injury. However, the underlying mechanisms have not been fully clarified. In the present study, rats were treated with METH (15 mg/kg B.W.) for 8 injections (i.p.), and the levels of alanine transaminase, asparatate transaminase and ammonia in serum were significantly elevated over those in the control group, suggesting hepatic injury, which was evidenced by histopathological observation. Analysis of the liver tissues with microarray revealed differential expressions of a total of 332 genes in METH-treated rats. According to the GO and KEGG annotations, a large number of down-regulated cell cycle genes were screened out, suggesting that METH induced cell cycle arrest and deficient of cell cycle checkpoint. Related genes and proteins were confirmed by RT-qPCR and western blotting in rat livers, respectively. Moreover, treatment of Brl-3A cells with METH caused significant cytotoxic response and marked cell cycle arrest. Furthermore, overexpressions of Cidea, cleaved caspase 3 and PARP 1 in METH-treated rats indicated activation of apoptosis, while its inhibition alleviated cell death in Brl-3A cells, suggesting that activation of apoptosis took an important role in METH-induced hepatotoxicity. Taken together, the present study demonstrates that METH induced hepatotoxicity via inducing cell cycle arrest and activating apoptosis.

Effects of gap junction intercellular communication on the docetaxel-induced cytotoxicity in rat hepatocytes

The effect of gap junction intercellular communication (GJIC) on docetaxel-induced hepatotoxicity and its underlying mechanisms are largely unknown. The present study involved investigating the effect of downregulating GJs derived from connexin (Cx) 32 in BRL-3A cells by three different mechanisms: Using a low-density culture; suppression of Cx32 using small interfering RNA; and use of the chemical inhibitor 2‑aminoethoxydiphenyl borate (2‑APB), all of which led to attenuated docetaxel hepatotoxicity. In order to investigate the relevant mechanisms involved, apoptosis and caspase activities of BRL‑3A cells were determined. The increase of apoptosis and the activation of caspase‑3 and caspase‑9, but not caspase-8, were detected following cell exposure with docetaxel, demonstrating that the mitochondrial‑mediated apoptosis pathway is largely responsible for docetaxel hepatotoxicity. However, reduced apoptosis and caspase‑3, and ‑9 activities were observed following docetaxel application when BRL‑3A GJIC was deficient from the knockdown of Cx32 expression or pretreatment with 2‑APB. These observations illustrate that GJs are important in docetaxel-induced hepatotoxicity. Furthermore, inhibition of GJIC could prevent amplification of toxicity to docetaxel. Due to GJIC blockage, this hepatoprotection was associated, in part, with decreasing apoptosis of BRL‑3A cells through the mitochondrial pathway. The present study provides evidence for potential therapeutic targets for the treatment of docetaxel-induced liver injury.

Standardisation and in Vitro Evaluation of Flavonide Containing Medicinal Plants for its Hepatoprotective Activity - Review Article

A review article confirming the hepatoprotective activity done in-vitro using BRL-3A cell lines for five plants naming P.amarus, C.asiatica, E.alba, T.cordifolia and R.communis based on the substantial data of preliminary phytochemical estimation revealing good phenol and flavonoid content; proved to have effective hepatoprotective activity supported with HPTLC elucidation justifies that P.amarus and C.asiatica endowes the hepatoprotective activity and could further be used for the formulation (poly herbal). All the given plant extract concentrations ranging from 62.5 μg/ml - 250 μg/ml were studied, using 1% CCl 4 as toxicant. All the extracts showed considerable protectively against CCI 4 induced toxicity in BRL-3A cells. All the biochemical parameters were estimated and compared with that of the control. In this study an innovator product (Liv-52, Himalaya) has been used along with the tests extracts. This innovator product showed very good restoration of enzyme levels to normal.

Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions.

ObjectivesThe cytotoxicity induced by cobalt ions (Co2+) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co2+ and Co-NPs on liver cells, and explain further the potential mechanisms.MethodsCo-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co2+ or Co-NPs treatment.ResultsResults showed cytotoxic effects of Co2+ and Co-NPs were dependent upon time and dosage, and the cytotoxicity of Co-NPs was greater than that of Co2+. In addition, Co-NPs elicited a significant (p < 0.05) reduction in cell viability with a concomitant increase in lactic dehydrogenase release, reactive oxygen species generation, IL-8 mRNA expression, Bax/Bcl-2 mRNA expression and DNA damage after 24 hours of exposure.ConclusionCo-NPs induced greater cytotoxicity and genotoxicity in BRL-3A cells than Co2+. Cell membrane damage, oxidative stress, immune inflammation and DNA damage may play an important role in the effects of Co-NPs on liver cells.Cite this article: Y. K. Liu, X. X. Deng, H.L. Yang. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions. Bone Joint Res 2016;5:461–469. DOI: 10.1302/2046-3758.510.BJR-2016-0016.R1.

Apoptosis induced by NaYF4:Eu3+ nanoparticles in liver cells via mitochondria damage dependent pathway

As lanthanide-doped sodium yttrium flouride (NaYF4) nanoparticles have great potential in biomedical applications, their biosafety is important and has attracted significant attention. In the present work, three different sized NaYF4:Eu3+ nanoparticles have been prepared. Liver BRL 3A cell was used as a cell model to evaluate their biological effects. Cell viability and apoptosis assays were used to confirm the cytotoxicity induced by NaYF4:Eu3+ NPs. Apart from the elevated malondialdehyde (MDA), the decrease of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) activity indicated reactive oxygen species (ROS) generation, which were associated with oxidative damage. The decrease of mitochondrial membrane potential (MMP) value demonstrated the occurrence of mitochondria damage. Then, release of cytochrome c from mitochondria and activation of caspase-3 confirmed that NaYF4:Eu3+ NPs induced apoptosis was mitochondria damage-dependent.

Corosolic acid protects hepatocytes against ethanol-induced damage by modulating mitogen-activated protein kinases and activating autophagy

The reactive oxygen species(ROS)/mitogen-activated protein kinase (MAPK) destroyed autophagy and the reactive oxygen species/mitogen-activated protein kinase (MAPK) pathway are considered closely related to ethanol-induced hepatocellular injury. Previous work indicated that corosolic acid, the natural extracts of leaves of the banaba tree, Lagerstroemia speciosa L., could protect the liver against ethanol-induced damage, but the underlying mechanism is unclear. In the study we found that corosolic acid significantly inhibited ethanol-induced apoptosis, increased level of tumor necrosis factor-α(TNF-α) and reactive oxygen species accumulation in vitro. Corosolic acid inhibited ethanol-activated p38 and c-Jun N-terminal kinase MAPK signaling in BRL-3A and HepG2 cells as well as in experimental rats. Corosolic acid restored the ethanol-suppressed expression of autophagy-related genes, including beclin-1 and the ratio of microtubule-associated protein light chain 3II/I (LC3II/I) via AMP-activated protein kinase (AMPK) activation both in vitro and in vivo. In experimental rats, corosolic acid ameliorated the detrimental histopathological findings. Corosolic acid may protect the liver against ethanol-induced injury by modulation of MAPK signaling and autophagy activation. These findings suggested that corosolic acid might be a promising agent in treatment of alcoholic liver diseases.

Mitochondria-Mediated Protein Regulation Mechanism of Polymorphs-Dependent Inhibition of Nanoselenium on Cancer Cells.

The present study was (i) to prepare two types of selenium nanoparticles, namely an amorphous form of selenium quantum dots (A-SeQDs) and a crystalline form of selenium quantum dots (C-SeQDs); and (ii) to investigate the nano-bio interactions of A-SeQDs and C-SeQDs in MCF-7, HepG2, HeLa, NIH/3T3, L929 cells and BRL-3A cells. It was found that A-SeQDs could induce the mitochondria-mediated apoptosis, necrosis and death of cells, while C-SeQDs had much weaker effects. This polymorphs-dependent anti-proliferative activity of nano-selenium was scarcely reported. Further investigation demonstrated that A-SeQDs could differentially regulate 61 proteins and several pathways related to stress response, protein synthesis, cell migration and cell cycle, including “p38 MAPK Signaling”, “p53 Signaling”, “14-3-3-mediated Signaling”, “p70S6K Signaling” and “Protein Ubiquitination Pathway”. This was the first report to demonstrate the involvement of protein synthesis and post-translational modification pathways in the anti-proliferative activity associated with NMs. Compared with previously fragmentary studies, this study use a nanomics approach combining bioinformatics and proteomics to systematically investigate the nano-bio interactions of selenium nanoparticles in cancer cells.

Toxicity assessment of engineered Mn–ZnS quantum dots in vitro

In recent years, the Mn-doped ZnS quantum dots (QDs) have been found to be excellent materials for fluorescence imaging of cells and for the detection of molecules such as folic acid, acetone etc. The fluorescence efficiency of this particular probe is due to the changes occurred in the electronic states of Mn and ZnS by means of doping. However, this report deals with the negative shades of Mn doping onto ZnS QDs as the formed Mn–ZnS nanocomposite is investigated to produce the Mn-induced oxidative stress that can be lethal to the tested cells in vitro. For that, we first synthesized Mn2+-doped ZnS nanocrystals by the co-precipitation method and the physical characterization was performed by means of HRTEM, EDAX, FTIR, XRD and fluorescence spectroscopies. Following that, we tested for the toxicity effects of Mn–ZnS QDs formed at room temperature by the co-precipitation method with BRL 3A cells of hepatic tissue of rat origin. The formed QDs investigated to show significant levels of toxicity toward the cells at 100 µg/mL concentration and over an exposure period of 16 h. Further, the cells also investigated to generate the reactive oxygen species which is further responsible for the fragmentation of DNA and reduction in mitochondrial transmembrane potentials. From the analysis of results, we believe that this report of its kind provides a preliminary piece of information toward the designing and applicability of Mn-containing compounds to biomedical sector due to its severe oxidative stress effect.

Effect of fluid shear stress on proliferation of immortalized rats BRL-3A liver cell lines

Objective To investgate the effect of shear stress on proliferation of immortalized rat BRL-3A liver cell lines. Methods Cell culture device which could load with fluid shear stress was built, in which the immortalized rat BRL-3A liver cell lines were cultured. The experiment was divided into group A (added hepatocyte growth factor (HGF)) and group B (did not add HGF), in each group 0、12 dyn/cm2 and 24 dyn/cm2 fluid shear stress was loaded separately. Then the cell proliferation dynamics was detected by direct cell counting or cell counting kit-8 (CCK-8) technology in 12, 24, 48, 168 h. Results Without loading fluid shear stress, the proliferation of group B was better than group A; the higher the fluid shear stress was loaded, the more cells proliferated; When loaded the same scale fluid shear stress at the same time point, the proliferation of group B was better than group A (P<0.05). With loading fluid shear stress of 24 dyn/cm2 at the 24 h time point, all groups reached the peak of cell proliferation, in which group B was still better than Group A(cell counting was (15.93±2.00)×106 cells in group B and (10.73±2.54)×106 cells in group A, as well as A of CCK-8 was 3.09±0.40 in group B and 2.04±0.51 in group A respectively (P<0.05); The cell proliferation dropped gradually during 24-72 h, but it still higher than the group which without loading fluid shear stress (P<0.05), it got close to or a little higher than the non-stress group at 168 h time point. Conclusion Fluid shear stress could promote the proliferation of immortalized rats BRL-3A liver cell lines, the effect of cell proliferation was more apparent under the interaction of physical and chemical factors (fluid shear stress combined with HGF). Key words: Liver regeneration; Immortalized rats BRL-3A liver cell lines; Fluid shear stress; Hepatocyte growth factor