scholarly journals Genetic and Functional Evaluation of the Role of FOXO1 in Antituberculosis Drug-Induced Hepatotoxicity

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jingwei Zhang ◽  
Lin Jiao ◽  
Jiajia Song ◽  
Tao Wu ◽  
Hao Bai ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Hepg2 Cells ◽  
Nuclear Translocation ◽  
Functional Evaluation ◽  
Antituberculosis Drug ◽  
Nucleotide Polymorphisms ◽  
Drug Induced ◽  
Cell Survival Rate ◽  
Foxo1 Gene

Background. The accumulation of the hepatotoxic substance protoporphyrin IX (PPIX) induced by aminolevulinate synthase 1 (ALAS1) activation is one of the important mechanisms of antituberculosis drug-induced hepatotoxicity (ATDH). Forkhead box protein O1 (FOXO1) may activate ALAS1 transcription. However, little is known about their roles in ATDH; we performed a study to determine the association between polymorphisms in the two genes and ATDH susceptibility. Then, we verified this possible association by cellular functional experiments. Materials and Methods. Tag single-nucleotide polymorphisms (TagSNPs) in the two genes were genotyped in 746 tuberculosis patients. The frequencies of the alleles, genotypes, genetic models, and haplotype distribution of the variants were compared between the case and control groups. L-02 cells and HepG2 cells were incubated with the indicated concentration of isoniazid (INH) and rifampicin (RIF) for the desired times, and then the expression levels of ALAS1 and FOXO1 mRNAs and proteins were detected. HepG2 cells were transiently transfected with FOXO1 siRNA to observe the effect of changes in the FOXO1 expression on the cell survival rate and ALAS1 expression. Results. The C allele at rs2755237 and the T allele at rs4435111 in the FOXO1 gene were associated with a decreased risk of ATDH. The expression of ALAS1 in both L-02 cells and HepG2 cells was increased by the coadministration of INH/RIF (600/200 μM) for 24 h. Although FOXO1 expression was reduced slightly by the same treatment, its content in the nucleus was significantly increased. However, the cell survival rate and ALAS1 expression level were not significantly altered by the downregulation of FOXO1 in HepG2 cells. Conclusions. Variants of the rs4435111 and rs2755237 loci in the FOXO1 gene were associated with susceptibility to ATDH. Coadministration of INH/RIF promoted the transfer of FOXO1 from the cytoplasm to the nucleus, but the functional significance of its nuclear translocation requires further verification.

A naphthalimide derivative can release COS and form H2S in a light-controlled manner and protect cells against ROS with real-time monitoring ability

The Analyst ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 3878-3884
Author(s):  
Wuyang Hua ◽  
Jian Zhao ◽  
Shaohua Gou
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Real Time ◽  
Uv Light ◽  
Real Time Monitoring ◽  
Cell Survival Rate

Triggered by UV light, the donor could release H2S to protect cells against the damage of ROS and prompt the cell survival rate, meanwhile turning on its fluorescence to be monitored in real time.

scholarly journals Survival Rate of Cells Sent by a Low Mechanical Load Tube Pump: The “Ring Pump”

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 447 ◽  
Author(s):  
Kaoru Uesugi ◽  
Keizo Nishiyama ◽  
Koki Hirai ◽  
Hiroaki Inoue ◽  
Yoichi Sakurai ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Saline Solution ◽  
Mechanical Load ◽  
Survival Rates ◽  
Cell Culture System ◽  
Large Size ◽  
Cell Survival Rate ◽  
Peristaltic Pumps ◽  
Phosphate Buffered Saline

A ring pump (RP) is a useful tool for microchannels and automated cell culturing. We have been developing RPs (a full-press ring pump, FRP; and a mid-press ring pump, MRP). However, damage to cells which were sent by the RP and the MRP was not investigated, and no other studies have compared the damage to cells between RPs and peristaltic pumps (PPs). Therefore, first, we evaluated the damage to cells that were sent by a small size FRP (s-FRP) and small size MRPs (s-MRPs; gap = 25 or 50 μm, respectively). “Small size” means that the s-FRP and the s-MRPs are suitable for microchannel-scale applications. The survival rate of cells sent by the s-MRPs was higher than those sent by the s-FRP, and less damage caused by the former. Second, we compared the survival rate of cells that were sent by a large size FRP (l-FRP), a large size MRP (l-MRP) (gap = 50 μm) and a PP. “Large size” means that the l-FRP and the l-MRP are suitable for automated cell culture system applications. We could not confirm any differences among the cell survival rates. On the other hand, when cells suspended in Dulbecco’s phosphate-buffered saline solution were circulated with the l-MRP (gap = 50 μm) and the PP, we confirmed a difference in cell survival rate, and less damage caused by the former.

Comparison of Effects of Curcumin and Nano-curcumin on the Survival of Human-Derived Mesenchymal Stem Cells: An Experimental Study

2020 ◽  
Vol 11 (2) ◽  
pp. 148-155
Author(s):  
Pinjari Hameeda ◽  
Sandeep Katti ◽  
Rajkishore Jammalamadugu ◽  
Kishore Bhatt ◽  
Malleswara Rao Peram ◽  
...  
Keyword(s):  
Stem Cells ◽  
Experimental Study ◽  
Mesenchymal Stem Cells ◽  
Survival Rate ◽  
Cell Viability ◽  
Cell Survival ◽  
Dependent Manner ◽  
Cell Survival Rate ◽  
Post Hoc ◽  
Dose Dependent

Aim: To evaluate and compare the effect of curcumin (CUR) and Nano-curcumin (N-CUR) on human-derived mesenchymal stem cells (MSCs) in a dose-dependent manner. Materials and Methods: An experimental study performed with putative MSCs from a total of five systemically healthy subjects with chronic periodontitis. These putative MSCs were isolated by cell culture and were further characterized and identified by colony-forming unit assay and immunocytochemical analysis using cell surface markers CD105, CD146, CD45 and CD73. The identified MSCs were treated with different doses of CUR and N-CUR, and compared with α-minimum essential medium (α -MEM) for its cell viability by performing MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay for 48 and 72 hr. The statistically analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test and Bonferroni’s post hoc test. Results: Compared to the α-MEM group, both CUR and N-CUR treated cells have shown significantly ( P = .029) higher survival rate at lower concentration (0.1 and 0.5 µM/L), at 48 hr incubation. However, there was no statistically significant difference between the CUR and N-CUR groups on cell survival rate at both 48 and 72 hr incubation. When compared between the concentrations of the same group, significantly higher cell viability ( P = .001) was observed at lower concentrations (0.1, 0.5 µM/L) in both test groups after incubation for 48 and 72 hr. Conclusion: Both CUR and N-CUR have a dose-dependent effect on human derived MSCs survival when incubated for 48 hr, whereas N-CUR shows increased cell survival rate even at 72 hr of incubation. Although, the cautious use of CUR and N-CUR at higher concentrations is recommended.

scholarly journals Biocompatible Parylene Neurocages for Action Potential Recording and Stimulation

2006 ◽  
Vol 926 ◽  
Author(s):  
Angela Tooker ◽  
Jon Erickson ◽  
Yu-Chong Tai ◽  
Jerry Pine
Keyword(s):  
Neural Networks ◽  
Survival Rate ◽  
Cell Survival ◽  
Action Potentials ◽  
Fabrication Process ◽  
Glass Substrates ◽  
Cell Survival Rate ◽  
Potential Recording

ABSTRACTParylene neurocages are biocompatible and very robust, making them ideally suited for studying neural networks. We present a design and fabrication process for building parylene neurocages for in vitro studies of neural networks. The fabrication process, on either silicon or glass substrates, incorporates electrodes into the neurocages to allow for stimulation and recording of action potentials. The resulting neurocages have a long-term cell survival rate of ∼50% and have proven to be 99% effective in trapping neurons.

Synergistic Suppression of Human Multiple Myeloma Cell Growth by the Natural Product TBL-12 in Combination with Low Doses of Velcade: Insight Into Mechanisms

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5109-5109
Author(s):  
Bhagavathi A Narayanan ◽  
Amitabha Mazumder
Keyword(s):  
Multiple Myeloma ◽  
Survival Rate ◽  
Side Effects ◽  
Cell Growth ◽  
Cell Survival ◽  
Treatment Efficacy ◽  
Low Doses ◽  
Myeloma Cells ◽  
Cell Survival Rate ◽  
Isobologram Analysis

Abstract Abstract 5109 Targeting Multiple Myeloma (MM) cells with potential natural agents could overcome the side effects of current treatment drugs while increasing the efficacy at very low doses. In this study we tested the efficacy of proteasome inhibitor Velcade (Bortezomib) with TBL-12, (an extract from Sea Cucumber, Unicorn Pacific Corporation) in human myeloma cells. Based on the findings from cell survival and proliferation assays we believe that as a single agent TBL-12 is effective in inducing cell growth inhibition with a dose of 100ug/ml in myeloma cells MM1, U266 and ARP1 cells and 200ug/ml in KMSI cells. We further examined the combined effect of Velcade with TBL-12 to test the hypothesis that a natural agent in combination with a pharmaceutical drug at low doses (but with different modes of action) can reduce toxicity while enhancing the treatment efficacy that may increase the survival rate. In this study we report the in vitro effect of low doses of Velcade in combination with TBL-12. We performed cell survival assays in MM1 and U266 cells using very low doses of Valcade ranging from 1–10ngs/ml in combination with an already established dose for TBL-12 (100ugs/ml) showed a time and dose dependent inhibitory effect on cell growth. We observed a cell survival rate that was reduced from 100 % to 30% at 48h and 20% at 72h (p<0.001) in both MM1 and U266 cells. These findings suggest the possibility of using very low doses of Velcade in combination with TBL-12 to be more effective and reduce the toxicity. Mechanistically, stimulation of MM cells with TNFa could trigger the activation of IL-6 and vasculendothelial growth factor (VEGF) and its receptors which will lead to progressive angiogenesis in preclinical models for myeloma. To address the effect of TBL-12 on angiogenesis, we conducted several independent assays by stimulating MM and U266 cells with TNFa or IL-6 for duration of 8h. First we determined the rate of cell survival in MM1 and U266 cells at different time points of 24, 48 and 72h in cells stimulated with TNFa (5ng/ml) followed by treatment with TBL-12 (100ug/ml) alone and in combination with Velcade. Although our data showed a 50% decrease in the cell survival rate by TBL-12 alone, we observed a significant decrease (70–80%, p<0.001)) in the cell survival rate in combination with Velcade in TNFa stimulated cells compared to the control. Co-culturing of myeloma cells MM1 and U266 with human umbilical vein endothelial cells (HUVEC) followed by treatment with an already established dose of TBL-12 showed a significant decrease (45%) in cells adhering to the surface of HUVEC determined by phase contrast and immunofluorescence microscopic observations. These findings suggest that TBL-12 may have potential to inhibit angiogenesis by targeting VEGF receptors in combination with Velcade at low doses (determined by isobologram analysis). Evidence from Western blot analysis of the MM1 and U266 cells treated with TBL-12 indicates a significant accumulation of caspase -3 and caspase -9 indicating the underlying targets of TBL-12 in mediating apoptosis. Findings on the isobologram analysis indicating synergistic effects exerted by TBL-12 in combination with Velcade on VEGFR1 receptor, and modulation of Bcl2 and Bax that is associated with apoptosis will be discussed during presentation. Overall findings from this study suggest the potential use of TBL-12 in combination with Velcade could improve treatment efficacy with reduced side effects related to high dose toxicity. Currently we are doing trials with TBL-12 at NYUCI and this data could form the basis for future trials. Disclosures: No relevant conflicts of interest to declare.

Hippophae rhamnoides L. polysaccharide enhances antioxidant enzyme activity, cytokine level, and related mRNA expression in intestinal porcine epithelial cells

2020 ◽  
Vol 100 (1) ◽  
pp. 193-204
Author(s):  
Lei Zhao ◽  
Mu-Yang Li ◽  
Shuai Su ◽  
Ting-Ting Geng ◽  
Hui Sun
Keyword(s):  
Survival Rate ◽  
Epithelial Cells ◽  
Cell Survival ◽  
Immunoglobulin M ◽  
Hippophae Rhamnoides ◽  
Control Group ◽  
Mrna Levels ◽  
Hippophaë Rhamnoides ◽  
Cell Survival Rate ◽  
Hippophae Rhamnoïdes L

Hippophae rhamnoides L. polysaccharide (HRP) has antioxidant and immunomodulatory actions. It has been reported that HRP can reduce the release of reactive oxygen species (ROS). The objective of this study was to investigate the effects of HRP on immunomodulatory and antioxidant activity in intestinal porcine jejunum epithelial (IPEC-J2) cells. Effective conditions of HRP (0, 200, 400, 600, and 800 μg mL−1) were evaluated by pretreatment of IPEC-J2 cells for 24 h. The results showed that pretreatment with 0–600 μg mL−1 of HRP enhanced cell survival rate, while more than 600 μg mL−1 posed a threat to IPEC-J2 cell viability and lowered cell survival rate (p < 0.05). In addition, results revealed that, compared with the control group, the treatment of IPEC-J2 cells with 200–600 μg mL−1 of HRP for 24 h decreased ROS, malondialdehyde, protein carbonyl levels, and cell apoptosis. Meanwhile, the levels of superoxide dismutase, glutathione peroxidase, interleukin-1 beta, interleukin-2, interleukin-6, interleukin-8, tumour necrosis factor-alpha were elevated, and enhanced relative mRNA levels were also shown in the IPEC-J2 cells. Both the contents of immunoglobulin M, immunoglobulin A, and immunoglobulin G elevated with the increases of HRP concentration (200, 400, and 600 μg mL−1), and an increase of catalase relative mRNA levels were also observed in IPEC-J2 cells. Data indicated that 600 μg mL−1 of HRP had a potent protective effect on IPEC-J2 cells. Taken together, these results suggested that HRP was effective in regulating intestinal epithelial cells in piglets.

Cell Survival Rate Assay

BIO-PROTOCOL ◽  
2012 ◽  
Vol 2 (12) ◽  
Author(s):  
FengZhi Liu
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Cell Survival Rate

Modified Gelatin-Based Cell Assembling Process Using Glycerin

2012 ◽  
Vol 476-478 ◽  
pp. 443-447
Author(s):  
Hai Xia Liu ◽  
Sheng Jie Li ◽  
Feng Lin ◽  
Yong Nian Yan
Keyword(s):  
Composite Materials ◽  
Survival Rate ◽  
Cell Survival ◽  
Cell Damage ◽  
Cell Assembly ◽  
Assembly Process ◽  
Cell Survival Rate ◽  
Assembly Technology ◽  
Cell Assembling

Cell assembly technology adopting the gelatin-based composite materials has found broad application in the field of disease mechanism research, drug development and organ reconstruction etc. But there are still several troublesome problems, such as the necessaries of high forming concentration of gelatin-based materials and the cell damage produced during extrusion. In view of existing situation, a modified gelatin-based cell assembling process using glycerin was brought forward. The results showed that adding 10% (v/v) glycerin to the existing gelatin-based composite materials, the cells inactivation effect under 4 °C or lower temperature environment can be reduced obviously, meanwhile, the glycerin has a compensatory effect of gelatin. It can significantly improve the forming temperature and the cell survival rate, get high cell survival rate even when the scanning speed is on 40 mm/s. In addition, the glycerin is easier to dissolve in culture medium in the tissue analog training process; it is more conducive to the rapid materials degradation, as well as cell proliferation and tissue regeneration. Therefore, modified gelatin-based cell assembly process with glycerin will be more widely used in tissue or organ in vitro assembly process.

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