Publications by authors named "Shanshan Ran"

4 Publications

  • Page 1 of 1

JAK2/STAT3 in role of arsenic-induced cell proliferation: a systematic review and meta-analysis.

Rev Environ Health 2021 Jul 29. Epub 2021 Jul 29.

Department of Public Health, College of Medicine, Shihezi University, Shihezi, Xinjiang, China.

Objectives: Malignant cell proliferation is one of the important mechanisms of arsenic poisoning. A large number of studies have shown that STAT3 plays an important role in cell malignant proliferation, but there are still many contradictions in the effect of arsenic on JAK2/STAT3. This study aims to explore the role of JAK2/STAT3 in arsenic-induced cell proliferation.

Methods: By taking normal cells as the research object and using Standard Mean Difference (SMD) as the effect size, meta-analysis was used to explore the effect of arsenic on JAK2/STAT3. Then, the dose-effect Meta was used to further clarify the dose-effect relationship of arsenic on JAK2/STAT3.

Results: Through meta-analysis, this study found that arsenic could promote the phosphorylation of STAT3 (SMD=4.21, 95%CI [1.05, 7.37]), and increase IL-6 and p-JAK2, Vimentin, VEGF expression levels, thereby inducing malignant cell proliferation. In addition, this study also found that arsenic exposure dose (<5 μmol m), time(<24 h) and cell type were important sources of heterogeneity in the process of exploring the effects of arsenic on p-STAT3, IL-6 and p-JAK2. Dose-effect relationship meta-analysis results showed that arsenic exposure significantly increased the expression level of IL-6. When the arsenic exposure concentration was less than 7 μmol m, the expression level of p-JAK2 upregulated significantly as the arsenic exposure concentration gradually increasing. Moreover, the expression level of p-STAT3 elevated significantly with the gradual increase of the arsenic concentration under 5 μmol m of arsenic exposure, but the expression level of p-STAT3 gradually decreases when the concentration is greater than 5 μmol m.

Conclusions: Exposure to low dose of arsenic could promote the expression of JAK2/STAT3 and induce the malignant proliferation of cells through upregulating IL-6, and there was dose-effect relationship among them.
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http://dx.doi.org/10.1515/reveh-2021-0051DOI Listing
July 2021

CX3CR1 deficiency aggravates brain white matter injury and affects expression of the CD36/15LO/NR4A1 signal.

Biochem Biophys Res Commun 2021 04 1;549:47-53. Epub 2021 Mar 1.

Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objective: To study the effects of CX3CR1 on white matter injury, neurofunction, recognition, and expression of the CD36/15LO/NR4A1 signal in mice with traumatic brain injury (TBI).

Methods: CX3CR1, CX3CR1 and C57BL/6 male mice were randomly divided into 3 groups. We used a controlled cortical impact (CCI) to establish a TBI model and T2wt MRI to detect the TBI lesion. FA and DTI allowed for quantitative evaluation of the structural integrity of white matter tracts. Several behavior tests were used to investigate nerve function; a computer-based tracing system was used to trace and analyze dendrites and cell bodies of microglia and astrocytes in the peri-lesional brain areas. We also used RT-PCR and western blot to detect the effect of CX3CL1/CX3CR1 axis on CD36/15LO/NR4A1 signal.

Results: The fractional anisotropy (FA) at the corpus callosum area of brain was decreased at 3 days post TBI, the average lesion volume CX3CR1 group was increased, and the neurologic deficit scores of mice of Cx3Cr1 and wild-type groups were significantly increased compared to Cx3Cr1 group mice. In the Corner turn test, TBI induced impairments in forelimb function that were more severe than Cx3Cr11 and wild-type TBI mice. We operated the Y-maze at 3 days post-TBI and the NOR test at 28 days after TBI. There was a significant TBI effect induced in decreased percentage entries into the novel arm in Cx3Cr1 and wild-type TBI mice, compared with Cx3Cr1; Cx3Cr1. Wild-type mice showed decreased exploration time in new objects compared with Cx3Cr1. Those two behavior tests demonstrated that Cx3Cr1 knock-out increased the damage caused by TBI to memory. In the tail suspension and force swimming tests, there was no significant difference between those three groups. CD36 increased in Cx3Cr1 compared with the other three groups at 3 days after TBI. TBI inhibited the expression of NR4A1 at 3 d after damage. Cx3Cr1 deficiency can induce high expression of 15LO, this was unaffected by TBI.

Conclusion: CX3CR1 deletion can enhance white matter injury. It increased the expression of CD36 and 15LO and increased expression of NR4A1. The lack of CX3CR1 can affect the recovery of nerve function.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.053DOI Listing
April 2021

A Systematic Review of the Various Effect of Arsenic on Glutathione Synthesis In Vitro and In Vivo.

Biomed Res Int 2020 28;2020:9414196. Epub 2020 Jul 28.

School of Public Health, Capital Medical University, Beijing, China.

Background: Arsenic is a toxic metalloid widely present in nature, and arsenic poisoning in drinking water is a serious global public problem. Glutathione is an important reducing agent that inhibits arsenic-induced oxidative stress and participates in arsenic methylation metabolism. Therefore, glutathione plays an important role in regulating arsenic toxicity. In recent years, a large number of studies have shown that arsenic can regulate glutathione synthesis in many ways, but there are many contradictions in the research results. At present, the mechanism of the effect of arsenic on glutathione synthesis has not been elucidated.

Objective: We will conduct a meta-analysis to illustrate the effects of arsenic on GSH synthesis precursors Glu, Cys, Gly, and rate-limiting enzyme -GCS in mammalian models, as well as the regulation of p38/Nrf2 of -GCS subunit GCLC, and further explore the molecular mechanism of arsenic affecting glutathione synthesis.

Results: This meta-analysis included 30 studies in vivo and 58 studies in vitro, among which in vivo studies showed that arsenic exposure could reduce the contents of GSH (SMD = -2.86, 95% CI (-4.45, -1.27)), Glu (SMD = -1.11, 95% CI (-2.20,-0.02)), and Cys (SMD = -1.48, 95% CI (-2.63, -0.33)), with no statistically significant difference in p38/Nrf2, GCLC, and GCLM. In vitro studies showed that arsenic exposure increased intracellular GSH content (SMD = 1.87, 95% CI (0.18, 3.56)) and promoted the expression of p-p38 (SMD = 4.19, 95% CI (2.34, 6.05)), Nrf2 (SMD = 4.60, 95% CI (2.34, 6.86)), and GCLC (SMD = 1.32, 95% CI (0.23, 2.41)); the p38 inhibitor inhibited the expression of Nrf2 (SMD = -1.27, 95% CI (-2.46, -0.09)) and GCLC (SMD = -5.37, 95% CI (-5.37, -2.20)); siNrf2 inhibited the expression of GCLC, and BSO inhibited the synthesis of GSH. There is a dose-dependent relationship between the effects of exposure on GSH in vitro. These indicate the difference between in vivo and in vitro studies of the effect of arsenic on glutathione synthesis. In vivo studies have shown that arsenic exposure can reduce glutamate and cysteine levels and inhibit glutathione synthesis, while in vitro studies have shown that chronic low-dose arsenic exposure can activate the p38/Nrf2 pathway, upregulate GCLC expression, and promote glutathione synthesis.
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http://dx.doi.org/10.1155/2020/9414196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411465PMC
April 2021

The Mechanism of Trivalent Inorganic Arsenic on HIF-1α: a Systematic Review and Meta-analysis.

Biol Trace Elem Res 2020 Dec 2;198(2):449-463. Epub 2020 Mar 2.

Department of Public Health, School of Medicine, Shihezi University, Shihezi, 832000, Xinjiang, China.

The purpose of our study was to investigate the role of hypoxia-inducible factor-1α (HIF-1α) in arsenic-induced carcinogenesis. We included 39 articles for meta-analysis. The results showed that low-dose exposure to arsenic (≤ 10 μmol/L) could promote the expression of phosphatidylinositol 3-kinase (PI3K) and phosphorylation-protein kinase B (p-AKT). High-dose arsenic exposure (> 10 μmol/L) promoted the expression of PI3K, HIF-1α, vascular endothelial growth factor (VEGF), and p38MAPK (P38). Acute arsenic exposure (< 24 h) promoted the expression of PI3K, HIF-1α, and VEGF. Chronic arsenic exposure (≥ 24 h) promoted the expression of PI3K, p-AKT, and P38. Moreover, for normal tissue-derived cells, arsenic could induce the increased expression of PI3K, p-AKT, HIF-1α, and VEGF. For tumor tissue-derived cells, arsenic could induce the expression of PI3K, p-AKT, and P38. We found that arsenic exposure could activate the PI3K/AKT pathway, further induce the high expression of HIF-1α, and then upregulate the levels of miRNA-21 and VEGF, promote the expression of proliferating cell nuclear antigen (PCNA), and ultimately lead to malignant cell proliferation. Our findings indicated that arsenic could increase the expression of HIF-1α by activating the PI3K/AKT pathway and eventually induce malignant cell proliferation.
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http://dx.doi.org/10.1007/s12011-020-02087-xDOI Listing
December 2020
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