Acteoside and isoacteoside alleviate renal dysfunction and inflammation in lipopolysaccharide-induced acute kidney injuries through inhibition of NF-κB signaling pathway.

Acute kidney injury (AKI) is a sudden loss of renal function with a high mortality rate and inflammation is thought to be the underlying cause. The phenylpropanoid components acteoside (ACT) and isoacteoside (ISO), which were isolated from Cistanche deserticola Y.C.Ma, have been reported to have preventive effects against kidney disorders. This study aimed to investigate the anti-inflammatory properties and protective mechanisms of ACT and ISO. In this investigation, kidney function was assessed using a semi-automatic biochemical analyzer, histopathology was examined using Hematoxylin-Eosin staining and immunohistochemistry, and the concentration of inflammatory cytokines was assessed using an enzyme-linked immunosorbent assay (ELISA) test. In addition, using Western blot and q-PCR, the expression of proteins and genes connected to the NF-κB signaling pathway in mice with lipopolysaccharide (LPS)-induced AKI was found. The findings showed that under AKI intervention in LPS group, ACT group and ISO group, the expression of Rela (Rela gene is responsible for the expression of NFκB p65 protein) and Tlr4 mRNA was considerably elevated (P<0.01), which led to a significant improvement in the expression of MyD88, TLR4, Iκ-Bɑ and NF-κB p65 protein (P<0.001). The levels of Alb, Crea and BUN (P<0.001) increased along with the release of downstream inflammatory factors such as IL-1ß, IL-6, Cys-C, SOD1 and TNF-α (P<0.001). More importantly, the study showed that ISO had a more favorable impact on LPS-induced AKI mice than ACT. In conclusion, by inhibiting NF-κB signaling pathway, ACT and ISO could relieve renal failure and inflammation in AKI, offering a fresh possibility for the therapeutic management of the condition.

Correction to: m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis.

An amendment to this paper has been published and can be accessed via the original article.

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.

BACKGROUND: Recent evidence indicates that metformin inhibits mammalian cancer growth and metastasis through the regulation of microRNAs. Metformin regulates miR-381 stability, which plays a vital role in tumor progression. Moreover, increased YAP expression and activity induce non-small cell lung cancer (NSCLC) tumor growth and metastasis. However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown. METHODS: Levels of RNA and protein were analyzed using qPCR, western blotting and immunofluorescence staining. Cellular proliferation was detected using a CCK8 assay. Cell migration and invasion were analyzed using wound healing and transwell assays. Promoter activity and transcription were investigated using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect the binding of YAP to the promoter of Snail. The interaction between miR-381 and the 3'UTR of YAP mRNA was analyzed using the MS2 expression system and co-immunoprecipitation with biotin. RESULTS: We observed that miR-381 expression is negatively correlated with YAP expression and plays an opposite role to YAP in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. The miR-381 function as a tumor suppressor was significantly downregulated in lung cancer tissue specimens and cell lines, which decreased the expression of its direct target YAP. In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381. Moreover, YAP, which functions as a co-transcription factor, enhanced NSCLC progression and metastasis by upregulation of Snail. Snail knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin in lung cancer cells. Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT. CONCLUSIONS: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis. Thus, we believe that the miR-381-YAP-Snail signal axis may be a suitable diagnostic marker and a potential therapeutic target for lung cancer.

m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis.

BACKGROUND: METTL3 is an RNA methyltransferase that mediates m6A modification and is implicated in mRNA biogenesis, decay, and translation. However, the biomechanism through which METTL3 regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance and metastasis is not very clear. METHODS: The expression of mRNA was analyzed by qPCR assays. Protein levels were analyzed by western blotting and immunofluorescent staining. Cellular proliferation was detected by CCK8 assays. Cell migration and invasion were analyzed by wound healing and transwell assays, respectively. Promoter activities and gene transcription were analyzed by luciferase reporter assays. Finally, m6A modification was analyzed by MeRIP. RESULTS: METTL3 increased the m6A modification of YAP. METTL3, YTHDF3, YTHDF1, and eIF3b directly promoted YAP translation through an interaction with the translation initiation machinery. Moreover, the RNA level of MALAT1 was increased due to a higher level of m6A modification mediated by METTL3. Meanwhile, the stability of MALAT1 was increased by METTL3/YTHDF3 complex. Additionally, MALAT1 functions as a competing endogenous RNA that sponges miR-1914-3p to promote the invasion and metastasis of NSCLC via YAP. Furthermore, the reduction of YAP m6A modification by METTL3 knockdown inhibits tumor growth and enhances sensitivity to DDP in vivo. CONCLUSION: Results indicated that the m6A mRNA methylation initiated by METTL3 promotes YAP mRNA translation via recruiting YTHDF1/3 and eIF3b to the translation initiation complex and increases YAP mRNA stability through regulating the MALAT1-miR-1914-3p-YAP axis. The increased YAP expression and activity induce NSCLC drug resistance and metastasis.

Clinical Values of Long Non-coding RNAs in Bladder Cancer: A Systematic Review.

Background: Increasing evidence shows that dysregulated expression of long non-coding RNAs (lncRNAs) can serve as diagnostic or prognostic markers in bladder cancer. The aim of this study was to evaluate the clinical values of dysregulated lncRNAs in bladder cancer. Methods: Eligible studies were systematically searched in PubMed, Embase, and Web of Science databases from inception to December 2017. Odds ratios (OR) were calculated to investigate the correlation between lncRNAs and clinicopathological parameters. Pooled hazard ratios (HR) and 95% confidence interval (CI) were calculated to explore the prognostic value of lncRNAs in bladder cancer. Pooled diagnostic parameters were also calculated to estimate the performance of lncRNAs in diagnosing bladder cancer. All statistical analyses were performed by using STATA 13.1 program. Results: A total of 37 relevant studies were included to the present systematic review according to the inclusion and exclusion criteria, including 26 on clinicopathological parameters, 19 on prognosis, and 7 on diagnosis. For clinicopathological parameters, MALAT1 expression was significantly associated with lymph node metastasis (OR = 2.731; 95% CI: 1.409-5.292; p = 0.003), and high-level expression of XIST was related to larger tumor size (OR = 2.473; 95% CI: 1.159-5.276; p = 0.019) and higher TNM stage (OR = 0.400; 95% CI, 0.184-0.868; p = 0.020). For the prognostic values, the most significant association was observed between increased expressions of SPRY4-IT1 and poor overall survival (OS) (HR = 3.716; 95% CI: 2.084-6.719; p < 0.001); high MALAT1 expression was significantly associated with poor OS (HR = 1.611; 95% CI: 1.076-2.412; p = 0.020). For the diagnostic values, UCA1 expression profile achieved a combined AUC of 0.92, with sensitivity of 0.84 and specificity of 0.89 in distinguishing patients with bladder cancer from non-cancerous controls. Conclusions: In summary, systematic review elaborated that abnormal lncRNAs expression can serve as potential markers for prognostic evaluation in bladder cancer patients. In addition, the diagnostic meta-analysis concluded that abnormally expressed UCA1 can function as potential diagnostic markers for bladder cancer.

Epidemiology of Echinococcosis Among Schoolchildren in Golog Tibetan Autonomous Prefecture, Qinghai, China.

Echinococcosis is a serious zoonotic parasitic disease that is highly endemic in Qinghai Province. The present study aimed to investigate the prevalence of echinococcosis among schoolchildren in Golog Tibetan Autonomous Prefecture to improve early diagnosis and treatment of patients and to provide information for echinococcosis prevention and control. A total of 11,260 schoolchildren from five counties (Maqin, Gander, Dari, Jiuzhi, and Banma) in Golog Tibetan Autonomous Prefecture, Qinghai Province, were screened for echinococcosis. Screening involved ultrasound imaging combined with serologic examination as an auxiliary diagnostic test. The prevalence of echinococcosis in the schoolchildren was 2.1% (235/11,260), with a rate of 0.8% for cystic echinococcosis (CE; 89/11,260) and 1.3% for alveolar echinococcosis (AE; 146/11,260). Additionally, one child had a mixed infection. The prevalence ranged between 1.1% and 4.1% among the five investigated counties, and was highest in Dari County (4.1%). The prevalence of echinococcosis was higher in girls than in boys and gradually increased with age. In addition, children with CE mainly had type 1 (CE1) and type 3 (CE3) lesions, and children with AE mainly had small-diameter calcified lesions, suggesting that they were in the early asymptomatic stage of echinococcosis. In conclusion, children of Golog Tibetan Autonomous Prefecture appear to exhibit the highest recorded prevalence of CE and AE globally. Ultrasound is useful for screening populations in regions where both CE and AE are endemic.

[An Epidemiological Survey on Echinococcosis in Yushu Prefecture of Qinghai Province].

Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% （457/2 790）. The mobidity of hydatid disease was highest in Chengduo County （7.41%, 181/2 444）, and the rate of serum antibody was highest in Yushu County （23.18%, 127/548）. The morbidity and serum antibody in males were 3.91% （118/3 018） and 13.93% （172/1 235） respectively, and those in females were 5.02% （201/4 007） and 18.33% （285/1 555）. In terms of age distribution, the morbidity was relatively higher in residents of 60- （8.39%, 38/453） and 40- years （6.61%, 67/1 014）; and the rate of serum antibody was highest in residents over 70 years （33.93%, 19/56）. In terms of occupation, the morbidity was relatively higher in herdsmen （5.28%, 252/4 777）, Herdsmen-peasants （6.52%, 24/368）, and religious workers（3.37%, 11/326）, while the rate of serum antibody was relatively higher in children（24%, 6/25）, religious workers （18.79%, 31/165） and herdsmen（18.34%, 328/1 788）. In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducated（5.04%, 41/4 779; 18.34%, 359/1 958, respectively）. In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer （8.25%, 227/2 753; 19.48%, 158/811, respectively）. There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% （4/872）, while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% （82/809）. The fecal antigen positive rate in 838 samples of dog feces was 10.74%（90/838）. Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.