Regulatory mechanism of miR-20a-5p in neuronal damage and inflammation in lipopolysaccharide-induced BV2 cells and MPTP-HCl-induced Parkinson's disease mice.

BACKGROUND: Parkinson's disease (PD) is a prevailing neurodegenerative disorder increasingly affecting the elderly population. The involvement of microRNAs (miRNAs) in PD has been confirmed. We sought to explore the molecular mechanism of miR-20a-5p in PD. METHODS: Lipopolysaccharide (LPS)-induced BV2 cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP-HCl)-induced PD mouse model were established. miR-20a-5p, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, and IL-10 expression in BV2 cells was examined by reverse transcription - quantitative polymerase chain reaction. Cell viability was assessed by MTT assay. The apoptotic rate and levels of Bcl-2, Bax, cleaved caspase-3, and signal transducer and activator of transmission (STAT)3 were examined by flow cytometry and Western blot. Bioinformatics software predicted the potential binding sites of miR-20a-5p and STAT3. Dual-luciferase experiment verified the binding relationship. Iba1-positive and tyrosine hydroxylase (TH)-positive cell numbers in substantia nigra pars compacta were detected by immunohistochemistry. The effect of miR-20a-5p on motor function in MPTP-induced PD mice was detected by Rota-rod test, Pole test, Traction test and Beam-crossing task. RESULTS: miR-20a-5p was under-expressed in LPS-induced BV2 cells. Overexpression of miR-20a-5p increased the viability of LPS-induced BV2 cells and reduced apoptosis rates. Moreover, overexpression of miR-20a-5p reduced cleaved caspase-3, Bax, iNOS, IL-6, and TNF-α and increased Bcl-2 and TGF-ß1, and IL-10. miR-20a-5p targeted STAT3. STAT3 overexpression partially reversed miR-20a-5p overexpression-mediated effects on LPS-induced BV2 cell viability, apoptosis, and inflammatory responses. miR-20a-5p overexpression inhibited MPTP-induced STAT3 and α-synuclein levels, microglia activation, and inflammatory response, and reduced the loss of TH-positive cells in mice. miR-20a-5p overexpression ameliorated MPTP-induced dyskinesia in PD model mice. CONCLUSION: miR-20a-5p alleviates neuronal damage and suppresses inflammation by targeting STAT3 in PD.

Rapid immunoassay for dual-mode detection of HPV16 and HPV18 DNA based on Au@PdPt nanoparticles.

Cervical cancer (CC) remains one of the most severe global health challenges affecting women, primarily due to persistent infection with high-risk human papillomavirus (HPV) subtypes, particularly with HPV16 and HPV 18. Effective detection of these high-risk HPV strains is crucial for CC prevention. Current screening programs for HPV DNA include PCR and in situ hybridization, which are accurate and sensitive. However, these approaches demand a high level of expertise, along with expensive instruments and consumables, thus hindering their widespread use. Therefore, there is a compelling demand to develop an efficient, straightforward, and cost-effective method. Herein, we propose a lateral flow immunoassay (LFIA) method based on Au@PdPt nanoparticles for the simultaneous detection and genotyping of HPV16 and HPV18 within 15 min. This innovative approach allows for qualitative assessment by the naked eye and enables semi-quantitative detection through a smartphone. In this study, under optimal conditions, the qualitative visual limits of detection (vLOD) for HPV16 and HPV18 reached 0.007 nM and 0.01 nM, respectively, which were 32-fold and 20-fold more sensitive than conventional AuNPs-LFIA for HPV16 and HPV18, respectively. Meanwhile, semi-quantitative limits of detection (qLOD) for HPV16 and HPV18 were 0.05 nM and 0.02 nM, respectively. In conclusion, our formulated approach represents a significant step forward in HPV detection and genotyping, with the potential to enhance accessibility and effectiveness in the early diagnosis of CC at the point of care and beyond.

Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Short-term high-fat diet favors the appearances of apoptosis and gliosis by activation of ERK1/2/p38MAPK pathways in brain.

High-fat diet (HFD) has been associated with neuroinflammation and apoptosis in distinct brain regions. To explore the effect of short-term (7, 14 and 21 days) high-fat overfeeding on apoptosis, inflammatory signaling proteins, APP changes and glial cell activities in cerebral cortex and cerebellum. Mice were fed with HFD for different lengths (up to 21 days) and after each time body weights of mice was tested, then the apoptotic proteins, IL-1ß, APP, BACE1and MAPKs, Akt and NF-κB signaling activity were evaluated by western blots. Results demonstrate that short period of high-fat overnutrition significantly promotes apoptosis, APP expression at day 21 of cerebral cortex and at day 7 of cerebellum compared to chow diet. In addition, increased GFAP+astrocytes, Iba-1+microglia and IL-1ß 30 were observed in cerebral cortex after 21 days HFD, but no changes for 7 days overfeeding of cerebellum. Serendipitously, ERK1/2 pathway was activated both in cerebral cortex and cerebellum for different time course of HFD. Furthermore, increased phospho-p38 MAPK level was observed in cerebellum only. In consistent with in vivo results, SH-SY5Y cells treatment with cholesterol (50 µM, 100 µM) for 48 h culture in vitro demonstrated that pro-apoptotic proteins were enhanced as well. In brief, short-term HFD consumption increases sensitivity to apoptosis, APP and IL-1ß production as well as gliosis in cerebral cortex and cerebellum, which may be related to enhancement of ERK1/2 and p38 MAPK activation.

Clinical application of individualized total arterial coronary artery bypass grafting in coronary artery surgery.

BACKGROUND: Total arterial revascularization is associated with increased patency and long-term efficacy and decreased perioperative morbidity and mortality and incidence of cardiac-related events and sternal wound infection compared with conventional coronary artery bypass surgery (CABG), in which the left internal mammary artery (LIMA) is typically grafted to the left anterior descending artery with additional saphenous vein grafts often used. This study determined whether these favorable clinical results could be realized at the authors' institute. AIM: To summarize the early efficacy and clinical experience of individualized total arterial coronary artery bypass grafting surgery. METHODS: CABG was performed on 35 patients with non-single-vessel coronary artery disease by adopting total arterial grafts at Fourth Affiliated Hospital of Harbin Medical University between April 2016 and December 2019. LIMA was used in 35 patients, radial artery (RA) was used in 35 patients, and right gastroepiploic artery (RGEA) was used in 9 patients. Perioperative complications were observed, short-term graft patency rate was followed-up, and quality of life was assessed. RESULTS: All patients underwent off-pump coronary artery bypass and the surgeries were successful. All of them were discharged without any complications or deaths. During the follow-up, it was found that patients' angina symptoms were relieved and New York Heart Association classification for cardiac function was class I to class II. A total of 90 vessels were grafted with no occlusion for internal mammary artery, three occlusions for RA, and one occlusion for RGEA. CONCLUSION: The individualized total arterial strategy based on the vessels targeting individual anatomic characteristics can achieve complete revascularization with satisfactory short-term grafting patency rate.

Enhanced removal of cadmium from wastewater with coupled biochar and Bacillus subtilis.

Shortcomings of individual biochar or microbial technologies often exist in heavy metal removal from wastewater and may be circumvented by coupled use of biochar and microorganisms. In this study, Bacillus subtilis and each of three biochars of different origins (corn stalk, peanut shell, and pine wood) were coupled forming composite systems to treat a cadmium (Cd, 50 mg/L) wastewater formulated with CdCl2 in batch tests. Biochar in composite system enhanced the activity and Cd adsorption of B. subtilis. Compared with single systems with Cd removal up to 33%, the composite system with corn stalk biochar showed up to 62% Cd removal, which was greater than the sum of respective single B. subtilis and biochar systems. Further analysis showed that the removal of Cd by the corn stalk composite system could be considered to consist of three successive stages, that is, the biochar-dominant adsorption stage, the B. subtilis-dominant adsorption stage, and the final biofilm formation stage. The final stage may have provided the composite system with the ability to achieve prolonged steady removal of Cd. The biochar-microorganism composite system shows a promising application for heavy metal wastewater treatment.

[Corrigendum] High expression of FUSE binding protein 1 in breast cancer stimulates cell proliferation and diminishes drug sensitivity.

Subsequently to the publication of the above article, the authors have realized that they inadvertently uploaded an incorrectly labelled version of Fig. 5D; essentially, the row of data panels labelled as 'FBPI-KD' were the data derived from the experiments performed with the FBP1-C cells, and vice versa. The revised and correctly labelled version of Fig. 5, showing the data obtained from the experiments for the FBP1-C and the FBPI-KD cells for Fig. 5D, is shown below. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused.[the original article was published in International Journal of Oncology 57: 488-499, 2020; DOI: 10.3892/ijo.2020.5080].

Nogo-A-Δ20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling.

Nogo-A protein consists of two main extracellular domains: Nogo-66 (rat amino acid [aa] 1019-1083) and Nogo-A-Δ20 (extracellular, active 180 amino acid Nogo-A region), which serve as strong inhibitors of axon regeneration in the adult CNS (Central Nervous System). Although receptors S1PR2 and HSPGs have been identified as Nogo-A-Δ20 binding proteins, it remains at present elusive whether other receptors directly interacting with Nogo-A-Δ20 exist, and decrease cell death. On the other hand, the key roles of EphA4 in the regulation of glioblastoma, axon regeneration and NSCs (Neural Stem Cells) proliferation or differentiation are well understood, but little is known the relationship between EphA4 and Nogo-A-Δ20 in NSCs apoptosis. Thus, we aim to determine whether Nogo-A-Δ20 can bind to EphA4 and affect survival of NSCs. Here, we discover that EphA4, belonging to a member of erythropoietin-producing hepatocellular (Eph) receptors family, could be acting as a high affinity ligand for Nogo-A-Δ20. Trans-membrane protein of EphA4 is needed for Nogo-A-Δ20-triggered inhibition of NSCs apoptosis, which are mediated by balancing p38 inactivation and JNK MAPK pathway activation. Finally, we predict at the atomic level that essential residues Lys-205, Ile-190, Pro-194 in Nogo-A-Δ20 and EphA4 residues Gln-390, Asn-425, Pro-426 might play critical roles in Nogo-A-Δ20/EphA4 binding via molecular docking.

Simple transabdominal minimally invasive direct coronary artery bypass surgery with right gastroepiploic artery.

For three patients with isolated right coronary artery disease who had drug resistance and were intolerant to interventional therapy, simple transabdominal small incision bypass grafting of the right gastroepiploic artery and the posterior descending branch of the right coronary artery was conducted without cardiopulmonary. All three patients were discharged smoothly without complications, and were followed up for three months, during which time the myocardial bridges were unobstructed and the cardiac functions were good. The surgery needs no thoracotomy and the injury is small, and avoids influences of sternum and pericardium adhesion on other cardiac surgery in the future. The risk of median sternotomy can be avoided for patients undergoing reoperation for coronary artery bypass surgery.

High expression of FUSE binding protein 1 in breast cancer stimulates cell proliferation and diminishes drug sensitivity.

Breast cancer is the most common malignant tumor affecting women worldwide and is divided into the following subtypes: Luminal A, Luminal B, HER­2 overexpression and triple­negative breast cancer (TNBC). TNBC accounts for approximately 15­20% of all breast cancer cases. Due to the characteristics of low differentiation, the likelyhood of recurrence and metastasis, strong invasiveness and the lack of hormone receptors and human epidermal growth factor receptor 2 (HER2), patients with TNBC cannot benefit from endocrine therapy or other available targeted agents. Chemotherapy is one of the main treatments for patients with TNBC, and cisplatin is one of the most commonly used and effective drugs. The human far upstream element binding protein 1 (FBP1) is a potent pro­proliferative and anti­apoptotic oncoprotein, which is overexpressed in numerous tumor types. The present study demonstrated that FBP1 and its target, c­Myc, were more highly expressed in breast cancer tissues compared with para­carcinoma tissues, and the FBP1 and c­Myc levels are decreased by cisplatin treatment. The knockdown of FBP1 in TNBC cells decreased cell proliferation by arresting the cell cycle at the G2 phase. The knockdown of FBP1 decreased the expression of G2 phase­associateed protein cyclin A2, whereas it increased that of cyclin B1 and p­CDC2. Furthermore, the knockdown of FBP1 decreased cell migration and metastasis by downregulating matrix metalloproteinase 2 expression, and enhanced the sensitivity of TNBC cells to cisplatin by inducing apoptosis. These results thus suggest that FBP1 is a potential novel biological marker for the diagnosis and treatment of TNBC.

Synthesis, characterization, catalytic and biological application of half-sandwich ruthenium complexes bearing hemilabile (κ2-C,S)-thioether-functionalised NHC ligands.

A series of cationic Ru(ii)(η6-p-cymene) complexes with thioether-functionalised N-heterocyclic carbene ligands have been prepared and fully characterized. Steric and electronic influence of the R thioether substituent on the coordination of the sulfur atom was investigated. The molecular structure of three of them has been determined by means of X-ray diffractrometry and confirmed the bidentate (κ2-C,S) coordination mode of the ligand. Interestingly, only a single diastereomer, as an enantiomeric couple, was observed in the solid state for complexes 1c, 1i and 1j. DFT calculations established a low energy inversion barrier between the two diastereomers through a sulfur pyramidal inversion pathway with R donating group while a dissociative/associative mechanism is more likely with R substituents that contain electron withdrawing group, thus suggesting that the only species observed by the 1H-NMR correspond to an average resonance position of a fluxional mixtures of isomers. All these complexes were found to catalyse the oxydant-free double dehydrogenation of primary amine into nitrile. Ru complex bearing NHC-functionalised S-tBu group was further investigated in a wide range of amines and was found more selective for alkyl amine substrates than for benzylamine derivatives. Finally, preliminary results of the biological effects on various human cancer cells of four selected Ru complexes are reported.

Young age at diagnosis is associated with better prognosis in stage IV breast cancer.

Numerous studies have shown that young age is a risk factor in early breast cancer. But for stage IV breast cancer, it is unclear whether age has a similar effect on patient survival. We collected and analyzed data from patients with stage IV breast cancer between January 2010 and December 2015 in SEER database. Multivariate Cox proportional hazard model was used in this study. 13,069 patients with stage IV breast cancer were included in the analysis, of which 1,135 were young breast cancer patients (≤40 years old). In a multivariate analysis that adjusted for sociodemographic factors, clinical-pathological characteristics and therapeutic methods, the risk of death in patients with stage IV ≤40 years was significantly reduced (hazard ratio [HR], 0.72; 95% CI, 0.65-0.79). Subgroup analyses showed that, with the same adjustment of all factors, young age only significantly reduced the risk of death in patients with luminal A (HR, 0.78; 95% CI, 0.68-0.89) and luminal B (HR 0.46; 95% CI, 0.35-0.60) subtypes. Young age at diagnosis is associated with better survival in patients with stage IV breast cancer. The effect of young age at diagnosis on the survival outcome of stage IV breast cancer varies by subtypes.

Formation Mechanism, Geometric Stability and Catalytic Activity of a Single Iron Atom Supported on N-Doped Graphene.

Based on density functional theory (DFT) calculations, the formation geometries, stability and catalytic properties of single-atom iron anchored on xN-doped graphene (xN-graphene-Fe, x=1, 2, 3) sheet are systemically investigated. It is found that the different kinds and numbers of gas reactants can effectively regulate the electronic structure and magnetic properties of the 3 N-graphene-Fe system. For NO and CO oxidation reactions, the coadsorption configurations of NO/O2 and CO/O2 molecules on a reactive substrate as the initial state are comparably analyzed. The NO oxidation reactions through the Langmuir-Hinshelwood (LH) and Eley-Rideal (ER) mechanisms have relatively smaller energy barriers than those of the CO oxidation processes. In comparison, the preadsorbed 2NO reacting with 2CO molecules (2NO+2CO→2CO2 +N2 ) through ER reactions (<0.4 eV) are energetically more favorable processes. These results can provide beneficial references for theoretical studies on NO and CO oxidation and designing graphene-based catalyst for toxic gas removal.

Cripto-1 expression in patients with clear cell renal cell carcinoma is associated with poor disease outcome.

BACKGROUND: Cripto-1 (CR-1) has been reported to be involved in the development of several human cancers. The potential role of CR-1 in clear cell renal cell carcinoma (ccRCC) is still not clear. METHODS: CR-1 expression was evaluated in ccRCC tissues by Real-time quantitative PCR, Western blot and immunohistochemistry. Serum levels of CR-1 were tested by enzyme-linked immunosorbent assay (ELISA). The clinical significance of CR-1 was analyzed. The effects of CR-1 on cell proliferation, migration, invasion and angiogenesis were investigated in ccRCC cell lines in vitro and in vivo, and markers of the epithelial -mesenchymal transition (EMT) were analyzed. The impact of CR-1 on Wnt/ß-catenin signaling pathway was also evaluated in vitro and in vivo. RESULTS: CR-1 expression was elevated in ccRCC tumor tissues and serum samples. CR-1 expression was correlated with aggressive tumor phenotype and poor survival. Ectopic expression of CR-1 significantly promoted cell proliferation, migration, invasion and angiogenesis whereas knockdown of CR-1 inhibited these activities both in vitro and in vivo. Moreover, we found that CR-1 induced EMT and activated Wnt/ß-catenin signaling pathway both in vitro and in vivo. CONCLUSIONS: These results suggest that CR-1 is likely to play important roles in ccRCC development and progression, and that CR-1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

Dexmedetomidine Improves Cerebral Ischemia-Reperfusion Injury in Rats via Extracellular Signal-Regulated Kinase/Cyclic Adenosine Monophosphate Response Element Binding Protein Signaling Pathway.

OBJECTIVE: To investigate the mechanism of dexmedetomidine (Dex) in improving brain damage induced by cerebral ischemia-reperfusion injury in rats. METHODS: Rats were randomly divided into a sham operation group, ischemia-reperfusion group, Dex group, piracetam group, and yohimbine + Dex group, with 12 rats per group. 2,3,5-Triphenyltetrazolium chloride staining was used to analyze cerebral infarct size. Hematoxylin-eosin staining and immunohistochemistry were used to observe brain damage caused by ischemia-reperfusion. Cognitive and memory functions was detected by Morris water maze test, and the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (CREB) were measured by Western blot. RESULTS: Cognitive dysfunction was improved in the Dex group and the piracetam group compared with the ischemia-reperfusion group. Compared with the ischemia-reperfusion group, infarct size and neuronal cell death rates were decreased in the Dex group and the piracetam group. The expression of phosphorylated ERK1/2 and phosphorylated CREB in the Dex group was increased, whereas the expression of phosphorylated ERK1/2 and phosphorylated CREB in the yohimbine + Dex group was lower than in the Dex group (P < 0.05). CONCLUSIONS: Dex improved ischemic brain damage by promoting signal transduction of the ERK/CREB pathway, which may provide new ways for clinical treatment of cerebral ischemia-reperfusion injury.

Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy.

Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to investigate the combined antitumor effect of paclitaxel with small interfering RNA modified by cationic liposome formed from modified octadecyl quaternized carboxymethyl chitosan. The cationic liposome was composed of 3ß-[N-(N', N'-dimethylaminoethane)-carbamoyl]-cholesterol, dioleoylphosphatidylethanolamine, and octadecyl quaternized carboxymethyl chitosan. The cationic liposome properties were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and zeta potential measurements, transmission electron microscopy, atomic force microscopy, and gel retardation assay. The cationic liposome exhibited good properties, such as a small particle size, a narrow particle size distribution, a good spherical shape, a smooth surface, and a good binding ability with small interfering RNA. Most importantly, when combined with paclitaxel and small interfering RNA, the composite cationic liposome induced a great enhancement in the antitumor activity, which showed a significantly higher in vitro cytotoxicity in Bcap-37 cells than liposomal paclitaxel or small interfering RNA alone. In conclusion, the results indicate that cationic liposome could be further developed as a codelivery system for chemotherapy drugs and therapeutic small interfering RNAs.

[Research progress in co-delivery of gene and chemotherapy drugs with nanocarriers for cancer therapy].

Current trends in nanotechnology and RNA interference technology have made the application of nanocarriers (NCS) as a novel gene and drug delivery systems very promising for the field of multidrug resistance (MDR) cancer treatment. Co-delivery of gene and chemotherapy drugs with NCS has a good synergistic effect compared with the traditional chemotherapy which can increase the amount of the drug distribution in target organ in order to reduce the toxic side effects thereby enhancing efficacy. Therefore, the advent of co-delivery systems with NCS especially in the clinical treatment of MDR has had a significant impact on the cancer treatment.

[Research progress in co-delivery of gene and chemotherapy drugs with cationic liposome carrier for cancer therapy].

Despite recent advances in conventional therapeutic approaches for cancer, the efficacy of chemotherapy for cancer is limited due to the drug resistance and toxic side effects during treatment. To overcome drug resistance, higher doses of the toxic chemotherapy drugs are frequently administered, thus leading to even severe adverse side effects, which have limited their clinical application. Cationic liposome as a novel non-viral carrier for co-delivery of gene and chemotherapy drugs in cancer gene therapy has already attracted more and more attention in recent years. Most importantly, this combined strategy can generate a significant synergistic effect, which can silence the related gene expression and increase the concentration of the intracellular chemotherapy drugs. This approach allows the use of a much lower dose of the chemotherapy drugs to achieve same therapeutic effect, which may have the potential for overcoming some major limitations of the conventional chemotherapy. In conclusion, co-delivery of gene and chemotherapy drugs with cationic liposome delivery system will play a vital role in the future and especially could be a promising clinical treatment for drug-resistant tumors.