Inhibition of macrophage migration inhibitory factor alleviates LPS-induced inflammation response of HEI-OC1 cells via suppressing NF-κB signaling.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is acute and unexplained. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine in several inflammatory diseases. However, its role in SSNHL remains elusive. METHODS: Lipopolysaccharide (LPS) was used to induce the inflammatory response of murine auditory cells, HEI-OC1. Silencing of MIF in HEI-OC1 cells was achieved by transfection of short hairpin RNA against MIF. 740Y-P and IMD0354 were used to stimulate the PI3K pathway and suppress the NF-κB pathway, respectively. RT-qPCR and western blotting were used to examine MIF and cyclooxygenase 2 (COX2) expression in LPS-treated HEI-OC1 cells. ELISA was employed to assess prostaglandin E2 (PGE2) concentrations. RESULTS: MIF was upregulated in LPS-treated HEI-OC1 cells. MIF knockdown reduced PGE2 synthesis and COX2 expression in LPS-treated HEI-OC1 cells. Moreover, MIF knockdown suppressed activation of the PI3K/AKT and NF-κB pathway in LPS-treated HEI-OC1 cells. Additionally, inhibition of MIF decreased PGE2 production and COX2 expression via inactivation of the NF-κB pathway. CONCLUSION: Inhibition of MIF alleviated LPS-induced inflammation in HEI-OC1 cells via inactivating the NF-κB signaling, which might provide a better understanding for SSNHL development.

MIF protects against oxygen-glucose deprivation-induced ototoxicity in HEI-OC1 cochlear cells by enhancement of Akt-Nrf2-HO-1 pathway.

Ischemia and oxidative stress play crucial roles in the pathophysiology of sudden sensorineural hearing loss (SSNHL). Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and serves an important role in hearing function. The present study was designed to evaluate the effect of MIF on oxygen-glucose deprivation (OGD)-induced ototoxicity and to elucidate its molecular mechanism. In HEI-OC1 auditory cells, OGD reduced cell viability and increased supernatant lactate dehydrogenase (LDH) and MIF in a time-dependent manner. However, the reduced cell viability exerted by OGD was attenuated by antioxidant and MIF. Luciferase reporter assay demonstrated that MIF could activate NF-E2-related factor 2 (Nrf2), and real-time PCR showed increased mRNA expressions of Nrf2 and two Nrf2-responsive genes, including heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). MIF also suppressed oxidative stress induced by OGD, as demonstrated by decreased MDA and increased GSH in cellular supernatant. Inhibition of Nrf2 using siRNA suppressed HO-1 protein expression, the protective effect on OGD-induced injury and decrease in oxidative stress by MIF. Moreover, MIF prevented OGD-induced reduction of Akt1 phosphorylation at Ser473. LY294002, an inhibitor of PI3K/Akt signaling, attenuated the enhancement of Nrf2 protein and protective effect of MIF in OGD-treated cochlear cells. We demonstrate that MIF protects cochlear cells against OGD-induced injury through activation of Akt-Nrf2-HO-1 pathway.

[Retracted] MicroRNA­425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma­derived growth factor.

[This retracts the article DOI: 10.3892/ol.2018.8128.].

An International Comparative Study on the Resilience of Urban Communities after COVID-19 Pandemic: A One-Year Case Study between Lanzhou, China and Sarajevo, Bosnia and Herzegovina.

After the prevailing of the COVID-19 pandemic, urban communities around the world took initiatives to bring their cities back to life. In this research, 45 indicators and 55 elements were selected to make comparisons between urban communities in Lanzhou, China and Sarajevo, Bosnia and Herzegovina from five dimensions of social resilience, economic resilience, institutional resilience, infrastructural resilience, and community capital resilience. At the same time, the ArcGIS platform tool was used for spatial interpolation analysis. In this paper, the inverse distance weighting (IDW) method was used to carry out the spatial analysis of the perceived resilience of the two cities. Due to the heterogeneity of the neighborhood physical environment, operation and management mode, individual attribute characteristics, and internal relations, the resilience of the two urban communities showed disparity in different dimensions. Overall, the communities with good urban property management services, high-income owners, and the convenient transportation have stronger resilience in the face of pandemic. On the contrary, scattered communities, which are scattered in the inner cities, lack effective management, and based on unstable employment, people become the most affected by the epidemic with the lowest resilience power. The importance of social capital, represented by community understanding, identity, and mutual help and cooperation between neighbors, is highlighted in the resilience assessment of the two cities, respectively, in the East and West, indicating that to build more resilient cities, in addition to improving government management and increasing investment in urban infrastructure, building the residents' sense of belonging, identity, and enduring community culture is even more important in the construction of resilient cities.

Scenario analysis on optimal farmed-fish-species composition in China: A theoretical methodology to benefit wild-fishery stock, water conservation, economic and protein outputs under the context of climate change.

Fish production from aquaculture and wild captures suffers from the rising risk of climate change. This impacts the livelihoods of fishers and fish farmers by shrinking wild fishery stocks, inland water scarcity, and consequent declines in economic and protein productions. China, feeding the most fish of the world with water-intensive crops, faces challenges of water scarcity but still be premature in developing strategies to adapt to climate change. Here, focusing on methodology development, we quantified the water footprint of fish-farming and economic and protein productions in the baseline year 2014. Then, 29 scenarios of farmed-fish-species composition (FFSC, i.e., tons of each farmed fish species) were developed for the target year 2020. The baseline 2014 shows that fish farming generates an average of 150 billion m3 of water footprint, 4.70 million tons of protein, and 263 billion RMB of economic output (~39 billion USD). Uncertainty optimizations were conducted to generate the optimal FFSC solutions that show a potential to increase fish production by 22%, economic and protein output by 18% and 29%, respectively and simultaneously lower water footprint by 22% to the maximum extent. Nine scenarios that lower wild fishery captures were further examined, with optimal FFSC solution that encourages aquaculture of Grass carp, Bighead Carp, and Silver Carp, and discourages Black carp, Tilapia, Crucian carp, Sea bass, and Wuchang bream. From a methodology aspect, this study pulls back policymakers from only focusing on the short-term economic interest of fish-farming and persuades them to rethink long-term adaptive strategies to climate change from multiple sustainable dimensions.

China's sponge city development for urban water resilience and sustainability: A policy discussion.

China recently introduced a national policy initiative called sponge city development as a holistic, ecosystem-based approach integrated with urban planning and development to address storm-induced pluvial flooding as well as other urban water and environmental issues. The initiative, while following the U.S. low impact development with a concept also similar to the U.K. sustainable drainage systems and Australian water sensitive cities, is subject to a major design issue in practice with infrastructure projects of similar types adopted unanimously across regions despite spatially diverse and heterogeneous hydrological and biophysical conditions. The ecosystem services framework as applied to the urban setting, particularly its holistic consideration of ecosystem structure and management intervention in relation to services or benefits delivery, can and should guide the planning, design, development, and evaluation of relevant projects or nature-based practices for carrying out the policy initiative, a perspective of practical value with foreseeable transformative impact that has received little recognition in China's current green urban movement toward water resilience and sustainability.

Correlations of MIF polymorphism and serum levels of MIF with glucocorticoid sensitivity of sudden sensorineural hearing loss.

OBJECTIVE: This study explored the relationship between macrophage migration inhibitory factor (MIF) gene polymorphism (-173G/C) and glucocorticoid sensitivity in sudden sensorineural hearing loss (SSNHL). METHODS: A total of 120 patients with SSNHL were divided into a glucocorticoid-sensitive group and a glucocorticoid-resistant group. A group of 93 healthy individuals served as the control group. Serum MIF levels of the participants were measured and MIF genotyping was performed. RESULTS: The frequency of the MIF -173C allele was significantly higher in glucocorticoid-sensitive patients than in glucocorticoid-resistant patients. Serum MIF levels were significantly higher in SSNHL patients than in healthy controls, and higher in the glucocorticoid-sensitive group than in the glucocorticoid-resistant group of SSNHL patients, which was unexpected. Compared with patients with the GG genotype, patients with the -173C allele (GC and CC genotypes) had significantly higher levels of serum MIF and superoxide dismutase activity and lower levels of tumor necrosis factor-α and malondialdehyde. CONCLUSION: The MIF -173G/C polymorphism is associated with glucocorticoid sensitivity in SSNHL patients. The C allele can result in higher MIF production, reduced oxidative stress, and greater glucocorticoid sensitivity.

CUL4A expression is associated with tumor stage and prognosis in nasopharyngeal carcinoma.

Cullin 4A (CUL4A) is a protein of E3 ubiquitin ligase with many cellular processes. CUL4A could regulate cell cycle, development, apoptosis, and genome instability. This study aimed to analyze the expression of CUL4A in nasopharyngeal carcinoma (NPC) tissues and the associations of CUL4A expression with prognostic significance. A total of 115 NPC patients were collected to assess the protein expression of CUL4A by immunohistochemistry, so as to analyze the relationships between CUL4A expression and clinicopathological and prognostic parameters. All patients were followed-up until death or 5 years. The results showed that high expression of CUL4A was significantly associated with larger primary tumor size (P = .026), higher nodal status (P = .013), more distant metastasis (P = .020), and higher TNM stage (P = .005). Kaplan-Meier curves showed that patients with higher CUL4A expression had significantly shorter overall survival (OS) and progression-free survival (PFS) (both P < .001). In multivariate Cox analysis, CUL4A is an independent prognostic factor for OS (P = .016; hazard ratio [HR] = 2.770, 95% CI: 1.208-6.351) and PFS (P = .022; HR = 2.311, 95% CI: 1.126-4.743). In conclusion, high expression of CUL4A was associated with advanced disease status of NPC, and might serve as an independent prognostic factor.

MicroRNA-425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma-derived growth factor.

Nasopharyngeal carcinoma (NPC), which arises from the nasopharynx epithelium, is most common in Southeast Asia, particularly in Southern China. To date, a variety of microRNAs have been demonstrated to serve key functions in the progression and development of NPC. microRNA-425 (miR-425) has previously been reported to be frequently abnormally expressed in a number of different types of human cancer, including lung, gastric, cervical, breast and prostate cancer. However, to the best of our knowledge, the expression patterns, functions and underlying mechanisms of miR-425 in NPC remain largely unexplored. In the present study, the expression of miR-425 was revealed to be low in NPC tissues and cell line. Resumption of miR-425 expression suppressed cell viability and invasion in NPC. Hepatoma-derived growth factor (HDGF) was identified as a direct target gene of miR-425 in NPC. HDGF was highly expressed at mRNA and protein levels in NPC tissues. Additionally, HDGF mRNA was negatively correlated with miR-425 expression in NPC tissues. Furthermore, overexpression of HDGF almost completely rescued the tumor-suppressing effects of miR-425 on NPC cell viability and invasion. Taken together, these results demonstrated that miR-425 acted as a tumor suppressor in NPC by targeting HDGF, suggesting that it may be a novel therapeutic target for the treatments of patients with NPC.