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Previous studies have demonstrated the potential antifibrotic effects of baicalin in vitro, via examination of 21 compounds isolated from plants. However, its biological activity and underlying mechanisms of action in vivo remain to be elucidated. The present study aimed to evaluate the effect of baicalin on renal fibrosis in vivo, and the potential signaling pathways involved. A unilateral ureteral obstruction (UUO)-induced renal fibrosis model was established using Sprague-Dawley rats. Baicalin was administrated intraperitoneally every 2 days for 10 days. The degree of renal damage and fibrosis was investigated by histological assessment, and detection of fibronectin and collagen I mRNA expression levels. Epithelial-mesenchymal transition (EMT) markers, transforming growth factor-β1 (TGF-β1) levels and downstream phosphorylation of mothers against decapentaplegic 2/3 (Smad2/3) were examined in vivo and in an NRK-52E rat renal tubular cell line in vitro. Baicalin was demonstrated to markedly ameliorate renal fibrosis and suppress EMT, as evidenced by reduced interstitial collagen accumulation, decreased fibronectin and collagen I mRNA expression levels, upregulation of N- and E-cadherin expression levels, and downregulation of α-smooth muscle actin and vimentin expression. Furthermore, baicalin decreased TGF-β1 expression levels in serum and kidney tissue following UUO, and suppressed Smad2/3 phosphorylation in rat kidney tissue. In vitro studies identified that baicalin may inhibit the phosphorylation of Smad2/3 under the same TGF-β1 concentration. In conclusion, baicalin may protect against renal fibrosis, potentially via inhibition of TGF-β1 production and its downstream signal transduction.

The survival benefits of sorafenib treatment for patients with hepatocellular carcinoma (HCC) are limited due to drug resistance and side effects. Therefore, combinations of sorafenib with other low toxicity drugs, including arsenic trioxide (As2O3) require investigation. The present study aimed to evaluate the potency of apoptosis-induction by As2O3/sorafenib treatment in HCC cell lines, Huh7, 97H and freshly-isolated HCC cells, and also to elucidate the underlying mechanism. A total of 10 patients with HCC were enrolled in the present study. Freshly-isolated HCC cells were purified from HCC tissues collected at surgery. HCC-cell apoptosis was measured by flow cytometry using proprium iodide/Annexin-V staining. The impacts of As2O3 and/or sorafenib on Huh7, 97H and fresh-isolated HCC-cell proliferation were evaluated by Cell Counting Kit-8 assay. The expression of TNF-related apoptosis-inducing ligand (TRAIL) was determined by reverse transcription-quantitative polymerase chain reaction and western blotting. The downregulation of TRAIL protein expression was achieved using small interfering RNA. The combination of As2O3 and sorafenib had anti-proliferative and pro-apoptotic effects in the liver cancer cell line, Huh7, via increased expression of TRAIL, but not in 97H cells. TRAIL-knockdown increased the drug-resistance of Huh7 cells. Freshly-isolated HCC cells were more sensitive to the As2O3 and sorafenib combination than the single drug treatments. Overall, the combination of As2O3 and sorafenib demonstrated potent anti-tumor activity in Huh7 and freshly-isolated HCC cells via a TRAIL-dependent pathway. This may be a potential therapeutic approach for advanced HCC treatment.

Early diagnosis of kidney allograft injury contributes to proper decisions regarding treatment strategy and promotes the long-term survival of both the recipients and the allografts. Although biopsy remains the gold standard, non-invasive methods of kidney allograft evaluation are required for clinical practice. Recently, novel ultrasonic technologies have been applied in the evaluation and diagnosis of kidney allograft status, including tissue elasticity quantification using acoustic radiation force impulse (ARFI) and contrast-enhanced ultrasonography (CEUS). In this review, we discuss current opinions on the application of ARFI and CEUS for evaluating kidney allograft function and their possible influencing factors, advantages and limitations. We also compare these two technologies with other non-invasive diagnostic methods, including nuclear medicine and radiology. While the role of novel non-invasive ultrasonic technologies in the assessment of kidney allografts requires further investigation, the use of such technologies remains highly promising.

Soluble fibrinogen-like protein 2 (sFGL2) is the soluble form of fibrinogen like protein 2. As a novel immunoregulatory molecule, sFGL2 is secreted mainly by T cells, especially regulatory T cells, and exerts an immunoregulatory property rather than a prothrombinase function in the immune system. sFGL2 changes not only the proliferation and differentiation of T cells but also the maturation of antigen presenting cells. Besides its innate and adaptive immunoregulatory functions, sFGL2 also induces apoptosis in cells including renal tubular epithelial cells through Fcγ receptors (FcγRs). It may affect transplantation via regulation of immunity and induction of apoptosis of different cells in a spatiotemporal manner. Here, we review the research progresses on sFGL2 including its structure, functions, and molecular mechanisms via which sFGL2 might affect organ transplantation, as well as discuss its characteristics and potential of becoming a therapeutic target in patients with rejection.

Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post-transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation.

Ras-VEGF-concerned angiogenesis is correlated with oncogene maintenance, tumorigenesis, metastasis and resistance to anti-cancer therapies; however, this association is not clearly elucidated by serum VEGF, due to VEGF signalling in blood cells themselves. The present study aimed to elucidate tumorigenic VEGF signalling in eight human HCC cell types and reveal the kinetics of tumorigenic VEGF signalling in three time intervals, thereby discovering the relationships of VEGF-concerned angiogenesis signalling with the extent of the human HCC cell growth, metastasis and resistance to anti-cancer drugs, by using the poorly metastatic SMMC7721, 7402/D+ (doxorubicin-resistance) and 7402/D- (doxorubicin-withdrawal), the highly metastatic MHCC1 non-transfected human HCC cell lines, and the highly metastatic A3-1, F8, F11 and E3 human HCC cell lines transfected with expressing green fluorescence protein into the phenotype of MHCC1 cells, and quantitative 'sandwich' ELISA analyses. The unique results indicated attributes and objective laws as follows. Human HCC cell growth requires time-dependent tumorigenic VEGF signalling; levels of VEGF signalling are positively correlated with each cell phenotype itself; and levels of VEGF signalling are inversely correlated with the possibility of metastasis and drug resistance. The contrast data first reveal important clues for exploring dual metastatic mechanisms via tumor cell-generated non-endothelium vasculogenesis and VEGF-endothelium-attached angiogenesis that may be essential for developing novel strategies aimed at VEGF-concerned signal networks in ischemic/metastatic diseases and transgenic models.

The ‘angiogenic switch’ concept has been used to discover various pro- and anti-angiogenic molecules as pharmacotherapeutic strategies for cancers and other ischemic and inflammatory diseases; however, surprisingly little is known about the ‘tumor angiogenic switch’ in response to complex interplay between environmental and genetic mechanisms that are most importantly, hypothesis-driven, largely unsolved at the postgenomic level. The present study’s aim is to identify those interplays between the expressing green fluorescence protein (EGFP) transcript and redox-driven vascular endothelial growth factor (VEGF) upstream mechanisms that influence tumorigenic VEGF signalling, by using multifactorial orthogonal statistical analyses, the non-transfected and transfected human hepatocellular carcinoma (HCC) cell lines, and quantitative ‘sandwich’ Elisa immunoassays. The unique results indicate valuable findings on the postgenomic level as follows. Fusion of the EGFP significantly triggers tumorigenic VEGF signalling in three E3-, F11- and A3-1-transfected human HCC cell lines, compared with the parental EGFP-free malignant hepatocellular carcinoma (MHCC)1 cell line; Redox-regulated VEGF upstream mechanism interplays dramatically mediate dual responses, either down- or upregulating tumorigenic VEGF signalling, which depends on individual post-transcriptional regulation or upstream modification of the VEGF promoter in the three MHCC1, SMCC7721 and doxorubicin-resistance 7402/D+ non-transfected human HCC cell lines; and mechanism-based strategies for stimulating β-adrenergic and P2-purinergic signal transduction and counteracting O2–. and Ca2+-inflow significantly trigger tumorigenic VEGF signalling in ATRA/ATRP-driven networks, compared with controls of the non-transfected cell types examined. The contrast data offer first pilot paradigms of searching for hypothesis-driven multifactorial interplays on tumorigenic VEGF signalling, which are valuable for further deciphering postgenome-wide VEGF upstream regulatory networks of switching on the tumor angiogenesis, and developing mechanism-based novel pharmacotherapeutic strategies.