Molecular mechanism and therapeutic strategy of bile acids in Alzheimer's disease from the emerging perspective of the microbiota-gut-brain axis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood-brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota-gut-brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

The impact of genetic variants in the CYP2C8 gene on bladder cancer susceptibility.

Background: Bladder cancer is the most common leading cause of mortality around the world. Previous studies have indicated that genetic factors are significantly associated with bladder cancer progression-for instance, the CYP2C8 gene is involved in bladder cancer progression. However, little is known about the impact of CYP2C8 genetic polymorphisms on bladder cancer risk. We aimed to detect the association between CYP2C8 variations and bladder cancer susceptibility. Methods: This study included 550 healthy subjects and 217 bladder cancer patients. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the correlation of CYP2C8 polymorphisms with bladder cancer risk. Multifactor dimensionality reduction (MDR) was carried out to investigate the influence of single-nucleotide polymorphism (SNP)-SNP interactions on bladder cancer. Results: Our study showed that two SNPs were significantly associated with an increased risk of bladder cancer (rs1934951: OR 1.96, 95% CI 1.37-2.82, p = 2.67E-04; rs17110453: OR 1.89, 95% CI 1.35-2.67, p = 2.53E-04). On the contrary, two SNPs identified in the study had protective effects on bladder cancer (rs1934953: OR 0.26, 95% CI 0.14-0.47, p = 1.20E-05; rs2275620: OR 0.40, 95% CI 0.21-0.76, p = 0.005). The MDR analysis suggested that the combination of rs1934953, rs1934951, rs2275620, and rs17110453 was the best model to predict bladder cancer (CVC 10/10, testing accuracy 0.6720, p < 0.0001). Conclusion: There was a significant association between CYP2C8 polymorphisms (rs1934953, rs1934951, rs2275620, and rs17110453) and susceptibility to bladder cancer.

NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/ß-Catenin Pathway.

Objective: Currently, cumulative evidence has shown that loss of NEK2 function suppresses tumor growth. However, complete studies on the regulatory role of NEK2 in clear-cellrenal-cell carcinoma (ccRCC) are rarely reported. Methods: The GEPIA database was used for information mining to analyze the gene expression differences between ccRCC tumor and normal tissues. At the same time, we analyzed the protein expression of NEK2 in clinical ccRCC samples and ccRCC cell lines. We detected the effect of NEK2 on the biological behavior of ccRCC at the cell level and further verified the biological effect of NEK2 on ccRCC cells in vivo by nude mouse tumorigenesis experiment. The expression of WNT/ß-cateninpathway-related proteins and downstream proteins related to cell function were detected by Western blotting. Results: Using the GEPIA database, we observed that NEK2 expression level in ccRCC tissues was significantly higher than that in normal kidney tissues and was also related to tumor grade. The survival time of patients with ccRCC with high NEK2 expression was shorter than that of patients with low NEK2 expression. Compared with adjacent carcinoma and normal renal tubular epithelial cells, NEK2 levels were highly expressed in ccRCC tissues and ccRCC cell lines. NEK2 interference restrained ccRCC cell growth, migration, and invasion. NEK2 regulated the malignant behavior of ccRCC cells through the WNT/ß-catenin pathway. Nude mouse tumorigenesis assay results showed that the transplanted tumors from NEK2 silenced mice grew more slowly and were smaller in size than those from control mice. Conclusions: NEK2 elevation may be associated with poor prognosis in ccRCC, and NEK2 enhances ccRCC cell proliferation, migration, and invasion ability by activating the WNT/ß-catenin signaling pathway.

MiR-1273 g-3p Promotes Malignant Progression and has Prognostic Implications in Prostate Cancer.

Prostate cancer (PCa) is the most popular cancer of mankind. Our study aimed to provide the expression and the predictive significance of miR-1273 g-3p in PCa. Moreover, the effects on cell biological activities were also investigated. The relative expression of miR-1273 g-3p in PCa tissues and cell lines was validated by quantitative real-time PCR. Kaplan-Meier curve and Cox regression analyses were performed to indicate the prognostic value. The implications of miR-1273 g-3p on cell proliferation, migration, and invasion were validated using the CCK-8 and Transwell assay. Our results provided that the expression of miR-1273 g-3p was increased in PCa tissues and cell lines. The levels of miR-1273 g-3p were associated with Gleason score, TNM stage, clinical stage, and lymph node metastasis. Overexpression of miR-1273 g-3p indicated a promising overall survival rate. Cox regression results indicated miR-1273 g-3p might be an independent marker for PCa patients. Silenced miR-1273 g-3p inhibited PCa cell proliferation, migration, and invasion. In total, miR-1273 g-3p was increased in PCa and identified as a therapeutic target and a prognostic factor for PCa patients. Overexpression of miR-1273 g-3p might be an oncogene via accelerating cell proliferation, migration, and invasion.

miR-30d-5p suppresses proliferation and autophagy by targeting ATG5 in renal cell carcinoma.

Previous reports have shown that miR-30d-5p functions as a tumor suppressor in prostate cancer and gallbladder carcinoma, but its role in renal cell carcinoma (RCC) remains elusive. This study was designed to explore the functional role of miR-30d-5p in proliferation and autophagy of RCC. Our results show that miR-30d-5p is significantly down-regulated in RCC tissues compared with normal tissues. miR-30d-5p overexpression suppressed cell proliferation, cell-cycle G1/S transition and autophagy, but promoted apoptosis in RCC cell lines (786-O and ACHN). Intriguingly, autophagy-related gene 5 (ATG5) was directly targeted by miR-30d-5p, as shown using luciferase reporter assay and biotin-avidin pull-down assay. Moreover, overexpression of ATG5 attenuated the inhibitory effect of miR-30d-5p on proliferation and autophagy in 786-O cells. These results suggest that miR-30d-5p suppresses proliferation and autophagy in RCC cells by targeting ATG5, and this pathway may be a suitable basis for the design of novel cancer therapeutics.

The linkage between methane production activity and prokaryotic community structure in the soil within a shale gas field in China.

Soil methane generation mainly driven by soil prokaryotic microbes can be coupled with the degradation of petroleum hydrocarbons (PHCs); however, the relationship between prokaryotic community structure and methane production activity in soil with the potential risk of PHC contamination is seldom reported. In this study, 3 soil samples (CS-1 to CS-3) in the area nearby an exploratory gas well and 5 soil samples (DC-1 to DC-5) in a drill cutting dump area were obtained from the Fuling shale gas field (Chongqing City, China). Then, the prokaryotic community structure was examined by Illumina Miseq sequencing, and the linkage between soil methane production rate (MPR) and prokaryotic community composition was analyzed. The results indicated that 2 samples (DC-4 and DC-5) collected from the drill cutting dump area had significantly higher MPR than the other samples, and a significant and positive relationship (r = 0.44, P < 0.05) was found between soil MPR and soil organic matter (OM) content. The prokaryotic community composition in the sample (DC-5) with the highest MPR was different from those in the other samples, and soil OM and MPR were the major factors significantly correlated with the prokaryotic community structure in this soil. The samples (DC-4 and DC-5) with higher MPR had a higher relative abundance of Archaea and different archaeal community structures from the other samples, and the MPR was the sole factor significantly correlated with the archaeal genus composition in this soil. Therefore, both the prokaryotic and archaeal community structures are essential in the determination of soil MPR, and the bacterial genus of Saccharibacteria and the archaeal genus of Methanolobus might be the key contributors for methane generation in this soil from the shale gas field.

Total-Factor Eco-Efficiency and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration, China.

Urban agglomerations are not only the core areas leading economic growth but also the fronts facing severe resource and environmental challenges. This paper aimed to increase our understanding of urban eco-efficiency and its influencing factors and thus provide the scientific basis for green development. We developed a model that incorporates super-efficiency, slacks-based-measure, and global-frontier technology to calculate the total-factor eco-efficiency (TFEE) and used a spatial panel Tobit model to take into account spatial spillover effects. An empirical study was conducted utilizing a prefecture-level dataset in the Yangtze River Delta Urban Agglomeration (YRDUA) from 2003 to 2016. The main findings reveal that significant spatial differences exist in TFEE in the YRDUA: high-TFEE cities were majorly located in the coastal areas, while low-TFEE cities were mostly situated inland. Overall, TFEE shows a trend of "decline first and then rise with fluctuation"; the disparity between inland and coastal regions has expanded. Further regression analysis suggests that industrial structure, environmental regulation, and innovation were positively related to TFEE, while foreign direct investment was not conducive to the growth in TFEE. The relationship between population intensity and urban eco-efficiency is an inverted U-shaped curve. Finally, several specific policy implications were raised based on the results.

Transurethral endoscopic submucosal en bloc dissection for nonmuscle invasive bladder cancer: A comparison study of HybridKnife-assisted versus conventional dissection technique.

SUBJECTS: The aim of this study is to compare the efficacy and safety of en bloc bladder tumor-endoscopic submucosal dissection (BT-ESD) and conventional transurethral resection of BT (TURBT) in nonmuscle invasive bladder cancer (NMIBC) patients. METHODS: A retrospective cohort study was carried out in Shaanxi Provincial People's Hospital. A total of 193 eligible NMIBC (Ta/T1) patients were enrolled in this study (95 cases in BT-ESD group and 98 cases in TURBT group), between November 2013 and January 2017. The operation time, blood loss, postoperative bladder irrigation time, catheter indwelling time, hospital stay time, and complications were compared. Data were presented as median (range). Chi-squared or rank-sum test, two-way ANOVA, and Mantel-Cox (Log-Rank) test were performed using statistical software. A threshold of P < 0.05 was defined as statistically significant. RESULTS: The average operation time in the BT-ESD group was longer than that of in the TURBT group (40.0 [5.0, 100.0] min vs. 19.5 [3.0, 55.5] min); however, no significant longer operating time (P < 0.05) were observed in the smaller tumor (0 cm-3 cm). The postoperative bladder irrigation time, catheter indwelling time, and hospital stay in BT-ESD group were significantly shorter than that of in TURBT group (9.0 [5.0, 18.0] h, 2.5 [1.0, 4.0] d and 3.5 [2.0, 5.0] d for BT-ESD; 18.0 [12.0, 48.0] h, 3.5 [2.0, 7.0] d, and 4.5 [3.0, 8.0] d for TURBT). In addition, the BT-ESD group showed the decreased overall incidence of complications (2.1% vs. 9.2%). The univariate and multivariate analyses indicated an association between surgical option and tumor recurrence (hazard ratio = 5.624, odds ratio = 95% confidence interval = 1.582-19.991), Kaplan-Meir analysis showed significant difference in recurrence-free survival (RFS) (94.7% for ESD group vs. 78.4% for TURBT group) at 33 months. CONCLUSIONS: The application of the HybridKnife lead to a decrease in complications and RFS rate, which was a more safe and effective approach for NMIBC than conventional TURBT.

Decomposition Analysis of Factors Affecting Changes in Industrial Wastewater Emission Intensity in China: Based on a SSBM-GMI Approach.

This paper investigated the factors driving the changes in industrial wastewater emission intensity (IWEI) across provinces in China. To do this, we proposed a Super-efficiency Slacks-based Measure-Global Malmquist Index (SSBM-GMI) to decompose the change in IWEI into the effects from efficiency change (ECE), technological change (TCE), capital⁻wastewater substitution (KWE) and labor⁻wastewater substitution (LWE). The method was applied to conduct an empirical study using Chinese provincial data from 2003⁻2015. The main findings include the following: firstly, TCE was the dominant driving force behind the reduction in IWEI with an average annual contribution of -6.4% at the national level, followed by KWE (-5.3%), LWE (-1.8%) and ECE (1.2%). Secondly, significant differences exist in the driving factors behind the reduction in IWEI across regions. The reduction in IWEIs in the Northeast area and the Great Northwest area was mainly driven by productivity growth, while the reduction in IWEIs in the other areas was mainly driven by factor substitution. Thirdly, the shortage of KWE and LWE has impeded IWEI reduction in the Great Northwest area, the Middle Reaches of the Yellow River, the Northeast area and the North area. Finally, some particular policy implications were also recommended for reducing industrial wastewater emission in China.

[Investigation of the Coupling Mechanism Between Naphthalene Degradation and Denitrification of a Naphthalene Degraded Bacterial Consortium Under Denitrification].

To investigate the coupling mechanism between naphthalene degradation and denitrification using a liquid media containing naphthalene (sole carbon source) and nitrate, a naphthalene degradation bacterial consortium under denitrification was enriched from a soil with potential risk of PAH (polycyclic aromatic hydrocarbon) contamination. The bacterial community composition of the enriched consortium was analyzed by Illumina MiSeq Sequencing. Subsquently, the enriched consortium was cultured under anaerobic conditions for 9 days, and the concentrations of electron acceptors (nitrate and nitrite) for denitrification, gaseous reduction products (N2O and N2) involved in denitrification, and abundances of denitrification concerned genes (narG:periplasmic nitrate reeducates gene; nirS:cd1-nitrite reductase gene) were detected at days 1, 3, 7, and 9. The result of Illumina MiSeq Sequencing showed that Pseudomonas (Proteobacteria) was the most dominant genus in this enriched consortium. Under anaerobic conditions, the naphthalene removal rate of this enriched consortium was 49.11% within 9 days. Relative higher naphthalene degradation rates were found both at the beginning (day 1-3) and the end (day 7-9) of incubation, and these were significantly higher than at the middle (day 3-7) of the incubation stage (P<0.05). The concentration of nitrate decreased during the whole culture period, while the concentration of nitrite increased during the initial incubation (day 1-3) and rapidly decreased from day 3 to 9. Furthermore, obvious productions of N2O[3.39 µg ·(L ·h)-1] and N2[8.97 µg ·(L ·h)-1] were only measured at the end of incubation (day 7-9). The abundances of both narG and nirS increased during the incubation, indicating the continuous growth of denitrifiers in the enriched consortium during the incubation period. In summary, this study illustrated that both the nitrate reducing stage and gas producing steps of denitrification could be coupled with anaerobic naphthalene degradation, which might be helpful for a deeper investigation regarding the coupling mechanism between denitrification and anaerobic PAH degradation.

Common Variants in ALPL Gene Contribute to the Risk of Kidney Stones in the Han Chinese Population.

OBJECTIVE: Kidney stone formation is a complex disorder that likely results from both dietary and genetic factors. A recent study identified an association between the risk of kidney stones and polymorphisms in the ALPL gene, but the study needs replication. To confirm whether the ALPL gene is universally associated with kidney stones, the present study further investigated polymorphisms of the ALPL gene in a Han Chinese population. METHODS: A total of 331 kidney stone patients and 553 unrelated healthy controls were included in the present case-control study. We conducted genetic analyses to detect the association of 19 tagging single nucleotide polymorphisms (SNPs) with kidney stones. In addition, we examined the relations between targeted SNP(s) and several clinical characteristics of kidney stones in the patients. RESULTS: Genetic association analyses using logistic regression models identified one ALPL SNP, rs1256328, which was significantly associated with the kidney stone disease status (OR = 1.52, p = 0.0009). No significant results were obtained through association tests between genotypes of this SNP and the various clinical characteristics of kidney stone patients. CONCLUSION: The ALPL SNP, rs1256328, was identified as being significantly associated with kidney stone disease status in a large Chinese Han cohort. Our study replicated a previous genome-wide association study that was conducted in an Icelandic population.

Silibinin suppresses bladder cancer cell malignancy and chemoresistance in an NF-κB signal-dependent and signal-independent manner.

Because bladder cancer (BCa) is the 9th most common malignant tumor and 13th leading cause of death due to cancer, therapeutic approaches have attracted a great deal of attention from both clinicians and BCa patients. Although the development of surgery and targeted drugs has brought new challenges for the traditional concept of BCa therapy, various types of chemotherapy remain the final treatment method for many BCa patients. However, chemoresistance inevitably appears, leading to the failure of chemotherapy. Silibinin, a polyphenolic flavonoid component isolated from the fruits or seeds of milk thistle, has been reported to play important roles in inhibiting tumor chemoresistance in breast cancer and head and neck squamous cell carcinomas. Our previous study indicated that silibinin inhibited BCa progression in some mechanisms but with no conclusion of chemoresistance inhibition. Therefore, in the present study, we dissected the role of silibinin in BCa progression and chemoresistance. Our results revealed that in BCa, chemodrug-induced chemoresistance was reversed in the presence of silibinin. Further mechanistic study indicated that silibinin suppressed chemoresistance and BCa malignancy in an NF-κB-dependent and -independent manner. In addition, all of the inhibitory effects were dose­dependent. Thus, our results provide a potential use for silibinin in BCa therapeutics.

SPOP promotes tumor progression via activation of ß-catenin/TCF4 complex in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, about one third of the cases are diagnosed at advanced stages with metastases and effective treatments for metastatic RCC are lacking. The molecular events supporting RCC progression remain poorly understood. SPOP, an E3 ubiquitin ligase component, was recently showed to sufficiently promote RCC tumorigenesis, however, other potential functions of SPOP in RCC have not been studied. In the present investigation, by assessing the immunohistochemical staining of SPOP in urological tumors, we found the protein was highly expressed in RCC, in particular, it was specifically expressed in clear cell RCC. cDNA microarray data showed that SPOP mRNA level was significantly increased in clear cell RCC compared to normal kidney tissues, which might be the result of the abnormal DNA copy number of this gene. More interestingly, SPOP was positive in tumors with local invasion or metastasis, and it was associated with tumor recurrence-free survival of clear cell RCC patients. Further in vitro assays demonstrated that SPOP drove RCC epithelial-mesenchymal transition (EMT) and promoted cell invasion. Mechanistically, SPOP enhanced ß-catenin protein expression as well as its nuclear translocation, and elevated TCF4 expression. Both ß-catenin and TCF4 upregulated the critical EMT-inducing transcription factor ZEB1, which functioned as an effector of ß-catenin/TCF4 signaling in RCC invasion. These data identified SPOP as a new marker and prognostic factor for clear cell RCC, and its functions provide new insight into the molecular mechanisms of RCC progression, in which SPOP appears to be an EMT activator.

HIF-1α/MDR1 pathway confers chemoresistance to cisplatin in bladder cancer.

Bladder cancer (BCa) is the 9th most common malignant tumor and the 13th leading cause of death due to cancer. The development of surgery and target drugs bring new challenges for the traditional concept for BCa therapy, and chemotherapy is still the final option for many BCa patients, and cisplatin-containing regimen the most effective one. However, the ubiquitous application of cisplatin-containing regimen in BCa results in the cisplatin-resistance, in addition, the cisplatin­resistant BCa manifests enhanced malignant behavior, the mechanism of which is unclear. In the present study, we used BCa cell lines to to clarify this point. BCa cell lines T24/J82 were pretreated with cisplatin >3 months to construct stable cisplatin-resistant cell lines (tagged T24(Cis-R) and J82(Cis-R)), which manifested as enhanced capacity of proliferation and malignant behavior in vivo and in vitro, accompanied by cisplatin, and even doxorubicin resistance. The following mechanism dissection revealed that prolonged treatment time of T24/J82 cells led to elevated expression of HIF-1α, which targeted the increased expression of MDR1 on the one hand, and contributed to BCa cell proliferation, migration/invasion on the other hand. Finally, IHC staining of human BCa tissue supported our conclusion that the expression of HIF-1α and MDR1 was higher in chemoresistant tissue vs. chemosensitive tissue. Our results provided a new view of HIF-1α in chemotherapy.

miR-489 Suppresses Proliferation and Invasion of Human Bladder Cancer Cells.

MicroRNAs (miRNAs) have been shown to be involved in bladder cancer progression. miR-489 (also known as miR-489-3p) was recently reported to be a tumor suppressor in several cancers. However, its exact role and mechanism in the progression of bladder cancer are largely unknown. In this study, we explore the role of miR-489 in the proliferation and invasion of human bladder cancer cells. The miR-489 expression levels were detected in bladder cancer and normal adjacent tissues, as well as in human normal bladder epithelial cells and bladder cancer cell lines. The results showed that miR-489 was sharply reduced in bladder cancer tissues and cell lines. Then the miR-489 mimic or oligo anta-miR-489 was transfected into T24 and UMUC3 bladder cancer cell lines. The results showed that the miR-489 mimic greatly increased the miR-489 level and significantly decreased the proliferation and invasion of T24 and UMUC3 cells. In contrast, the anta-miR-489 had a completely opposite effect on miR-489 expression, cell proliferation, and cell invasion. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-489 targeted the mRNA 3'-untranslated region (3'-UTR) region of Jagged1 (JAG1), a Notch ligand. In conclusion, miR-489 suppressed proliferation and invasion of human bladder cancer cells.

NF-κB signaling plays irreplaceable roles in cisplatin-induced bladder cancer chemoresistance and tumor progression.

Bladder cancer (BCa) is the most vital urogenital malignant disease worldwide, bringing huge economic and social burden every year. Clinically, BCa is subdivided into superficial type and invasive type according to clinic-pathology, accompanied with different strategy of therapy. Number of reports indicate that 10-30% of superficial BCa will inevitable progress into invasive type, manifesting enhanced malignant behavior compared to original invasive type. Regardless of the original being an original invasive type or invasive type that progressed from superficial type of BCa, chemotherapy (including adjuvant or neo-adjuvant chemotherapy) in line with radiotherapy is the final regimen for BCa patients. Previous reports pointed out the high efficiency of cisplatin-containing chemotherapeutic regimen for BCa patients, leading to wide use of this regimen in BCa therapeutics. However, cisplatin-resistance inevitably appear, resulting in the failure of the BCa chemotherapy, the mechanism of which is still unknown. In the present study, parental BCa cell lines T24/J82 were used to obtain stable-cisplatin-resistance cell lines T24R/J82R, which showed enhanced capacity of malignancy, tumorigenesis and drug resistance, accompanied by elevated expression of EMT markers. The further mechanism investigation suggested that prolonged time of cisplatin-treatment contributed to the activation of the NF-κB signal, resulting in the upregulation of EMT markers, the maintenance of stem cell marker and the elevated expression of ABCB1. Thus, our study provides us a new view of the role of NF-κB signaling in BCa therapeutics.

IL-37 mediates the antitumor activity in renal cell carcinoma.

Interleukin (IL)-37 is a natural suppressor of innate inflammatory and immune responses. IL-37 plays an important role in renal function and antitumor activity. The aim of this study was to investigate the role of IL-37 in renal cell carcinoma (Rcc). Serum IL-37 levels in 120 Rcc patients and 50 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA). The Rcc cell lines A498 and Caki-1 were cultured with 0-100 ng/mL of recombinant human IL-37 protein (rhIL-37). Cancer cells were transfected with or without pcDNA3.1-IL-6 to alter IL-6 expression. Cell migration, proliferation, and apoptosis were tested by wound-healing assay, MTT, and flow cytometry, respectively. Levels of IL-6, pSTAT3 Y705, Bcl-2, cyclin D1, and HIF-1α were detected by qRT-PCR, ELISA, or western blot. Additionally, therapeutic effect of rhIL-37 was also confirmed in SCID mice. The expression of IL-37 was decreased in Rcc patients and was negatively correlated with tumor progression. In vitro, IL-37 markedly inhibited the migration and proliferation, and promoted apoptosis in Rcc cells. Furthermore, the expressions of IL-6, pSTAT3 Y705, HIF-1α, Bcl-2, and cyclin D1 were decreased by IL-37. However, these effects were reversed by the transfection of pcDNA3.1-IL-6. In vivo, tumor growth and gene expressions of IL-6 and HIF-1α were suppressed by IL-37. In conclusion, IL-37 might serve as a novel tumor suppressor in Rcc and exert its antitumor activity through inhibiting IL-6/STAT3 signaling.

[Environmental geochemical baseline of heavy metals in soils of the Ili river basin and pollution evaluation].

Environmental geochemical baseline models of Cu, Zn, Pb, As, Hg were established by standardized method in the ehernozem, chestnut soil, sierozem and saline soil from the Ili river valley region. The theoretical baseline values were calculated. Baseline factor pollution index evaluation method, environmental background value evaluation method and heavy metal cleanliness evaluation method were used to compare soil pollution degrees. The baseline factor pollution index evaluation showed that As pollution was the most prominent among the four typical types of soils within the river basin, with 7.14%, 9.76%, 7.50% of sampling points in chernozem, chestnut soil and sierozem reached the heavy pollution, respectively. 7.32% of sampling points of chestnut soil reached the permitted heavy metal Pb pollution index in the chestnut soil. The variation extent of As and Pb was the largest, indicating large human disturbance. Environmental background value evaluation showed that As was the main pollution element, followed by Cu, Zn and Pb. Heavy metal cleanliness evaluation showed that Cu, Zn and Pb were better than cleanliness level 2 and Hg was the of cleanliness level 1 in all four types of soils. As showed moderate pollution in sierozem, and it was of cleanliness level 2 or better in chernozem, chestnut soil and saline-alkali soil. Comparing the three evaluation systems, the baseline factor pollution index evaluation more comprehensively reflected the geochemical migration characteristics of elements and the soil formation processes, and the pollution assessment could be specific to the sampling points. The environmental background value evaluation neglected the natural migration of heavy metals and the deposition process in the soil since it was established on the regional background values. The main purpose of the heavy metal cleanliness evaluation was to evaluate the safety degree of soil environment.