The inhibition of the NF-κB signaling pathway attenuated the expression of TGF-β in RL95-2 cells.

<p>RL95-2 cells were treated with SN50 (30 μg·ml^-1), an inhibitor of the NF-κB signaling pathway, and the expression of p65 and TGF-β was measured by western blotting. (A) A representative blot and (B) quantitative analysis of p65 expression. (C) A representative blot and (D) quantitative analysis of TGF-β expression. Results were expressed as the mean±SD of three independent experiment performed in triplicate, ** P<0.01 vs.SN50(-).</p

The rate of recurrence in patients with intrauterine adhesions.

<p>The rate of recurrence in patients with intrauterine adhesions.</p

The expression TGF-β and CCN2 was positively correlated with p65 expression in IUA endometrial tissue.

<p>The correlation between TGF-β, CCN2 and p65 expression was analyzed using Pearson’s correlation test. (A) TGF-β expression was positively correlated with p65 expression in IUA endometrial tissue. (B) CCN2 expression was positively correlated with p65 expression in IUA endometrial tissue.</p

Classification of 70 patients with intrauterine adhesions.

<p>Classification of 70 patients with intrauterine adhesions.</p

Immunohistochemical staining for TGF-β and CCN2 in endometrial tissue.

<p>15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were stained by immunohistochemistry, respectively. The representative localization of TGF-β and CCN2 expression is shown (magnification, 40×). The expression of TGF-β and CCN2 in IUA was higher than that seen in normal endometrium and uterine septum.</p

TGF-β and CCN2 were overexpressed in IUA endometrial tissue.

<p>(A) The expression of TGF-β and CCN2 in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by western blotting. Representative blots are shown. (B) A quantitative analysis of TGF-β and CCN2 expression in normal endometrium, uterine septum and intrauterine adhesions normalized to β-actin expression. The levels of TGF-β (C) and CCN2 (D) transcripts in 15 cases of normal endometrium, 15 cases of uterine septum and 70 cases of intrauterine adhesions were measured by qRT-PCR. Results are expressed as the mean±SD. One way ANOVA(Tukey’ post hoc test); * P<0.05, ** P<0.01 vs. normal endometrium, ^##P<0.05, ^## P<0.01 vs. uterine septum.</p

Critical Role of Organic Anion Transporters 1 and 3 in Kidney Accumulation and Toxicity of Aristolochic Acid I

Ingestion of aristolochic acid (AA), especially its major constituent aristolochic acid I (AAI), results in severe kidney injury known as aristolochic acid nephropathy (AAN). Although hepatic cytochrome P450s metabolize AAI to reduce its kidney toxicity in mice, the mechanism by which AAI is uptaken by renal cells to induce renal toxicity is largely unknown. In this study, we found that organic anion transporters (OATs) 1 and 3, proteins known to transport drugs from the blood into the tubular epithelium, are responsible for the transportation of AAI into renal tubular cells and the subsequent nephrotoxicity. AAI uptake in HEK 293 cells stably transfected with human OAT1 or OAT3 was greatly increased compared to that in the control cells, and this uptake was dependent on the AAI concentration. Administration of probenecid, a well-known OAT inhibitor, to the mice reduced AAI renal accumulation and its urinary excretion and protected mice from AAI-induced acute tubular necrosis. Further, AAI renal accumulation and severe kidney lesions induced by AAl in <i>Oat1</i> and <i>Oat3</i> gene knockout mice all were markedly suppressed compared to those in the wild-type mice. Together, our results suggest that OAT1 and OAT3 have a critical role in AAl renal accumulation and toxicity. These transporters may serve as a potential therapeutic target against AAN

Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer

The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). The metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC

Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer

The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). The metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC

Metallic Cation-Mediated Entrapment of Nucleic Acids on Mesoporous Silica Surface: Application in Castration-Resistant Prostate Cancer

The use of exogenous nucleic acid technologies to modulate aberrant protein expression resulting from genetic mutations is a promising therapeutic approach for the treatment of diseases such as advanced prostate cancer (PC). The promise of nucleic-based therapeutics is dependent on the development of platforms that effectively protect nucleic acids from nuclease degradation and deliver the nucleic acids to the cytosol of target cells. In this work, we present the development of a divalent metal-mediated nucleic acid entrapment strategy with a porous silica matrix. This simple strategy results in efficient loading percentages of both siRNA (>60%) and mRNA (>80%) as well as their release within relevant biological environments (80%). Additionally, our data supports that the current method reduces endosomal entrapment and supports the lipid coating of mesoporous silica nanoparticles (LC-MSNs). The metal-enhanced nanosystem is assessed for biocompatibility, stability, and circulation within in vitro, ex ovo, and in vivo models of PC