MIR222HG/LIN28B/ATG5 Axis Drives M2 Macrophage Polarization and Proliferation of Hepatocellular Carcinoma Cells.

Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aimed to investigate the potential of MIR222HG in HCC. HCC cells were co-cultured with U937 cells. Gene expression was determined using reverse transcription-quantitative (RT-q) PCR and western blot. Functional analysis was performed using Cell Counting Kit 8 (CCK-8), colony formation, and flow cytometry assays. We found that MIR222HG was overexpressed in HCC patients as well as HepG2 and Huh7 cells. MIR222HG-mediated upregulation of autophagy related 5 (ATG5) promoted tumor cell autophagy and the activation of M2-like tumor-associated macrophages (TAM2). Moreover, MIR222HG-mediated the activation of TAM2 drove the proliferation of HCC cells. Additionally, MIR222HG increased the mRNA expression as well as promoted the mRNA stability of ATG5 via binding to lin-28 homolog B (LIN28B). In conclusion, MIR222HG-mediated autophagy and the activation of TAM2 promote the aggressiveness of HCC cells via regulating LIN28B/ATG5 signaling.

A pilot clinical risk model to predict polymyxin-induced nephrotoxicity: a real-world, retrospective cohort study.

OBJECTIVES: Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN. METHODS: Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model. RESULTS: Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696-0.787) for internal validation, of 0.708 (95% CI: 0.605-0.810) for temporal validation and of 0.874 (95% CI: 0.759-0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from -3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%. CONCLUSIONS: This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%.

Thermostable vacuum foam dried Newcastle disease vaccine: Process optimization and pilot-scale study.

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.

Identification and analysis of differently expressed transcription factors in aristolochic acid nephropathy.

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.

Vacuum Foam Drying Method Improved the Thermal Stability and Long-Term Shelf Life of a Live Attenuated Newcastle Disease Virus Vaccine.

Vaccines used for managing Newcastle disease virus (NDV) rely heavily on cold chain, and this results in major constraints in their successful application, shipping, and storage. This study was undertaken to improve the thermotolerance properties of live attenuated NDV vaccines using vacuum foam drying (VFD) technology. The live attenuated NDV vaccine formulated in 15% trehalose, 2.5% gelatin, 0.05% pluronic, and 25 mmol/L potassium phosphate buffer (T5) and dried using VFD showed improved heat tolerance in comparison to the vaccine formulated in T5 as well, but dried using freeze-drying (FD) method. The T5-formulated VFD vaccine was stored at 37°C for 120 days, 45°C for 7 days, and 60°C for 3 days; the virus titer loss decreased by no more than 1.0 Log10. In contrast, the FD vaccine prepared in T5 could only be stored at 37°C for 7-10 days. Furthermore, the T5-formulated NDV-VFD vaccine remained infectious when heated at 100°C for 30 min. Shelf-life studies confirmed the improved thermal tolerance of the T5-formulated NDV-VFD vaccine since it could be stably stored at 2-8°C for 42 months and 25°C for 15 months. Moreover, immunization of 1-month-old specific pathogen-free (SPF) chickens with the T5-formulated NDV-VFD vaccine stored at 25 and 37°C could produce hemagglutination inhibition (HI) antibody levels comparable to those of commercial NDV-FD vaccines, which require strict adherence to the cold chain. In conclusion, not only did the VFD technology improve the thermostability and long-term shelf life of the vaccine, it also maintained its immunogenicity.

Iron-Catalyzed Contrasteric Functionalization of Allenic C(sp2)-H Bonds: Synthesis of α-Aminoalkyl 1,1-Disubstituted Allenes.

An iron-catalyzed C-H functionalization of simple monosubstituted allenes is reported. An efficient protocol for this process was made possible by the use of a newly developed electron-rich and sterically hindered cationic cyclopentadienyliron dicarbonyl complex as the catalyst and N-sulfonyl hemiaminal ether reagents as precursors to iminium ion electrophiles. Under optimized conditions, the use of a mild, functional-group-tolerant base enabled the conversion of a range of monoalkyl allenes to their allenylic sulfonamido 1,1-disubstituted derivatives, a previously unreported and contrasteric regiochemical outcome for the C-H functionalization of electronically unbiased and directing-group-free allenes.

Comparative effects of pollen limitation, floral traits and pollinators on reproductive success of Hedysarum scoparium Fisch. et Mey. in different habitats.

BACKGROUND: Reproduction in most flowering plants may be limited because of the decreased visitation or activity of pollinators in fragmented habitats. Hedysarum scoparium Fisch. et Mey. is an arid region shrub with ecological importance. We explored the pollen limitation and seed set of Hedysarum scoparium in fragmented and restored environments, and examined whether pollen limitation is a significant limiting factor for seed set. We also compared floral traits and pollinator visitation between both habitats, and we determined the difference of floral traits and pollinators influenced reproductive success in Hedysarum scoparium. RESULTS: Our results indicated that supplementation with pollen significantly increased seed set per flower, which is pollen-limited in this species. Furthermore, there was greater seed set of the hand cross-pollination group in the restored habitat compared to the fragmented environment. More visits by Apis mellifera were recorded in the restored habitats, which may explain the difference in seed production between the fragmented and restored habitats. CONCLUSIONS: In this study, a positive association between pollinator visitation frequency and open flower number was observed. The findings of this study are important for experimentally quantifying the effects of floral traits and pollinators on plant reproductive success in different habitats.

miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro.

Tripartite motif-containing protein 14 (TRIM14) is a tumor-promoter in papillary thyroid carcinoma (PTC). We found that miR-4443 expression was significantly downregulated in PTC tumor tissue, and was negatively associated with TRIM14. This study was designed to investigate the relationship between miR-4443 and TRIM14 on metastasis and energy metabolism in PTC and the underlying mechanisms. To this end, human PTC cells (SW1736 and MZ-CRC-1) were transfected with a miR-4443 mimic or miR-4443 inhibitor + siRNA-TRIM14, and then dual-luciferase assay, Transwell, Seahorse, and western blot analyses were performed to assess the function of miR-4443 and the underlying mechanism. We found that ectopic expression of miR-4443 inhibited PTC cell migration, invasion, ATP production, and aerobic glycolysis, while inhibition of miR-4443 had the opposite effect. miR-4443 directly targeted TRIM14 and reduced both TRIM14 mRNA and protein levels. Silencing TRIM14 significantly reversed miR-4443 inhibition-induced PTC cell migration, invasion, ATP production, aerobic glycolysis, and phosphorylation of the transcription factor STAT3. These findings suggest that miR-4443 is a tumor suppressor in PTC and inhibits metastasis and energy metabolism via the suppression of TRIM14 signaling.

Thermographic follow-up of postherpetic neuralgia (PHN) subsequent to Ramsay Hunt syndrome with multicranial nerve (V, VII, VIII and IX) involvement: a case report.

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Associations of coenzyme Q10 with endothelial function in hemodialysis patients.

BACKGROUND: Endothelial dysfunction is common in patients undergoing hemodialysis (HD). However, little is known about the relationship between endothelial dysfunction and coenzyme Q10 (CoQ10) levels in HD patients. METHODS: Eligible HD patients were enrolled in this study according to prespecified inclusion and exclusion criteria. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Plasma CoQ10, serum malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. The potential confounders identified by univariate analyses (P < 0.15) were selected in a stepwise multiple regression model. RESULTS: In total, 111 HD patients were enrolled in this study. The mean CoQ10 level was 633.53 ± 168.66 ng/mL, and endothelial dysfunction was prevalent (91.0%) using a cut-off value of 10% FMD. A significant correlation was observed between FMD and plasma CoQ10 level (r = 0.727, P < 0.001). After adjusting for potential parameters, a stepwise multivariate linear regression analysis revealed that CoQ10 level was an independent predictor of FMD (ß = 0.018, P < 0.001). When CoQ10 was dichotomized using the median value (639.74 ng/mL), the conclusion remained unchanged (ß = 0.584, P < 0.001). Pearson's correlation analyses revealed that plasma CoQ10 level was negatively correlated with MDA (r = -0.48, P < 0.001) and 8-OHdG (r = -0.43, P < 0.001) levels. CONCLUSION: Our data demonstrate that impaired brachial artery FMD was common in HD patients. CoQ10 level was independently associated with FMD, and oxidative stress may constitute a link between CoQ10 level and endothelial dysfunction in these patients.

Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilm-forming capabilities.

BACKGROUND: To compare the adhesion properties and biofilm-forming capabilities of 27 Candida isolates obtained from catheter-related candidemia patients and to evaluate the inhibitory effects of antifungal agents on different Candida species. MATERIAL AND METHODS: Seven C. albicans, six C. parapsilosis, five C. guilliermondii, five C. tropicalis, and four C. glabrata clinical isolates were investigated. We quantified the adherence of these Candida species by flow cytometric method and evaluated the formation of biofilms by XTT reduction and crystal violet methods. Actions of micafungin (MF), fluconazole (FZ), and N-acetylcysteine (NAC) on the adhesion and biofilm formation of different Candida species were determined. RESULTS: Non-albicans Candida species were demonstrated to have stronger adhesion abilities compared with C. albicans. The biofilm-forming capabilities of different Candida species were varied considerably, and the degree of biofilm formation might be affected by different assay approaches. Interestingly, C. parapsilosis displayed the highest biofilm formation abilities, while C. glabrata exhibited the lowest total biomass and metabolic activity. Furthermore, the inhibitory activities of MF, FZ, and NAC on fungal adhesion and biofilm formation were evaluated, and the results indicated that MF could reduce the adhesion ability and biofilm metabolism more significantly (p < 0.05), and its antifungal activity was elevated in a dose-dependent manner. CONCLUSION: Non-albicans Candida species, especially C. guilliermondii, C. tropicalis, and C. parapsilosis, exhibited higher adhesion ability in catheter-related candidemia patients. However, these Candida species had varied biofilm-forming capabilities. MF tended to have stronger inhibitory effects against both adhesion and biofilm formation of different Candida species.

Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death.

Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion channels in vivo, we showed that they potently protect brain cells from death after an ischemic stroke. Thus, the methodology described here should be general, thereby allowing selection of antibodies to other important ASICs, such as those involved in pain, neurodegeneration, and other conditions.

Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma.

BACKGROUND: Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma. METHODS: BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed. RESULTS: THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A). CONCLUSIONS: Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.

Correction to: Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin α2ß1-contacting-mediated activation of Wnt-ß-catenin pathway.

An amendment to this paper has been published and can be accessed via the original article.

A Novel Laboratory-Based Model to Predict the Presence of Obstructive Coronary Artery Disease.

Commonly used tools to assess the probability of obstructive-coronary artery disease (CAD) were derived based on Caucasian cohorts, with their performance in China is still unknown. Furthermore, most were established based on non-laboratory variables, contributing to the limited predictive ability to some extent. Thus, we developed and internally validated a laboratory-based model with data from a Chinese cohort of 8963 inpatients, with suspected stable chest pain, referred to catheter-based coronary angiography (CAG) from September 2007 to April 2019, and then compared the present model's performance with the four most commonly used prediction tools, Coronary Artery Disease Consortium 1/2 Score (CAD1/2), Duke clinical score (DCS), and Diamond-Forrester score (DF). The final model was developed by random forest method, including 8 predictors derived from 70 variables. Five-fold cross-validation was performed to evaluate the model's prediction accuracy. In the external validation set, the present model showed a superior area under the receiver-operating curve (0.816), followed by DCS (0.66), CAD2 (0.61), CAD1 (0.59) and at last DF (0.58), respectively. Furthermore, the present model correctly classified 74.4% of obstructive-CAD patients as high-risk, and correctly classified more than one third of non-obstructive-CAD patients as low-risk. The present model's net reclassification improvement (NRI) showed a significant positive reclassification over CAD1 (NRI = 0.60, P < 0.001), DF (NRI = 0.59, P < 0.001), CAD2 (NRI = 0.57, P < 0.001), and DCS (NRI = 0.43, P < 0.001). Decision curve analysis demonstrated that the present model provided a larger net benefit compared with CAD1/2, DCS, and DF. In conclusion, the novel model, using 8 laboratory and non-laboratory variables, performed well in risk stratifying patients with suspected chest pain regarding the presence of obstructive-CAD in the present Chinese cohort.

Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 µmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

Platelets promote breast cancer cell MCF-7 metastasis by direct interaction: surface integrin α2ß1-contacting-mediated activation of Wnt-ß-catenin pathway.

BACKGROUND: Integrin-mediated platelet-tumor cell contacting plays an important role in promoting epithelial-mesenchymal transition (EMT) transformation of tumor cells and cancer metastasis, but whether it occurs in breast cancer cells is not completely clear. OBJECTIVE: The purpose of this study was to investigate the role of integrin α2ß1 in platelet contacting to human breast cancer cell line MCF-7 and its effect on the EMT and the invasion of MCF-7 cells. METHODS: Human platelets were activated by thrombin, and separated into pellets and releasates before the co-incubation with MCF-7 cells. Cell invasion was evaluated by transwell assay. The surface integrins on pellets and MCF-7 cells were inhibited by antibodies. The effect of integrin α2ß1 on Wnt-ß-catenin pathway was assessed by integrin α2ß1-silencing and Wnt-ß-catenin inhibitor XAV. The therapeutic effect of integrin α2ß1-silencing was confirmed in the xenograft mouse model. RESULTS: Pellets promote the invasion and EMT of MCF-7 cells via direct contacting of surface integrin α2ß1. The integrin α2ß1 contacting activates Wnt-ß-catenin pathway and promotes the expression of EMT proteins in MCF-7 cells. The activated Wnt-ß-catenin pathway also promotes the autocrine of TGF-ß1 in MCF-7 cells. Both Wnt-ß-catenin and TGF-ß1/pSmad3 pathways promote the expression of EMT proteins. Integrin α2ß1-silencing inhibits breast cancer metastasis in vivo. CONCLUSIONS: The direct interaction between platelets and tumor cells exerts its pro-metastatic function via surface integrin α2ß1 contacting and Wnt-ß-catenin activation. Integrin α2ß1-silencing has the potential effect of inhibiting breast cancer metastasis.

A novel rat model of contrast-induced nephropathy based on dehydration.

BACKGROUND: Contrast-induced nephropathy (CIN) is a frequent cause of hospital-acquired acute kidney injury. Previous animal models developed to explore the pathogenesis of CIN were based primarily on surgery or indomethacin treatment. Thus, we sought to explore a novel CIN rat model comparable to the human CIN. METHODS AND RESULTS: Both serum creatinine and tubular injury score were used to assess the successful establishment of the present model. In our study, dehydration duration and the iohexol dosage were found to be the two most important factors to develop a rat CIN model. And, dehydration for 3 days plus furosemide (10 mL/kg) injection before iohexol (15 mL/kg) administration was demonstrated the optimal strategy. Renal injury induced by 15 mL/kg iohexol was almost twice more severe than 10 mL/kg. Moreover, significant renal function decrease, morphological damage and mitochondrial dysfunction occurred as early as 6 h after iohexol injection, not 24 h as previous studies reported. Unexpectedly, we firstly discovered that dehydration after iohexol administration did not increase the extent of renal damage, indicating that hydration after contrast media exposure may be ineffective. CONCLUSIONS: A novel CIN rat model based on dehydration and iohexol exposure was established and validated to assist in understanding and preventing CIN.

[Investigation on protective effect and efficacy difference of extract of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus against acetaminophen-induced liver injury].

The study was aimed to investigate the protective effect and pharmacodynamic difference of the ethanol extracts of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus on the drug-induced liver injury induced by acetaminophen.The cell activations of LO2 cells treated by Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts were tested by CCK-8 essay.The effects of ethanol extracts on cell survival rate,the activities of ALT and AST in culture medium were detected based on the injury model of LO2 cells induced by APAP.Further,in purpose to observe the protective effect of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts on a mouse model of liver injury induced by intraperitoneal injectionof acetaminophen was established.Mice were randomly divided into control group,model group,positive drug group and Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts administration groups.The activities of ALT and AST in the serum and the levels of MDA,SOD,GSH and GSH-PX in the liver homogenate of the mice were detected by commercial kits.The HEstaining was used to observe the histopathological changes of liver tissue in each group and the TUNEL staining was used to observe the hepatocyte apoptosis.The results showed that the ethanol extracts at less than 1 g·L~(-1)did not affect the activity of LO2 cell.Compared with the model group,the cell survival rates of the Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups was significantly increased;the ALT and AST in the culture medium were distinct decreased(P<0.05 or P<0.01).The survival rate of Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract from different batches were similar,while that of the Schisandrea Sphenatherae Fructus ethanol extract from different batches were quite different(P<0.05or P<0.01).Further,animal experiments showed that Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extract administration groups could markedly inhibit the increase of ALT and AST levels in serum(P<0.01),decrease MDA content significantly(P<0.01),and increase GSH,GSH-PX and SOD activity significantly(P<0.01).Among them,compared with other groups,Schisandrae Sphenantherae Fructus ethanol extract-2 group showed the best effect(P<0.05 or P<0.01)while Schisandrae Sphenantherae Fructus ethanol extract-1 showed a poor effect(P<0.05 or P<0.01).In conclusion,both Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts have protective effect on APAP-induced drug-induced liver injury and there was a certain difference in the efficacy between Schisandrae Sphenantherae Fructus and Schisandrae Chinensis Fructus ethanol extracts from different habitats.

Protective effects of thymol on LPS-induced acute lung injury in mice.

Thymol, a naturally occurring phenol isolated from thyme, has been known to exhibit anti-inflammatory and anti-oxidative effects. The aim of this study was to determine the effect of thymol on acute lung injury (ALI) within an lipopolysaccharide (LPS)-induced mouse model. ELISA and western blotting were performed to detect the pro-inflammatory cytokines and signaling pathways. The myeloperoxidase (MPO) activity and MDA content in lung tissues, lung wet/dry (W/D) ratio and histopathological examination were detected. The results showed that thymol inhibit LPS-induced TNF-α, IL-6 and IL-1ß production in BALF. Furthermore, thymol significantly reduced the MPO activity, MDA content, lung wet/dry weight ratio and histopathological changes induced by LPS. In addition, thymol inhibited LPS-induced NF-κB signaling pathway and up-regulated the expression of Nrf2 and HO-1. In conclusion, we found that thymol had anti-inflammatory and anti-oxidative effects against LPS-induced ALI and the mechanism was through suppressed NF-κB signaling pathway and activating Nrf2 signaling pathway.