Determination and Prediction of Time-Varying Parameters of Mooney-Rivlin Model of Rubber Material Used in Natural Rubber Bearing under Alternating of Aging and Seawater Erosion.

In this paper, we examined the parameters of the Mooney-Rivlin model based on the effects of alternative aging and sea corrosion tests for natural rubber bearings and rubber materials in seawater. The model parameters for rubber material used in natural rubber bearings were determined using the least-squares method. Meanwhile, the time-varying law formula of the Mooney-Rivlin model parameters of rubber were fitted, and the fitting and calculated values were compared. Both fitting values and calculated values coincide with each other well. Then, the rubber material parameters were predicted based on the calculated results and combined with nonlinear auto-regressive (NAR). The predicted values were compared with both the fitting and calculated values. The average deviations between predicted and fitting values for C10 and C01 were 2.6% and 5.1%, respectively, and average deviations between predicted and calculated values for C10 and C01 were 5.2% and 4.1%. Compared results show that the predicted values are in good agreement with both the fitting and calculated values; meanwhile, the proposed time-varying law formula of the Mooney-Rivlin model parameters of rubber material have been well verified.

Critical analysis on the transformation and upgrading strategy of Chinese municipal wastewater treatment plants: Towards sustainable water remediation and zero carbon emissions.

In the light of circular economy aspects, processing of large-scale municipal wastewater treatment plants (WWTPs) needs reconsideration to limit the overuse of energy, implement of non-green technologies and emit abundant greenhouse gas. Along with the huge increase in the worldwide population and agro-industrial activities, global environmental organizations have issued several recent roles to boost scientific and industrial communities towards sustainable development. Over recent years, China has imposed national and regional standards to control and manage the discharged liquid and solid waste, as well as to achieve carbon peaking and carbon neutrality. The aim of this report is to analyze the current state of Chinese WWTPs routing and related issues such as climate change and air pollution. The used strategies in Chinese WWTPs and upgrading trends were critically discussed. Several points were addressed including the performance, environmental impact, and energy demand of bio-enhanced technologies, including hydrolytic acidification pretreatment, efficient (toxic) strain treatment, and anaerobic ammonia oxidation denitrification technology, as well as advanced treatment technologies composed of physical and chemical treatment technologies, biological treatment technology and combined treatment technology. Discussion and critical analysis based on the current data and national policies were provided and employed to develop the future development trend of municipal WWTPs in China from the construction of sustainable and "Zero carbon" WWTPs.

Experimental Investigation of Pre-Flawed Rocks under Dynamic Loading: Insights from Fracturing Characteristics and Energy Evolution.

Different fractures exist widely in rock mass and play a significant role in their deformation and strength properties. Crack rocks are often subjected to dynamic disturbances, which exist in many fields of geotechnical engineering practices. In this study, dynamic compression tests were carried out on rock specimens with parallel cracks using a split hopkinson pressure bar apparatus. Tests determined the effects of strain rate and crack intensity on dynamic responses, including progressive failure behavior, rock fragmentation characteristics, and energy dissipation. Based on the crack classification method, tensile-shear mixed cracking dominates the failure of rock specimens under the action of impact loading. Increasing the flaw inclination angle from 0°-90° changes the predominant cracking mechanism from tensile cracking to mixed tensile-shear cracking. The larger the loading rate, the more obvious the cracking mechanism, which indicates that the loading rate can promote the cracking failure of rock specimens. The fragmentation analysis shows that rock samples are significantly broken at higher loading rates, and higher loading rates lead to smaller average fragment sizes; therefore, the larger the fractal dimension is, the more uniform the broken fragments of smaller sizes are. Energy utilization efficiency decreases while energy dissipation density increases with increasing strain rate. For a given loading rate, the energy absorption density and energy utilization efficiency first decrease and then increase with increasing flaw inclination, while the rockburst tendency of rock decreases initially and then increases. We also find that the elastic-plastic strain energy density increases linearly with the total input energy density, confirming that the linear energy property of granite has not been altered by the loading rate. According to this inherent property, the peak elastic strain energy of the crack specimen can be calculated accurately. On this basis, the rockburst proneness of granite can be determined quantitatively using the residual elastic energy index, and the result is consistent with the intensity of actual rockburst for the specimens.

Electrocoagulation coupled with conductive ceramic membrane filtration for wastewater treatment: Toward membrane modification, characterization, and application.

Membrane separation is an effective solution for pollutant removal, however, achieving high permeability and antifouling ability remains a pressing challenge for its widespread application. In this study, a novel method of coating flat ceramic membranes (CMs) with a conductive film (Sb-SnO2) was developed to enhance the filtration and antifouling performance of CMs when the membrane filtration was coupled with electrocoagulation. After comparing the parameters, including the film sheet resistance and pure water flux, with those of other coating methods (i.e., gel coating and immersion hydrolysis), a well-fixed conductive coating with optimal permeability and stability was generated using spray pyrolysis with a substrate ceramic membrane surface temperature of 475 °C, precursor concentration of 0.5 M (calculate as SnO2), and spraying amount of 50 mL (120 cm2), during membrane modification. Batch filtration experiments using wastewater from the mechanical industry demonstrated that the conductive ceramic membrane (CCM) cathode integrated with electrocoagulation at an electric field of 2.8 V/cm (3.0 mA/cm2) achieved permeate fluxes that were 0.34, 0.70, 0.75 and 1.41 times higher than those of sole CM separation after four cycles. Moreover, the membrane separation process was dominated by the standard pore-blocking model, and its correlation coefficient decreased with the exertion of the electric field, indicating that membrane filtration fouling changed from irreversible to reversible. This CCM combined with electrocoagulation exhibited significant potential for alleviating membrane fouling and widespread application, and could act as a promising technology for industrial wastewater treatment.

Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL.

BACKGROUND: Neuroblastoma (NB) is a common solid malignancy in children that is associated with a poor prognosis. Although the novel small molecular compound Dimethylaminomicheliolide (DMAMCL) has been shown to induce cell death in some tumors, little is known about its role in NB. METHODS: We examined the effect of DMAMCL on four NB cell lines (NPG, AS, KCNR, BE2). Cellular confluence, survival, apoptosis, and glycolysis were detected using Incucyte ZOOM, CCK-8 assays, Annexin V-PE/7-AAD flow cytometry, and Seahorse XFe96, respectively. Synergistic effects between agents were evaluated using CompuSyn and the effect of DMAMCL in vivo was evaluated using a xenograft mouse model. Phosphofructokinase-1, liver type (PFKL) expression was up- and down-regulated using overexpression plasmids or siRNA. RESULTS: When administered as a single agent, DMAMCL decreased cell proliferation in a time- and dose-dependent manner, increased the percentage of cells in SubG1 phase, and induced apoptosis in vitro, as well as inhibiting tumor growth and prolonging survival in tumor-bearing mice (NGP, BE2) in vivo. In addition, DMAMCL exerted synergistic effects when combined with etoposide or cisplatin in vitro and displayed increased antitumor effects when combined with etoposide in vivo compared to either agent alone. Mechanistically, DMAMCL suppressed aerobic glycolysis by decreasing glucose consumption, lactate excretion, and ATP production, as well as reducing the expression of PFKL, a key glycolysis enzyme, in vitro and in vivo. Furthermore, PFKL overexpression attenuated DMAMCL-induced cell death, whereas PFKL silencing promoted NB cell death. CONCLUSIONS: The results of this study suggest that DMAMCL exerts antitumor effects on NB both in vitro and in vivo by suppressing aerobic glycolysis and that PFKL could be a potential target of DMAMCL in NB.

Case Report and Literature Review: Primary Pulmonary NUT-Midline Carcinoma.

Nuclear protein of the testis (NUT) carcinoma is a very rare and aggressive carcinoma characterized by chromosomal rearrangement. NUT-midline carcinoma (NMC) can occur anywhere in the body, but most of the tumors are found in the midline anatomic structure or mediastinum. Pulmonary-originated NMC is extremely rare and often difficult to be distinguished from other poorly differentiated tumors, making the diagnosis awfully challenged in clinical practice. There are less than 100 cases of NUT carcinoma reported so far. In this study, the diagnosis and molecular mechanisms of reported NUT carcinoma cases were reviewed. Furthermore, a case of primary pulmonary NUT-midline carcinoma and its pathological features was reported. The process of pathological identification and genomic analysis for establishing the diagnosis was discussed. We found that NUT carcinoma could be identified by combining CT, H&E staining, immunohistochemistry (IHC), and molecular tests. The development of NUT carcinoma might be associated with mutation of MYC, p63, and MED24 genes and the Wnt, MAPK, and PI3K signaling pathways. Our study provided a detailed molecular mechanistic review on NMC and established a procedure to identify pulmonary NMC.

Recovery of iron from iron-rich pickling sludge for preparing P-doped polyferric chloride coagulant.

The pickling sludge produced from rolling process contains a large amount of Fe, Ca, Al as well as other metals. If these metals can be extracted and used, it will promote the recycling of pickling sludge. Herein, we proposed a two-step extraction method to extract Fe ions out from the pickling sludge, and then the extracted Fe was oxidized by H2O2 and prepared into Fe-containing coagulant in the presence of Na2HPO4 as stabilizer. The three main factors that affect the color removal efficiency and COD removal efficiency are identified as P:Fe ratio, H2O2 adding amount, and curing time. Results show that the optimal preparation conditions are: P:Fe = 0.05, H2O2 amount = 115%, and the curing time = 6 d, at which the color and COD removal efficiency reached 96.25% and 65.91%, respectively. The assessment of toxicity of the PPFC indicated that the content of harmful substances meets the thresholds in Chinese national standard GB141591-2016. The findings in this study are expected to provide new implications in treating different kinds of Fe-containing sludge.

MiR-6869-5p Induces M2 Polarization by Regulating PTPRO in Gestational Diabetes Mellitus.

The role of microRNA (miRNA) in gestational diabetes mellitus has been widely investigated during the last decade. However, the altering effect of miR-6869-5p on immunity and placental microenvironment in gestational diabetes mellitus is largely unknown. In our study, the expression of miR-6869-5p was documented to be significantly decreased in placenta-derived mononuclear macrophages, which was also negatively related to PTPRO. Besides, PTPRO was negatively regulated by miR-6869-5p in placenta-derived mononuclear macrophages. In vitro, miR-6869-5p inhibited macrophage proliferation demonstrated by EdU and CCK-8 experiments. The inflammatory response in macrophages was also significantly inhibited by miR-6869-5p, which could regulate PTPRO as a target documented by luciferase reporter assay. Moreover, miR-6869-5p promoted M2 macrophage polarization and thus restrain inflammation. Accordingly, miR-6869-5p is involved in maintaining placental microenvironment balance by preventing from inflammation and inducing M2 macrophages in gestational diabetes mellitus.

Association of Static Posturography With Severity of White Matter Hyperintensities.

Background: Impaired gait and balance are associated with severity of leukoaraiosis. Evaluation of balance is based on neurological examination using Romberg's test with bipedal standing, assessment scale, and posturographic parameters. The goal of this study was to determine the relationship between static equilibrium and grades of white matter hyperintensities (WMHs) using static posturography as a quantitative technical method. Method: One hundred and eighteen (118) patients with lacunar infarct were recruited and assessed on MRI with Fazekas's grading scale into four groups. On admission, age, gender, height, weight, Berg Balance Scale (BBS), mini-mental state examination (MMSE), and static posturography parameters were recorded, and their correlations with WMHs were determined. Results: Age was significantly and positively correlated with severity of WMHs (r = 0.39, p < 0.05). WMH score was negatively correlated with BBS score (r = -0.65, p < 0.05) and MMSE score (r = -0.79, p < 0.05). There was a significant positive correlation between track length anteroposterior (AP, with eyes closed) and severity of WMHs (r = 0.70, p < 0.05). Partial correlation analysis and multiple logistic regression analysis indicated that track length AP with eyes closed, was a predictor for the severity of WMHs (p< 0.05). Conclusion: The severity of WHMs is associated with age, cognitive decline, and impairment in balance. Posturography parameter in track length in AP direction with eyes closed in relation to cognition and balance, may be a potential marker for disease progression in WMHs.

Nicotinamide Improves Cognitive Function in Mice With Chronic Cerebral Hypoperfusion.

Normal brain function requires steady blood supply to maintain stable energy state. When blood supply to the brain becomes suboptimal for a long period of time, chronic cerebral hypoperfusion (CCH) and a variety of brain changes may occur. CCH causes white matter injury and cognitive impairment. The present study investigated the effect of nicotinamide (NAM) on CCH-induced cognitive impairment and white matter damage in mice. Male C57Bl/6J mice aged 10-12 weeks (mean age = 11 ± 1 weeks) and weighing 24 - 29 g (mean weight = 26.5 ± 2.5 g) were randomly assigned to three groups (eight mice/group): sham group, CCH group and NAM group. Chronic cerebral hypoperfusion (CCH) was induced using standard methods. The treatment group mice received intraperitoneal injection of NAM at a dose of 200 mg/kg body weight (bwt) daily for 30 days. Learning, memory, anxiety, and depression-like behaviors were measured using Morris water maze test (MWMT), open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), respectively. White matter damage and remodeling were determined via histological/ immunohistochemical analyses, and western blotting, respectively. The results showed that the time spent in target quadrant, number of crossings and escape latency were significantly lower in CCH group than in sham group, but they were significantly increased by NAM (p < 0.05). Mice in NAM group moved significantly faster and covered longer distances, when compared with those in CCH group (p < 0.05). The percentage of time spent in open arms and the number of entries to the open arms were significantly lower in CCH group than in NAM group (p < 0.05). Moreover, anhedonia and histologic scores (index of myelin injury) were significantly higher in CCH group than in sham group, but they were significantly reduced by NAM (p < 0.05). The results of immunohistochemical staining and Western blotting showed that the protein expressions of 2', 3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and synaptophysin were significantly downregulated in CCH group, relative to sham group, but they were significantly upregulated by NAM (p < 0.05). These results indicate that NAM improves cognitive function in mice with CCH.

Association of RAGE with acute ischemic stroke prognosis in type 2 diabetes.

BACKGROUND: In experimental models, the receptor for advanced glycation end products (RAGE) has been reported as a key mediator in cerebral ischemia. In this study, the clinical significance of serum RAGE levels in acute ischemic stroke patients with type 2 diabetes was determined. METHOD: Three hundred seven patients (165 patients without diabetes and 142 patients with diabetes) with acute cerebral infarction (ACI) were enrolled over 3 consecutive months. On admission, their National Institute of Health Stroke Scale (NIHSS) scores were recorded. The clinical laboratory data of all subjects were collected, and their serum levels of RAGE were assayed using enzyme-linked immunosorbent assay (ELISA). On admission and 3 months after stroke, the clinical outcomes were assessed using the Barthel index (BI) and modified Rankin scale (mRS). RESULTS: Patients with diabetes (PwD) had significantly higher levels of triglycerides (TGs), RAGE, fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), and worse stroke prognosis than patients without diabetes (p < 0.05). Hypertension history, RAGE, and FBG in patients without diabetes in ischemic stroke were increased, relative to stroke prognosis. Weight, RAGE, and FBG data showed significant correlation with stroke outcome in PwD (p < 0.05). Multiple logistic regression analysis indicated that the RAGE level was an independent risk factor for poor prognosis of stroke, especially in PwD with ACI (p < 0.05). CONCLUSION: Acute ischemic stroke is associated with elevated serum RAGE level, which, at admission, is an independent predictor of poor outcome for stroke in type 2 diabetes.

Hemostatic effect of tourniquet combined with tranexamic acid in total knee arthroplasty: a network meta-analysis.

BACKGROUND: There are various techniques to reduce blood loss in total knee arthroplasty (TKA), including the use of a tourniquet and tranexamic acid (TXA). In this study, we studied the combined effect of TXA with a tourniquet on blood loss in the setting of primary TKA. METHODS: Randomized controlled trials (RCTs) of nine treatment methods were included (placebo, intravenous [i.v.] TXA, topical TXA, i.v.-combined topical TXA, oral TXA, placebo + tourniquet, i.v. TXA +tourniquet, topical TXA + tourniquet, and i.v.-combined topical TXA + tourniquet). The patients were divided into eight groups according to the different treatment strategies, with 30 cases per group. The differences in the total blood volume, the number of patients transfused, the hemoglobin before and after the operation, and complications after the operation were compared. RESULTS: Totally 15 RCTs meeting our inclusion criteria were collected in this study. Compared with the placebo + tourniquet group, the i.v. TXA + tourniquet group displayed lower hemoglobin reduction value, pulmonary embolism (PE) incidence, total blood loss, and blood transfusion risk; the topical TXA + tourniquet group showed reduced PE incidence, total blood loss, and blood transfusion risk, and the i.v.-combined topical TXA and i.v.-combined topical TXA + tourniquet groups showed decreased total blood loss and lower blood transfusion risk. Retrospective clinical study results also demonstrated that the efficacy of i.v.-combined topical TXA was the best. CONCLUSIONS: Our meta-analysis indicates that i.v.-combined topical TXA provides a low total blood loss without increasing the blood transfusion risk in patients undergoing total knee replacement surgery.

Combination of Rapamycin and MK-2206 Induced Cell Death via Autophagy and Necroptosis in MYCN-Amplified Neuroblastoma Cell Lines.

Neuroblastoma (NB) is the most common pediatric malignant extracranial solid tumor. Despite multi-modality therapies, the emergence of drug resistance is an obstacle in the treatment of high-risk NB patients (with MYCN amplification). In our previous study, we found that rapamycin and MK-2206 synergistically induced cell death in MYCN-amplified cell lines but the mechanisms remained unclear. In our present study, either 3-MA or necroatatin-1 blocked the cell death induced by rapamycin and MK-2206, but z-VAD-fmk did not block this cell death. The expressions of autophagy markers (ATG5, ATG7, Beclin-1, LC3 B) and the necroptosis marker RIPK3 increased and another necroptosis marker RIPK1 decreased after the combination treatment of rapamycin and MK-2206, and were accompanied by the morphological characteristics of autophagy and necroptosis. In NB xenograft tumor tissues, the expressions of autophagy and necroptosis markers were consistent with observations in vitro. These data suggested that autophagy and necroptosis contributed to the cell death induced by rapamycin and MK-2206 in NB cells. To understand the role of MYCN in this process, MYCN expression was downregulated in MYCN-amplified cell lines (NGP, BE2) using siRNAs and was upregulated in MYCN non-amplified cell lines (AS, SY5Y) using plasmid. We found the cell death induced by rapamycin and MK-2206 was MYCN-dependent. We also found that the metabolic activity in NB cells was correlated with the expression level of MYCN. This study delineates the role of MYCN in the cell death induced by combination treatment of rapamycin and MK-2206 in MYCN-amplified NB cells.

ATM-CHK2-Beclin 1 axis promotes autophagy to maintain ROS homeostasis under oxidative stress.

The homeostatic link between oxidative stress and autophagy plays an important role in cellular responses to a wide variety of physiological and pathological conditions. However, the regulatory pathway and outcomes remain incompletely understood. Here, we show that reactive oxygen species (ROS) function as signaling molecules that regulate autophagy through ataxia-telangiectasia mutated (ATM) and cell cycle checkpoint kinase 2 (CHK2), a DNA damage response (DDR) pathway activated during metabolic and hypoxic stress. We report that CHK2 binds to and phosphorylates Beclin 1 at Ser90/Ser93, thereby impairing Beclin 1-Bcl-2 autophagy-regulatory complex formation in a ROS-dependent fashion. We further demonstrate that CHK2-mediated autophagy has an unexpected role in reducing ROS levels via the removal of damaged mitochondria, which is required for cell survival under stress conditions. Finally, CHK2-/- mice display aggravated infarct phenotypes and reduced Beclin 1 p-Ser90/Ser93 in a cerebral stroke model, suggesting an in vivo role of CHK2-induced autophagy in cell survival. Taken together, these results indicate that the ROS-ATM-CHK2-Beclin 1-autophagy axis serves as a physiological adaptation pathway that protects cells exposed to pathological conditions from stress-induced tissue damage.

Knockdown of periostin attenuates 5/6 nephrectomy-induced intrarenal renin-angiotensin system activation, fibrosis, and inflammation in rats.

To simulate clinical features in human chronic kidney disease (CKD), SD rats were subjected to 5/6 nephrectomy in this study. We found that periostin gene was upregulated in the remnant kidneys using Agilent gene microarrays, and further explored its role via in vivo and in vitro experiments. Intrarenal renin-angiotensin system (RAS) was activated in 5/6 nephrectomized rats and partly deactivated by injection of adenoviruses encoding short hairpin RNA against periostin (sh-periostin). Renal fibrosis in nephrectomized rats and profibrotic transforming growth factor-ß-induced epithelial-mesenchymal transition (EMT) and ERK1/2 activation in NRK-52E cells were suppressed by sh-periostin. Moreover, knockdown of periostin decreased the generation of Interleukin 6 (IL6) and tumor necrosis factor-α (TNF-α) and accelerated p62 degradation in the remnant kidneys. Both HK-2 cells treated with recombinant periostin and NRK-52E cells infected with adenoviruses expressing periostin produced more IL6 and TNF-α than control cells and displayed impaired autophagy as evidenced by inhibition of LC3II to LC3I conversion, Beclin 1 expression, and p62 degradation. By treating cells with rapamycin, an inhibitor of mamalian target of rapamycin known to activate autophagy, we noted that periostin-induced inflammation was inhibited. Additionally, HK-2 cells transfected with periostin overexpression plasmid generated more CCL2 and CXCL10, two important chemotactic factors, than untransfected cells. Conditioned medium from HK-2 cells overexpressing periostin augmented chemotaxis of THP-1 macrophages. Collectively, our work demonstrates that knockdown of periostin attenuates 5/6 nephrectomy-induced intrarenal RAS activation, fibrosis, and inflammation in rats. These findings advance our understanding of periostin's role in CKD induced by nephron loss.

miR-548c-5p inhibits colorectal cancer cell proliferation by targeting PGK1.

Accumulating studies have implicated that microRNAs (miRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, the role of miR-548c-5p, a novel identified miRNA in malignancies, in colorectal carcinogenesis remains largely unknown. The present study is aimed to investigate the effect and molecular mechanism of miR-548c-5p in CRC by a sequence of cellular experiments. miR-548c-5p was significantly downregulated, whereas phosphoglycerate kinase 1 (PGK1), a key enzyme for glycolysis, was obviously upregulated in peripheral blood mononuclear cells and cancer tissues from patients with CRC. Besides, miR-548c-5p and PGK1 were negatively associated with each other. The luciferase reporter assay revealed that PGK1 was a targeted gene of miR-548c-5p. Moreover, the proliferation and generation of inflammatory cytokines (TNF-α and IL-6) were significantly inhibited in miR-548c-5p-overexpressed SW480 CRC cells stimulated by lipopolysaccharide (LPS). Accordingly, miR-548c-5p may serve as a cancer suppressor in CRC by targeting PGK1.

Periostin contributes to renal and cardiac dysfunction in rats with chronic kidney disease: Reduction of PPARα.

POSTN knockdown inhibits the formation of NLRP3 inflammasome in rat myocardium.Periostin (POSTN), an extracellular matrix protein, and peroxisome proliferator-activated receptor alpha (PPARα), a ligand-activated nuclear transcription factor, are reported to be involved in renal and cardiac dysfunction associated with chronic kidney disease (CKD), respectively. This study is performed to investigate how POSTN-PPARα axis affects the progress of CKD. In vivo, adenovirus particles containing POSTN short hairpin RNA (Ad-shPOSTN) were intravenously given to Sprague Dawley rats following 5/6 nephrectomy. The effects of Ad-shPOSTN on CKD and CKD-associated cardiovascular disease were evaluated. In vitro, NRK-52E renal tubular epithelial cells were infected with Ad-shPOSTN or Ad-POSTN (overexpression) to explore whether POSTN affected collagen deposition by regulating PPARα. We found that POSTN expression was upregulated, while PPARα was downregulated in the injured renal and left ventricular tissues of nephrectomized rats. Ad-shPOSTN improved renal function, prevented cardiac dysfunction, and attenuated organ fibrosis in nephrectomized rats. The expression levels of renal and myocardial PPARα were increased following Ad-shPOSTN administration. Furthermore, POSTN silencing suppressed the formation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in the myocardium: the levels of NLRP3, anti-apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase 1, mature interleukin (IL)-1ß and IL-18 were reduced. In NRK-52E cells, forced overexpression of POSTN directly inhibited PPARα expression and induced collagen deposition. WY14643, a PPARα agonist, suppressed POSTN-induced collagen deposition. In summary, our study demonstrates that POSTN negatively regulates PPARα expression. Targeting POSTN-PPARα axis may present a novel protective intervention to alleviate CKD and CKD-associated cardiac dysfunction.

miR-222 promotes invasion and migration of ovarian carcinoma by targeting PTEN.

Ovarian carcinoma is the most lethal of the gynecologic malignancies worldwide. Increasing evidence suggests dysfunction of microRNAs (miRNAs) plays an important role in human cancers. The function of miR-222 was detected in ovarian carcinoma to verify the regulation of phosphatase and tensin homolog (PTEN) by miR-222. miR-222 expression in ovarian carcinoma tissues and cell lines were examined using RT-qPCR. Transwell assay was used to detect miR-222 effects on ovarian carcinoma cell migration and invasion. Western blot analysis and luciferase assays were performed to validate PTEN as miR-222 targets. miR-222 expression was upregulated in ovarian carcinoma tissues and three cell lines (A2780, SKOV-3 and OVCAR-3). Ectopic overexpression of miR-222 in ovarian carcinoma cells was sufficient to promote invasion and migration. PTEN acted as a direct target of miR-222. Overexpression of PTEN inhibited human ovarian carcinoma cell migration and invasion. In summary, our findings suggest that miR-222 plays an important role in promoting ovarian carcinoma cell invasion and migration and miR-222/PTEN may be a novel therapeutic target of miRNA-mediated promotion of cell invasion and migration in ovarian carcinoma.

The nucleocytoplasmic translocation and up-regulation of ING5 protein in breast cancer: a potential target for gene therapy.

Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression. ING5 expression was higher in breast cancer than normal tissue at both mRNA and protein levels. ING5 mRNA expression was positively correlated with relapse- and distant metastasis-free survival rates. Nuclear ING5 expression showed gradual decrease from breast normal tissue, fibroadenoma, adenomatosis, primary to metastatic cancers, while versa for cytoplasmic ING5. Nuclear ING5 expression was negatively correlated with distant metastasis and p53 hypoexpression, while cytoplasmic ING5 expression was positively correlated with tumor size and ER expression. These data suggested that up-regulated expression and nucleocytoplasmic translocation of ING5 protein were observed in breast cancer. The higher expression of nuclear ING5 was inversely linked to worse clinicopathological behaviors of breast cancer by in vivo and vitro reversing aggressive phenotypes. Therefore, it should be employed as a biomarker to indicate the tumorigenesis and aggressiveness of breast cancer, and as a potential target for gene therapy.

Cytokeratin 19 promoter directs the expression of Cre recombinase in various epithelia of transgenic mice.

Cytokeratin 19 (K19) is expressed in various differentiated cells, including gastric, intestinal and bronchial epithelial cells, and liver duct cells. Here, we generated a transgenic mouse line, K19-Cre, in which the expression of Cre recombinase was controlled by the promoter of K19. To test the tissue distribution and excision activity of Cre recombinase, K19-Cre transgenic mice were bred with Rosa26 reporter strain and a mouse strain that carries PTEN conditional alleles (PTENLoxp/Loxp). At mRNA level, Cre was strongly expressed in the stomach, lung and intestine, while in stomach, lung, and liver at protein level. The immunoreactivity to Cre was strongly observed the cytoplasm of gastric, bronchial and intestinal epithelial cells. Cre activity was detectable in gastric, bronchial and intestinal epithelial cells, according to LacZ staining. In K19-Cre/PTEN Loxp/Loxp mice, PTEN was abrogated in stomach, intestine, lung, liver and breast, the former two of which were verified by in situ PCR. There appeared breast cancer with PTEN loss. These data suggest that K19 promoter may be a useful tool to study the pathophysiological functions of cytokeratin 19-positive cells, especially gastrointestinal epithelial cells. Cell specificity of neoplasia is not completely attributable to the cell-specific expression of oncogenes and cell-specific loss of tumor suppressor genes.