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A circular capacitive rainfall sensor can operate from non-touch mode to touch mode; that is, under the action of enough rainwater, its movable electrode plate can form a circular contact area with its fixed electrode plate. Therefore, the weight of rainwater is borne by only its movable electrode plate in non-touch mode operation but by both its movable and fixed electrode plates in touch mode operation, and the total capacitance of its touch mode operation is much larger than that of its non-touch mode operation. Essential to its numerical design and calibration is the ability to predict the deflection shape of its moveable electrode plate to determine its total capacitance. This requires the analytical solution to the fluid-structure interaction problem of its movable electrode plate under rainwater. In our previous work, only the analytical solution for the fluid-structure interaction problem before its movable electrode plate touches its fixed electrode plate was obtained, and how to numerically design and calibrate a circular non-touch mode capacitive rainfall sensor was illustrated. In this paper, the analytical solution for the fluid-structure interaction problem after its movable electrode plate touches its fixed electrode plate is obtained, and how to numerically design and calibrate a circular touch mode capacitive rainfall sensor is illustrated for the first time. The numerical results show that the total capacitance and rainwater volume when the circular capacitive rainfall sensor operates in touch mode is indeed much larger than that when the same circular capacitive rainfall sensor operates in non-touch mode, and that the average increase in the maximum membrane stress per unit rainwater volume when the circular capacitive rainfall sensor operates in touch mode can be about 20 times smaller than that when the same circular capacitive rainfall sensor operates in non-touch mode. This is where the circular touch mode capacitive rainfall sensor excels.

The design, especially the numerical calibration, of a circular touch mode capacitive pressure sensor is highly dependent on the accuracy of the analytical solution of the contact problem between the circular conductive membrane and the rigid plate of the sensor. In this paper, the plate/membrane contact problem is reformulated using a more accurate in-plane equilibrium equation, and a new and more accurate analytical solution is presented. On this basis, the design and numerical calibration theory for circular touch mode capacitive pressure sensors has been greatly improved and perfected. The analytical relationships of pressure and capacitance are numerically calculated using the new and previous analytical solutions, and the gradually increasing difference between the two numerical calculation results with the gradual increase in the applied pressure is graphically shown. How to use analytical solutions and analytical relationships to design and numerically calibrate a circular touch mode capacitive pressure sensor with a specified pressure detecting range is illustrated in detail. The effect of changing design parameters on capacitance-pressure analytical relationships is comprehensively investigated; thus, the direction of changing design parameters to meet the required or desired range of pressure or capacitance is clarified.

Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1β and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Polymer-based conductive membranes play an important role in the development of elastic deflection-based pressure sensors. In this paper, an analytical solution-based method is presented for the design and numerical calibration of polymer conductive membrane-based circular capacitive pressure sensors from non-touch mode of operation to touch mode of operation. The contact problem of a circular membrane in frictionless contact with a rigid flat plate under pressure is analytically solved, and its analytical solution is used for the design of touch mode circular capacitive pressure sensors for the first time. The analytical relationship with input pressure as independent variable and output capacitance as dependent variable is precisely derived and is used for the numerical calibrations of the analytical relationships with input capacitance as the independent variable and output pressure as the dependent variable in order to meet the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance. For the first time, an example showing the design and numerical calibration of a given (given design parameters) polymer conductive membrane-based circular capacitive pressure sensor from non-touch mode of operation to touch mode of operation is provided. Then, the influence of changing several important design parameters on input capacitance-output pressure relationships is comprehensively investigated in order to clarify the desired input-output relationships when changing design parameters.

In this paper, an analytical solution-based method for the design and numerical calibration of polymer conductive membrane-based non-touch mode circular capacitive pressure sensors is presented. The accurate analytical relationship between the capacitance and applied pressure of the sensors is derived by using the analytical solution for the elastic behavior of the circular polymer conductive membranes under pressure. Based on numerical calculations using the accurate analytical relationship and the analytical solution, the analytical relationship between the pressure as output and the capacitance as input, which is necessary to achieve the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance, is accurately established by least-squares data fitting. An example of how to arrive at the design and numerical calibration of a non-touch mode circular capacitive pressure sensor is first given. Then, the influence of changing design parameters such as membrane thickness and Young's modulus of elasticity on input-output relationships is investigated, thus clarifying the direction of approaching the desired input-output relationships by changing design parameters.

For diagnosing cardiovascular disease, an accurate segmentation method is needed. There are several unresolved issues in the complex field of cardiac magnetic resonance imaging, some of which have been partially addressed by using deep neural networks. To solve two problems of over-segmentation and under-segmentation of anatomical shapes in the short-axis view from different cardiac magnetic resonance sequences, we propose a novel two-stage framework with a weighted decision map based on convolutional neural networks to segment the myocardium (Myo), left ventricle (LV), and right ventricle (RV) simultaneously. The framework comprises a decision map extractor and a cardiac segmenter. A cascaded U-Net++ is used as a decision map extractor to acquire the decision map that decides the category of each pixel. Cardiac segmenter is a multiscale dual-path feature aggregation network (MDFA-Net) which consists of a densely connected network and an asymmetric encoding and decoding network. The input to the cardiac segmenter is derived from processed original images weighted by the output of the decision map extractor. We conducted experiments on two datasets of multi-sequence cardiac magnetic resonance segmentation challenge 2019 (MS-CMRSeg 2019) and myocardial pathology segmentation challenge 2020 (MyoPS 2020). Test results obtained on MyoPS 2020 show that the average Dice coefficients of the proposed method on the segmentation tasks of Myo, LV and RV are 84.70%, 86.00%, and 86.31%, respectively.

Endometrial cancer is one of the three most common malignant tumors in the female reproductive system. Advanced and recurrent endometrial cancers have poor prognoses and lack effective treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors have been applied to many different types of tumors, and they can selectively kill tumor cells that are defective in homologous recombination repair. Endometrial cancer is characterized by mutations in homologous recombination repair genes; accordingly, PARP inhibitors have achieved positive results in off-label treatments of endometrial cancer cases. Clinical trials of PARP inhibitors as monotherapies and within combination therapies for endometrial cancer are ongoing. For this review, we searched PubMed with "endometrial cancer" and "PARP inhibitor" as keywords, and we used "olaparib", "rucaparib", "niraparib" and "talazoparib" as search terms in clinicaltrials.gov for ongoing trials. The literature search ended in October 2020, and only English-language publications were selected. Multiple studies confirm that PARP inhibitors play an important role in killing tumor cells with defects in homologous recombination repair. Its combination with immune checkpoint inhibitors, PI3K/AKT/mTOR pathway inhibitors, cell cycle checkpoint inhibitors, and other drugs can improve the treatment of endometrial cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Ren, Chen, Yang, Zhang, Wang, Zhu, Li, Yang and Zhang.)

Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Background/aims: The study was designed to explore the potential relationship of TLR4 and endothelial PAS domain-containing protein 1 (EPAS1) in vivo and vitro experiments., Methods: Bronchoalveolar lavage fluid (BALF) samples were collected from 55 chronic obstructive pulmonary disease (COPD) patients and 25 healthy subjects. The differential cell count was performed using Wright-Giemsa staining. The expression levels of TLR4 and TLR5 were detected by RT-qPCR. The levels of methylation and mRNA expression of EPAS1 were assayed by bisulfite sequencing PCR and real-time PCR. The correlation of TLR4 and EPAS1 was also analyzed in TLR 4-overexpressing endothelial cells., Results: The results showed that the number of neutrophils, lymphocytes and macrophages and expression of TLR 4 were significantly increased in lower respiratory tract of COPD patients. Moreover, decreased EPAS1 mRNA and increased EPAS1 promoter methylation were detected in COPD, which were closely associated with increased TLR4 expression. According to in vitro experiments, TLR 4 inhibited EPAS1 mRNA expression and promoted promoter methylation in endothelial cells., Conclusion: These findings suggest that TLR4 over-expression decreased EPAS1expression which contributes to the progress of COPD., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2', 7'-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results.

Background: Fibroblast specific protein-1 (S100A4) is related with many fibrotic diseases, but its role in the pathogenesis of pleural fibrosis has not been fully elucidated. Then we aim to investigate the expression and effect of fibroblast specific protein-1 (S100A4) in pleural tuberculosis and, subsequently, pleural fibrosis., Methods: The expression of S100A4 in pleura was examined in 30 patients with pleural tuberculosis and 5 control (disease-free) patients by immunohistochemistry using the streptavidin-peroxidase (S-P) conjugated method., Results: The expression of S100A4 in pleura was mainly distributed in the nucleus and cytoplasm of fibroblasts and vascular endothelial cells, and the positive rate was 90.0% (27 out of 30 patients with pleural tuberculosis). There were no expressions of S100A4 in the control group. In the pleura of all 30 patients with pleural tuberculosis, S100A4 had a higher expression in the two- to eight-week duration of the disease., Conclusions: S100A4 plays an important role in the phenotypic transformation of pleural mesothelial cells and the development of pleural fibrosis.

Background: To investigate the related risk factors of postoperative nosocomial pneumonia (POP) in patients with I-IIIa lung cancer., Methods: Medical records of 511 patients who underwent resection for lung cancer between January 2012 to December 2012 were retrospectively reviewed. Risk factors of postoperative pneumonia were identified and evaluated by univariate and multivariate analyses., Results: The incidence of postoperative pneumonia in these lung cancer patients was 2.9% (15 cases). Compared with 496 patients who had no pneumonia infection after operation, older age (>60), histopathological type of squamous cell carcinoma and longer surgery time (>3h) were significant risk factors by univariate analysis. Other potential risk factors such as alcohol consumption, history of smoking, hypersensitivity, hypertension, diabetes mellitus and so on were not showed such significance in this study. Further, the multivariate analysis revealed that old age (>60 years) (OR 5.813, p=0.018) and histopathological type of squamous cell carcinoma (OR 5.831, p<0.001) were also statistically significant independent risk factors for postoperative pneumonia., Conclusions: This study demonstrated that being old aged (>60 years) and having squamous cell carcinoma histopathological type might be important factors in determining the risk of postoperative pneumonia in lung cancer patients after surgery.

Aim: To identify and quantify the major metabolites of salvianolic acid B (SAB) after intravenous injection in rats., Methods: LC-IT/TOF-MS was used to identify the metabolites in rat bile, plasma, and urine; LC-MS/MS was used to quantify the two major metabolites., Results: In rat bile, plasma, and urine, nine metabolites were identified, including methylated metabolites of SAB, lithospermic acid (LSA), the decarboxylation and methylation metabolites of LSA, salvianolic acid S (SAS), and dehydrated-SAS. The t1/2 of monomethyl-SAB and LSA were both very short, and monomethyl-SAB had a larger AUC than LSA in rats., Conclusion: Nine metabolites were found, the metabolic pathway was described, and the pharmacokinetic profiles of LSA and monomethyl-SAB were studied, thereby clarifying that methylation was the dominant metabolic pathway for SAB in rats., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Aim: This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate (GLN) on the pharmacokinetics of entecavir (ETV) in rats., Methods: Male SD rats were randomized into short-term and long-term experimental groups, respectively. In the short-term experiment, the control group received saline, the low dose group received GLN 13.5 mg·kg(-1) and the high dose group received GLN 40.5 mg·kg(-1). ETV (0.09 mg·kg(-1)) was given i.g. 0.5 h after saline/GLN administration. For the long-term experiment, rats were allocated into two experimental designs. The control group received saline/ETV (0.09 mg·kg(-1)), the low dose group received GLN 13.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 13.5 mg·kg(-1), while the high dose group received GLN 40.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 40.5 mg·kg(-1); all administration was continued for 15 days. On the 16(th) day, 0.09 mg·kg(-1) ETV was administrated to all groups. Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations., Results: Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments., Conclusion: Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

We sought to develop a mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model to characterize the effects of ginsenoside Rb1 (Rb1) and estradiol (E(2)) on neural 5-hydroxytryptamine (5-HT) concentration in ovariectomized mice. PK data of Rb1 and E(2) were obtained in plasma and brain. Brain levels of 5-HT, tryptophan (TRP), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5-HIAA) were determined after a single intravenous injection of Rb1 (20mg/kg) and E(2) (0.2mg/kg) in ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD), and monoamine oxidase (MAO) were also evaluated. Rb1 and E(2) elevated neural 5-HT levels via TPH activation and MAO inhibition, respectively. Effects were well described by the mechanism-based PK-PD model. The net effect of increased 5-HT induced by MAO inhibition is greater than TPH activation. The increased brain levels of 5-HT induced by Rb1 and E(2) were well described by the present PK-PD model, suggesting the use and further development of this mechanism-based model for the effects of ginsenoside on brain 5-HT levels., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Decreased 5-hydroxytryptamine (5-HT) concentration in the brain has been linked to central nervous system dysfunctions, especially in menopausal women. Ginsenoside Rb1, a potential phytoestrogen, has been shown to improve central nervous system dysfunctions, comparable to the estrogen treatment. To investigate the estrogen-like effects of ginsenoside Rb1 on neural 5-HT disposition and behavioral tasks, we quantified the concentrations of 5-HT and other related endogenous substances in the frontal cortex and striatum of ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD) and monoamine oxidase (MAO) were also measured to evaluate the synthesis and metabolism of neural 5-HT. Our work shows that both ginsenoside Rb1 and estradiol increased the neural 5-HT concentration. Ginsenoside Rb1 and estradiol administration resulted in elevated TPH and depressed MAO activities, indicating that modulating the synthesis and metabolism of neural 5-HT successfully elevated 5-HT concentration. Ginsenoside Rb1 and estradiol also improved object recognition and decreased immobility time in the forced swimming test. However, a pretreatment with clomiphene (an estrogen receptor antagonist) blocked the beneficial effects of ginsenoside Rb1 and estradiol, suggesting that the estrogen-like effects of ginsenoside Rb1 were estrogen receptor-dependent., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of leukemia inhibitory factor (LIF) on renal interstitial fibroblast activation following induction by transforming growth factor beta 1 (TGF-beta1)., Methods: Normal rat interstitial fibroblast cells (NRK/49F) were treated with TGF-beta1 and TGF-beta1, combining with LIF respectively for different duration with different concentration. Changes in cell morphology and expression of alpha-SMA were evaluated with electronic microscope and Western blot respectively. The collagen I in the supernatant was detected with ABC-ELISA., Results: TGF-beta1 induced renal interstitial fibroblast activation, and this was accompanied by significant morphological transformations and secretion of collagen I. Co-culturing of cells with LIF blocked the morphological transformation. In addition, LIF inhibited TGF-beta1-induced expression of alpha-SMA mRNA and protein (P < 0.01), and decreased the levels of collagen I (P < 0.01) in a dose-dependent manner., Conclusion: LIF suppresses TGF-beta1-induced activation and collagen I secretion of cultured renal interstitial fibroblasts.

The removal of Cr (VI) from aqueous solutions using black carbon (BC) isolated from the burning residues of wheat straw was investigated as a function of pH, contact time, reaction temperature, supporting electrolyte concentration and analytical initial Cr (VI) concentration in batch studies. The effect of surface properties on the adsorption behavior of Cr (VI) was investigated with scanning electron microscope (SEM) equipped with the energy dispersive X-ray spectroscope (EDS) and Fourier transform-infrared (FTIR) spectroscopy. The removal mechanism of Cr (VI) onto the BC was investigated and the result showed that the adsorption reaction consumed a large amount of protons along the reduction of Cr (VI) to Cr (III). The oxidation of the BC took place concurrently to the chromium reduction and led to the formation of hydroxyl and carboxyl functions. An initial solution pH of 1.0 was most favorable for Cr (VI) removal. The adsorption process followed the pseudo-second order equation and Freundlich isotherm very well. The Cr (VI) adsorption was temperature-dependent and almost independent on the sodium chloride concentrations. The maximum adsorption capacity for Cr (VI) was found at 21.34 mg/g in an acidic medium, which is comparable to other low-cost adsorbents., ((c) 2009 Elsevier B.V. All rights reserved.)

The effects of LSKL, the peptide antagonist of thrombospondin-1 (TSP-1), on renal interstitial fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Rats were divided randomly into three groups (n = 20 each): UUO group, sham-operation group and UUO plus LSKL treatment group. Collagen deposition was studied using histopathology and reverse transcription polymerase chain reaction analysis (RT-PCR). TSP-1, transforming growth factor beta 1 (TGF-beta1), phosphorylated Smad2 (pSsmad2) and alpha-smooth muscle actin (alpha-SMA) in the kidney were measured using immunocytochemistry, western blotting analysis, RT-PCR and enzyme-linked immunosorbent assay. Biochemical analyses in the serum and urine were made. Histopathology showed severe tubular dilatation and atrophy, interstitial inflammation and collagen accumulation after surgery and LSKL significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. The protein and mRNA levels of TSP-1 increased notably at different time point and significantly decreased in the presence of LSKL. The expression of TGF-beta1 and pSmad2 were upregulated in the obstructed kidney and substantially suppressed by LSKL treatment. Myofibroblast accumulation could be alleviated after administration of LSKL. Biochemical parameters did not show differences among the three groups. As TSP-1 is the major activator of TGF-beta1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-beta1 activation.

Objective: To investigate the effect and possible mechanism of salidroside on the transdifferentiation of normal rat kidney tubular epithelia cells (NRK52E) under cobaltous chloride (Co) induced hypoxic status., Methods: Cultured NRK52E cells were divided into control group, Co group and Co plus salidroside treatment groups at a dosage of 10 micromol/L, 50 micromol/L, and 100 micromol/L. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of oxygen homeostasis was measured as a marker of hypoxic status. Morphologic alteration of cells was observed by inverted phase contrast microscope. The expression of alpha-SMA in NRK52E cells was detected by fluorescent immunocytochemistry (FICC) and immunohistochemistry (IHC). The alpha-SMA and TGF-beta1 mRNA were assessed using reverse transcription-polymerase chain reaction (RT-PCR). The expressions of HIF-1alpha and alpha-SMA protein were detected by Western blot analyses. The enzyme-linked immunosorbent assay was performed to detect collagen I (Col-I) and fibronectin (FN) in the supernatant., Results: The expression of HIF-1alpha in NRK52E cells was induced by 100 micromol/L of Co in vitro. Co induced transdifferentiation of NRK52E cells, showing fibroblast-like in morphology. Salidroside partly blocked morphologic transformation of tubular epithelial cells. Salidroside decreased the expressions of alpha-SMA protein and mRNA and TGF-beta1 mRNA significantly (P < 0.05), although they were still higher than the controls (P <0 .05). Salidroside, especially in high dosage, inhibited the increase in Col-I and FN induced by Co (P < 0.05)., Conclusion: Hypoxia can induce tubular epithelial-myofibroblast transdifferentiation (TEMT). Salidroside improves Co-induced hypoxic status and inhibits TEMT possibly through reducing Col I and FN in NRK52E cells.

Objective: The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated., Methods: We applied hydraulic pressure (50 cm H2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-beta1 (TGF-beta1) of NRK52E cells were examined., Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of alpha-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-beta1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-beta1., Conclusion: We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-beta1 secretion.