Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.

Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8+ T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ). Increased IFN-γ secretion can induce macrophage pyroptosis and the release of interleukin 1-ß (IL-1ß), aggravating lung injury. In this study, lung injury in C57BL/6 mice was induced by subcutaneous micro-osmotic pump infusion of aldosterone. After 12 weeks of administration, the kidney, heart, blood vessels and lungs all showed obvious inflammatory injury, which manifested as rapid accumulation of macrophages. The overexpression of IFN-γ in the lungs of aldosterone-treated mice and the stimulation of MH-S and RAW264.7 alveolar macrophages (AMs) with aldosterone in vitro showed that IFN-γ induced pyroptosis of macrophages via the activation of the inflammasome, and the MR blocker esaxerenone effectively inhibited this effect and alleviated lung injury. In addition, IFN-γ secreted by CD8+ T cells is associated with macrophage pyroptosis. In conclusion, the inhibition of macrophage pyroptosis can effectively alleviate lung injury.

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis.

Na, K-ATPase interaction (NKAIN) is a transmembrane protein family, which can interact with Na, K-ATPase ß1 subunit. NKAIN1 plays an important role in alcohol-dependent diseases such as endometrial and prostate cancers. However, the relationship between NKAIN1 and human breast cancer has not been studied. Hence, this study aimed to explore the relationship between NKAIN1 expression and breast cancer. Data used in this study were mainly from the Cancer Genome Atlas, including differential expression analysis, Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, multiple Cox regression analysis, co-expression gene analysis, and gene set enrichment analysis. Analyses were performed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunohistochemistry on 46 collected samples. The knockdown or overexpression of NKAIN1 in vitro in MCF-7 and MDA-MB-231 cell lines altered the proliferation and migration abilities of tumor cells. In vivo experiments further confirmed that NKAIN1 knockdown effectively inhibited the proliferation and migration of cancer cells. Therefore, our study identified NKAIN1 as an oncogene that is highly expressed in breast cancer tissues. The findings highlight the potential of NKAIN1 as a molecular biomarker of breast cancer.

Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-ß1 Pathways in Aldosterone-Infused Mice.

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix. Aldosterone stimulates mineralocorticoid receptor (MR) activation and induces inflammation, which is important for angiogenesis. Clinically, MR blockers (MRBs) have a protective effect on damaged kidneys, which may be associated with inhibition of angiogenesis. In this study, we used aldosterone-infused mice and found that aldosterone induced angiogenesis and that endothelial-mesenchymal transition (EndMT) in neovascular endothelial cells was involved in renal fibrosis. Notably, aldosterone induced inflammation and stimulated macrophages to secrete vascular endothelial growth factor (VEGF) A to regulate angiogenesis by activating MR, whereas EndMT occurred in response to transforming growth factor-ß1 (TGF-ß1) induction and participated in renal fibrosis. These effects were antagonized by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.

E2EFP-MIL: End-to-end and high-generalizability weakly supervised deep convolutional network for lung cancer classification from whole slide image.

Efficient and accurate distinction of histopathological subtype of lung cancer is quite critical for the individualized treatment. So far, artificial intelligence techniques have been developed, whose performance yet remained debatable on more heterogenous data, hindering their clinical deployment. Here, we propose an end-to-end, well-generalized and data-efficient weakly supervised deep learning-based method. The method, end-to-end feature pyramid deep multi-instance learning model (E2EFP-MIL), contains an iterative sampling module, a trainable feature pyramid module and a robust feature aggregation module. E2EFP-MIL uses end-to-end learning to extract generalized morphological features automatically and identify discriminative histomorphological patterns. This method is trained with 1007 whole slide images (WSIs) of lung cancer from TCGA, with AUCs of 0.95-0.97 in test sets. We validated E2EFP-MIL in 5 real-world external heterogenous cohorts including nearly 1600 WSIs from both United States and China with AUCs of 0.94-0.97, and found that 100-200 training images are enough to achieve an AUC of >0.9. E2EFP-MIL overperforms multiple state-of-the-art MIL-based methods with high accuracy and low hardware requirements. Excellent and robust results prove generalizability and effectiveness of E2EFP-MIL in clinical practice. Our code is available at https://github.com/raycaohmu/E2EFP-MIL.

Selective adsorption and separation of methylene blue by facily preparable xanthan gum/amantadine composites.

In this work, xanthan gum-based composites were successfully graft-modified by amantadine (XG-Fe3+/AM) with higher adsorption capacity and selectivity on recycling cationic dye (methylene blue, MB) from aqueous solution. The adsorption equilibrium of MB could be achieved approximately within 5 min when the initial concentration was 100 mg/L, and the maximum adsorption capacity was up to 565 mg/g. After 5 desorption-regeneration cycles, the removal rate of XG-Fe3+/AM for MB could still be as high as 95 % with slight decrement. Additionally, the effects of pH, contact time, temperature and initial dye concentration on the adsorption performance of MB were systematically examined. Furthermore, the adsorbent was characterized by FT-IR, BET and XPS analysis. In mixed anionic and cationic dyes, the adsorption selectivity of XG-Fe3+/AM on MB in the mixture of MB and methyl orange (MO) reached up to 99.69 %. Molecular dynamics simulation revealed that the trend of adsorption energy for dyes was in good agreement of the experimental order of adsorption capacities and molecular sizes among seven anionic and cationic dyes based on molecular matching effect and electrostatic interaction. Therefore, XG-Fe3+/AM is an eco-friendly, facile-synthesis and high-selectivity adsorbent, which remove cationic dyes in multi-component systems through electrostatic interaction and molecular matching effect.

Efficient selective recycle of acid blue 93 by NaOH activated acrolein/chitosan adsorbent via size-matching effect.

Here we report an efficient strategy to separate and recycle acid blue 93 (AB93) from mixed anionic dyes selectively within sodium hydroxide activated A/CS adsorbent (N-A/CS). This work broke the common sense that the larger the specific surface area, the better the adsorption property is, which provided an alternative strategy to separate dyes. The adsorption equilibrium of AB93 could be achieved approximately within 1-2 min, and the maximum adsorption capacity was up to 2500 mg/g. Besides, it can be activated continuously and reused at least 15 times. In mixed anionic dyes, the adsorption selectivity of N-A/CS on AB93 in the mixture of AB93 and acid fuschin (AF) reached up to 99.7 %. Molecular dynamics simulation revealed that the trend of adsorption energy for dyes qualifies well with the experimental order of adsorption capacities and molecular sizes among five anionic dyes based on molecular matching effect. Thus, N-A/CS is a low-cost, easily-preparable, significantly-effective-and-reusable adsorbent, providing a promising "size-matching" strategy to adsorb multi-component dye systems.

Evaluation of Axial Preload in Different-Frequency Smart Bolts by Laser Ultrasound.

We report here on a laser ultrasonic system to indirectly evaluate the preload force of different-frequency piezoelectric bolts. This newly developed system enables us to achieve the goal of non-contact excitation and synchronously collects the laser-induced ultrasonic signal by the combination of a smart piezoelectric sensor and a magnetically mounted transducer connector. A numerical model based on the finite element method (FEM) was developed to simulate the propagation and displacement distribution of laser-generated ultrasonic waves along the axial direction. The measured A-scan waveform basically coincided with the counterpart obtained from a theoretical simulation, confirming the effectiveness of the proposed system to measure a bolt. By comparison, a laser spot diameter of 6 mm was the optimal beam diameter for the excitation of the ultrasonic wave in the bolt. The linear relationship between time of flight (TOF) of the ultrasonic longitudinal wave and bolt torque was almost independent from the center frequency of the smart bolt. By contrast, a piezoelectric patch centered at 5 MHz was more suitable as an ultrasonic sensor in terms of the nonlinear effects component suppression and linear fitting degree between TOF and torque. The results indicate that the proposed system based on a surface-mounted piezoelectric sensor is a promising system for evaluating the axial preload change of connector and fastener and is an additional potential laser ultrasonic system for nondestructive tests.

Efficiently ion-enhanced adsorption of anion dyes by acrolein crosslinked polyethylenimine/chitosan hydrogel with excellent recycling stability.

A novel adsorbent acrolein crosslinked polyethylenimine/chitosan hydrogel (A-PEI/CS) was developed with excellent recycling stability and ion-enhanced effect on removing anionic dye (acid blue 93, AB93) from aquatic environment. For AB93, A-PEI/CS was such an adsorbent with the characteristics of high adsorption capacity up to 1212.4 mg/g and continuous recyle ability of more than 15 times. After 15 desorption-regeneration cycles, the removal rate of A-PEI/CS for AB93 could still be as high as 96 % with imperceptibly downward trend. In addition, the addition of salts (KCl, NaCl and CaCl2) could promote the adsorption of A-PEI/CS, and the removal rate would be enhanced with increasing concentration of the salt. The effects of pH (2-7), contact time (30-600 min), temperature (30-50 °C) on the adsorption performance of A-PEI/CS were systematically examined. Furthermore, the physicochemical properties of the adsorbent were analyzed by FT-IR, XPS and zeta potential. The adsorption mechanism can be explained by electrostatic interaction, hydrogen bond interaction, chemical interaction. Intriguing to note that, the adsorption energy of adsorbents was investigated by molecular simulation, and the low pH and common salt environment can promote the adsorption effect, indicating that the prepared adsorbent has excellent application value in the treatment of practical high-salinity wastewater.

Rheological, Surface Tension and Conductivity Insights on the Electrospinnability of Poly(lactic-co-glycolic acid)-hyaluronic Acid Solutions and Their Correlations with the Nanofiber Morphological Characteristics.

In this study, solutions were prepared with fixed concentrations of hyaluronic acid (HA) but varied concentrations of poly (lactic-co-glycolic acid) (PLGA) to emphasize the effects of PLGA concentration and HA addition on solution properties and to further evaluate their electrospinning performance. The dependence of specific viscosity on PLGA concentration was studied to determine the concentration regimes and evaluate the critical concentration (Ce) for successful fiber generation. The Ce of PLGA solutions is 12.07% compared to 10.09% for PLGA-HA solutions. Blending with HA results in a lower concentration dependence and better consistency to the theoretical scaling mechanisms due to the additional topological constrains, which thus result in more chain entanglements. Solutions in semi-dilute entangled regimes show the crossover of complex moduli, verifying the stable and reliable entanglement network. Higher concentrations and HA addition both led to lower crossover frequencies and, thus, a longer relaxation time. The effects of a higher PLGA concentration and HA addition on the surface tension were not evident. However, the HA addition significantly improved the solution conductivity up to three times in the pure PLGA solutions due to its polyelectrolyte nature. Defect-free and uniform nanofibers were generated from 35% to 40% of the PLGA-HA solutions, yet fibers with bead-on-string structures were produced from all studied pure PLGA solutions. Such solution characteristics and parametric correlations can provide predictive insights on tailoring the morphological characteristics of nanofibers for specific applications.

Eplerenone ameliorates lung fibrosis in unilateral ureteral obstruction rats by inhibiting lymphangiogenesis.

Chronic kidney disease (CKD) involves progressive and irreversible loss of renal function, often causing complications and comorbidities and impairing the function of various organs. In particular, lung injury is observed not only in advanced CKD but also in early-stage CKD. The present study investigated the potential involvement of mineralocorticoid receptors (MRs) and lymphatic vessels in lung injury using a 180-day unilateral ureteral obstruction (UUO) model for CKD. Changes in lung associated with lymphangiogenesis and inflammatory were analyzed in UUO rats. The pathology of the lung tissue was observed by hematoxylin and eosin and Masson's staining. Detection of the expression of lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), Podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3) and VEGF C to investigate lymphangiogenesis. The mRNA and protein expression levels of IL-1ß, monocyte chemotactic protein 1, tumor necrosis factor-α, nuclear factor κB, phosphorylated serum and glucocorticoid-induced protein kinase-1 and MR were evaluated using western blot, reverse transcription-quantitative PCR, immunohistochemical staining and immunofluorescence staining. In the present study, long-term UUO caused kidney damage, which also led to lung inflammation, accompanied by lymphangiogenesis. However, treatment with eplerenone, an MR blocker, significantly reduced the severity of lung injury and lymphangiogenesis. Therefore, lymphangiogenesis contributed to lung fibrosis in UUO rats due to activation of MRs. In addition, transdifferentiation of lymphatic epithelial cells into myofibroblasts may also be involved in lung fibrosis. Collectively, these findings provided a potential mechanism for lung fibrosis in CKD and suggested that the use of eplerenone decreased kidney damage and lung fibrosis.

A Study of Familial Amyloid Polyneuropathy Induced by the TTR Val30Leu Mutation in China.

INTRODUCTION: Familial amyloid polyneuropathy is currently prevalent worldwide as the transthyretin (TTR) Val30Met mutation, and there are other types of mutations. The purpose of this study was to understand the clinical manifestations, electrophysiological characteristics, and outcomes of hormone-related therapy in patients with the TTR Val30Leu mutation in China. METHODS: Clinical data were collected from 9 members of a family with the TTR Val30Leu mutation in China, and blood samples of 7 members of the family were sequenced. The electrophysiological examinations of 4 of them were collected and analysed. RESULTS: A total of 7 people had the TTR gene c.148G>T missense mutation and the TTR protein Val30Leu mutation in this family, and the positive members all had similar symptoms, such as limb paraesthesia and gastrointestinal symptoms. In addition, electrophysiological examination showed abnormal nerve conduction velocity in all 4 patients. CONCLUSIONS: The clinical manifestations of this mutation involve mainly limb sensory or motor disorders or gastrointestinal symptoms or both, and the electrophysiological examination shows neurogenic damage.

Repeated intracerebral hemorrhage after craniotomy for a distal middle cerebral artery aneurysm: A case report.

RATIONALE: Distal middle cerebral artery aneurysms are very rare in the clinic, and craniotomy clipping is the better treatment after diagnosis. However, patients can also have repeated acute intracerebral hemorrhage after craniotomy for aneurysm, which has not been previously reported. PATIENT CONCERNS: A 24-year-old male patient was admitted to our hospital with headache, nausea, and vomiting. He was well before, had no family history of cerebrovascular disease or hypertension, and had no history of trauma. DIAGNOSES: Computer tomography and digital subtraction angiography of the brain revealed intracranial hematoma and an aneurysm located at the M4 segment of the left middle cerebral artery. INTERVENTIONS: The patient underwent 2 surgeries to treat the aneurysm, followed by 2 operations for acute cerebral hemorrhage. OUTCOMES: Despite repeated surgical treatments, the patient had a poor prognosis and eventually died of respiratory and circulatory failure after repeated brain bleeding. LESSONS: Briefly, it is of great importance to consider the risk factors of cerebral hemorrhage, and provide individualized treatment and psychological counseling for patients with intracerebral hemorrhage.

Eplerenone inhibits UUO-induced lymphangiogenesis and cardiac fibrosis by attenuating inflammatory injury.

Cardiorenal syndrome (CRS) is the leading cause of death associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, the underlying mechanisms of CRS are still poorly understood. Here, we studied a CKD model of unilateral ureteral obstruction (UUO) and observed pathological cardiac fibrosis and lymphangiogenesis in 180-day old UUO rats, in which inflammatory injury plays a major role. In addition, treatment of UUO rats with eplerenone, a mineralocorticoid receptor blocker (MRB), significantly reduced cardiac lymphangiogenesis and fibrosis. In conclusion, our experimental results showed that cardiac lymphangiogenesis in long-term UUO rats may be involved in the formation of cardiac fibrosis and that eplerenone can alleviate lymphangiogenesis and cardiac fibrosis by inhibiting inflammation.

Oxidative RNA Damage in the Pathogenesis and Treatment of Type 2 Diabetes.

Excessive production of free radicals can induce cellular damage, which is associated with many diseases. RNA is more susceptible to oxidative damage than DNA due to its single-stranded structure, and lack of protective proteins. Yet, oxidative damage to RNAs received little attention. Accumulating evidence reveals that oxidized RNAs may be dysfunctional and play fundamental role in the occurrence and development of type 2 diabetes (T2D) and its complications. Oxidized guanine nucleoside, 8-oxo-7, 8-dihydroguanine (8-oxoGuo) is a biomarker of RNA oxidation that could be associated with prognosis in patients with T2D. Nowadays, some clinical trials used antioxidants for the treatment of T2D, though the pharmacological effects remained unclear. In this review, we overview the cellular handling mechanisms and the consequences of the oxidative RNA damage for the better understanding of pathogenesis of T2D and may provide new insights to better therapeutic strategy.

Optimizing the distribution and proportion of various active sites for better NH3-SCR property over Cu/SSZ-13.

The Cu/SSZ-13 catalyst with Si/Al ratio of 10 and Cu/Al ratio in the range of 0.005 to 0.5 was synthesized by ion exchange method. The effect of Cu/Al ratio on the performance, selectivity, and active center of the catalyst SCR was studied. The samples with too low Cu/Al ratio have low catalytic activity in the entire temperature range due to the small number of active sites. The samples with too high Cu/Al ratio have good performance in the low temperature range due to the large number of active sites. However, a large amount of copper that has not undergone ion exchange will generate CuO, which greatly enhances the oxidation of NH3 at high temperatures, which in turn leads to a decrease in catalytic performance at high temperatures. XRD and BET experiments show that all catalyst samples have good CHA crystal structure and microporous structure, and the pore size is mostly about 2 nm. In situ DRIFTS analysis shows that when the Cu/Al ratio is low, the proportion of Z2Cu in the active sites is higher, and the stability of the catalyst is enhanced. When the copper-aluminum ratio is high, the proportion of ZCuOH increases, and the low-temperature activity of the catalyst is higher.

Accelerated wound closure: Systematic evaluation of cellulose acetate effects on biologically active molecules release from amniotic fluid stem cells.

Despite a lot of intensive research on cell-scaffold interaction, the focus is mainly on the capacity of construct scaffolds to regulate cell mobility, migration, and cytotoxicity. The effect of the scaffold's topographical and material properties on the expression of biologically active compounds from stem cells is not well understood. In this study, the influence of cellulose acetate (CA) on the electrospinnability of gelatin and the roles of gelatin-cellulose acetate (Ge-CA) on modulating the release of biologically active compounds from amniotic fluid stem cells (AFSCs) is emphasized. It was found that the presence of a small amount of CA could provide a better microenvironment that mimics AFSCs' niche. However, a large amount of CA exhibited no significant effect on AFSCs migration and infiltration. Further study on the effect of surface topography and mechanical properties on AFSCs showed that the tailored microenvironment provided by the Ge-CA scaffolds had transduced physical cues to biomolecules released into the culture media. It was found that the AFSCs seeded on electrospun scaffolds with less CA proportions have profound effects on the secretion of metabolic compounds compared to those with higher CA contained and gelatin coating. The enhanced secretion of biologically active molecules by the AFSCs on the electrospun scaffolds was proven by the accelerated wound closure on the injured human dermal fibroblast (HDF) model. The rapid HDF cell migration could be anticipated due to a higher level of paracrine factors in AFSCs media. Our study demonstrates that the fibrous topography and mechanical properties of the scaffold are a key material property that modulates the high expression of biologically active compounds from the AFSCs. The discovery elucidates a new aspect of material functions and scaffolds material-AFSC interaction for regulating biomolecules release to promote tissue regeneration/repair. To the best of our knowledge, this is the first report describing the scaffolds material-AFSC interaction and the efficacy of scratch assays on quantifying the cell migration in response to the AFSCs metabolic products.

Team Flexibility in Organizational Change Context: Antecedents and Consequences.

PURPOSE: The purpose of our study is to explore the antecedents and consequences of team flexibility in an organizational change context. In this regard, we considered team flexibility as an important theoretical mechanism under which the insiders would adapt to organizational change. PARTICIPANTS AND METHODS: A sample of 602 individual data that was nested in 108 teams and 43 organizations was used in this study, collecting from 43 enterprises located in mainland China through questionnaires. We adopted HLM 6.08 to testify all the hypothesized relationships and used the Monte Carlo method to create the confidence intervals for all the indirect effects. RESULTS: The empirical results show that 1) balance dimension of ambidexterity and change leadership have a significant positive effect on team flexibility; 2) balance dimension of ambidexterity only has marginal significant effects on employee change-specific adaptive behavior, change-specific proactive behavior, and change fairness. And change leadership has significant positive effects on the three outcomes; 3) team flexibility has a positive influence on the three outcomes. 4) Team flexibility plays a significant mediating role in the links between the balance dimension of ambidexterity and the three outcomes. In addition, team flexibility only has a significant indirect effect on the relationship between change leadership and change-specific adaptive behavior and proactive behavior. CONCLUSION: The current study reveals how team flexibility is established and how such flexibility is associated with employee-level change-specific behavior and perception under an organizational change context. The study indicates that team flexibility is contingent on two factors across two levels: change leadership at team level and balanced ambidexterity at organizational level, which also contributes to individual outcomes of organizational change.

Cardiomyocyte mitochondrial dynamic-related lncRNA 1 (CMDL-1) may serve as a potential therapeutic target in doxorubicin cardiotoxicity.

Doxorubicin (DOX)-induced cardiotoxicity has been one of the major limitations for its clinical use. Although extensive studies have been conducted to decipher the molecular mechanisms underlying DOX cardiotoxicity, no effective preventive or therapeutic measures have yet been identified. Microarray analysis showed that multiple long non-coding RNAs (lncRNAs) are differentially expressed between control- and DOX-treated cardiomyocytes. Functional enrichment analysis indicated that the differentially expressed genes are annotated to cardiac hypertrophic pathways. Among differentially expressed lncRNAs, cardiomyocyte mitochondrial dynamic-related lncRNA 1 (CMDL-1) is the most significantly downregulated lncRNA in cardiomyocytes after DOX exposure. The protein-RNA interaction analysis showed that CMDL-1 may target dynamin-related protein 1 (Drp1). Mechanistic analysis shows that lentiviral overexpression of CMDL-1 prevents DOX-induced mitochondrial fission and apoptosis in cardiomyocytes. However, overexpression of CMDL-1 cannot effectively reduce mitochondrial fission when Drp1 is minimally expressed by small interfering RNA Drp1 (siDrp1). Overexpression of CMDL-1 promotes the association between CMDL-1 and Drp1, as well as with phosphorylated (p-)Drp1, as evidenced by RNA immunoprecipitation analysis. These data indicate the role of CMDL-1 in posttranslational modification of a target protein via regulating its phosphorylation. Collectively, our data indicate that CMDL-1 may play an anti-apoptotic role in DOX cardiotoxicity by regulating Drp1 S637 phosphorylation. Thus, CMDL-1 may serve as a potential therapeutic target in DOX cardiotoxicity.

Aldosterone Induces the Proliferation of Renal Tubular Epithelial Cells In Vivo but Not In Vitro.

OBJECTIVE: To investigate the proliferation effect of aldosterone on renal tubular epithelial cells in vivo and in vitro. METHODS: Thirty-two male C57BL/6J mice (20-22 g) were divided randomly into four groups: sham, unilateral nephrectomy (UN), unilateral nephrectomy plus aldosterone infusion (UA), and UA plus eplerenone (UAE). The kidneys were removed 6 weeks after treatment. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry and western blotting. Human kidney proximal tubular epithelial (HK2) and mouse distal convoluted tubule (mDCT) cell lines were stimulated by aldosterone (0, 10-9, 10-8, 10-7, and 10-6 mol/L) in vitro. Cells were collected after 3, 6, 12, 24, 36, and 48 h, and proliferation of each group detected by western blotting, flow cytometry, live imaging, and the MTT assay. In addition, mDCT cells were costimulated with a medium containing a final concentration of 161 mmol/L Na+ and different concentrations of aldosterone, and the number of cells and cellular DNA content was measured by the MTT assay and flow cytometry. RESULTS: Aldosterone could induce a significant increase in the number of PCNA-positive cells in mouse kidneys accompanied by increased deposition of collagen fibers. Eplerenone could inhibit aldosterone-induced cell proliferation and collagen deposition. HK2 cells and mDCT cells administered different concentrations, and different times of aldosterone stimulation failed to cause cell proliferation, and costimulation of aldosterone and salt did not cause proliferation changes in mDCT cells. CONCLUSIONS: Aldosterone perfusion can induce proliferation of mouse kidney cells in vivo, and eplerenone can inhibit this change, but aldosterone stimulates HK2 cells and mDCT in vitro without causing their proliferation.

Surface engineering of biomaterials in orthopedic and dental implants: Strategies to improve osteointegration, bacteriostatic and bactericidal activities.

BACKGROUND: The success of biomedical implants in orthopedic and dental applications is usually limited due to insufficient bone-implant integration, and implant-related infections. Biointerfaces are critical in regulating their interactions and the desirable performance of biomaterials in biological environment. Surface engineering has been widely studied to realize better control of the interface interaction to further enhance the desired behavior of biomaterials. PURPOSE AND SCOPE: This review aims to investigate surface coating strategies in hard tissue applications to address insufficient osteointegration and implant-related infection problems. SUMMARY: We first focused on surface coatings to enhance the osteointegration and biocompatibility of implants by emphasizing calcium phosphate-related, nanoscale TiO2 -related, bioactive tantalum-based and biomolecules incorporated coatings. Different coating strategies such as plasma spraying, biomimetic deposition, electrochemical anodization and LENS are discussed. We then discussed techniques to construct anti-adhesive and bactericidal surface while emphasizing multifunctional surface coating techniques that combine potential osteointegration and antibacterial activities. The effects of nanotopography via TiO2 coatings on antibacterial performance are interesting and included. A smart bacteria-responsive titanium dioxide nanotubes coating is also attractive and elaborated. CONCLUSION: Developing multifunctional surface coatings combining osteogenesis and antimicrobial activity is the current trend. Surface engineering methods are usually combined to obtain hierarchical multiscale surface structures with better biofunctionalization outcomes.