Integrating Network Pharmacology and In Vitro Experiments for Assessing the Anti-Tumor Effects of Phyllanthus Urinaria L Anti-neoplastic Decoction in Hepatocellular Carcinoma.

Background: In China, traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese herb formulas with the effect of "yiqi jianpi jiedu huayu" (replenishing qi, strengthening spleen, and removing toxicity and blood stasis) are the common and efficient treatments for HCC. However, the mechanism of these formulas in treating HCC remain unclear. Objective: In this paper, our goal is to explore the potential mechanism of Phyllanthus urinaria L anti-neoplastic decoction (PAD), the representative formula of "yiqi jianpi jiedu huayu", in treating HCC. Design: The research team performed the network pharmacology and in vitro experiment (preparation of PAD aqueous extract, cell cultures and MTT assay, cell apoptosis assay, wound healing assay, transwell assays, western blot). Setting: The study took place in the Department of Hepatology, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), China. Outcome Measures: The active components and targets of PAD and HCC targets were screened by five Chinese herbs and two disease databases respectively. The network pharmacology was utilized to construct the relationship network between PAD and HCC, and the mechanism was predicted by pathway enrichment analysis. The experiment was performed to verify the intervention effect of PAD on HCC and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. Results: The relationship network between PAD and HCC suggested that PAD mainly regulated the potential therapeutic targets of HCC by key active components such as quercetin, luteolin, calycosin, wogonin, and pinocembrin. Pathway analysis demonstrated PAD could play an anti-HCC effect via multiple pathways (e.g., PI3K/Akt). Results of the experiment showed that PAD could effectively inhibit the proliferation and migration of HCC cells, and promote HCC cells apoptosis in a concentration-dependent behavior. Additionally, PAD could decrease the protein expression of phosphorylated PI3K/Akt. Conclusion: PAD mainly exerts an anti-HCC effect through multiple active components represented by quercetin and multiple pathways represented by the PI3K/Akt pathway. This study provided an experimental basis for the clinical application of PAD.

NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1.

Breast cancer (BC) is a serious threat to women's health worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is a regulatory subunit of the coagulin I complex, which is mainly involved in chromosome coagulation and separation. The clinical significance, biological behavior, and potential molecular mechanism of NCAPD2 in BC were investigated in this study. We found that NCAPD2 was frequently overexpressed in BC, and it had clinical significance in predicting the prognosis of BC patients. Moreover, loss-of-function assays demonstrated that NCAPD2 knockdown restrained the progression of BC by inhibiting proliferation and migration and enhancing apoptosis in vitro. It was further confirmed that the downregulation of NCAPD2 inhibited tumor growth in vivo. NCAPD2 promoted the progression of BC through the extracellular signal-regulated kinase 5 (ERK5) signaling pathway. Additionally, NCAPD2 could transcriptionally activate CDK1 by interacting with E2F transcription factor 1 (E2F1) in MDA-MB-231 cells. Overexpression of CDK1 alleviated the inhibitory effects of NCAPD2 knockdown in BC cells. In summary, the NCAPD2/E2F1/CDK1 axis may play a role in promoting the progression of BC, which may provide a blueprint for molecular therapy.

Organoid models derived from patients with malignant phyllodes tumor of the breast.

PURPOSE: Phyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It's urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients. METHODS: Two surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively. RESULTS: We successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines. CONCLUSION: Organoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

Fbxo22 inhibits metastasis in triple-negative breast cancer through ubiquitin modification of KDM5A and regulation of H3K4me3 demethylation.

The importance of Fbxo22 in carcinogenesis has been highly documented. Here, we discussed downstream regulatory factors of Fbxo22 in TNBC. RNA-sequencing was conducted for identifying differentially expressed genes, followed by construction of a regulatory network. Expression patterns of Fbxo22/KDM5A in TNBC were determined by their correlation with the prognosis analyzed. Then, regulation mechanisms between Fbxo22 and KDM5A as well as between KDM5A and H3K4me3 were assayed. After silencing and overexpression experiments, the significance of Fbxo22 in repressing tumorigenesis in vitro and in vivo was explored. Fbxo22 was poorly expressed, while KDM5A was highly expressed in TNBC. Patients with elevated Fbxo22, decreased KDM5A, or higher p16 had long overall survival. Fbxo22 reduced the levels of KDM5A by ubiquitination. KDM5A promoted histone H3K4me3 demethylation to downregulate p16 expression. Fbxo22 reduced KDM5A expression to enhance p16, thus inducing DNA damage as well as reducing tumorigenesis and metastasis in TNBC. Our study validated FBXO22 as a tumor suppressor in TNBC through ubiquitination of KDM5A and regulation of p16.

Unveiling interactions of norfloxacin with microplastic in surface water by 2D FTIR correlation spectroscopy and X-ray photoelectron spectroscopy analyses.

Microplastics (MPs) has shown adsorption of hydrophilic organic matters (HOMs) in aqueous environments. However, it is still difficult to predict the adsorption behaviors of HOMs by different MPs, especially in authentic water systems. In this study, the adsorption behaviors and mechanisms of norfloxacin (NOR) onto polyamide (PA) MPs were investigated in both simulated and real surface water. The results showed that the adsorption equilibrium of NOR by PA in simulated surface water could be achieved within 15 h, while the adsorption rate of NOR in real surface was slowed down, with the equilibrium time of 25 h. Pseudo-second-order model could well describe the adsorption kinetics data. The experimental maximum adsorption capacity of NOR on PA in real surface water (e. g. 132.54 ug/g) was dramatically reduced by 37.5 % compared with that in simulated surface water (e. g. 212.25 ug/g), and the adsorption isotherm would obey Freundlich model. Besides, the leaching of NOR from the surface of PA could occur obviously at acidic environment. Furthermore, the salinity and natural organic matter exhibited significantly adverse effects on the NOR adsorption. Finally, the results of 2D Fourier transform infrared correlation spectroscopy and X-ray photoelectron spectroscopy indicated that the electrostatic, H-bond and van der Waals interactions were involved in the adsorption. More importantly, the sequential functional groups in the adsorption process followed the orders: 1638 (CO) > 1542 amide II (-NH-CO) > 717 (CH2) > 1445 (CO) > 973 amide IV (CONH). This study could provide an insight into the interactions between PA and NOR in different water environments.

Ultrasound-based advanced oxidation processes for landfill leachate treatment: Energy consumption, influences, mechanisms and perspectives.

Advanced oxidation processes (AOPs) based on ultrasound (US) have attracted considerable attention in recent years due to its advantages in the degradation of landfill leachate. The review summarizes the existing treatment methods of leachate from lab-scale, compares their advantages and disadvantages by focusing on the degradation of emerging contaminants (ECs) in the leachate. Then the US-based AOPs are introduced emphatically, including their degradation mechanisms, influencing factors, energy consumption, further optimization methods as well as the possibility of field-scale application are systematically described. Moreover, this review also expounds on the advantages of dual-frequency US (DFUS) technology compared with single-frequency US, and a theoretically feasible DFUS process is proposed to treat ECs in the leachate. Finally, suggestions and prospects for US technologies in treating landfill leachate are put forward to aid future research on landfill leachate treatment. Meaningfully, this manuscript will provide reference values of US-based technologies in landfill leachate treatment for the practical use, facilitating the development of US-based AOPs in landfill leachate management and disposal.

Comparative Transcriptome Sequencing and Endogenous Phytohormone Content of Annual Grafted Branches of Zelkova schneideriana and Its Dwarf Variety HenTianGao.

Zelkova schneideriana is a fast-growing tree species endemic to China. Recent surveys and reports have highlighted a continued decline in its natural populations; therefore, it is included in the Red List of Threatened Species by The International Union for Conservation of Nature. A new variety "HenTianGao" (H) has been developed with smaller plant height, slow growth, and lower branching points. In this study, we attempted to understand the differences in plant height of Z. schneideriana (J) and its dwarf variety H. We determined the endogenous hormone content in the annual grafted branches of both J and H. J exhibited higher gibberellic acid (GA)-19 and trans-Zeatin (tZ) levels, whereas H had higher levels of indole-3-acetic acid (IAA) catabolite 2-oxindole-3-acetic acid (OxIAA), IAA-Glu conjugate, and jasmonic acid (JA) (and its conjugate JA-Ile). The transcriptome comparison showed differential regulation of 20,944 genes enriched in growth and development, signaling, and metabolism-related pathways. The results show that the differential phytohormone level (IAA, JA, tZ, and GA) was consistent with the expression of the genes associated with their biosynthesis. The differences in relative OxIAA, IAA-Glu, GA19, trans-Zeatin, JA, and JA-Ile levels were linked to changes in respective signaling-related genes. We also observed significant differences in the expression of cell size, number, proliferation, cell wall biosynthesis, and remodeling-related genes in J and H. The differences in relative endogenous hormone levels, expression of biosynthesis, and signaling genes provide a theoretical basis for understanding the plant height differences in Z. schneideriana.

Comprehensive improvement of soil quality and rice yield by flooding-midseason drying-flooding.

Many water-saving technologies have been developed to reduce water input and the associated irrigation costs. However, the influence of water management technologies on soil quality is unclear. Soil quality is fundamental to rice yield and sustainable productivity of ecosystems. Therefore, it is important to understand the effect of water management on soil quality and its linkage with rice yield. In this work, a field experiment was conducted to assess the influence of water management on soil physico-chemical properties, microbial biomass, bacterial community, and rice yield in paddy fields. Three water treatments were selected for the study, including flooding-rain-fed (F-RF), flooding-midseason drying-flooding (F-D-F), and continuous flooding (CF). Total nitrogen (TN), total phosphorus (TP), dissolved carbon content (DOC), available phosphorus (AP), nitrate nitrogen (NO3-), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) contents were 11%, 20%, 29%, 30%, 11%, 183%, and 215% higher in F-D-F, respectively, than those in the CF (p < 0.05). Additionally, the bacterial diversity in F-D-F and CF was significantly higher compared to the F-RF (p < 0.05). Correspondingly, soil quality index (SQI) was higher in the F-D-F (0.8) than that of F-RF (0.53) and CF (0.5). Compared with the F-RF, water management remarkably altered bacterial community composition, with higher enrichment of anaerobic bacteria (such as Firmicutes and Chloroflexi) in flooding treatments (CF and F-D-F). Differences in the bacterial community were closely related to key soil quality indicators, such as AP. Parallel increases in soil quality and bacterial diversity resulted in increased rice yield in the F-D-F, which was 53% and 12% higher than that in F-RF and CF, respectively. Therefore, F-D-F is the suggested water management method because it can comprehensively improve soil microbial diversity, soil quality, and rice yield. KEY POINTS: • Water management changed bacterial community mainly via SMC (soil moisture content), TP, AP, and NO3-contents. • The F-D-F had greater SQI and higher rice yield in comparison with F-RF and CF.

Inhibition of chemotherapy resistant breast cancer stem cells by a ROR1 specific antibody.

Breast cancers enduring treatment with chemotherapy may be enriched for cancer stem cells or tumor-initiating cells, which have an enhanced capacity for self-renewal, tumor initiation, and/or metastasis. Breast cancer cells that express the type I tyrosine kinaselike orphan receptor ROR1 also may have such features. Here we find that the expression of ROR1 increased in breast cancer cells following treatment with chemotherapy, which also enhanced expression of genes induced by the activation of Rho-GTPases, Hippo-YAP/TAZ, or B lymphoma Mo-MLV insertion region 1 homolog (BMI1). Expression of ROR1 also enhanced the capacity of breast cancer cells to invade Matrigel, form spheroids, engraft in Rag2-/-[Formula: see text] mice, or survive treatment with paclitaxel. Treatment of mice bearing breast cancer patient-derived xenografts (PDXs) with the humanized anti-ROR1 monoclonal antibody cirmtuzumab repressed expression of genes associated with breast cancer stemness, reduced activation of Rho-GTPases, Hippo-YAP/TAZ, or BMI1, and impaired the capacity of breast cancer PDXs to metastasize or reengraft Rag2-/-[Formula: see text] mice. Finally, treatment of PDX-bearing mice with cirmtuzumab and paclitaxel was more effective than treatment with either alone in eradicating breast cancer PDXs. These results indicate that targeting ROR1 may improve the response to chemotherapy of patients with breast cancer.

Adsorption of Cu2+ by UV aged polystyrene in aqueous solution.

Microplastics are the critical carriers of heavy metals in the environment. Thus, investigating the adsorption mechanisms between the microplastics and heavy metals is helpful to understand the migration and transformation pattern of the heavy metals in the environment. The adsorption of microplastics towards heavy metals can be largely affected by natural aging (e.g., UV-aging), environmental pH, and salinity. In this study, the adsorption of polystyrene (PS) towards Cu2+ and the effects of UV-aging, environment pH, and salinity on the adsorption were systematically investigated. The results show that the adsorption capacity of PS towards Cu2+ increased with the UV-aging time, as UV-aging increased the microcracks and oxygen-containing functional groups on the surface of the PS. Adsorption kinetics data followed the pseudo-second-order model, indicating that the interaction between PS and Cu2+ is chemical adsorption. Adsorption isotherms data could be well-described by both the Langmuir and Freundlich models, indicating that the adsorption was multilayer adsorption. As the solution pH and salinity can influence the surface charge of the PS, they could also affect the performance of the PS on Cu2+ adsorption. High pH facilitated the adsorption of PS towards Cu2+, while high salinity (above 1‰) inhibited the adsorption.

Estimated glomerular filtration rate and postoperative mortality in patients undergoing non-cardiac and non-neuron surgery: a single-center retrospective study.

BACKGROUND: There is limited evidence to clarify the specific relationship between preoperative estimated glomerular filtration rate (preop-eGFR) and postoperative 30-day mortality in Asian patients undergoing non-cardiac and non-neuron surgery. We aimed to investigate details of this relationship. METHODS: We reanalyzed a retrospective analysis of the clinical records of 90,785 surgical patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. The main outcome was postoperative 30-day mortality. RESULTS: The average age of these recruited patients was 53.96 ± 16.88 years, of which approximately 51.64% were female. The mean of preop-eGFR distribution was 84.45 ± 38.56 mL/min/1.73 m2. Multivariate logistic regression analysis indicated that preop-eGFR was independently associated with 30-day mortality (adjusted odds ratio: 0.992; 95% confidence interval [CI] 0.990-0.995; P < 0.001). A U-shaped relationship was detected between preop-eGFR and 30-day mortality with an inflection point of 98.688 (P for log likelihood ratio test < 0.001). The effect sizes and confidence intervals on the right and left sides of the inflection point were 1.013 (1.007 to 1.019) [P < 0.0001] and 0.984 (0.981 to 0.987) [P < 0.0001], respectively. Preoperative comorbidities such as congestive heart failure (CHF), type 1 diabetes, ischemic heart disease (IHD), and anemia were associated with the odds ratio of preop-eGFR to 30-day mortality (interaction P < 0.05). DISCUSSION: The relationship between preop-eGFR and 30-day mortality is U-shaped. The recommended preop-eGFR at which the rate of the 30-day mortality was lowest was 98.688 mL/min/1.73 m2.

The insufficient extraction of DNA from swine manures may underestimate the abundance of antibiotic resistance genes as well as ignore their potential hosts.

Swine manure is considered as an extensive reservoir of antibiotic resistance genes (ARGs) spreading in the natural environment after application in soils. To understand whether ARGs abundance in swine manure is underestimated and the hosts are ignored, this study successively extracted DNA from swine manure six times and determined the abundance of several ARGs, class I integron (intI1), and 16S rRNA as well as the microbial communities. It is found that successive six DNA extraction of swine manures elevated the yield of DNA and strongly increased the abundance of ARGs, intI1, and 16S rRNA. Compared with single DNA extraction, the most dominant bacterial phylum in swine manures shifted from Proteobacteria to Firmicutes, and the dominant bacterial genera changed from Acinetobacter Clostridium after six DNA extraction. The ignored abundance of bacterial phylum and genus emphasized the possible hosts carrying these genes should be paid more attention. It is suggested that the successive DNA extraction of manures is required in the future study to improve the knowledge of estimating the risk and hosts of ARGs in manures entering the environment.

Progress in the application of organoids to breast cancer research.

Breast cancer is the most common cancer diagnosed in women. Breast cancer research is currently based mainly on animal models and traditional cell culture. However, the inherent species gap between humans and animals, as well as differences in organization between organs and cells, limits research advances. The breast cancer organoid can reproduce many of the key features of human breast cancer, thereby providing a new platform for investigating the mechanisms underlying the development, progression, metastasis and drug resistance of breast cancer. The application of organoid technology can also promote drug discovery and the design of individualized treatment strategies. Here, we discuss the latest advances in the use of organoid technology for breast cancer research.

Anemia and perioperative mortality in non-cardiac surgery patients: a secondary analysis based on a single-center retrospective study.

BACKGROUND: Evidence regarding the relationship between anemia and perioperative prognosis is controversial. The study was conducted to highlight the specific relationship between anemia and perioperative mortality in non-cardiac surgery patients over 18 years of age. METHODS: This study was a retrospective analysis of the electronic medical records of 90,784 patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. Multivariate regression, propensity score analysis, doubly robust estimation, and an inverse probability-weighting model was used to ensure the robustness of our findings. RESULTS: We identified 85,989 patients, of whom75, 163 had none or mild anemia (Hemoglobin>90g/L) and 10,826 had moderate or severe anemia (Hemoglobin≤90g/L). 8,857 patients in each study exposure group had similar propensity scores and were included in the analyses. In the doubly robust model, postoperative 30-day mortality rate was increased by 0.51% (n = 219) in moderate or severe anemia group (Odds Ratio, 1.510; 95% Confidence Interval (CI), 1.049 to 2.174) compared with none or mild anemia group (2.47% vs.1.22%, P<0.001). Moderate or severe anemia was also associated with increased postoperative blood transfusion rates (OR, 5.608; 95% CI, 4.026 to 7.811, P < 0.001). There was no statistical difference in Intensive Care Unit (ICU) admission rate among different anemia groups within 30 days after surgery (P=0.104). DISCUSSION: In patients undergoing non-cardiac surgery over 18 years old, moderate or severe preoperative anemia would increase the occurrence of postoperative blood transfusion and the risk of death, rather than ICU admission within 30 days after surgery.

Identifying potential serum biomarkers of breast cancer through targeted free fatty acid profiles screening based on a GC-MS platform.

Recent advances suggest that abnormal fatty acid metabolism highly correlates with breast cancer, which provide clues to discover potential biomarkers of breast cancer. This study aims to identify serum free fatty acid (FFA) metabolic profiles and screen potential biomarkers for breast cancer diagnosis. Gas chromatography-mass spectrometry and our in-house fatty acid methyl ester standard substances library were combined to accurately identify FFA profiles in serum samples of breast cancer patients and breast adenosis patients (as controls). Potential biomarkers were screened by applying statistical analysis. A total of 18 FFAs were accurately identified in serum sample. Two groups of patients were correctly discriminated by the orthogonal partial least squares-discriminant analysis model based on FFA profiles. Seven FFA levels were significantly higher in serum from breast cancer patients than that in controls, and exhibited positive correlation with malignant degrees of disease. Furthermore, five candidates (palmitic acid, oleic acid, cis-8,11,14-eicosatrienoic acid, docosanoic acid and the ratio of oleic acid to stearic acid) were selected as potential serum biomarkers for differential diagnosis of breast cancer. Our study will help to reveal the metabolic signature of FFAs in breast cancer patients, and provides valuable information for facilitating clinical noninvasive diagnosis.

Effects of disinfection efficiency on microbial communities and corrosion processes in drinking water distribution systems simulated with actual running conditions.

The effects of disinfection efficiency on microbial communities and the corrosion of cast iron pipes in drinking water distribution systems (DWDSs) were studied. Two annular reactors (ARs) that simulated actual running conditions with UV/Cl2 disinfection and chlorination alone were used. High chlorine consumption and corrosion rate were found in the AR with UV/Cl2. According to functional genes and pyrosequencing tests, a high percentage of iron recycling bacteria was detected within the biofilm of the AR with Cl2 at early running stage, whereas siderophore-producing bacteria were dominant in the biofilm of the AR with UV/Cl2. At the early running stage, the sequential use of UV light and an initial high chlorine dosage suppressed the biomass and iron-recycling bacteria in both bulk water and biofilms, thereby forming less protective scales against further corrosion, which enhanced chlorine consumption. Non-metric multidimensional scaling analysis showed that the bacterial communities in the ARs shaped from within rather than being imported by influents. These results indicate that the initial high disinfection efficiency within the distribution system had not contributed to the accumulation of iron-recycling bacteria at the early running stages. This study offer certain implications for controlling corrosion and water quality in DWDSs.

The characterization of biochars derived from rice straw and swine manure, and their potential and risk in N and P removal from water.

Nowadays, the plant residual derived biochars have been widely applied to remove nitrogen (N) and phosphorus (P) from water. However, the application of animal manure derived biochars in N and P removal was less studied. To compare the different efficiency and risk of plant residual- and animal manure-derived biochar in removing N and P from water, this study chose rice straw and swine manure as representative to produce biochar at 700 °C, and modified the produced biochar by MgCl2. Then, the characteristics, removal efficiency and release of N and P of biochars were investigated. The results showed swine manure-biochars generally had higher ash content and cation exchange capacity (CEC), but lower pH and surface area relative to rice straw-biochars. Besides, MgCl2 modification reduced the ash content and surface area of both raw biochars, whereas the pH, CEC and pore size were enhanced. Furthermore, this work demonstrated that ammonium and nitrate could be removed by all biochars to certain extent, and MgCl2 modified biochars generally had higher removal efficiency. However, none of phosphate removal was achieved by all biochars. Additionally, the release of ammonium, nitrate and phosphate from biochars was observed, suggesting there might be a risk for applying biochars in N and P removal from water. Notably, the MgCl2 modification seemed to accelerate N and P release from biochars. This work provided important information that the production and modification of biochars should be carefully designed for higher removal efficiency of pollutants. Meanwhile, the risk of released pollutants as well as the release mechanisms should be paid more attention in the future.

[Tea polyphenols delays human glomerular mesangial cells senescence induced by high glucose via regulating STAT3/miR-126/telomere signaling pathway activation].

The aim of this paper was to explore the effects and possible mechanisms in vitro of tea polyphenols (TP) delaying human glomerular mesangial cells (HGMCs) senescence induced by high glucose (HG). HGMCs were cultured in vitro and divided into the normal group (N, 5.5 mmol·L⁻¹ glucose), the mannitol group(MNT, 5.5 mmol·L⁻¹ glucose plus 24.5 mmol·L⁻¹ mannitol), the high dose of D-glucose group (HG, 30 mmol·L⁻¹ glucose), the low dose of TP group (L-TP, 30 mmol·L⁻¹ glucose plus 5 mg·L⁻¹ TP) and the high dose of TP group (H-TP, 30 mmol·L⁻¹ glucose plus 20 mg·L⁻¹ TP), which were cultured in 5% CO2 at 37 °C, respectively. Firstly, the effects of TP on the cell morphology of HGMCs were observed after 72 h-intervention. Secondly, the cell cycle, the positive rate of senescence-associated-ß-galactosidase (SA-ß-gal) staining and the telomere length were detected, respectively. Finally, the protein expressions of p53, p21 and Rb in the p53-p21-Rb signaling pathway were investigated, respectively. And the expressions of p-STAT3 and miR-126 were examined severally. The results indicated that HG not only arrested the cell cycle in G1 phase but also increased the positive rate of SA-ß-gal staining, and shortened the telomere length. HG led to the protein over-expressions of p53, p21 and Rb and HGMCs senescence by activating the p53-p21-Rb signaling pathway. In addition, L-TP delayed HGMCs senescence by improving the cell cycle G1 arrest, reducing SA-ß-gal staining positive rate and lengthening the telomere length. L-TP reduced the protein over-expressions of p53, P21 and Rb induced by HG and inhibited the telomere-p53-p21-Rb signaling pathway. Moreover, the expression of p-STAT3 was increased and the expression of miR-126 was decreased in HGMCs induced by HG. L-TP reduced the expression of p-STAT3 and increased the expression of miR-126 in HGMCs. In conclusion, HG could induce HGMCs senescence by activating the telomere-p53-p21-Rb signaling pathway in vitro. L-TP could delay HGMCs senescence through regulating STAT3/miR-126 expressions and inhibiting the telomere-p53-p21-Rb signaling pathway activation. These findings could provide the effective interventions in clinic for preventing and treating renal cell senescence in diabetic kidney disease.

Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent anti-tumor agent that triggers apoptosis in cells from multiple types of carcinoma but not in normal cells. However, diverse mechanisms are associated with insensitivity to TRAIL in various cancers. TRAIL efficacy may be enhanced by combining TRAIL with a sensitizer. In this study, vernodalol, a sesquiterpene lactone, sensitized diffuse large B-cell lymphoma (DLBCL) cells to TRAIL-induced apoptosis. Vernodalol increased the expression of death receptor (DR) 5, and silencing of DR5 with a small interfering RNA (siRNA) reduced the effect of vernodalol on TRAIL-mediated apoptosis. Additionally, vernodalol up-regulated the expression of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), a transcription factor. Inhibition of CHOP with a siRNA diminished DR5 expression and vernodalol-induced sensitization to the TRAIL treatment. In addition, a c-Jun N-terminal kinase (JNK) inhibitor blocked the vernodalol-induced up-regulation of DR5, indicating that the effect depended on JNK activation. Furthermore, the down-regulation of induced myeloid leukaemia cell differentiation protein (Mcl-1) played an important role in vernodalol/TRAIL-induced apoptosis, as Mcl-1 overexpression prevented this apoptotic effect. Moreover, the vernodalol/TRAIL combination inhibited tumor growth in a xenograft model. Based on our results, vernodalol enhanced TRAIL-induced apoptosis by down-regulating Mcl-1 and up-regulating DR5, and the effects of DR5 depended on JNK activation and CHOP induction. Therefore, combining TRAIL with vernodalol, a naturally occurring agent, may represent a promising therapeutic approach for DLBCL.

Kinetics of sterilization of atomized slightly acidic electrolyzed water on tableware.

The aim of this study was to elucidate the kinetics of atomization of slightly acidic electrolyzed water (SAEW) for use in sterilization of secondary contaminated tableware surfaces. The sterilization efficacy of SAEW was assessed on the basis of the change in the total number of colonies with different contamination levels (101 CFU/mL and 102 CFU/mL), atomization time (10, 20, 30, 40, and 50 s), atomizing distance (5, 10, 15, 20, 25, and 30 cm), and available chlorine concentration (ACC; 25.2, 30.2, 34.9, 40.5, 44.8, and 53.3 mg/L) as the main influencing factors. According to the relationship among flux, atomization area, and time, a kinetic model of SAEW atomization for the sterilization of tableware surfaces was established. The results indicated that the sterilization efficacy of SAEW gradually improved with decreased contamination levels (12.69 %-15.74 %), extended atomization time (13.68 %-46.58 %), and increased ACC (36.89 %-95.14 %). Based on the kinetics analysis, the change law of the kinetic model of SAEW atomization and sterilization of tableware surfaces with secondary pollution was found to be consistent with the change law of sterilization (r2 > 0.8). The results of this study provide a theoretical basis for SAEW atomization for sterilization of secondary contaminated tableware surfaces and also contributes to the improvement of technological theory of SAEW sterilization.