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1.
J Cell Physiol ; 235(2): 1235-1246, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31267540

RESUMO

Prostate cancer (PCa) is the second leading cause of death among American men. Increasing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis of PCa. In this study, we explored the biological functions of small nucleolar RNA host gene 12 (SNHG12) and investigated the interaction between miR-133b and SNHG12 in the progression of PCa. Data was downloaded from The Cancer Genome Atlas and Human Cancer Metastasis Database, and clinicopathological characteristics were analyzed with relapse-free survival rate. We detected SNHG12 expression level in PCa cells and tissues, and then analyzed its clinical significance, which revealed that SNHG12 has the potent to predict prognosis of PCa. Bioinformatic analysis revealed that SNHG12 was closely related to the progression of PCa and could target candidate microRNA (miR-133b). After transfecting SNHG12 silencing plasmid and miR-133b mimic/sponge, biological function assays were conducted and results illustrated that SNHG12 associated with miR-133b exerted biological effects on cancer cell growth, migration, and invasion. Direct interactions between miR-133b and SNHG12 have been found and SNHG12 acts as an oncogene to promote tumorigenesis of PCa by sponging tumor suppressor gene miR-133b.

2.
BMC Complement Altern Med ; 19(1): 343, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791318

RESUMO

BACKGROUND: Chloranthus serratus (Chloranthaceae) has been used to treat bruises, rheumatoid and bone pain. However, the anti-inflammatory mechanisms of C. serratus in vitro have not been fully elucidated. The present study aimed to explore the anti-inflammatory activity and potential mechanisms of C. serratus's separated part of water (CSSPW) in lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: The concentrations of CSSPW were optimized by CCK-8 method. Nitric oxide (NO) content was detected by one-step method. The levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA). Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by real-time quantitative PCR (qPCR). Immunofluorescence and DCFH-DA fluorescent probes were used to detect p65 nuclear translocation and reactive oxygen species (ROS) content, respectively. Western blotting was used to assay the protein expression of mitogen-activated protein kinases (MAPK), nuclear factor-kappa B (NF-κB) and nuclear transcription factor E2 related factor 2/haem oxygenase-1 (Nrf2/HO-1) pathways. RESULTS: The final concentrations of 15 ng/mL, 1.5 µg/mL and 150 µg/mL were selected as low, medium and high doses of CSSPW, respectively. CSSPW treatment significantly reduced the generation of NO, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandinE2 (PGE2), iNOS mRNA and COX-2 mRNA in response to LPS stimulation. Furthermore, the protein expression of the MAPK and NF-κB pathways was suppressed by CSSPW treatment, as well as p65 nuclear translocation and ROS production. In contrast, the protein expression of the Nrf2/HO-1 pathway was markedly upregulated. CONCLUSIONS: CSSPW exerts its anti-inflammatory effect via downregulating the production of pro-inflammatory mediators, inhibiting the activation of NF-κB and MAPK pathways, as well as activating Nrf2/HO-1 pathway in LPS-induced RAW264.7 cells.

3.
Clin Cancer Res ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796514

RESUMO

PURPOSE: Emerging evidence indicates that castration-resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor (AR) or its V7 splice variant (AR-V7) and commonly becomes resistant to endocrine therapy. The aim of this work is to evaluate the function of a kinesin protein, KIF4A, in regulating AR/AR-V7 in prostate cancer endocrine therapy resistance. EXPERIMENTAL DESIGN: We examined KIF4A expression in clinical prostate cancer specimens by immunohistochemistry. Regulated pathways were investigated by qRT-PCR, immunoblot analysis, immunoprecipitation, and luciferase reporter and chromatin immunoprecipitation (ChIP) assays. A series of functional analyses were conducted in cell lines and xenograft models. RESULTS: Examination of the KIF4A protein and mRNA levels in prostate cancer patients showed that increased expression of KIF4A was positively correlated with AR levels. Patients with lower tumor KIF4A expression had improved overall survival (OS) and disease-free survival (DFS). Mechanistically, KIF4A and AR form an auto-regulatory positive feedback loop in prostate cancer: KIF4A binds AR and AR-V7 and prevents CHIP-mediated AR and AR-V7 degradation; AR binds the promoter region of KIF4A and activates its transcription. KIF4A promotes castration-sensitive and castration-resistant prostate cancer cell growth through AR- and AR-V7-dependent signaling. Furthermore, KIF4A expression is upregulated in enzalutamide (ENZ)-resistant prostate cancer cells, and KIF4A knockdown effectively reverses ENZ resistance and enhances the sensitivity of CRPC cells to endocrine therapy. CONCLUSION: These findings indicate that KIF4A plays an important role in the progression of CRPC and serves as a crucial determinant of the resistance of CRPC to endocrine therapy.

4.
Oncogene ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705065

RESUMO

Circular RNAs (circRNAs) have been increasingly indicated to be important participants in the development and progression of various malignant tumors. Our previous studies found that hundreds of circRNAs were aberrantly expressed in bladder cancer (BC) by high-throughput sequencing and we have confirmed that the downregulated circRNAs circHIPK3, circRNA BCRC-3, and circNR3C1 played inhibitory roles in BC progression. In this study, we focused on the upregulated circRNAs and identified a novel circular RNA, hsa_circ_0001361 (circ0001361), was expressed at high levels in BC tissues and cell lines based on RNA-Seq data and qRT-PCR analysis, and it was positively corelated with pathologic grade and muscle invasion. Moreover, Kaplan-Meier survival analysis implied that BC patients with high circ0001361 expression level had a poor overall survival. Functionally, circ0001361 promoted BC cell invasion and metastasis both in vitro and in vivo, but had no effect on cell cycle and proliferation. Mechanistically, RNA sequencing analysis indicated that MMP9 was upregulated in circ0001361-overexpressed BC cells, and MMP9 was verified to mediate circ0001361-induced cell migration and invasion. Furthermore, we demonstrated that circ0001361 could directly interact with miR-491-5p to upregulate MMP9 expression. Collectively, our findings indicate that circ0001361 plays oncogenic role in BC invasion and metastasis through targeting the miR-491-5p/MMP9 axis, and it might be a potential novel target for BC therapy.

5.
Food Funct ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742290

RESUMO

Bacillus amyloliquefaciens SC06 (BaSC06), a potential probiotic, plays a positive role in animal growth performance and immune function. The aim of the present study was to investigate the protective effect of BaSC06 against Salmonella infection and its association with macrophage polarization. C57BL/6 mice were fed with or without a BaSC06-containing diet before Salmonella enterica Typhimurium (ST) challenge. Results showed that BaSC06 had a protective effect against ST inoculation and induced both M1 and M2 macrophage polarization in the cecum. An in vitro co-culture model demonstrated that BaSC06 promoted M1 polarization directly, and thus increased the phagocytosis and bactericidal activity against ST. In addition, adoptive transfer of bone marrow-derived macrophages (BMDMs) stimulated by BaSC06 significantly decreased the counts of ST in the spleen. Furthermore, 16S rRNA-based analysis of cecal content showed that BaSC06 significantly increased the proportion of Verrucomicrobia and decreased Bacterodetes. Transplantation of the fecal microbiota from BaSC06-treated animals promoted M2 macrophage polarization in the cecum and significantly relieved inflammation caused by ST. In conclusion, BaSC06 polarized macrophages to the M1 type directly resulting in excellent bactericidal activity. Meanwhile, the microbiota modified by BaSC06 can induce M2 polarization which ameliorates the inflammation caused by ST.

6.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671660

RESUMO

Many dyes and pigments are used in textile and printing industries, and their wastewater has been classed as a top source of pollution. Biodegradation of dyes by fungal laccase has great potential. In this work, the influence of reaction time, pH, temperature, dye concentration, metal ions, and mediators on laccase-catalyzed Remazol Brilliant Blue R dye (RBBR) decolorization were investigated in vitro using crude laccase from the white-rot fungus Ganoderma lucidum. The optimal decolorization percentage (50.3%) was achieved at 35 °C, pH 4.0, and 200 ppm RBBR in 30 min. The mediator effects from syringaldehyde, 1-hydroxybenzotriazole, and vanillin were compared, and 0.1 mM vanillin was found to obviously increase the decolorization percentage of RBBR to 98.7%. Laccase-mediated decolorization percentages significantly increased in the presence of 5 mM Na+ and Cu2+, and decolorization percentages reached 62.4% and 62.2%, respectively. Real-time fluorescence-quantitative PCR (RT-PCR) and protein mass spectrometry results showed that among the 15 laccase isoenzyme genes, Glac1 was the main laccase-contributing gene, contributing the most to the laccase enzyme activity and decolorization process. These results also indicate that under optimal conditions, G. lucidum laccases, especially Glac1, have a strong potential to remove RBBR from reactive dye effluent.

7.
Sci Total Environ ; 703: 134617, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31715465

RESUMO

Soil structure plays a key role in soil organic carbon (SOC) dynamics. To determine how soil structure and aggregate affects SOC, we collected undisturbed soil cores of 0-5 cm layer (Typic Hapludoll) at an experimental site in Northeast China. The site had been under continuous tillage treatments of conventional tillage (CT) and no tillage (NT) for 17 years. We measured SOC by elemental analysis, aggregate size distribution by wet sieving, and soil pore parameters of pore size distribution, pore average diameter, pore numbers, pore connectivity, pore anisotropy, and pore fractal dimension by X-ray computer tomography. SOC content was significantly correlated with aggregate-associated SOC and soil water-stable aggregate content. CT with residue removal and annual plowing and cultivation increased <53 µm and 53-250 µm aggregates. CT decreased total SOC of 0-5 cm soil layer but increased aggregate-associated SOC of <53 µm. NT with greater residue input increased total SOC of 0-5 cm soil layer by 26.0% and aggregate mean weight diameter by 111.8% and increased aggregates of 250-1000 µm and >1000 µm. Soil under NT had a greater total number of micropores and greater connectivity whereas CT had a greater total number of macropores, average macropore diameter, anisotropy, and fractal dimension. Structural equation modeling showed that CT can decrease SOC of 0-5 cm soil layer by different paths, including increased anisotropy and macropore porosity, and NT can increase SOC of 0-5 cm soil layer by different paths, including increased mean weight diameter and connectivity. These results enhance our understanding of the relationship between soil structure and SOC, and could guide tillage management decisions to increase SOC.

8.
Can J Microbiol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31751146

RESUMO

Lipopolysaccharide (LPS) is essential for successful nodulation during the symbiosis of rhizobia and legumes. However, the detailed mechanism of the LPS in this process has not yet been clearly elucidated. In this study, the effects of exudates the common bean seeds on the growth, lipopolysaccharide production and lipopolysaccharide transport genes expression (lpt) of Rhizobium anhuiense were investigated. R. anhuiense exposed to exudates showed changes in LPS electrophoretic profiles and content, where the LPS band was wider and the LPS content was higher in R. anhuiense treated with seeds exudates. Exudates enhanced cell growth of R. anhuiense in a concentration dependent manner; R. anhuiense exposed to higher doses of the exudate showed faster growth. Seven ltp genes of R. anhuiense were amplified and sequenced. Sequences of six lpt genes, except for lptE, were the same as found in previously analyzed R. anhuiense strains, while lptE shared low sequence similarity with other strains. Exposure to the exudates strongly stimulated the expression of all lpt genes. An approximately 6.7- (lptG) to 301-fold (lptE) increase in the transcriptional levels were observed after only 15 min of exposure to exudates. These results indicate that seed exudates affect the LPS by making the cell wall structure more conducive to symbiotic nodulation.

9.
Anal Chem ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756075

RESUMO

The combination of gold nanoclusters (AuNCs) and nanomaterial-based quencher creates an innovative method for sensors design. In this work, we report a novel fluorescent sensing platform for sensitive detection of butyrylcholinesterase (BChE). The fluorescence of AuNCs can be quenched by iron oxyhydroxide (FeOOH) nanomaterials. In the presence of BChE and acetylthiocholine (ATCh), nano FeOOH can be effectively decomposed by the enzymatic hydrolysate (thiocholine), leading to the recovery of AuNCs fluorescence. The Au/FeOOH exhibits the highest fluorescence quenching efficiency compared with other transition metal oxyhydroxide based sensing systems, e.g., Au/CoOOH and Au/NiOOH. The corresponding fluorescence recovery efficiency is also the best for Au/FeOOH. The large surface area of nanomaterials and thin nanostructure provide a favorable platform for the reaction of enzymatic hydrolysate and eventually improve the high sensitivity of the probe. A linear detection range for BChE is achieved within 5-100 ng mL-1 along with a detection limit of 4 ng mL-1. By taking advantage of the high sensitivity, the Au/FeOOH was successfully used to BChE quantification in 2 µL of finger blood.

10.
Inflammation ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728743

RESUMO

The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31776906

RESUMO

Bamboo forests are one of the most important forest resources in subtropical China. A pure, single-layer bamboo forest is considered an optimal habitat for intercropping medicinal herbs. Soil microorganisms have an important role in various ecological processes and respond quickly to environmental changes. However, changes in soil nutrients and microbial communities associated with agroforestry cultivation methods remain poorly documented. In the present study, a pure moso bamboo (Phyllostachys edulis) forest (Con) and three adjacent moso bamboo-based agroforestry (BAF) systems (moso bamboo-Paris polyphylla (BP), moso bamboo-Tetrastigma hemsleyanum (BT) and moso bamboo-Bletilla striata (BB)) were selected; and their soil chemical properties and bacterial communities were studied and compared to evaluate the effects of agroforestry on soil bacterial communities and the relationship between soil properties and bacterial communities in BAF systems. Results showed that compared with soils under the Con, soils under the BAF systems had more (p < 0.05) soil organic carbon (SOC) and available nitrogen (AN) but lower (p < 0.05) pH and available potassium (AK). In addition, compared with the Con system, the BB and BT systems had significantly greater (p < 0.05) available phosphorus (AP). Compared with that in the Con system, the Shannon index in the BAF systems was significantly greater (p < 0.05), but the Chao1 index not different. On the basis of relative abundance values, compared with the Con soils, the BAF soils had a significantly greater abundance of (p < 0.05) Bacteroidetes and Planctomyces but a significantly lower abundance of (p < 0.05) Verrucomicrobia, Gemmatimonadetes and Candidatus Xiphinematobacter. Moreover, compared with the Con system, the BB and BT systems had a greater (p < 0.05) abundance of Actinobacteria, Rhodoplanes, Candidatus Solibacter and Candidatus Koribacter. Redundancy analysis (RDA) revealed that soil pH, SOC and AP were significantly correlated with bacterial community composition. Results of this study suggest that intercropping medicinal herbs can result in soil acidification and potassium (K) depletion; thus, countermeasures such as applications of K fertilizer and alkaline soil amendments are necessary for BAF systems.

12.
J Clin Pharmacol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31777097

RESUMO

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, inherited, progressively debilitating, and often fatal disease caused by deposition of mutated transthyretin (TTR) protein. Patisiran is an RNA interference therapeutic comprising a novel small interfering ribonucleic acid (ALN-18328) formulated with 2 novel lipid excipients, DLin-MC3-DMA and PEG2000 -C-DMG, in a lipid nanoparticle targeted to inhibit hepatic TTR synthesis. Here we report the pharmacokinetics (PK) of ALN-18328, DLin-MC3-DMA, and PEG2000 -C-DMG from a phase 2 multiple-ascending-dose study and its open-label extension (OLE) in patients with hATTR amyloidosis. Twenty-nine patients received 2 intravenous infusions of patisiran of 0.01, 0.05, 0.15, or 0.3 mg/kg at 3- or 4-week intervals; of these, 27 patients received 0.3 mg/kg once every 3 weeks over 24 months in the OLE study. Plasma PK profiles of ALN-18328 and DLin-MC3-DMA exhibited 2 phases, the first characterized by a short distribution half-life and the second by a minor peak and relatively long terminal elimination half-life. PK exposures to 3 analytes increased proportionally across the dose range of 0.01 to 0.3 mg/kg. For ALN-18328, mean terminal elimination half-life was 3.2 days, mean total clearance was 3.0 mL/h/kg, and urinary excretion was negligible. All 3 analytes exhibited stable PK profiles with chronic dosing over 2 years. The 2- to 3-fold plasma accumulation (AUCτ ) of ALN-18328 at steady state is attributable to the association of ALN-18328 with the cationic lipid DLin-MC3-DMA. There was no appreciable accumulation of PEG2000 -C-DMG.

13.
Aging (Albany NY) ; 11(21): 9597-9615, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727869

RESUMO

Kidney cancer ranked in the top 10 for both men and women in the estimated numbers of new cancer cases in the United States in 2018. Targeted therapies have recently been administered to patients with clear cell renal cell carcinoma (ccRCC), but the overall survival of patients at the terminal stage of the disease has not been as good as expected. It is therefore necessary to uncover efficient biomarkers for early diagnosis, and to clarify the molecular mechanisms underlying ccRCC progression and metastasis. Increased evidence has shown that long non-coding RNAs (lncRNAs) play important roles during tumor progression. In this study, 10 candidate lncRNAs with diagnostic and prognostic values in ccRCC were identified: IGFL2-AS1, AC023043.1, AP000439.2, AC124854.1, AL355102.4, TMEM246-AS1, AL133467.3, ZNF582-AS1, LINC01510 and PSMG3-AS1. Enrichment analysis revealed metabolic and functional pathways, which may be closely associated with kidney cancer tumorigenesis. Six representative processes were summarized, namely glycolysis, amino acid metabolism, lipid synthesis, reductive carboxylation, nucleotide metabolism, transmembrane transport and signal transduction. In combination, the present results provided prognostic and diagnostic biomarkers for ccRCC and might pave the way for targeted intervention and molecular therapies in the future.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31628706

RESUMO

An exceptionally strong solvation effect of dimethyl sulfoxide (DMSO) on I2 is identified by the largest shift observed so far of the I2 Raman peak with respect to I2 vapor and by elongated I-I bond lengths in first-principles molecular-dynamics simulations. This effect together with strong binding by an RuO2 surface to I2 is found to invert the direction of the reaction I- +I2 ⇌I3 - to the left-hand side. Inspired by this finding, we prepared a Li-O2 battery with the Li/DMSO+LiI/RuO2 structure. The synergic action of DMSO and RuO2 on I2 is found to suppress the shuttle effect of the redox mediator (RM) by anchoring I2 molecules, the oxidation product of the RM. Significantly enhanced stability is demonstrated over 100 cycles at charging voltage below 3.65 V.

15.
Surg Endosc ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586253

RESUMO

BACKGROUND: Emergency endoscopic retrograde cholangiopancreatography (ERCP) for ascending acute cholangitis in patients with severe comorbidities is challenging. Here, we evaluated the efficacy and safety of one-stage ERCP in such patients by performing a retrospective study. METHODS: We included all patients with ascending acute cholangitis and undergoing ERCP between January 2017 and March 2019. In total, we recruited 212 patients: 74 and 138 with and without severe comorbidities, respectively. We collected and analyzed data related to basal characteristics, ERCP, and clinical outcomes. RESULTS: Elderly age (76.20 ± 9.99 years vs. 66.52 ± 8.16 years, P = 0.000), higher levels of leukocyte count (15.86 ± 2.47 × 109/ml vs. 13.49 ± 1.65 × 109/ml, P = 0.000), and serum bilirubin (3.11 ± 1.29 mg/dl vs. 1.94 ± 0.90 mg/dl, P = 0.000) were present in patients with severe comorbidities. A significantly higher proportion of these patients were severe cases (32.4% vs. 6.5%, P = 0.000), American Society of Anesthesiologists (ASA) stage V status (37.8% vs. 10.1%, P = 0.000) and had undergone general anesthesia (56.8% vs. 18.8%, P = 0.000). Successful biliary cannulation and complete stone clearance in one session were achieved in 207 and 202 patients, respectively. Mean length of hospital stay was 8.02 ± 2.71 days. Forty-three patients required ICU stay with the mean length of 3.26 ± 3.51 days. In-hospital mortality occurred in seven patients; all these patients had severe comorbidities. ERCP details, including urgent and early ERCP, biliary cannulation, complete stone clearance in one session, stent insertion, and complications were not significantly different between the two groups. Patients with severe comorbidities had a longer in-hospital stay (9.39 ± 3.15 days vs. 7.29 ± 2.11 days, P = 0.000), a higher proportion of ICU admission (45.9% vs. 6.5%, P = 0.000), and a longer ICU stay length (4.88 ± 4.37 days vs. 1.44 ± 0.52 days, P = 0.000). Our data also revealed that early diagnosis is an important predictor associated with clinical outcomes. CONCLUSIONS: One-stage ERCP is safe and effective for ascending acute cholangitis caused by choledocholithiasis. Early diagnosis is a significant predictor of clinical outcomes.

16.
Environ Pollut ; 255(Pt 1): 113167, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31522008

RESUMO

Mine tailings contain toxic metals and can lead to serious pollution of soil environment. Phytoremediation using legumes has been regarded as an eco-friendly way for the rehabilitation of tailings-laden lands but little is known about the changes of microbial structure during the process. In the present study, we monitored the dynamic change of microbiota in the rhizosphere of Pongamia pinnata during a 2-year on-site remediation of vanadium-titanium magnetite tailings. After remediation, overall soil health conditions were significantly improved as increased available N and P contents and enzyme activities were discovered. There was also an increase of microbial carbon and nitrogen contents. The Illumina sequencing technique revealed that the abundance of taxa under Proteobacteria was increased and rhizobia-related OTUs were preferentially enriched. A significant difference was discovered for sample groups before and after remediation. Rhizobium and Nordella were identified as the keystone taxa at genus rank. The functional prediction indicated that nitrogen fixation was enhanced, corresponding well with qPCR results which showed a significant increase of nifH gene copy numbers by the 2nd year. Our findings for the first time elucidated that legume phytoremediation can effectively cause microbial communities to shift in favour of rhizobia in heavy metal contaminated soil.

17.
Mol Med Rep ; 20(5): 4226-4234, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545471

RESUMO

Damage to the blood­brain barrier (BBB) resulting from systemic inflammation caused by surgical trauma is associated with cognitive dysfunction, and individuals with hyperlipidemia are more sensitive to such impairment. The present study was designed to ascertain whether dexmedetomidine (Dex) treatment could reduce the incidence of cognitive dysfunction following surgery in a hyperlipidemia model. Hyperlipidemia was induced in Sprague­Dawley rats (male, 6­7 months old) by consuming a high­fat diet, and rats were divided into three groups (n=10 each) and underwent: exploratory laparotomy to introduce surgical trauma (surgery group), laparotomy and Dex treatment (surgery+Dex group), or sham surgery (sham group). Learning, memory and exploration behavior were assessed using the Morris water maze. Concentrations of tumor necrosis factor (TNF)­α and interleukin (IL)­1ß, were determined by enzyme­linked immunosorbent assay. BBB permeability was assessed by Evans blue staining. Relative major facilitator superfamily domain­containing protein 2 (Mfsd2a) mRNA expression was determined by quantitative PCR. In the Morris water maze test, the time and distance ratio for the surgery group was significantly lower than those of the sham and surgery+Dex groups (P<0.05). In addition, the TNF­α concentrations in the sham and surgery+Dex groups were lower than that in the surgery group (P<0.05 on days 1 and 3). Evans Blue staining was increased in the surgery group on day 1 (P<0.01). Mfsd2a mRNA expression was higher in the sham and surgery+Dex groups compared with that noted in the surgery group (P<0.05). In conclusion, Dex treatment decreased the incidence of cognitive dysfunction following surgical trauma in a hyperlipidemia rat model. We demonstrated that Dex stabilized BBB integrity through increased Mfsd2a gene expression.

18.
Oncogene ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501521

RESUMO

Renal cell carcinoma (RCC) is one of the most lethal urological tumors. Using sunitinib to improve the survival has become the first-line therapy for metastatic RCC patients. However, the occurrence of sunitinib resistance in the clinical application has curtailed its efficacy. Here we found TR4 nuclear receptor might alter the sunitinib resistance to RCC via altering the TR4/lncTASR/AXL signaling. Mechanism dissection revealed that TR4 could modulate lncTASR (ENST00000600671.1) expression via transcriptional regulation, which might then increase AXL protein expression via enhancing the stability of AXL mRNA to increase the sunitinib resistance in RCC. Human clinical surveys also linked the expression of TR4, lncTASR, and AXL to the RCC survival, and results from multiple RCC cell lines revealed that targeting this newly identified TR4-mediated signaling with small molecules, including tretinoin, metformin, or TR4-shRNAs, all led to increase the sunitinib sensitivity to better suppress the RCC progression, and our preclinical study using the in vivo mouse model further proved tretinoin had a better synergistic effect to increase sunitinib sensitivity to suppress RCC progression. Future successful clinical trials may help in the development of a novel therapy to better suppress the RCC progression.

19.
Int J Oncol ; 55(3): 645-656, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31364727

RESUMO

As one of the most commonly reported malignancies of the urinary system, clear cell renal cell carcinoma (ccRCC) is an advanced metastatic tumor with high mortality rates. The Rac family small GTPase 2 (RAC2) is a member of the Rho GTPases. Although Rho GTPases play an important role in numerous different types of tumor, whether they have functions in ccRCC remains uncertain. The present study utilized bioinformatics analyses in order to compare the expression levels of RAC2 in ccRCC tumors vs. adjacent tissues, and assessed the association between RAC2 expression and clinicopathological parameters. Furthermore, reverse transcription­quantitative PCR, western blotting and immunohistochemistry assays were performed to validate RAC2 expression levels in human ccRCC tissues and cell lines. Functional experiments were also conducted in order to identify the roles of RAC2 in vitro. The results revealed that RAC2 was upregulated in ccRCC tissues and cell lines. In addition, elevated expression levels of RAC2 were significantly associated with a poor overall survival (P=0.0061), higher Tumor­Node­Metastasis stage and worse G grade. Receiver operating characteristic analysis indicated that high expression levels of RAC2 could be a diagnostic index for ccRCC (area under the curve, 0.9095; P<0.0001). Furthermore, knockdown of RAC2 in vitro attenuated the proliferation, migration and invasion of renal carcinoma cells. In conclusion, the results of the present study demonstrated that RAC2 may act as a promising prognostic and diagnostic biomarker of ccRCC, and could be considered as a potential therapeutic target for treating ccRCC.

20.
Biomed Pharmacother ; 118: 109264, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31390578

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system. However, there are still no reliable biomarkers for the diagnosis and prognosis of ccRCC. In this study, we aimed to screen candidate biomarkers and potential therapeutic targets for ccRCC. METHODS: Differentially expressed genes (DEGs) were screened using NetworkAnalyst. Protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) were utilized to identify hub genes. Then, we assessed the prognostic and diagnostic values of hub genes to screen candidate biomarkers. Gene Set Enrichment Analysis (GSEA) was applied to reveal potential mechanisms of candidate biomarkers in ccRCC. Oncomine database and The Human Protein Atlas were used to verify the expression of candidate biomarkers online. In addition, qRT-PCR, Enzyme linked immunosorbent assay (ELISA) and Immunohistochemistry (IHC) assays were performed to validate the expression level of candidate biomarkers in ccRCC cells and tissues. RESULTS: A total of 771 genes were identified as DEGs. GO function analysis showed that DEGs were mostly enriched in excretion, apical part of cell and monovalent inorganic cation transmembrane transporter activity. KEGG pathway analysis demonstrated that DEGs were mostly involved in Neuroactive ligand-receptor interaction. After utilizing PPI network and WGCNA, nine genes (IFNG, CXCR3, PMCH, CD2, FASLG, CXCL13, CD8A, CD3D and GZMA) were identified as the hub genes. Moreover, survival analysis exhibited that high expression of CXCL13 predicted poor survival in both overall survival (OS) and disease free survival (DFS). The ROC curves indicated that CXCL13 could distinguish ccRCC samples from normal kidney samples. High expression of CXCL13 group was mostly associated with RB and MEL18 pathways by GSEA. Furthermore, qRT-PCR, ELISA and IHC results showed that the expression of CXCL13 was elevated in ccRCC. CONCLUSIONS: Our study illustrated that CXCL13 had good diagnostic and prognostic value, which may become a candidate biomarker and therapeutic target for ccRCC.

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