Effect of home cook interventions for salt reduction in China: cluster randomised controlled trial.

OBJECTIVE: To determine the effects of salt reduction interventions designed for home cooks and family members. DESIGN: Cluster randomised controlled trial. SETTING: Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019. PARTICIPANTS: 60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families). INTERVENTIONS: Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions. MAIN OUTCOME MEASURE: Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up. RESULTS: 1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly. CONCLUSIONS: The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016804.

Exosome-derived circTFDP2 promotes prostate cancer progression by preventing PARP1 from caspase-3-dependent cleavage.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play a significant role in tumorigenesis. However, the detailed function of circRNA in prostate cancer (PCa) is still largely unknown. METHODS: We quantified circTFDP2 expression in PCa tissues and adjacent normal tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and in vivo progression and metastasis assays were applied to reveal the proliferation and metastatic abilities of circTFDP2 in PCa cells. Mass spectrometry, RNA pulldown, RNA-immunoprecipitation (RIP), western blotting and immunofluorescence were used for the mechanistic studies. qRT-PCR and RIP assays were used to explore the regulatory role of eIF4A3 in the biogenesis of circTFDP2. Finally, functional assays showed the effect of circTFDP2-containing exosomes on PCa cell progression. RESULTS: circTFDP2 was upregulated in PCa tissues compared with adjacent normal tissues. Furthermore, high circTFDP2 expression was positively correlated with the Gleason score. Functionally, circTFDP2 promoted PCa cell proliferation and metastasis both in vivo and in vitro. Mechanistically, circTFDP2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) protein in its DNA-binding domain to prevent it from active caspase-3-dependent cleavage, and finally relieved PCa cells from DNA damage. In addition, RNA-binding protein eIF4A3 can interact with the flanking region of circTFDP2 and promote the biogenesis of circTFDP2. Moreover, exosome-derived circTFDP2 promoted PCa cell progression. CONCLUSIONS: In general, our study demonstrated that circTFDP2 promoted PCa cell progression through the PARP1/DNA damage axis, which may be a promising therapeutic target for PCa.

Effects of recombinant human growth hormone on proliferation and differentiation of cementoblast and ERK1 / 2, JNK / SAPK and p38MAPK signaling pathway.

To investigate the effects of recombinant human growth hormone on the proliferation and differentiation of cementoblast and the signal pathways of ERK1 / 2, JNK / SAPK and p38MAPK, osteoblasts (OCCM-30) were cultured in vitro. The OCCM-30 was treated with different concentrations of recombinant human growth hormone (rhGH) (0, 10, 50 ng/mL) for 1 d and 2 d, respectively. MTT assay was used to test the proliferation of OCCM-30 cells by rhGH. The effect of BSP, OPN, OCN and ALP genes was detected by RT-PCR after one day. The activity of alkaline phosphatase (ALP) was detected after treatment with OCCM-30 for five days at different concentrations of rhGH. After treatment with OCCM-30 at 100 ng/mL rhGH for 0 min, 5 min, 10 min, 15 min, 30 min and 60 min, the phosphorylation levels of ERK1/2, JNK/SAPK and p38MAPK were detected by Western blot. Results showed that rhGH could promote the proliferation of OCCM-30 cells, and the proliferation of OCCM-30 cells increases with the increase of rhGH concentration. After one day of culture, the levels of the BSP and ALP genes increased with the increase of rhGH concentration (P<0.05); the OPN gene level in the 10 ng/mL group was significantly higher than that in the blank group, and the 50 ng/mL group was significantly lower than the blank group. (P<0.05); OCN gene levels in the 10 ng/mL group and 50 ng/mL group were not significantly different from those in the blank group (P>0.05). Compared with the blank group, the ERK 1/2 phosphorylation level increased at 5 min in the 100 ng/mL group, reached the maximum at 10 min, decreased significantly at 15 min, decreased to the original level at 30 min, and had no significant change in ERK 1/2 total protein level; 100 ng/mL rhGH had no significant effect on SAPK/JNK, p38MAPK phosphorylation and total protein levels in OCCM-30 cells (P>0.05). It was concluded that 10ng/mL and 50ng/mL rhGH could promote the proliferation of OCCM-30 cells and promote the expression of the BSP gene and ALP gene. Low-dose rhGH is beneficial to OPN gene expression, and high-dose rhGH inhibits OPN gene expression. 100 ng/mL rhGH promoted the ERK 1/2 pathway and had no effect on the SAPK/JNK and p38 MAPK pathways.

Tunable color generation in CdTe-doped silicate glass enabled by ultrashort laser pulses: interior coloring and multilevel encryption.

The launch of the big data era puts forward challenges for information security. Herein, a new kind of silicate glass system co-doped with CdO and ZnTe, capable of achieving the controllable generation of intrinsic color centers (brown and green) and tiny nuclei of CdTe via direct laser writing (DLW), is developed. The controlled growth of CdTe QDs thermally, leads to a permanent color of orange at the cost of accelerated aging of the color centers of brown and green. On the one hand, going beyond traditional 2D surface coloration, the high transparency of the studied bulk medium makes 3D volumetric interior coloration possible. On the other hand, by encoding ciphertext into the tiny nuclei of CdTe, a strategy of color encryption and heat decryption is established, which brings about the merits of expanded storage capacity and improved information security. The demonstration application confirmed the user-defined multiscale interior coloration and an unprecedented multidimensional color-encryption scheme with a high-security level. The present work highlights a great leap in transparent materials for color encryption and hopefully stimulates the development of new color division multiplexing encryptions.

circPDE5A regulates prostate cancer metastasis via controlling WTAP-dependent N6-methyladenisine methylation of EIF3C mRNA.

BACKGROUND: Circular RNA (circRNA) is a novel class noncoding RNA (ncRNA) that plays a critical role in various cancers, including prostate cancer (PCa). However, the clinical significance, biological function, and molecular mechanisms of circRNAs in prostate cancer remain to be elucidated. METHODS: A circRNA array was performed to identified the differentially expressed circRNAs. circPDE5A was identified as a novel circRNA which downregulated in clinical samples. Functionally, the in vitro and in vivo assays were applied to explore the role of circPDE5A in PCa metastasis. Mechanistically, the interaction between circPDE5A and WTAP was verified using RNA pulldown followed by mass spectrometry, RNA Immunoprecipitation (RIP) assays. m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) was then used to identified the downstream target of circPDE5A. Chromatin immunoprecipitation assay (ChIP) and dual-luciferase reporter assay were used to identified transcriptional factor which regulated circPDE5A expression. RESULTS: circPDE5A was identified downregulated in PCa tissues compared to adjacent normal tissue and was negatively correlated with gleason score of PCa patients. circPDE5A inhibits PCa cells migration and invasion both in vitro and in vivo. circPDE5A blocks the WTAP-dependent N6-methyladenisine (m6A) methylation of eukaryotic translation initiation factor 3c (EIF3C) mRNA by forming the circPDE5A-WTAP complex, and finally disrupts the translation of EIF3C. Moreover, the circPDE5A-dependent decrease in EIF3C expression inactivates the MAPK pathway and then restrains PCa progression. CONCLUSIONS: Our findings demonstrate that FOXO4-mediated upregulation of circPDE5A controls PCa metastasis via the circPDE5A-WTAP-EIF3C-MAPK signaling pathway and could serve as a potential therapeutic targer for PCa.

DAPT Attenuates Cadmium-Induced Toxicity in Mice by Inhibiting Inflammation and the Notch/HES-1 Signaling Axis.

The small molecule DAPT inhibits the Notch signaling pathway by blocking γ-secretase mediated Notch cleavage. Given the critical role of the Notch signaling axis in inflammation, we asked whether DAPT could block Notch-mediated inflammation and thus exert neuronal protection. We established a mouse model of chronic exposure to cadmium (Cd)-induced toxicity and treated it with DAPT. DAPT was effective in ameliorating Cd-induced multi-organ damage and cognitive impairment in mice, as DAPT restored abnormal performance in the Y-maze, forced swimming and Morris water maze (MWM) tests. DAPT also reversed Cd-induced neuronal loss and glial cell activation to normal as observed by immunofluorescence and immunohistochemistry of brain tissue sections. In addition, Cd-intoxicated mice showed significantly increased levels of the Notch/HES-1 signaling axis and NF-κB, as well as decreased levels of the inflammatory inhibitors C/EBPß and COP1. However, DAPT down regulated the elevated Notch/HES-1 signaling axis to normal, eliminating inflammation and thus protecting the nervous system. Thus, DAPT effectively eliminated the neurotoxicity of Cd, and blocking γ-secretase as well as Notch signaling axis may be a potential target for the development of neuronal protective drugs.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination.

Clear cell renal cell carcinoma (ccRCC) is the most lethal urological cancer and is characterized by a high rate of metastasis and relapse. N6-Methyladenosine (m6A) is implicated in various stages of cancer development. However, a thorough understanding of m6A-modified lncRNAs in ccRCC is lacking. The results showed that METTL14 had decreased expression in ccRCC tissues. In addition, the expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. The silencing of METTL14 was shown to significantly increase metastasis in vitro and in vivo. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m6A levels of Lnc-LSG1 could be regulated by METTL14. Lnc-LSG1 can directly bind to ESRP2 protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination. However, m6A modification on Lnc-LSG1 can block the interaction between Lnc-LSG1 and ESRP2 via the m6A reader, YTHDC1. Taken together, our findings unraveled the novel mechanism of METTL14 inhibiting ccRCC progression, and explored the correlation between m6A and lncRNA in ccRCC for the first time.

PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression.

Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

Role of noncoding RNA in drug resistance of prostate cancer.

Prostate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.

The emerging role of small non-coding RNA in renal cell carcinoma.

Noncoding RNAs are transcribed in the most regions of the human genome, divided into small noncoding RNAs (less than 200 nt) and long noncoding RNAs (more than 200 nt) according to their size. Compelling evidences suggest that small noncoding RNAs play critical roles in tumorigenesis and tumor progression, especially in renal cell carcinoma. MiRNA, the most famous small noncoding RNA, has been comprehensively explored for its fundamental role in cancer. And several miRNA-based therapeutic strategies have been applied to several ongoing clinical trials. However, piRNAs and tsRNAs, have not received as much research attention, because of several technological limitations. Nevertheless, some studies have revealed the presence of aberration of piRNAs and tsRNAs in renal cell carcinoma, highlighting a potentially novel mechanism for tumor onset and progression. In this review, we provide an overview of three classes of small noncoding RNA: miRNAs, piRNAs and tsRNAs, that have been reported dysregulation in renal cell carcinoma and have the potential for advancing diagnosis, prognosis and therapeutic applications of this disease.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life-threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4-LBD) and induces a conformational change in the secondary structure of TR4-LBD. Bexarotene suppressed AtT-20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4-increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5' promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH-secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.

A Competing Endogenous RNA Network and an 8-lncRNA Prognostic Signature Identify MYO16-AS1 as an Oncogenic lncRNA in Bladder Cancer.

Recently, growing evidence has shed light on the competitive endogenous RNAs (ceRNAs) activity of long noncoding RNAs (lncRNAs) in carcinogenesis and tumor progression. To better elucidate the regulatory mechanisms of lncRNA in muscle-invasive bladder cancer (MIBC), we identified aberrantly expressed mRNAs, lncRNAs, and miRNAs in tumor tissues by using RNA sequence profiles from The Cancer Genome Atlas. The MIBC-specific ceRNA network, including 58 lncRNAs, 22 miRNAs, and 52 mRNAs, was constructed and visualized in Cytoscape. Further, using the univariate and multivariate Cox regression model, we screened 8 lncRNAs (AC078778.1, LINC00525, AC008676.1, AP000553.1, SACS-AS1, AC009065.1, AC127496.3, and MYO16-AS1) to construct an lncRNA signature for predicting the overall survival of MIBC patients. Kaplan-Meier analysis and a receiver operating characteristic curve were applied to evaluate the performance of the signature. Real-time quantitative PCR analysis was carried out to test expression levels of the 8 lncRNAs in MIBC patient tissues. Transwell assays demonstrated that overexpressing MYO16-AS1 can enhance UMUC2 migration and invasion. Our study offers a novel lncRNA-correlated ceRNA model to better understand the molecular mechanisms involved in MIBC. In addition, we developed an independent 8-lncRNAs biomarker for prognostic prediction and identified MYO16-AS1 as an oncogenic lncRNA in bladder cancer.

Oncometabolite L-2-hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma.

Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L-2-hydroxyglurate (L-2HG). L-2HG has been reported to inhibit the activity of some α-ketoglutarate-dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L-2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L-2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L-2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L-2HG-induced VM formation. In conclusion, these findings highlighted the pathogenic link between L-2HG and VM and suggested a novel therapeutic target for RCC.

Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening.

The testicular receptor 4 (TR4) is a nuclear receptor implicated in multiple pathological processes, including cancer development, chemotherapy, and radiotherapy resistance. However, no effective TR4 small-molecule regulator is available to date. Here, we assessed a physical-interaction-based surface plasmon resonance imaging assay for discovery of TR4 regulators. We screened 1018 FDA-approved drugs and obtained 126 drugs with K D values below 10-6 M. The dual-luciferase-based biological assay verified four activatory compounds and two inhibitory compounds against TR4. Among them, nilotinib exhibited the most potent inhibitor, with an EC50 of 1.05 µM, while genistein represented the most potent activator, with an EC50 of 2.42 µM. Both drugs were predicted to bind in the ligand binding pocket of TR4. The circular dichroism spectroscopic assay revealed differed conformation changes upon nilotinib or genistein binding. These results established our combined physical and biological approaches as a highly effective way to identify and develop new TR4 regulators.

Beta-1,6 glucan converts tumor-associated macrophages into an M1-like phenotype.

Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. We have reported that the ß-D-(1→6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the ß-1,6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo. On a cellular mechanistic level, the ß-1,6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-κB and MAPK. Further, TLR2 was identified as the receptor of ß-1,6-glucan in the transformation effect. In addition, a very similar ß-1,6-glucan with side chains of ß-Glc or α-Galρ which was purified from Lentinus edodes showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of ß-1,6-glucan in cancer immunotherapy.

Association of a Province-Wide Intervention With Salt Intake and Hypertension in Shandong Province, China, 2011-2016.

Importance: High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. Objective: To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. Design, Setting, and Participants: This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. Interventions: Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. Main Outcomes and Measures: The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. Results: Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. Conclusions and Relevance: The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide.

The prognostic value of miRNA-18a-5p in clear cell renal cell carcinoma and its function via the miRNA-18a-5p/HIF1A/PVT1 pathway.

Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

MiR-128-3p mediates TNF-α-induced inflammatory responses by regulating Sirt1 expression in bone marrow mesenchymal stem cells.

Tumor Necrosis Factor α (TNF-α), a multifunctional pro-inflammatory cytokine, is produced by macrophages/monocytes during acute inflammation, and plays a critical role in orchestrating the cytokine cascade in various inflammatory diseases. Previous studies demonstrated that TNF-α induces inflammatory responses in bone marrow mesenchymal stem cells (BMSCs) transplantation, leading to unsatisfactory effects and limit the clinical use of BMSCs. MicroRNAs are reported to involve in inflammation by regulating the expression of their targets in inflammatory response pathway. However, whether microRNAs mediate TNF-α-induced inflammatory responses in BMSCs remains elusive. Here, we found that TNF-α treatment induced an inflammatory response by increasing the levels of key inflammatory mediators, including IL-6, IL-1ß, matrix metalloproteinase 9 (MMP9) and monocyte chemotactic protein-1 (MCP-1) in BMSCs. Moreover, real-time PCR result showed dramatically up-regulation of miR-128-3p after exposure to TNF-α. Interestingly, miR-128-3p over-expression exacerbated the TNF-α-induced inflammatory response, while suppression of miR-128-3p effectively eliminated the inflammatory response in BMSCs. Bioinformatic analysis identified sirtuin 1 is a direct target of miR-128-3p. Up-regulation of sirtuin 1 induced by resveratrol also diminished the TNF-α-induced inflammatory response in BMSCs. Altogether, our results indicated that miR-128-3p targets sirtuin 1 to mediate the TNF-α-induced inflammatory response in BMSCs, which may provide new strategies to protect against inflammatory-dependent impairments in BMSCs.

Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals.

BACKGROUND: Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. METHODS: We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. RESULTS: Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. CONCLUSION: Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.