Epithelial to mesenchymal transition (EMT) of alveolar epithelial cells occurs in lung fibrotic diseases. Tanshinone IIA (Tan IIA) has been reported to exert anti-inflammatory effects in pulmonary fibrosis. Nonetheless, whether Tan IIA affects lung fibrosis-related EMT remains unknown and requires for further investigations.

Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone ⅡA (Tan ⅡA) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan ⅡA on bleomycin (BLM)‑induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan ⅡA and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLM‑treated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan ⅡA. In addition, BLM‑induced increased expression of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, cyclooxygenase‑2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan ⅡA injection. The present findings suggest therapeutic potential of Tan ⅡA for pulmonary fibrosis.

Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.

Mesothelial cell injury plays an important role in peritoneal fibrosis. Present clinical therapies aimed at alleviating peritoneal fibrosis have been largely inadequate. Mesenchymal stem cells (MSCs) are efficient for repairing injuries and reducing fibrosis. This study was designed to investigate the effects of MSCs on injured mesothelial cells and peritoneal fibrosis.

Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

We previously found that mesenchymal stem cells (MSCs) injected intravenously could attenuate peritoneal adhesion by secreting tumor necrosis alpha-stimulating gene (TSG)-6, while MSCs injected intraperitoneally could not. However, the underlying mechanism remains unclear. This study was designed to investigate the means by which MSCs exert their effects.

In order to develop an equation that integrates multiple clinical factors including signs and symptoms associated with uraemia to assess the initiation of dialysis, we conducted a retrospective cohort study including 25 haemodialysis centres in Mainland China. Patients with ESRD (n = 1281) who commenced haemodialysis from 2008 to 2011 were enrolled in the development cohort, whereas 504 patients who began haemodialysis between 2012 and 2013 were enrolled in the validation cohort comprised. An artificial neural network model was used to select variables, and a fuzzy neural network model was then constructed using factors affecting haemodialysis initiation as input variables and 3-year survival as the output variable. A logistic model was set up using the same variables. The equation's performance was compared with that of the logistic model and conventional eGFR-based assessment. The area under the bootstrap-corrected receiver-operating characteristic curve of the equation was 0.70, and that of two conventional eGFR-based assessments were 0.57 and 0.54. In conclusion, the new equation based on Fuzzy mathematics, covering laboratory and clinical variables, is more suitable for assessing the timing of dialysis initiation in a Chinese ESRD population than eGFR, and may be a helpful tool to quantitatively evaluate the initiation of haemodialysis.

To investigate the relationships between LncRNA NNT-AS1, CRP, PCT and their interactions and the refractory mycoplasma pneumoniae pneumonia (RMPP) in children. Serum levels of LncRNA NNT-AS1 of RMPP and non-RMPP (NRMPP) patients were detected by real-time PCR, and were analyzed together with serum c-reactive protein (CRP) and procalcitonin (PCT). Correlations between LncRNA NNT-AS1 and CRP and PCT were analyzed by Pearson correlation test. The ROC curve was used to analyze the potential of LncRNA NNT-AS1, CRP and PCT as biomarkers for predicting RMPP. Logistic regression crossover model and the Excel compiled by Andersson et al. were used to analyze the interactions among the biomarkers. We found that LncRNA NNT-AS1, CRP and PCT were all highly expressed in patients with RMPP. LncRNA NNT-AS1 could positively correlate with the expressions of CRP and PCT, and jointly promote the occurrence of RMPP. The combined diagnosis of LncRNA NNT-AS1, CRP and PCT could predict the occurrence of RMPP.

The main event in the progression of pulmonary fibrosis is the appearance of myofibroblasts. Recent evidence supports pericytes as a major source of myofibroblasts. TGFβ/Smad2/3 and PDGF/Erk signaling pathways are important for regulating pericyte activation. Previous studies have demonstrated that PDGFβR and TGFβR are modified by core fucosylation (CF) catalyzed by α-1,6-fucosyltransferase (FUT8). The aim of this study was to compare the effect of inhibiting CF versus the PDGFβR and TGFβR signaling pathways on pericyte activation and lung fibrosis. FUT8shRNA was used to knock down FUT8-mediated CF both in vivo and in isolated lung pericytes. The small molecule receptor antagonists, ST1571 (imatinib) and LY2109761, were used to block the PDGFβ/pErk and TGFβ/pSmad2/3 signaling pathways, respectively. Pericyte detachment and myofibroblastic transformation were assessed by immunofluorescence and Western blot. Histochemical and immunohistochemical staining were used to evaluate the effect of the intervention on pulmonary fibrosis. Our findings demonstrate that FUT8shRNA significantly blocked pericyte activation and the progression of pulmonary fibrosis, achieving intervention effects superior to the small molecule inhibitors. The PDGFβ and TGFβ pathways were simultaneously affected by the CF blockade. FUT8 expression was upregulated with the transformation of pericytes into myofibroblasts, and silencing FUT8 expression inhibited this transformation. In addition, there is a causal relationship between CF modification catalyzed by FUT8 and pulmonary fibrosis. Our findings suggest that FUT8 may be a novel therapeutic target for pulmonary fibrosis.

Cognitive impairment is widely prevalent in maintenance hemodialysis (MHD) patients, and seriously affects their quality of life. The intestinal flora likely regulates cognitive function, but studies on cognitive impairment and intestinal flora in MHD patients are lacking.

FUT8-mediated core fucosylation, which transfers a fucose residue from GDP-fucose to core-GlcNAc of the N-linked type glycoproteins, is crucial for signaling receptors function. Core fucosylation is involved in various biological processes such as cell proliferation, apoptosis, differentiation and immune regulation. Our previous studies demonstrated that inhibiting core fucosylation prevented renal interstitial fibrosis of UUO murine models, but its role in the development of diabetic kidney disease (DKD) remains unclear. This study aimed to clarify the protective effects and molecular mechanisms during the progress of DKD by inhibiting core fucosylation in vivo.

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.

Spinal cord development is precisely orchestrated by spatiotemporal gene regulatory programs. However, the underlying epigenetic mechanisms remain largely elusive. Here, we profiled single-cell chromatin accessibility landscapes in mouse neural tubes spanning embryonic days 9.5-13.5. We identified neuronal-cell-cluster-specific cis-regulatory elements in neural progenitors and neurons. Furthermore, we applied a novel computational method, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression data and identify the hub enhancers within enhancer networks. It was experimentally validated in vivo for Atoh1 that knockout of the hub enhancers, but not the non-hub enhancers, markedly decreased Atoh1 expression and reduced dp1/dI1 cells. Together, our work provides insights into the epigenetic regulation of spinal cord development and a proof-of-concept demonstration of enhancer networks as a general mechanism in transcriptional regulation.

Kidney renal clear cell cancer (KIRC) is a type of urological cancer that occurs worldwide. Core fucosylation (CF), as the most common post-translational modification, is involved in the tumorigenesis.

Peritoneal dialysis is an important type of renal replacement therapy for uremic patients. In peritoneal dialysis, fluids fill in and flow out of the abdominal cavity three to five times per day. Usually, the fluid is packed in a polyvinyl chloride (PVC) bag. Safety concerns have arisen over di-(2-ethylhexyl) phthalate, which is essential in the formation of PVC materials. In 2011, the National Development and Reform Commission of China released a catalog of industrial structural adjustments, mandating the elimination of PVC bags for intravenous infusion and food containers. Although bags for peritoneal dialysis fluid were not included in the elimination list, several manufacturers began to develop new materials for fluid bags. HUAREN peritoneal dialysis fluid consists of the same electrolytes and buffer agent as in Baxter fluid, but is packed in bags that do not contain PVC. This multicenter randomized controlled trial was designed to compare peritoneal dialysis fluid packed in non-PVC-containing and PVC-containing bags. Further, the study sought to determine the proper dose of peritoneal dialysis fluid and the actual survival rates of Chinese patients undergoing peritoneal dialysis.

Pericytes have been identified as a major source of myofibroblasts in renal interstitial fibrosis (RIF). The overactivation of several signaling pathways, mainly the TGF-β and PDGF pathways, initiates the pericyte-myofibroblast transition during RIF. Key receptors in these two pathways have been shown to be modified by fucosyltransferase 8 (FUT8), the enzyme that catalyzes core fucosylation. This study postulated that core fucosylation might play an important role in regulating the pericyte transition in RIF. The data showed that core fucosylation increased with the extent of RIF in patients with IgA nephropathy (IgAN). Similarly, core fucosylation of pericytes increased in both a unilateral ureteral occlusion (UUO) mouse model and an in vitro model of pericyte transition. Inhibition of core fucosylation by adenoviral-mediated FUT8 shRNA in vivo and FUT8 siRNA in vitro significantly reduced pericyte transition and RIF. In addition, the activation of both the TGF-β/Smad and PDGF/ERK pathways was blocked by core fucosylation inhibition. In conclusion, core fucosylation may regulate the pericyte transition in RIF by modifying both the TGF-β/Smad and PDGF/ERK pathways. Glycosylation might be a novel "hub" target to prevent RIF.

Peritoneal fibrosis (PF) ultimately causes ultrafiltration failure and peritoneal dialysis (PD) termination, but there are few effective therapies for it. Core fucosylation, which is catalyzed by α1,6-fucosyltransferase (Fut8) in mammals, may play a crucial role in PF development. This study aims to assess the effects of inhibiting core fucosylation of epidermal growth factor (EGF) receptor on PF rats.

Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China's drug review and approval process.