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Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism. [ABSTRACT FROM AUTHOR]

The limited selections of wide-bandgap polymer donors have prevented the further increase in the power conversion efficiency (PCE) of organic solar cells. In this work, we report two novel wide-bandgap alternating copolymers (PL4 and PL5), which were synthesized by copolymerizing a new benzodithiophene-derived electron-rich unit (D) with two electron-deficient units (A) of 5,6-difluoro-2- (2-hexyldecyl)-4,7-di(thiophen-2-yl)-2H-benzo[d][1,2,3]triazole and 1,3-bis(2-ethylhexyl)-5,7-di(thiophen-2-yl)-4H,8H-benzo[1,2-c:4,5-c']dithiophene-4,8-dione, respectively. PL5 shows a broader and red-shifted absorption spectrum compared to PL4 due to the more electron-withdrawing feature of its A moiety. Moreover, the energy levels of PL5 are relatively down-shifted compared to those of PL4. When blended with a low-bandgap non-fullerene acceptor (Y6), the best-performing PL5:Y6-based device exhibits a significantly higher PCE of 15.77% with an enhanced VOC of 0.818 V, an excellent JSC of 26.60 mA cm-2, and a higher fill factor (FF) of 72.47% in comparison with the PL4:Y6-based PSC which shows a PCE of 7.53% with a VOC of 0.718 V, a JSC of 21.60 mA cm-2, and a FF of 48.58%. The improved PCE of the PL5:Y6-based device can be ascribed to its more efficient charge transfer, dramatically increased charge carrier mobilities and reduced charge recombination. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the prognostic value of lymph node ratio (LNR) in patients with locally advanced gastric cancer who received neoadjuvant chemotherapy. Materials and Methods: We retrospectively enrolled gastric cancer patients treated with neoadjuvant chemotherapy and curative surgery at the First Affiliated Hospital of Zhejiang University from 2004 to 2015 as the study cohort. Patients with the same inclusion criteria treated in 2016–2017 were enrolled as the validation cohort. Kaplan-Meier curves were assessed using the log-rank test to analyze the differences in overall survival (OS). Multivariate survival analysis was performed using the Cox proportional hazards model. The areas under the receiver operating characteristic curve of ypN and LNR categories for predicting the actual 3-year OS were compared. Results: A total of 265 patients were included in the proposal cohort. The median number of retrieved lymph nodes (rLNs) was 32. The number of positive lymph nodes (pLNs) increased as rLN increased (P=0.037), but the LNR remained relatively constant (P=0.462). The LNR was categorized into 4 groups according to the prognosis: ypNr0, node-negative with rLN>25; ypNr1, node-negative with rLN≤25 or 00.3. In the validation cohort of 43 enrolled patients, there was a clear distinction in OS that significantly (P<0.001) varied depending on the LNR values and LNR was the only independent prognostic factor in multivariate analysis (P<0.001). Conclusions: LNR was an independent prognostic factor for survival of patients with gastric cancer after preoperative chemotherapy and might be an alternative predictor for ypN stage. [ABSTRACT FROM AUTHOR]

Wheat straw produced annually in the Shaanxi Guanzhong region is a potential biomass feedstock for the production of transportation fuels and specialized chemicals through combustion, pyrolysis, or gasification. In this work, the pyrolytic characteristics, evolved gas products, and kinetics of Guanzhong wheat straw and its components were first investigated with a thermogravimetry-Fourier infrared spectroscopy (TG-FTIR) system. A comparative kinetic study was conducted using different model-free methods of Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), Kissinger, and the Coats-Redfern methods. The main pyrolysis products identified by FTIR include H2O, CH4, CO2, and CO as well as aromatics, acids, ketones, and aldehydes. Kinetic results showed that the pyrolytic apparent activation energy of the straw is approximately 200 kJ/mol obtained via FWO and KAS methods at the conversion range of 0.4 to 0.75, which was 30 kJ/mol higher than the value 171.1 kJ/mol obtained by the Kissinger method. The apparent activation energy of cellulose in its main pyrolysis region is 135.5 kJ/mol and is about three times larger than that of hemicellulose (49.5 kJ/mol). The apparent activation energy of lignin at the temperature range of 45 to 116 °C was 34.5 kJ/mol, while that value at the temperature range of 120 to 252 °C was 6.64 kJ/mol. [ABSTRACT FROM AUTHOR]

Ammonia-driven carbonyl-to-imine conversion is an important formation pathway to the nitrogen-containing organic compounds (NOC) in secondary organic aerosols (SOA). Previous studies have mainly focused on the dicarbonyl compounds as the precursors of light-absorbing NOC. In this work, we investigated whether acrolein could also act as a NOC precursor. Acrolein is the simplest α,β-unsaturated mono-carbonyl compound, and it is ubiquitous in the atmosphere. Experiments probing gas-phase and surface reactions of acrolein as well as bulk liquid-phase experiments were carried out to study the reactivity of acrolein towards ammonia and ammonium ions. Molecular characterization of the products based on gas chromatography mass spectrometry, high resolution mass spectrometry, surface enhanced Raman spectrometry and Ultraviolet/visible spectrometry was used to propose possible reaction mechanisms. We observed 3-methyl pyridine (also called 3-picoline) in the gas phase in the Tedlar bag filled with gaseous acrolein and ammonia. In the liquid phase, oligomeric compounds with formulas (C3H4O)m(C3H5N)n and pyridinium compounds like (C3H4O)2C6H8N+ were observed as the products of acrolein reaction with ammonium ions. The 3-picoline could be the product of acrolein reaction with gaseous ammonia in the gas phase. The pathway to 3-picoline was proposed to be the intramolecular carbon-carbon addition of the hemiaminal which resulted from sequential carbonyl-to-imine conversions of acrolein molecules. The similar reaction of dissolved acrolein with ammonium ions leads to the formation of 3-methyl pyridinium (also called 3-picolinium) cations in the liquid phase. The (C3H4O)2C6H8N+ was a carbonyl-to-hemiaminal product from acrolein dimer and 3-picolinium cations, while the oligomeric products of (C3H4O)m(C3H5N)n were polymers of acroleins and propylene imines via carbonyl-to-imine conversion and condensation reactions. Part of the 3-picolinium could re-volatilize to the gas phase as 3-picoline, explaining the observation of gaseous 3-picoline in the bag filled with acrolein and ammonium sulfates (or chlorides) aerosols. The pH value effect on the liquid products was also studied in the bulk liquid-phase experiments. Compared to the oligomeric compounds forming in both acid and alkaline conditions, there is a tendency for the pyridinium products to be formed under moderately acidic conditions. Both the oligomeric products and the pyridinium salts are light absorbing materials. This work suggests a potential role for acrolein reaction with ammonia/ammonium as a source of light-absorbing heterocyclic NOC in SOA. Therefore, secondary reactions of α,β-unsaturated aldehydes with reduced nitrogen should be taken into account when evaluating climate and health effects of SOA. [ABSTRACT FROM AUTHOR]

Measurements of gaseous elemental Hg (GEM), other air pollutants including SO2, NOx, O3, PM2.5, CO, and meteorological conditions were carried out at Chongming Island in East China from March 1 in 2014 to December 31 in 2016. During the sampling period, GEM concentrations significantly decreased from 2.68 ± 1.07 ng m−3 in 2014 to 1.60 ± 0.56 ng m−3 in 2016. Monthly mean GEM concentrations showed a significant decrease with a rate of −0.60 ng m−3 yr−1 (R2 = 0.6389, p < 0.01 significance level). Combining the analysis of potential source contribution function (PSCF), principle component analysis (PCA), and emission inventory, we found that Yangtze River Delta (YRD) region was the dominant source region of atmospheric mercury in Chongming Island and the main source industries included coal-fired power plants, coal-fired industrial boilers, and cement clinker production. We further quantified the effect of emission change on the air Hg concentration variations at Chongming Island through a coupled method of trajectory clusters and air Hg concentrations. It was find that the reduction of domestic emissions was the main driver of GEM decline in Chongming Island, accounting for 66 % of the total decline. The results indicated that air pollution control policies targeting SO2, NOx and particulate matter reductions had significant co-benefits on atmospheric mercury. [ABSTRACT FROM AUTHOR]

The time-dependent Ginzburg-Landau equations have been solved numerically by a finite element analysis for the mesoscopic superconducting samples with cylindrical shape in a uniform axial magnetic field. We obtain the different vortex patterns as a function of the applied field perpendicular to its surface. We find that multi-vortex states are ground state in three-dimensional mesoscopic cylinders. These results show that our approach is an effective and useful to interpret experimental data on vortex states in the mesoscopic superconductors. [ABSTRACT FROM AUTHOR]

The current research was conducted to study the qualitative analysis and antimicrobial activity of different extracts of Viscum. album L. Screening of Viscum album for their chemicals was led by familiar qualitative procedures, which exposed the existence of a number of bioactive compounds including alkaloids, saponins, tannins, flavonoids, terpenoids, steroids, reducing sugar and phenols. The antimicrobial activities were investigated by disc diffusion method. Investigation of the data discovered that all of the five extracts of Viscum album stems, leaves and fruit showed diverse range of antimicrobial activities. Ethyl acetate, butanol, water and crude extracts showed maximum inhibitory effects against all the microbial species. Especially, Gram-positive bacterial and fungal pathogen. The most liable, gram-positive bacteria were Bacillus subtilis, Bacillus atrophaeus and Staphylococcus aureus, which were repressed by all extracts except n-hexane. The most susceptible gram-negative bacterial species were Escherichia coli, Erwinia carotovora and Agrobacterium tumefaciens where as the most resilient gram-negative bacterium was Salmonella typhi. The results have also supported the practice of aqueous extract were found to be in effect against Salmonella typhi and Escherichia coli. Thus, our findings have provided support for the use of Viscum album stems, leaves and fruit in traditional medicines. [ABSTRACT FROM AUTHOR]

Bio-stimulation is a new kind of processing technology to improve the efficiency of biological treatment of wastewater, especially in industry organic wastewater treatment in China, to meet the increasing rigid discharge regulations. In this study a new kind of Bio-stimulat(BS) for papermaking wastewater was developed, and the functional bio-stimulant was added in an aeration system aimed to enhance biological teratment efficiency. Experiments were performed at a lab scale process with papermaking wastewater as sample for 15 d, the process performance and the activity of the aerobic microorganism was thoroughly researched by determining Adenosine Triphosphate (ATP), TTC-dehydrogenase and protein content during addition of BS. Result shows the optimum BS fomular was as follows: Lassase 50U.mg-1 + Cellulose 5U.mg-1+ Hemi cellulase10 U.mg-1 + Gibberellins 1μg.mg-1 + Fulvic acid 10μg.mg-1+ NH4Cl 0.5mg.mg-1 + NaH2PO4 0.08mg.mg-1. Adding BS in aerobic basin of the PWTP can imcrease 10-15% removal of chemical oxygen demand (COD), and the effluent COD declined from 106 to 83 mg·L-1 (<90 mg·L-1, met the discharge standards), the enhanced efficiency of biological treatment was result from better microbial activity ,which can be proved by the increasing value of ATP (Adenosine Triphosphate), TTC-dehydrogenase and protein content of microbial comparing with that of black group during the 15 d (the activate sludge age) experiment period. Besides, SEM picture indicated that the overall health status of microbial cell enhanced, the absorption and flocculation property of the zoogloeaa improved, and the aerobic sludge bulking could obviously inhibited accordingly. [ABSTRACT FROM AUTHOR]

During July 2015, physicians at a hospital in Beijing, China, diagnosed rabies in 2 patients who had each received a kidney from a common organ donor who had died from acute progressive encephalitis of unknown cause. The patients had rabies incubation periods of 42 and 48 days. Altered mental status developed in both patients and progressively worsened to deep coma within 80 days after transplantation; both patients died. Two other transplant recipients received corneas but remained well after receiving timely rabies prophylaxis. An effective regulatory system for testing donors should be implemented to decrease the occurrence of donor-derived infectious diseases. In addition, health education should be improved to enhance public awareness of transplant-associated infectious diseases. Transplant recipients and other persons with exposure to organs or tissues from donors with rabies must be provided consistent health monitoring and follow-up, including rabies postexposure prophylaxis; any remaining organs and tissues must be quarantined and not transplanted. [ABSTRACT FROM AUTHOR]

We demonstrate that Fano resonance and even multipole Fano resonance can be obtained in a symmetry-reduced structure composed of gold bars with different bar sizes or bar shapes on a layer of dielectric. There is a transparency window opened within the frequency region of the absorptive dipole resonance by metallic bars, as long as the narrow grating waveguide mode induced by reducing symmetry is coincided in spectrum with the dipole resonance such that a destructive interference happens between these two resonant modes. Line shape of the transmission spectra of the nanostructure can be modulated effectively by changing the size or shape of the series of metal bars. The results found can be useful in the design of novel optical device. [ABSTRACT FROM AUTHOR]

Background Host cell autophagy is implicated in the control of intracellular pathogen. Escherichia coli (E.coli) is the most common organism caused single-germ enterobacterial peritonitis during peritoneal dialysis. In this study, we investigated autophagy of peritoneal mesothelial cells and its role in defense against E.coli. Results Autophagy in human peritoneal mesothelial cell line (HMrSV5) was induced by lipopolysaccharide (LPS) in a dose-dependent and time-dependent way, which was demonstrated by increased expression of Beclin-1 and light chain 3 (LC3)-II, the accumulation of punctate green fluorescent protein-LC3, and a higher number of monodansylcadaverine-labeled autophagic vacuoles. After incubation of HMrSV5 cells with E.coli following LPS stimulation, both the intracellular bactericidal activity and the colocalization of E.coli (K12-strain) with autophagosomes were enhanced. Conversely, blockade of autophagy with 3-methyladenine, wortmannin or Beclin-1 small-interfering RNA (siRNA) led to a significant reduction in autophagy-associated protein expression, attenuation of intracellular bactericidal activity, and reduced co-localization of E.coli with monodansylcadaverine-labeled autophagosomes. In addition, treatment of HMrSV5 cells with LPS caused a dose-dependent and time-dependent increase in Toll-like receptor 4 (TLR4) expression. Both knockdown of TLR4 with siRNA and pharmacological inhibition of TLR4 with Polymyxin B significantly decreased LPS-induced autophagy. Furthermore, TLR4 siRNA attenuated remarkably LPS-induced intracellular bactericidal activity. Conclusions Our findings demonstrated for the first time that LPS-induced autophagy in peritoneal mesothelial cells could enhance the intracellular bactericidal activity and the co-localization of E.coli with autophagosomes. The activation of TLR4 signaling was involved in this process. These results indicate that LPS-induced autophagy may be a cell-autonomous defense mechanism triggered in peritoneal mesothelial cells in response to E.coli infection. [ABSTRACT FROM AUTHOR]

A simple and rapid dual-wavelength spectroscopic method is used for simultaneous determination of pentoses and hexoses in the prehydrolyzate from lignocellulosic biomass. The method is based on the following reaction mechanism: in the solution of hydrochloric acid, phloroglucinol gives color reaction with sugars or their degradation products, showing maximum absorbance at 553 nm and 410 nm. Based on dual-wavelength spectrophotometric measurement, the pentoses and hexoses can separately be quantified. It was found that the derivatives from these two different sugars have an isosbestic point at 425 nm. According to the validation results, high accuracy and reasonable recovery rate is shown with the present method (pentoses recovery 97.1 to 100.0%, hexoses recovery 97.2 to 102.0%). Additionally, the interferences from substances including lignin, furfural, 5-hydroxymethyl furfural (HMF), glucuronic acid, and galacturonic acid are insignificant. All of the above results illustrate the suitability of this method for analyzing sugars in the lignocelluloses prehydrolyzate, especially hardwoods or herbaceous plants, based on forest-related biorefinery research. [ABSTRACT FROM AUTHOR]

Objective: To study the cost benefit analysis of using a telemedicine-based digital retinal imaging evaluation compared to conventional ophthalmologic fundus examination of diabetic patients for diabetic retinopathy. Methods: In this study, diabetic patients from Community Health Center, Inc. (CHCI), a large multi-site Federally Qualified Health Center) were evaluated by teleophthalmology using the Canon CR-1 nonmydriatic fundus camera. Digital images were acquired in the CHCI offices and saved on the EyePACS® server network. The images were later evaluated by retinal specialists at the Yale Eye Center, Yale University Department of Ophthalmology and Visual Science. The costs for the standard of care ophthalmic examinations were calculated based on 2009 Medicaid reimbursement rates. The process of telemedicine-based diagnosis was based on a take-store-forward-visualize system. The cost of telemedicine-based digital retinal imaging examination included cost for devices, training, annual costs and a transportation fee. Current Medicaid reimbursement, transportation, and staff labor costs were used to calculate the conventional retinal examination cost as a comparison. Results: Among the 611 patients digital retinal images screened in the first year of this program and for whom data are available, 166 (27.2%) cases of diabetic retinopathy were identified. Seventy-five (12.3%) patients screened positive with clinically significant disease and were referred for further ophthalmological evaluation and treatment. The primary direct cost of the telemedicine was $3.80, $15.00, $17.60, $1.50, and $2.50 per patient for medical assistant, ophthalmologist, capital cost (Equipment + Training), equipment maintenance, and transportation fee, respectively. The total cost in the telemedicine-based digital retinal imaging and evaluation was $40.40. The cost of conventional retinal examination was $8.70, $65.30, and $3.80 per patients for round-trip transportation, 2009 national Medicaid Physician Fee Schedule allowable for bilateral eye examination, and medical assistant personnel, respectively. The total costs of conventional fundus examination were $77.80. An additional conventional ophthalmologic retinal examination was required for 75 (12.3%) patients with clinically significant disease on telemedicine evaluation, which involves an averaged additional cost of $9.55 per patient for all the patients in the study. If the cost of subsequent examination was added, the total cost of telemedicine-based digital fundus imaging was $49.95 per patient in our group of 611 patients evaluated. Conclusions: Our cost analysis indicates that telemedicine-based diabetic retinopathy screening cost less ($49.95 vs $77.80) than conventional retinal examination and the telemedicine-based digital retinal imaging examination has the potential to provide an alternative method with greater convenience and access for the remote and indigent populations. Diabetes mellitus and diabetic retinopathy are growing problems in the United States and worldwide. Large scale adoption telemedicine should be encouraged as a means toward providing improved access, increasing compliance with annual evaluation, at a low cost for patients with diabetes with direct access to an eye care specialist. [ABSTRACT FROM AUTHOR]

Background: Health care system reform is a major issue in many countries and therefore how to evaluate the effects of changes is incredibly important. This study measured residents' satisfaction with community health care service in Shanghai, China, and aimed to evaluate the effect of recent health care system reform. Methods: Face-to-face interviews were performed with a stratified random sample of 2212 residents of the Shanghai residents using structured questionnaires. In addition, 972 valid responses were retrieved from internet contact. Controlling for sex, age, income and education, the study used logistic regression modeling to analyze factors associated with satisfaction and to explain the factors that affect the residents' satisfaction. Results: Comparing current attitudes with those held at the initial implementation of the reform in this investigation, four dimensions of health care were analyzed: 1) the health insurance system; 2) essential drugs; 3) basic clinical services; and 4) public health services. Satisfaction across all dimensions improved since the reform was initiated, but differences of satisfaction level were found among most dimensions and groups. Residents currently expressed greater satisfaction with clinical service (average score=3.79, with 5 being most satisfied) and the public health/preventive services (average score=3.62); but less satisfied with the provision of essential drugs (average score=3.20) and health insurance schemes (average score=3.23). The disadvantaged groups (the elderly, the retired, those with only an elementary education, those with lower incomes) had overall poorer satisfaction levels on these four aspects of health care (P<0.01). 25.39% of the respondents thought that their financial burden had increased and 38.49% thought that drugs had become more expensive. Conclusion: The respondents showed more satisfaction with the clinical services (average score=3.79) and public health services/interventions (average score=3.79); and less satisfaction with the health insurance system (average score=3.23) and the essential drug system (average score=3.20). Disadvantaged groups showed lower satisfaction levels overall relative to non-disadvantaged groups. [ABSTRACT FROM AUTHOR]

Dosage suppression is a genetic interaction in which overproduction of one gene rescues a mutant phenotype of another gene. Although dosage suppression is known to map functional connections among genes, the extent to which it might illuminate global cellular functions is unclear. Here we analyze a network of interactions linking dosage suppressors to 437 essential genes in yeast. For 424 genes, we curated interactions from the literature. Analyses revealed that many dosage suppression interactions occur between functionally related genes and that the majority do not overlap with other types of genetic or physical interactions. To confirm the generality of these network properties, we experimentally identified dosage suppressors for 29 genes from pooled populations of temperature-sensitive mutant cells transformed with a high-copy molecular-barcoded open reading frame library, MoBY-ORF 2.0. We classified 87% of the 1,640 total interactions into four general types of suppression mechanisms, which provided insight into their relative frequencies. This work suggests that integrating the results of dosage suppression studies with other interaction networks could generate insights into the functional wiring diagram of a cell. [ABSTRACT FROM AUTHOR]

Conditional temperature-sensitive (ts) mutations are valuable reagents for studying essential genes in the yeast Saccharomyces cerevisiae. We constructed 787 ts strains, covering 497 (?45%) of the 1,101 essential yeast genes, with ?30% of the genes represented by multiple alleles. All of the alleles are integrated into their native genomic locus in the S288C common reference strain and are linked to a kanMX selectable marker, allowing further genetic manipulation by synthetic genetic array (SGA)-based, high-throughput methods. We show two such manipulations: barcoding of 440 strains, which enables chemical-genetic suppression analysis, and the construction of arrays of strains carrying different fluorescent markers of subcellular structure, which enables quantitative analysis of phenotypes using high-content screening. Quantitative analysis of a GFP-tubulin marker identified roles for cohesin and condensin genes in spindle disassembly. This mutant collection should facilitate a wide range of systematic studies aimed at understanding the functions of essential genes. [ABSTRACT FROM AUTHOR]

In order to reduce channel noise, parameter mismatch, and cross talks in chaotic multi-user communication systems under a single channel, a feedback filter bank based on the square root unscented Kalman filter (SR-UKF) and its realization algorithm are proposed in this paper. The numerical simulation results indicate that the feedback SR-UKF (FSR-UKF) algorithm can effectively realize chaotic multi-user communications in a single channel, and is of a faster convergence speed than the recently reported alternative method.. [ABSTRACT FROM AUTHOR]

Abstract  Some aspects of the cellular responses to cadmium were extensively investigated in the yeast Rhodotorula sp. Y11. Scanning electron microscopy indicated that accumulation of cadmium in the Y11 did not cause any visible effects on cell morphology. More than 20% yeast cells still showed viability after 15 h of cadmium accumulation under 100 mg l−1 cadmium concentration, and transmission electron microscopy analysis showed that plasmolysis and thickened cell wall were not observed in all of the cells. In the presence of cadmium, the activities of superoxide dismutase (SOD) and catalase (CAT) were all greater than the control, but the increase was in a dose-independent manner. Changes in SOD and CAT activities were also dependent on the time of exposure. Therefore, it suggests that antioxidative defenses play an important role in cadmium tolerance in Rhodotorula sp. Y11. Nondenaturing polyacrylamide gels revealed only one SOD isoforms in Y11 even under exposure to cadmium. [ABSTRACT FROM AUTHOR]

Although heat shock protein 72 kDa (HSP72) protects tubular epithelium from a variety of acute insults, its role in chronic renal injury and fibrosis is poorly characterized. In this study, we tested the hypothesis that HSP72 reduces apoptosis and epithelial-to-mesenchymal transition (EMT), important contributors to tubular cell injury in vitro and in vivo. In rats, orally administered geranylgeranylacetone (GGA), an agent that selectively induces HSP72, markedly reduced both apoptosis and cell proliferation in tubular epithelium and decreased both interstitial fibroblast accumulation and collagen I deposition after unilateral ureteric obstruction, a model of chronic renal tubulointerstitial fibrosis and dysfunction. In cultured renal NRK52E cells, exposure to TGF-β1 induced EMT and apoptosis, major causes of renal fibrosis and tubular atrophy, respectively. Exposure to a pan-caspase inhibitor (ZVAD-FMK) prevented TGF-β 1-induced apoptosis but did not reduce EMT. In contrast, selective HSP72 expression in vitro inhibited EMT caused by TGF-β1 as indicated by preserving the E-cadherin expression level and α-smooth muscle actin induction. Small interfering RNA directed against HSP72 blocked the cytoprotective effects of HSP72 overexpression on EMT in TGF-β1-exposed cells. Taken together, our data indicate that HSP72 ameliorates renal tubulointerstitial fibrosis in obstructive nephropathy by inhibiting both renal tubular epithelial cell apoptosis and EMT. [ABSTRACT FROM AUTHOR]