Astragaloside IV protects renal tubular epithelial cells against oxidative stress-induced injury by upregulating CPT1A-mediated HSD17B10 lysine succinylation in diabetic kidney disease.

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress.

BACKGROUND: Accumulating evidence suggests that activated hepatocytes are involved in the deposition of the excess extracellular matrix during liver fibrosis via the epithelial to mesenchymal transition. Lipid accumulation in hepatocytes are implicated in the pathogenesis of chronic liver injury. CD36 is known to mediate long-chain fatty acid (LCFA) uptake and lipid metabolism. However, it is unclear whether LCFA directly promotes hepatocyte activation and the involved mechanisms have not been fully clarified. METHODS: Mice were fed with a high fat diet (HFD) and normal hepatocyte cells (Chang liver cells) were treated with palmitic acid (PA) in vivo and in vitro. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to examine the gene and protein expression of molecules involved in hepatic fibrogenesis and hepatocyte activation. CD36 was knocked down by transfecting CD36 siRNA into hepatocyte cells. Hydrogen peroxide (H2O2) and reactive oxygen species (ROS) levels were detected using commercial kits. RESULTS: HFD induced a profibrogenic response and up-regulated CD36 expression in vivo. Analogously, PA increased lipid accumulation and induced human hepatocyte activation in vitro, which was also accompanied by increased CD36 expression. Interestingly, knockdown of CD36 resulted in a reduction of hepatocyte lipid deposition and decreased expression of Acta2 (34% decrease), Vimentin (29% decrease), Desmin (60% decrease), and TGF-ß signaling pathway related genes. In addition, HFD and PA increased the production of H2O2 in vivo (48% increase) and in vitro (385% increase), and the antioxidant, NAC, ameliorated PA-induced hepatocyte activation. Furthermore, silencing of CD36 in vitro markedly attenuated PA-induced oxidative stress (H2O2: 41% decrease; ROS: 39% decrease), and the anti-activation effects of CD36 knockdown could be abolished by pretreatment with H2O2. CONCLUSIONS: Our study demonstrated that LCFA facilitates hepatocyte activation by up-regulating oxidative stress through CD36, which could be an important mechanism in the development of hepatic fibrosis.

Overexpression of microRNA-30a-5p inhibits liver cancer cell proliferation and induces apoptosis by targeting MTDH/PTEN/AKT pathway.

Increasing results suggest microRNAs (miRNAs) could function important roles in malignant tumor progression. miR-30a-5p is downregulated in variety of cancers and acts as a cancer suppressing gene. The functions and molecular mechanisms of miRNA-30a-5p in hepatocellular carcinoma (HCC) remain unclear. In the present study, quantitative real-time PCR (qRT-PCR) was used to detect miR-30a-5p expression in 16 pairs of HCC and their adjacent non-cancerous tissues and HCC cell lines. By overexpression of miRNA-30a-5p, CCK-8 and colon formation assay were used to evaluate cell growth and flow cytometry to evaluate cell apoptosis. Western blot was used to test protein expression. And potential mechanisms were analyzed with luciferase activity assay. In vivo HepG2 tumor growth was observed with nude mice. Our results showed that miR-30a-5p expression in HCC tissues was significantly lower compared to adjacent non-cancerous liver tissues, and lower miR-30a-5p expression was also observed in HCC cell lines compared to normal liver cell. Luciferase assay showed that metadherin (MTDH) mRNA was a direct target of miR-30a-5p. A significant reverse correlation between miR-30a-5p and MTDH in liver cancer tissues was observed. miR-30a-5p overexpression in HCC cells significantly inhibited cell proliferation, colon formation, and induced apoptosis while MTDH overexpression reversed growth inhibition and apoptosis induction of miRNA-30a-5p in HCC cells. miRNA-30a-5p upregulated phosphatase and tensin homolog (PTEN) protein expression and thus inhibited AKT activating by targeting MTDH. miRNA-30a-5p also significantly inhibited HepG2 tumor growth in vivo. Our results suggest that underexpression of miR-30a-5p might function as a tumor suppressing miRNA by directly targeting MTDH in HCC and is therefore a potential candidate biomarker for HCC targeting therapy.

Shear Wave Elastography of the Spleen for Monitoring Transjugular Intrahepatic Portosystemic Shunt Function: A Pilot Study.

OBJECTIVES: To assess the feasibility of splenic shear wave elastography in monitoring transjugular intrahepatic portosystemic shunt (TIPS) function. METHODS: We measured splenic shear wave velocity (SWV), main portal vein velocity (PVV), and splenic vein velocity (SVV) in 33 patients 1 day before and 3 days to 12 months after TIPS placement. We also measured PVV, SVV, and SWV in 10 of 33 patients with TIPS dysfunction 1 day before and 3 to 6 days after TIPS revision. Analyses included differences in portosystemic pressure gradient (PPG), PVV, SVV, and mean SWV before and after TIPS procedures; comparison of median SWV before and after TIPS procedures; differences in PVV, SVV, and SWV before and at different times up to 12 months after TIPS placement; accuracy of PVV, SVV, and SWV in determining TIPS dysfunction; and correlation between PPG and SWV. RESULTS: During 12 months of follow-up, 23 of 33 patients had functioning TIPS, and 10 had TIPS dysfunction. The median SWV was significantly different before and after primary TIPS placement (3.60 versus 3.05 m/s; P = .005), as well as before and after revision (3.73 versus 3.06 m/s; P = .003). The PPG, PVV, and SVV were also significantly different before and after TIPS placement and revision (P < .001). The PPG and SWV decreased, whereas PVV and SVV increased, after successful TIPS procedures. A positive correlation was observed between PPG and SWV (r = 0.70; P < .001), and a negative correlation was observed between PPG and PVV and SVV (r = -0.65; P < .001). The areas under the receiver operating characteristic curve for PVV, SVV, and SWV in determining TIPS dysfunction were 0.82, 0.84, and 0.81, respectively. CONCLUSIONS: Splenic SWV is compatible with splenoportal venous velocity in quantitatively monitoring TIPS function and determining TIPS dysfunction.

[Effect of miR-30a-5p on the proliferation, apoptosis, invasion and migration of SMCC-7721 human hepatocellular carcinoma cells].

OBJECTIVE: To explore the effect of microRNA-30a-5p (miRNA-30a-5p) on the biological behavior of human hepatoma cells. METHODS: The liver cancer cell line SMCC-7721 cells and the normal liver cell line L02 cells (control) were transiently transfected with miRNA-30a-5p mimics and an miRNA-30a-5p inhibitor by Lipofectamine 2000 (Life Technologies). miR-30a-5p mRNA expression was detected by quantitative real-time (q)PCR. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay and apoptosis was assessed by flow cytometry.Invasion and migration were measured by transwell chamber assays. The SMCC-7721 cells was injected subcutaneously into nude mice to establish a tumor animal model. RESULTS: The SMCC-7721 cells transfected with miRNA-30a-5p mimics showed significantly higher miRNA-30a-5p mRNA expression than the non-transfected SMCC-7721 cells and the transfected control L02 cells (P<0.01). The miRNA-30a-5p mRNA expression was significantly lower in the SMCC-7721 cells transfected with the miRNA-30a-5p inhibitor than the non-transfected SMCC-7721 cells the control L02 cells (P<0.01). The overexpression of miRNA-30a-5p inhibited the viability, colony formation rate, and invasion and migration abilities, as shown in the cells transfected with the miRNA-30a-5p mimics (P<0.05); in addition, the miRNA-30a-5p promoted proliferation of cells (P<0.05), as shown by more S phase cells detected by flow cytometry. SMCC-7122 cells transfected with miRNA-30a-5p mimics produced tumors with significantly higher average weight than tumors produced by SMCC-7122 cells that were untransfected or transfected with empty vector (both P<0.01). CONCLUSION: Overexpression ofmiR-30a-5p had an inhibitory effect on cell proliferation, induced apoptosis, increased the number of cells in S phase, and markedly inhibited invasion and migration of SMCC-7721 HCC cells in vitro and in vivo.

[Effect of inflammatory stress on hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice].

OBJECTIVE: To investigate whether inflammatory stress exacerbates hepatic cholesterol accumulation and liver fibrosis using a C57BL/6J mouse model of chronic inflammation. METHODS: Twelve male C57BL/6J mice were given a high-fat diet (15.0% fat, 1.25% cholesterol, 0.5% cholic acid) and randomly assigned to the normal control group (n=6; subcutaneously injected with 0.5 mL of isotonic saline, every other day for 14 weeks) or the chronic inflammation model group (n=6; subcutaneously injected with of 0.5 mL of 10% casein, every other day for 14 weeks). At the end of week 14, the animals were sacrificed and blood was collected from the left ventricle for serological analysis of inflammatory markers and lipid profile, including serum amyloid A (SAA), interleukin-6 (IL-6), total cholesterol (TC) and free cholesterol (FC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)). Extracted liver tissues were divided for use in histological analysis (lipid accumulation and fibrosis evaluated by Oil Red O, Sirius red and Masson's trichrome staining) and quantitative fluorescence real-time PCR (to measure b-actin normalized expression of TNF-a MCP1, SREBP-2, LDLr, HMGCoA-r, ATF-6, GRP78, BMP-7, TGF-b, and collagens type I and type IV). Comparisons between groups were made by the two-samples t-test or Satterthwaite t-approximation test, collagen type I and type IV. RESULTS: Compared to the normal control group, the inflammation model group showed elevated serum IL-6 (12.55+/-4.75 vs. 32.41+/-7.42 pg/mL, P less than 0.01), reduced serum TC (14.82+/-1.56 vs. 10.62+/-0.48 mmol/L, P less than 0.01), up-regulated hepatic TNF-a mRNA expression (1.05+/-0.35 vs. 2.12+/-0.72, P less than 0.01), and elevated hepatic TC (12.10+/-2.57 vs. 23.21+/-8.75 mmol/L, P less than 0.05). In addition, the inflammation group showed abnormal lipid deposition, and increased and thickened reticular fibers. The livers of the inflammation group also showed up-regulated mRNA expression of SREBP-2 (normal control: 1.01+/-0.19 vs. 2.63+/-0.13, P less than 0.05), GRP78 (1.07+/-0.47 vs. 2.21+/-0.99, P less than 0.05), TGF-b (1.01+/-0.14 vs. 1.38+/-0.28, P less than 0.05), and collagen type I (1.02+/-0.27 vs. 1.71+/-0.51, P less than 0.05) and down-regulation of BMP-7 (1.01+/-0.15 vs. 0.55+/-0.25, P less than 0.01). CONCLUSION: Activation of the inflammatory system exacerbates hepatic cholesterol accumulation and hepatic fibrosis in C57BL/6J mice.

[Sorafenib and octreotide combination therapy can inhibit proliferation of and induce apoptosis in human hepatoma cells].

To investigate the effects of sorafenib and octreotide combination treatment on cellular proliferation and explore the underlying molecular mechanisms by using an in vitro cell culture system with the human hepatoma cell line, HepG2. HepG2 cells were treated with different concentrations of sorafenib and octreotide alone or in combination. Untreated HepG2 cells were used as controls. Treatment-induced cytotoxicity was determined with the cell counting kit-8 by Sigma-Aldrich, and rate of apoptosis was detected by flow cytometry. Fluorescent microscopy was used to observe rates of cell growth under the various treatments. Treatment-induced changes in protein expressions were detected by enzyme-linked immunosorbent assay (for vascular endothelial growth factor (VEGF)) and Western blotting (for the Mcl-1 apoptosis mediator and the ERK1/2 and PERK1/2 kinases). Sorafenib and octreotide, used alone or in combination, inhibited proliferation and induced apoptosis in HepG2 cells. Combination treatment was more effective than either mono-treatment (F = 200.398, P less than 0.05). Fluorescent microscopy showed that combination treatment stimulated phosphatidylserine, the marker of early apoptosis, better than either mono-treatment. VEGF expression in cultures exposed to combination treatment was also significantly lower than in mono-treatment or untreated control cultures (F = 1019.725, P less than 0.05). Western blotting showed that octreotide mono-treatment had no effect on Mcl-1 expression (vs. control group; P more than 0.05) and that combination treatment significantly lowered Mcl-1 expression (vs. mono-treatment and control groups; P less than 0.05). None of the treatments affected ERK1/2 expression (all, P more than 0.05), while all treatments significantly lowered PERK1/2 expression (vs. control group; F = 2.401, P less than 0.05) and the combination treatment lowered PERK1/2 significantly more than either mono-treatment (P less than 0.05). Sorafenib and octreotide can inhibit proliferation and induce apoptosis in the human hepatoma cell line, HepG2. Combination treatment is significantly more efficacious (P less than 0.05) and produced synergistic effects. The mechanism underlying this phenomenon may depend on synergistic inhibition of VEGF, the anti-apoptotic protein Mcl-1, and the proliferation-inducing PERK1/2.

Integrated analysis of differentially expressed genes, differentially methylated genes, and natural compounds in hepatitis C virus-induced cirrhosis.

OBJECTIVE: To identify key genes in hepatitis C virus (HCV)-induced cirrhosis and to predict effective drugs for its treatment. METHODS: Three datasets were used to screen for differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in HCV-induced cirrhosis. DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses using the clusterProfiler R package. Their respective protein-protein interaction (PPI) networks were constructed using Cytoscape. Cross analysis of DEGs and DMGs was performed to identify the genetic landscape of HCV-induced cirrhosis, and five genes were validated by receiver operating characteristic curve analysis. Molecular autodocking between ISG15 and natural products was performed using AutoDock Tool 1.5.6. RESULTS: A total of 357 DEGs and 8,830 DMGs were identified. DEG functional analysis identified several pathways involved in the pathogenesis of HCV-induced cirrhosis. Cross analysis of DEGs and DMGs identified 212 genes, and PPI network analysis identified 25 hub genes. Finally, five genes including ISG15 were identified and confirmed in dataset GSE36411. Artesunate and betulinic acid were shown to have a strong binding affinity to ISG15. CONCLUSION: Our study provides novel insights into the mechanisms of HCV-induced cirrhosis which could lead to the identification of new therapeutics.

[Inhibitory effect of pyrrolidine dithiocarbamate combined with matrine on the growth of human hepatocellular carcinoma xenografts].

OBJECTIVE: To investigate the relationship between activation of nuclear factor-K-gene binding (NF-κB) and apoptosis induced by matrine(MT) in transplanted tumor of human hepatocellular carcinoma in nude mouse. METHODS: Tumors were established by injection of hepatocellular carcinoma cell line HepG2 into the back of nude mice. The mice were divided randomly into four groups: Control group, MT group (35 mg/kg), PDTC group (120 mg/kg) and Combination group: PDTC + MT group (120 mg/kg + 35 mg/kg), the reagents were injected peritoneally. The tumor growth curve of nude mice bearing transplanted tumor were observed and the inhibition ratios were evaluated. Apoptosis of carcinoma cells was analyzed by TUNEL. The DNA-binding activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Expression of bcl-2 and bax in carcinoma tissue were detected by immunohistochemical method. NF-κB mRNA, bcl-2 mRNA and bax mRNA in carcinoma tissue were detected by RT-PCR. RESULTS: Pyrrolidine dithiocarbamate (PDTC) could enhance the inhibition of matrine on carcinoma proliferation (P < 0.05). The apoptosis and activation of NF-κB in carcinoma cells could be induced by matrine. PDTC significantly suppressed NF-κB activation induced by matrine in carcinoma cells from 93.64 ± 2.95 to 65.78 ± 5.65 (F = 124.754, P < 0.01). Meanwhile, PDTC increased the apoptosis induced by matrine from 55.9% ± 2.8% to 74.3% ± 4.8% (P < 0.05).A positive correlation observed between the expressions of NF-κB and of bcl-2 (Pearson correlation coefficient = 0.983, P < 0.01). CONCLUSIONS: Matrine could induce apoptosis and activation of NF-κB in transplanted tumor. PDTC could increase apoptosis in hepatocellular carcinoma cells might be due to the suppression of NF-κB activation and the enhancement of bcl-2 expression.

Is rifaximin better than nonabsorbable disaccharides in hepatic encephalopathy?: A meta-analysis.

BACKGROUND: The purpose of the present meta-analysis was to compare the efficacy of rifaximin and nonabsorbable disaccharides (NADs) in hepatic encephalopathy (HE). METHODS: After the registration of the present meta-analysis on INPLASY, all procedures were performed according to PRISMA 2020. Relevant literature was retrieved on PubMed, Embase, and the Cochrane Library up to September 5, 2021. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the enrolled studies, and Review Manager software (version 5.3) was used to analyze the clinical efficacy, blood ammonia and adverse effects. RESULTS: Six studies with 559 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. Analysis of the complete resolution of HE showed that rifaximin was better than NADs (risk ratio [RR] = 1.87, 95% confidence interval [CI] = 1.03-3.39, P = .04). However, there were no significant differences in mental status (RR = 1.04, 95% CI = 0.92-1.18, P = .53), blood ammonia level (standard mean difference = -0.02, 95% CI = -0.40-0.02, P = .08), or drug adverse drug effects (OR = 0.43, 95% CI = 0.10-1.77, I2 = 56%, P = .24) between the rifaximin and NADs treatment groups. CONCLUSION: Rifaximin is not superior to NADs in the treatment of HE.

Diagnosis and treatment of juxta-ampullary duodenal diverticulum.

OBJECTIVE: To summarize the diagnosis and treatment of juxta-ampullary duodenal diverticulum (JAD) in our hospital. METHODS: Of 5000 consecutive endoscopic retrograde cholangiopancreatography (ERCP) performed in our department, 225 patients were diagnosed with JAD and treated. All patients were classified based on the location of Ampullae of Vater in relation to the duodenal diverticulum. Of the 225 JAD patients, 96 patients (43%) required surgery. RESULTS: The 225 patients with JAD were divided into Type A (146 cases, 65%) or Type B (79 cases, 35%). Type A patients presented with papillae near the diverticulum or in its margin. In this type, 36 patients (25%) presented with diverticulitis, bleeding, perforation or cholelithiasis, and were treated surgically. Type B patients presented with papillae inside the diverticulum. Among them, 60 patients (76%) had complications requiring surgery. CONCLUSIONS: JAD can be divided into two types based on location of the papillae. ERCP was the primary method of diagnosing JAD and patients with severe complications required surgical intervention.

Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma.

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe3O4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe3O4@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe3O4@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe3O4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe3O4@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe3O4@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe3O4@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.

[Intercellular transfer of P-glycoprotein in hepatocellular cell line HepG2].

OBJECTIVE: To investigate whether there is intercellular transfer of functional P-glycoprotein(P-gp) from P-gp-positive cells to P-gp-negative cells in vitro. METHODS: HepG2/GFP cells, a HepG2 cell line stably expressing GFP, were co-cultured with HepG2/ADM cells, an adriamycin-resistant cell line derived from HepG2 cells. The distribution of P-gp in hepatocellular carcinoma cell was observed under laser scanning confocal microscope (LSCM). Immunomagnetic beads were used to separate HepG2/GFP cells from the mixed culture. The abundance of P-gp was analyzed by western blot, and the expression of mdr1 mRNA was detected by qRT-PCR. RESULTS: Yellow fluorescence was detected in HepG2/aqMDR cells, green fluorescence was detected in HepG2/GFP cells, red fluorescence was detected in HepG2/ADM cells by LSCM. The level of P-gp protein in HepG2/aqMDR cells was lower than that in HepG2/ADM cells, but higher than that in HepG2/GFP cells (q = 35.07, P < 0.05) and HepG2 cells (q = 36.87, P < 0.05). The expression of mdr1 mRNA in HepG2/ADM cells was higher than that in HepG2/aqMDR, HepG2 and HepG2/GFP cells, but there was no significant difference in mdr1 mRNA among HepG2/aqMDR, HepG2 and HepG2/GFP cells (F = 2.30, P > 0.05). CONCLUSIONS: P-gp can transfer from drug resistant hepatocellular cells to sensitive hepatocellular carcinoma cells. This study suggests a novel mechanism of multidrug resistance in hepatocellular carcinoma.

Transcriptomics and metabonomics of the anti-aging properties of total flavones of Epimedium in relation to lipid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Total flavones of Epimedium (TFE) is the main active ingredient in Herba Epimedii, which is a well-known Chinese herbal medicine that is widely used to treat certain age-related diseases in oriental countries. AIM OF THE STUDY: The aim of this work was to investigate the anti-aging properties of TFE related to lipid metabolism. MATERIALS AND METHODS: Both transcriptomics and metabonomics were applied in this work to investigate the anti-aging properties of TFE. Microarray and LC-MS analysis were conducted on liver samples of three groups of rats, including young (4 months), old (24 months), and old rats administrated TFE. RESULTS: Transcriptomics analysis highlighted 287 transcripts related to the anti-aging effect of TFE, in which the expression ratio of 18 genes regulating lipid metabolism, including HMGCS1 and NR1H3, returned to normal levels after TFE treatment. In addition, 24 aging-related metabolites were discovered in a metabonomics study, and 15 of these were structurally identified, including palmitic amide, linoleamide, and oleamide. Bioinformatics and integral data analysis on the results of the transcriptomics and metabonomics suggest the involvement of 12 key metabolic pathways, half of which are highly related to lipid metabolism. CONCLUSIONS: This study demonstrates that the role played by TFE in the lipid metabolism of aging rats is multifaceted and multi-layered.

An artificially engineered "tumor bio-magnet" for collecting blood-circulating nanoparticles and magnetic hyperthermia.

It is a great challenge to directly endow a tumor with specific functions for theranostic treatment. In this study, we report on a novel approach to transform a tumor into a "bio-magnet", to be magnetized on demand, in order to create an intrinsic tumor magnetic field that would collect magnetic nanoparticles (MNPs) circulating in the blood and achieve simultaneous magnetic hyperthermia. This was achieved by the localized intratumoral injection of liquid Nd2Fe14B/Fe3O4-PLGA, followed by solvent exchange that induces a liquid-to-solid transformation. After the magnetism charging process, the solid Nd2Fe14B/Fe3O4-PLGA implant was endowed with permanent magnetic properties and in situ created the magnetic field within the tumor tissue, making the tumor a "bio-magnet". After the creation of the bio-magnet, intravenously injected MNPs accumulated into the tumor tissue due to the tumor magnetic field. Importantly, both the in vitro and ex vivo results demonstrated the high efficiency of the implanted bio-magnet for magnetic hyperthermia. This new approach achieves magnetic targeting by creating a tumor "bio-magnet", which generates a strong magnetic field within the tumor, paving a new way for the development of an efficient targeting strategy for tumor therapy.

Anatase TiO2 sheet-assisted synthesis of Ti3+ self-doped mixed phase TiO2 sheet with superior visible-light photocatalytic performance: Roles of anatase TiO2 sheet.

On the basis of measurements, such as field emission scanning electron microscope, UV-Vis diffuse reflectance spectra, X-ray diffraction, electron paramagnetic resonance, photoluminescence spectra, and photocurrent measurements, the roles of anatase TiO2 sheet on synthesizing Ti3+ self-doped mixed phase TiO2 nanosheets (doped TiO2 (A/R, TiO2 (A))) and on improving the performance for photocatalytic CO2 reduction were explored systematically. High surface area anatase TiO2 nanosheets (TiO2 (A)) as a substrate, structure directing agent, and inhibitor, mediated the synthesis of Ti3+ self-doped mixed phase TiO2 nanosheets. Addition of TiO2 (A) significantly improved not only visible light absorption of doped TiO2 (A/R, TiO2 (A)), but also the efficiency of photo-excited charges separations due to the existence of interfacial regions of anatase-rutile TiO2 junctions. Finally, a possible mechanism for interfacial charge transfer at the anatase-rutile TiO2 interface and for photocatalytic CO2 reduction over Pt loaded doped TiO2 (A/R, TiO2 (A)) were proposed.

Effect of CD16a, the surface receptor of Kupffer cells, on the growth of hepatocellular carcinoma cells.

FcγRIIIa (CD16) is a low-affinity Fc receptor of IgG. As the idio-binding receptor of IgG Fc, it plays an important role in the antibody-dependent cellular cytotoxicity of natural killer cells. The aim of the present study was to investigate the distribution of Kupffer cells (KCs) and the expression of their surface receptor FcγRIIIa in hepatocellular carcinoma. Furthermore, we also aimed to observe the functional mechanism of FcγRIIIa. Immunohistochemical analysis was employed to study KCs and FcγRIIIa. In order to explore the role of FcγRIIIa in the growth of cancer cells, KCs and H22 tumor cells were co-cultured in different serum. The mRNA expression levels of tumor necrosis factor (TNF)-α and FcγRIIIa were analyzed by RT-qPCR; the TNF-α and FcγRIIIa protein expression levels were examined by enzyme­linked immunosorbent assay and western blot analysis, respectively. Our results showed that the number of Kuppfer cells in cancerous tissues (21.6±7.8) was lower than those in para-cancerous (68.8±9.1) tissues and adjacent normal hepatic tissues (62.0±1.9) (P<0.01); this decreased with the reduction in the differentiation degree of cancer (P<0.05). FcγRIIIa-positive cells were similar in morphology to KCs, and their distributive tendency was coincident (P<0.05). The increase in CD16a mRNA levels in the group treated with immune serum was 3.9-, 4.9- and 3.9-fold greater than that in the ordinary serum group at different time points, and CD16a protein expression also markedly increased (P<0.05). However, these effects were inhibited by the addition of anti-IgG Fc serum (P<0.05). The results of the present study suggested that FcγRIIIa resided in KCs, and it contributed to the inhibition of the growth of liver tumor cells.