Evaluation of osteogenic properties of a novel injectable bone-repair material containing strontium in vitro and in vivo.

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05). Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

Effect of in situ vermicomposting combined with biochar application on soil properties and crop yields in the tomato monoculture system.

Vermicompost and biochar have been widely used to improve soil conditions. However, little information is available regarding the efficiency and effectiveness of in situ vermicomposting with biochar (IVB) in monoculture soils. In this study, we estimated the effects of IVB on soil physiochemical and microbial properties, crop yields, and fruit quality under the tomato monoculture system. The soil treatments considered were (i) untreated monoculture soil (MS, control), (ii) MS plus 1.5 t/ha biochar applied to soil surface (MS+1.5BCS), (iii) MS plus 3 t/ha biochar applied to soil surface (MS+3BCS), (iv) MS mixed with 1.5 t/ha biochar (MS+1.5BCM), (v) MS mixed with 3 t/ha biochar (MS+3BCM), (vi) in situ vermicomposting (VC), (vii) VC plus 1.5 t/ha biochar applied to VC surface (VC+1.5BCS), (viii) VC plus 3 t/ha biochar applied to VC surface (VC+3BCS), (ix) VC mixed with 1.5 t/ha biochar (VC+1.5BCM), and (x) VC mixed with 3 t/ha biochar (VC+3BCM). In general, soil pH varied from 7.68 to 7.96 under VC-related treatments. The microbial diversity was much higher in bacterial communities (OTU: 2284-3194, Shannon index: 8.81-9.91) than in fungal communities (OTU: 392-782, Shannon index: 4.63-5.71) in VC-related treatments. Specifically, Proteobacteria was the dominant bacterial phylum, followed by Bacteroidota, Chloroflexi, Patescibacteria, Acidobacteriota, Firmicutes, and Myxococcota. It is worth noting that IVB-related treatments could increase the relative abundance of Acidobacteria and reduced the relative abundance of Bacteroidetes. In addition, the VC+1.5BCM treatment exhibited the greatest yield (9377.6 kg/667m2) and simultaneously showed higher fruit quality (vitamin C, 28.94 mg/100g; soluble sugar, 20.15%) as compared to other treatments. Our results suggested that in situ vermicomposting with biochar can improve soil properties and enhance both crop yields and fruit quality under the tomato monoculture system.

In silico identification of A1 agonists and A2a inhibitors in pain based on molecular docking strategies and dynamics simulations.

Most recently, the adenosine is considered as one of the most promising targets for treating pain, with few side effects. It exists in the central nervous system, and plays a key role in nociceptive afferent pathway. It is reported that the A1 receptor (A1R) could inhibit Ca2+ channels to reduce the pain like analgesic mechanism of morphine. And, A2a receptor (A2aR) was reported to enhance the accumulation of AMP (cAMP) and released peptides from sensory neurons, resulting in constitutive activation of pain. Much evidence showed that A1R and A2aR could be served as the interesting targets for the treatment of pain. Herein, virtual screening was utilized to identify the small molecule compounds towards A1R and A2aR, and top six molecules were considered as candidates via amber scores. The molecular dynamic (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) were employed to further analyze the affinity and binding stability of the six molecules towards A1R and A2aR. Moreover, energy decomposition analysis showed significant residues in A1R and A2aR, including His1383, Phe1276, and Glu1277. It provided basics for discovery of novel agonists and antagonists. Finally, the agonists of A1R (ZINC19943625, ZINC13555217, and ZINC04698406) and inhibitors of A2aR (ZINC19370372, ZINC20176051, and ZINC57263068) were successfully recognized. Taken together, our discovered small molecules may serve as the promising candidate agents for future pain research.

Updates and advances on pharmacological properties of Taraxacum mongolicum Hand.-Mazz and its potential applications.

As a well-recognized dietary and medicinal plant, Taraxacum mongolicum Hand.-Mazz (TMHM) has been used for making wines, candies, energy drinks, and other functional foods. The TMHM contains a diverse range of active phytoconstituents, including flavonoids, triterpenoids, phenolic acids, sesquiterpene lactones, pigments, coumarins and sterols. Recent pharmacological evidence has revealed multiple biological effects of TMHM, including anti-inflammatory, antioxidant, antibacterial, and gastric-protective effects, which contribute to the ameliorative effects of TMHM on inflammation-associated diseases, constipation, gastric disorders, empyrosis, hyperlipidemia, and swollen carbuncles. Although recent advances have highlighted the potential of TMHM to be applied in the clinical practice, food, and nutraceutical industry, the mechanistic understanding and systematic information on TMHM are still scarce. Here, in this timeline review, we have attempted to compile literary documents on pharmacological potential of TMHM concerning its chemical composition, biological activities, toxicity, and pharmacokinetics to promote further researches on clinical and therapeutic potential of TMHM and its food/nutraceutical applications.

Glucocappasalin Induces G2/M-Phase Arrest, Apoptosis, and Autophagy Pathways by Targeting CDK1 and PLK1 in Cervical Carcinoma Cells.

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.

Complete chloroplast genomes of Chinese wild-growing Vitis species: molecular structures and comparative and adaptive radiation analysis.

As a basalmost family of Vitaceae, Chinese wild Vitis species offer key insights into the demographic history of grapes. In this study, we obtained 10 complete chloroplast (cp) genomes from Chinese wild-growing Vitis species based on our whole genome re-sequencing data. These chloroplast genomes ranged from 160,838 to 232,020 bp in size and exhibited typical quadripartite structures. Comparative analyses revealed that inverted repeat (IR) regions are especially abundant and contribute to cp genome arrangements. Phylogenetic analysis of the whole Vitis cp genomes supported three clearly partitioned main origins, in keeping with their geographic distributions, among which East Asian species from China were found to be sister species with Eurasian Vitis species but exhibited significant divergence from the North American group. Two well-supported subgroups were observed within the Chinese wild-growing Vitis species. Among these species, Vitis piasezkii and Vitis betulifolia were closely related species, exhibiting a support rate of 100%. The molecular clock-based divergence time suggested that the earliest split subspecies was Vitis pseudoreticulata, which further indicated that the origin and initial gene pool are located in southern China (the habitat of V. pseudoreticulata is located in the region). Coincidentally, the divergence time was during the Pleistocene period (2.6-0.1 Ma). Due to glacial/interglacial temperature fluctuations, cold-adapted subspecies, e.g., Vitis amurensis, could re-colonize new habitats. Our results may help to elucidate the adaptive radiation of Chinese wild Vitis species in different environments.

Bioinformatics Analysis of Key Candidate Genes and Pathways in Ulcerative Colitis.

Ulcerative colitis (UC) is chronic, idiopathic disease that affects the colon and the rectum and the underlying pathogenesis of UC remains to be known. The clinical drugs are mainly work based on anti-inflammation and immune system. However, most of them are expensive and have severe side effects. Therefore, identification of novel targets and exploring new drugs are urgently needed. In this study, several bioinformatics approaches were used to discover key genes and further in order to explore the pathogenesis of UC. Two microarray datasets, GSE38713 and GSE9452 were selected from NCBI-Gene Expression Omnibus database. Differentially expression genes (DEGs) were identified by using LIMMA Package of R. Then, we filtered clustered candidate genes into Gene Ontology (GO) and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery (DAVID), KEGG pathway based on functions and signaling pathways with significant enrichment analysis. The protein-protein interaction (PPI) network was constructed by the Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) analysis, and visualized by Cytoscape and further analyzed by Molecular Complex Detection. Lastly, 353 up-regulated and 145 down-regulated genes were than recognized. After consulting a number of references and network degree analysis, four hub genes, namely FCGR2A, C3, INPP5A, and ACAA1 were identified, and these genes were mainly enriched in complement and coagulation cascades, mineral absorption, and Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathways. In conclusion, this study would provide new clues for the pathogenesis and identification of drug targets of UC in the near future.

Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer.

Breast cancer is the second most common types of cancer worldwide. Molecular strategies have developed rapidly; however, novel treatments strategies with high efficacy and lower toxicity are still urgently demanded. Notably, biological networks estimated from microarray data and functional activity network analysis could be utilized to identify and validate potential targets. In this study, two microarray data (GSE13477, GSE31192) were firstly selected, and analyzed by multi-functional activity network analysis to generate the core protein-protein-interaction (PPI) network. Several potential targets were subsequently identified and c-Met and poly (ADP-ribose) polymerase-1 (PARP-1) were manually chosen as the key targets in breast cancer. Furthermore, virtual screening and molecular dynamics (MD) simulations were utilized to recognize novel c-Met/PARP-1 inhibitors in Specs products database. Three small molecules, namely, ZINC19909930, ZINC20032678 and ZINC13562414 were selected. Additionally, these compounds were synthesized, and two breast cancer cell lines, MDA-MB-231 and MCF-7 cells were used to validate our bioinformatic findings in vitro. MTT assay and Hoechst staining showed that ZINC20032678 significantly induced breast cancer cell death, which was mediated through apoptosis by flow cytometry. Furthermore, ZINC20032678 was shown to target the active sites of the both targets and recruitment of downstream apoptotic signaling pathways, eventually inducing breast cancer cell apoptosis. Collectively, our findings not only offer systems biology approaches based drug target identification, but also provide the new clues for developing novel inhibitors for future breast cancer research.

Improving the Anti-Ovarian Cancer Activity of Docetaxel by Self-Assemble Micelles and Thermosensitive Hydrogel Drug Delivery System.

In recent decades, a large number of research studies have been conducted to improve the treatment strategy against epithelial ovarian cancer, but women in advanced stage still have poor outcomes. The development of advanced treatments must be continued to overcome the limitation. Docetaxel, a semi-synthetic product derived from the Pacific Taxus extract, has been studied for many years for its potent anticancer applications. Aiming to solve the problems of its highly lipophilicity, insolubility and adverse side effects, nanocarriers were applied. Relying on the integration of nanoparticles which had optimized sizes, shapes, and surface properties, the effect of docetaxel was enhanced. In this study, we designed a novel drug loaded gel-forming nanoparticle system (Doc-NMs-hydrogel composites), which acted as a sustained drug depot for docetaxel. Docetaxel was encapsulated into MPEG-PCL and then into blank thermosensitive hydrogel Pluronic F-127. Characterization showed that the prepared Doc-NMs had high drug loading (7%), minor particle size (37 nm), relatively good water solubility. Moreover, the cytotoxicity, apoptosis induction and the antitumor effects of Doc-NMs-hydrogel composites on mice abdominal SKOV-3 ovarian cancer model were investigated in vivo. Compared with other groups, at the same dosage, Doc-NMs-hydrogel composites show better apoptosis induction and cell growth inhibition. In conclusion, the prepared Doc-NMs-hydrogel composites enhanced anti-tumor activity by increasing local docetaxel concentration, maintaining stable and sustained drug release, prolonging drug retention time in tumors, and reducing toxicity to normal tissues. Doc-NMs-hydrogel composites might have great potential clinical application in anti-ovarian cancer activity.

Targeting EZH2 for glioma therapy with a novel nanoparticle-siRNA complex.

BACKGROUND: For the past few years, gene-therapy has recently shown considerable clinical benefit in cancer therapy, and the applications of gene therapies in cancer treatments continue to increase perennially. EZH2, an ideal candidate for tumor gene therapy, plays an important role in the tumorigenesis. METHODS: In this study, we developed a novel gene delivery system with a self-assembly method by Methoxy polyethylene glycol-polycaprolactone (MPEG-PCL) and DOTAP(DMC). And EZH2si-DMC was used to research anti-glioma both in vitro and in vivo. RESULTS: DMC with zeta-potential value of 36.7 mV and size of 35.6 nm showed good performance in the delivery siRNA to glioma cell in vitro with high 98% transfection efficiency. EZH2si-DMC showed good anti-glioma effect in vitro through inducing cell apoptosis and inhibiting cell growth. What's more, treatment of tumor-bearing mice with DMC-EZH2si complex had significantly inhibited tumor growth at the subcutaneous model in vivo by inhibiting EZH2 protein expression, promoting apoptosis and reducing proliferation. CONCLUSION: The EZH2 siRNA and DMC complex may be used to treat the glioma in clinical as a new drug.

Correction: Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system.

[This corrects the article DOI: 10.1039/C8RA03274B.].

Enhancing the anti-ovarian cancer activity of quercetin using a self-assembling micelle and thermosensitive hydrogel drug delivery system.

Ovarian cancer, as one of the killers that threaten women's health, has been studied extensively. As a natural bioflavonoid with prospective effects, quercetin is highly recognized for its anti-cancer applications. However, one of the major challenges that quercetin faces is its poor water solubility, instability in physiological media, and subsequent poor bioavailability. Thus, optimizing the ideal drug delivery options is necessary to facilitate the harnessing of the maximum benefits from quercetin. In this study, a quercetin-loaded thermosensitive injectable hydrogel system (Qu-M-hydrogel composites) was constructed based on nanotechnology. Quercetin was encapsulated into MPEG-PCL (with a high drug loading of 7% and minor particle size of 32 nm) and then added into the blank thermosensitive hydrogel Pluronic F-127. The Qu-M-hydrogel composites showed a much slower release than Qu-M in vivo. Moreover, the cytotoxicity, apoptosis induction, and anti-tumor effects of the Qu-M-hydrogel composites on the abdominal SKOV-3 ovarian cancer mouse models were investigated in vivo. Compared with other groups, the Qu-M-hydrogel composites exhibited improved apoptosis induction and cell growth inhibition effects and in vivo trials showed a better balance between the anti-tumor efficacy in the Qu-M-hydrogel composite group than in other groups at an equal drug dose. In conclusion, the prepared Qu-M-hydrogel composites enhanced the anti-tumor activity by providing a high local quercetin concentration, sustained and stable drug release, extended drug retention inside the tumor, and low toxicity to normal tissues. The Qu-M-hydrogel composites might have great potential for clinical application in anti-ovarian cancer activity.

Enhancing the anti-glioma therapy of doxorubicin by honokiol with biodegradable self-assembling micelles through multiple evaluations.

Combination chemotherapy is an important protocol in glioma therapy and honokiol shows synergistic anticancer effects with doxorubicin. In this paper, honokiol (HK) and doxorubicin (Dox) co-loaded Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) nanoparticles were prepared with a assembly method. The particle size (about 34 nm), morphology, X-ray Powder Diffraction (XRD), in vitro release profile, cytotoxicity and cell proliferation effects were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PCL nanoparticles simultaneously, and could be released from the micelles in an extended period in vitro. In addition, honokiol and doxorubicin loaded in MPEG-PCL nanoparticles could efficiently suppress glioma cell proliferation and induce cell apoptosis in vitro. Furthermore, Dox-HK-MPEG-PCL micelles inhibited glioma growth more significantly than Dox-MPEG-PCL and HK-MPEG-PCL in both nude mice and zebrafish tumor models. Immunohistochemical analysis indicated that DOX-HK-MPEG-PCL micelles improved Dox's anti-tumor effect by enhancing tumor cell apoptosis, suppressing tumor cell proliferation, and inhibiting angiogenesis. Our data suggest that Dox-HK-MPEG-PCL micelles have the potential to be applied clinically in glioma therapy.

Subinhibitory Concentrations of Allicin Decrease Uropathogenic Escherichia coli (UPEC) Biofilm Formation, Adhesion Ability, and Swimming Motility.

Uropathogenic Escherichia coli (UPEC) biofilm formation enables the organism to avoid the host immune system, resist antibiotics, and provide a reservoir for persistent infection. Once the biofilm is established, eradication of the infection becomes difficult. Therefore, strategies against UPEC biofilm are urgently required. In this study, we investigated the effect of allicin, isolated from garlic essential oil, on UPEC CFT073 and J96 biofilm formation and dispersal, along with its effect on UPEC adhesion ability and swimming motility. Sub-inhibitory concentrations (sub-MICs) of allicin decreased UPEC biofilm formation and affected its architecture. Allicin was also capable of dispersing biofilm. Furthermore, allicin decreased the bacterial adhesion ability and swimming motility, which are important for biofilm formation. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed that allicin decreased the expression of UPEC type 1 fimbriae adhesin gene fimH. Docking studies suggested that allicin was located within the binding pocket of heptyl α-d-mannopyrannoside in FimH and formed hydrogen bonds with Phe1 and Asn135. In addition, allicin decreased the expression of the two-component regulatory systems (TCSs) cognate response regulator gene uvrY and increased the expression of the RNA binding global regulatory protein gene csrA of UPEC CFT073, which is associated with UPEC biofilm. The findings suggest that sub-MICs of allicin are capable of affecting UPEC biofilm formation and dispersal, and decreasing UPEC adhesion ability and swimming motility.

Enhancing the anti-colon cancer activity of quercetin by self-assembled micelles.

Colorectal cancer, a type of malignant neoplasm originating from the epithelial cells lining the colon and/or rectum, has been the third most frequent malignancy and one of the leading causes of cancer-related deaths in the US. As a bioflavonoid with high anticancer potential, quercetin (Qu) has been proved to have a prospective applicability in chemotherapy for a series of cancers. However, quercetin is a hydrophobic drug, the poor hydrophilicity of which hinders its clinical usage in cancer therapy. Therefore, a strategy to improve the solubility of quercetin in water and/or enhance the bioavailability is desired. Encapsulating the poorly water-soluble, hydrophobic agents into polymer micelles could facilitate the dissolution of drugs in water. In our study, nanotechnology was employed, and quercetin was encapsulated into the biodegradable nanosized amphiphilic block copolymers of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL), attempting to present positive evidences that this drug delivery system of polymeric micelles is effective. The quercetin-loaded MPEG-PCL nanomicelles (Qu-M), with a high drug loading of 6.85% and a minor particle size of 34.8 nm, completely dispersed in the water and released quercetin in a prolonged period in vitro and in vivo. At the same time, compared with free quercetin, Qu-M exhibited improved apoptosis induction and cell growth inhibition effects in CT26 cells in vitro. Moreover, the mice subcutaneous CT26 colon cancer model was established to evaluate the therapy efficiency of Qu-M in detail, in which enhanced anti-colon cancer effect was proved in vivo: Qu-M were more efficacious in repressing the growth of colon tumor than free quercetin. In addition, better effects of Qu-M on inducing cell apoptosis, inhibiting tumor angiogenesis, and restraining cell proliferation were observed by immunofluorescence analysis. Our study indicated that Qu-M were a novel nanoagent of quercetin with an enhanced antitumor activity, which could serve as a promising potential candidate for colon cancer chemotherapy.

Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder epithelial cells and inhibits UPEC biofilm formation.

Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility.

[The effect of compressive stress on the factors for liver regeneration in hepatocytes Chang cell line].

OBJECTIVE: To investigate the effect of compressive stress on the factors for liver regeneration including NF-kappaB, signal transducers and activators of transcription 3 (STATS), c-fos and c-jun in hepatocytes Chang cell line. METHODS: Human hepatocytes Chang cell line were subjected to compressive stress at 1000 microstain or 2000 microstain, expression of NF-kappaB P65, p-STAT3, c-fos and c-jun were detected by Western blot or RT-PCR at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h after application of compressive stress to indicate the priming of hepatocytes proliferation. RESULTS: Enhanced expressions of NF-kappaB P65 and p-STAT3 were observed in hepatocytes under compressive stress indicated by Western blot, the magnitude of compressive stress loaded significantly affected the level of expression of NF-kappaB P65 at 2 h (P = 0.046) and p-STAT3 at 1 h (P = 0.039), the peak of expression of p-STAT3 was at 30 minutes after stress-loading while NF-kappaB P65 was at 1 hour; RT-PCR showed that expression of c-fos was not significantly different between 1000 microstain and 2000 microstain at each time point, and expression of c-jun was significantly different at 30 minutes (P = 0.026), 1 h (P = 0.031), 2 h (P = 0.033) after compressive stress loading. CONCLUSION: These results indicate that compressive stress may play an important role in initiating the process of liver regeneration.