The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

OBJECTIVE: This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. CONCLUSIONS: NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

Clinical value and effectiveness profiles of oblique lateral interbody fusion and posterior lumbar interbody fusion in the treatment of lumbar brucellosis spondylitis.

OBJECTIVE: The aim of this study was to assess the clinical efficacy of oblique lateral interbody fusion (OLIF) and posterior lumbar interbody fusion (PLIF) for lumbar brucellosis spondylitis. PATIENTS AND METHODS: Between April 2018 and December 2021, 80 cases of lumbar brucellosis spondylitis admitted to our institution were evaluated for eligibility and randomly assigned to either PLIF (group A, lesion removal by posterior approach + interbody fusion + percutaneous pedicle screw internal fixation) or OLIF (group B, lesion removal by anterior approach + interbody fusion + percutaneous pedicle screw internal fixation). The outcome measures included operative time, intraoperative bleeding, hospital stay, preoperative and postoperative visual analogue scale (VAS) ratings, American Spinal Injury Association (ASIA) classification, Cobb angle, and interbody fusion time. RESULTS: PLIF resulted in shorter operative time and hospital stay and less intraoperative bleeding vs. OLIF (p<0.05). All eligible patients showed significantly lower VAS scores, and smaller ESR values and Cobb angles after treatment (p<0.05), but no significant intergroup differences were observed (p>0.05). The two groups showed similar preoperative ASIA (American Spinal Injury Association) classification and interbody fusion time (p>0.05). PLIF was associated with better ASIA classification at three months postoperatively vs. OLIF (p<0.05). CONCLUSIONS: Both surgical techniques are efficient at removing the lesion, relieving pain, maintaining spinal stability, promoting implant fusion, and facilitating prognostic inflammation control. PLIF features a shorter surgical duration and hospital stay, less intraoperative bleeding, and greater neurological improvement vs. OLIF. Nevertheless, OLIF outperforms PLIF in the excision of peri-vertebral abscesses. PLIF is indicated for posterior spinal column lesions, particularly those with spinal nerve compression in the spinal canal, whereas OLIF is indicated for structural bone deterioration in the anterior column, particularly for those with perivascular abscesses.

Comparison of long non-coding RNAs in adipose and muscle tissues between seven indigenous Chinese and the Yorkshire pig breeds.

lncRNAs play crucial roles in fat metabolism in animals. Previously, we have compared the mRNA transcriptome profiles between seven fat-type Chinese pig breeds and one lean-type Western breed (Yorkshire, YY). The associations between differentially expressed (DE) genes and phenotypical traits were investigated. In the present study, to further explore the underlying regulatory mechanisms, lncRNAs were sequenced and compared between YY and Chinese indigenous breeds. The results showed 9114 and 7538 DE lncRNAs between at least one Chinese breed and the YY breed in the adipose and muscle tissue respectively. KEGG enrichment analysis revealed that the target genes of these DE lncRNAs mainly influenced the glucolipid metabolism, which is an important process affecting meat quality. Correlation analyses between the DE lncRNA and DE mRNA genes related to meat quality and growth traits were performed. The results showed that LTCONS_00073280 was associated with intramuscular fat content. Four lncRNAs (LTCONS_00101781, LTCONS_00037879, LTCONS_00088260 and LTCONS-00128343) might mediate backfat thickness. Overall, this study provides candidate lncRNAs that potentially affect meat quality, which might be useful for molecular breeding of pig breeds in future.

Evaluation of two intensive care models in relation to successful extubation after cardiac surgery / Evaluación de 2 modelos de cuidados intensivos en cuanto a extubación exitosa de pacientes después de cirugía cardíaca

Objective: To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models. Design: This retrospective, historical-control study was performed in a cohort of adult cardiac surgical patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015-June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. Setting: Tertiary Zhongshan Hospital (Fudan University, China). Patients: Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery. Interventions: Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists. Main variables of interest: Successful extubation, ICU LOS and in-hospital mortality. Results: A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p=0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19h; p<0.001). In relation to patients with MV duration >48h, those in phase II had a comparatively higher successful extubation rate (p=0.033), shorter ICU LOS (p=0.038) and a significant decrease in in-hospital mortality (p=0.039). Conclusions: The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery

Objetivo: Comparar el manejo entre intensivistas y cirujanos de pacientes de cirugía cardíaca en la unidad de cuidados intensivos. Diseño: Este estudio de control retrospectivo se llevó a cabo con una cohorte de pacientes adultos de cirugía cardíaca. Durante la primera fase (de marzo a agosto de 2015), los cirujanos cardíacos estuvieron a cargo del manejo médico en la unidad; y durante la segunda fase (septiembre de 2015 a junio de 2016), lo hicieron intensivistas. Comparamos las fases en cuanto al número de extubaciones exitosas, el tiempo de estancia y la mortalidad. Lugar del estudio: Hospital Zhongshan de la Universidad de Fudan, China. Pacientes: Adultos admitidos secuencialmente a la unidad de cuidados intensivos cardíacos después de intervenciones quirúrgicas. Intervenciones: Manejo médico por cirujanos en la primera fase, y por intensivistas en la segunda fase. Variables prioritarias: Extubación exitosa, tiempo de estancia en la unidad de cuidados intensivos y mortalidad. Resultados: Participaron 1.792 pacientes en la fase i y 3.007 en la fase ii. Los pacientes de la fase II tuvieron más extubaciones exitosas (99,17 frente al 98,55%, p=0,043), y necesitaron menos tiempo de ventilación mecánica (mediana de 18 frente a 19h, p<0,001). De entre los pacientes con ventilación mecánica de más de 48h, los de la fase iifueron extubados exitosamente más veces, tuvieron una estancia más corta (p=0,038), y una menor mortalidad (p=0,039). Conclusiones: El manejo médico por intensivistas aumentó significativamente el número de extubaciones exitosas y disminuyó el tiempo de ventilación mecánica

Evaluation of two intensive care models in relation to successful extubation after cardiac surgery.

OBJECTIVE: To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models. DESIGN: This retrospective, historical-control study was performed in a cohort of adult cardiac surgical patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015-June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. SETTING: Tertiary Zhongshan Hospital (Fudan University, China). PATIENTS: Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery. INTERVENTIONS: Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists. MAIN VARIABLES OF INTEREST: Successful extubation, ICU LOS and in-hospital mortality. RESULTS: A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p=0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19h; p<0.001). In relation to patients with MV duration >48h, those in phase II had a comparatively higher successful extubation rate (p=0.033), shorter ICU LOS (p=0.038) and a significant decrease in in-hospital mortality (p=0.039). CONCLUSIONS: The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery.

PTEN expression in U251 glioma cells enhances their sensitivity to ionizing radiation by suppressing DNA repair capacity.

OBJECTIVE: Mutations in phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor gene, lead to altered sensitivity to drugs and radiation in various types of cancer. Restoring PTEN expression in tumor cells can increase radiosensitivity by inhibiting the repair of DNA double-strand breaks (DSBs). Thus, determining the mechanism of action of this protein may lead to novel therapeutic strategies. MATERIALS AND METHODS: In this study, we transduced U251 cells with a lentiviral vector expressing PTEN to examine the mechanism of radiosensitization. Specifically, we examined the formation of radiation-induced DNA DSBs and apoptosis, as well as the expression of several proteins involved in repairing DSBs (p53, ataxia-telangiectasia mutated, DNA-dependent protein kinase C, Ku70-80). RESULTS: Our results showed that PTEN transduction sensitized U251 cells to X-rays, increasing the number of DSBs per cell and fraction of cells undergoing apoptosis. Additionally, the average size of γH2AX nuclear foci was increased following irradiation. These findings were accompanied by a PTEN-dependent irradiation-independent increase in p53 levels and decrease in phosphorylated Ku70/80 levels. CONCLUSIONS: Our results suggest that PTEN affects radiosensitivity by reducing DSB repair and by enhancing the p53 pathway, leading to increased apoptosis.

Integrin-linked kinase is overexpressed in laryngeal squamous cell carcinoma and correlates with tumor proliferation, migration and invasion.

OBJECTIVE: To investigate the role of integrin-linked kinase (ILK) in invasion and metastasis of the laryngeal squamous cell carcinomas (LSCC) and to evaluate the effects of antisense oligonucleotide sequence (ASONs) targeting the ILK gene on the proliferation, epithelial-mesenchymal transition (EMT), migration and invasion of LSCC. PATIENTS AND METHODS: 116 patients who had previously undergone complete resection of the tumor for LSCC were studied retrospectively. The ILK expression level in tumor tissues and adjacent normal tissues were determined by immunohistochemistry. The changes of ILK expression from each group were assessed and correlated to the clinical parameters of the patients. Secondly, ILK antisense oligonucleotide (ILK-ASONS) was used to silence the ILK gene of LSCC cell from Hep-2 cell line. The expression of ILK, epithelial marker E-cadherin and mesenchymal marker Vimentin were evaluated by Western blotting. The proliferation of cells after transfection was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The apoptosis was detected by flow cytometry. The migration and invasion activity of Hep-2 cells was detected by Matrigel invasion and cell migration assays. RESULTS: The expression of the ILK protein was significantly associated with tumor differentiation (p=0.046), lymph node metastasis (p=0.020) and pTNM stage (p=0.019). ILK ASONS-transfected cells showed a significant decrease in cell proliferation, cell migration and invasive activity compared to mock-transfected cells. ILK ASONS-transfected cells increased the expression of E-cadherin, whereas the expression of ILK and Vimentin decreased, compared with mock-transfected cells. CONCLUSIONS: The expression of ILK was significantly correlated with differentiation and metastasis of the laryngeal carcinomas. The inhibition of the ILK gene could downregulate the proliferation, migration and invasion of Hep-2 cells. These findings suggest that the ILK gene could be a potential target for the treatment of laryngeal cancer.

Low-level laser irradiation promotes the differentiation of bone marrow stromal cells into osteoblasts through the APN/Wnt/ß-catenin pathway.

OBJECTIVE: The relationship between adiponectin (APN) pathway and Wnt pathway was explored through BMSCs, and the effect of low-level laser irradiation (LLLI) on bone marrow stromal cells (BMSCs) and its mechanism were further studied. MATERIALS AND METHODS: 3-week-old Sprague-Dawley (SD) rats were selected, and mesenchymal stem cells were separately cultured and purified. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze cell proliferation. After osteogenic and adipogenic induction, cultures were conducted, respectively, cells were stained with alizarin red and oil red O. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of osteogenesis-related genes, runt-related transcription factor 2 (RUNX2), and osteocalcin (OC) and those of adipogenesis-related genes, peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (c/EBPα). Western blotting was used to detect the expressions of ß-catenin in the cytoplasm and nucleus. The lentiviral expression vector of adiponectin receptors (APN-R) was constructed, and the expression of APN receptor genes was silenced. The expressions of ß-catenin in APN receptors and the nucleus within cells were detected. RESULTS: LLLI promoted the bone formation by inducing the differentiation direction of mesenchymal stem cells, increasing the number of osteoblasts in the bone marrow and inhibiting the reduction of the number of adipocytes. LLLI regulates the Wnt pathway, promotes the entry of ß-catenin into the nucleus, activates the osteogenic effect of the Wnt pathway so as to promote the bone formation of osteoblasts and inhibit bone resorption of osteoclasts. LLLI promotes the entry of ß-catenin into the nucleus and the osteogenic differentiation of BMSCs through the APN pathway. CONCLUSIONS: In summary, LLLI can promote osteogenesis and inhibit adipocytes formation, thus attenuating bone resorption of osteoclasts. The mechanism of LLLI is that it promotes the entry of ß-catenin into the nucleus and regulates the Wnt pathway and the differentiation direction of mesenchymal stem cells through the APN signal pathway, thus promoting bone formation.

miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer.

Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.

Phenanthrene biodegradation by halophilic Martelella sp. AD-3.

AIMS: To investigate the phenanthrene-degrading abilities of the halophilic Martelella species AD-3 under different conditions and to propose a possible metabolic pathway. METHODS AND RESULTS: Using HPLC and GC-MS analyses, the phenanthrene-degrading properties of the halophilic strain AD-3 and its metabolites were analysed. This isolate efficiently degraded phenanthrene under multiple conditions characterized by different concentrations of phenanthrene (100-400 mg l(-1) ), a broad range of salinities (0·1-15%) and varying pHs (6·0-10·0). Phenanthrene (200 mg l(-1) ) was completely depleted under 3% salinity and a pH of 9·0 within 6 days. The potential toxicity of phenanthrene and its generated metabolites towards the bacterium Vibrio fischeri was significantly reduced 10 days after the bioassay. On the basis of the identified metabolites, enzyme activities and the utilization of probable intermediates, phenanthrene degradation by strain AD-3 was proposed in two distinct routes. In route I, metabolism of phenanthrene was initiated by the dioxygenation at C-3,4 via 1-hydroxy-2-naphthoic acid, 1-naphthol, salicylic acid and gentisic acid. In route II, phenanthrene was metabolized to 9-phenanthrol and 9,10-phenanthrenequinone. Further study indicated that strain AD-3 exhibited a wide spectrum of substrate utilization including other polycyclic aromatic hydrocarbons (PAHs). CONCLUSIONS: The results suggest that strain AD-3 possesses a high phenanthrene biodegradability and that the degradation occurs via two routes that remarkably reduce toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this work presents the first report of phenanthrene degradation by a halophilic PAH-degrading strain via two routes. In the future, the use of halophilic strain AD-3 provides a potential application for efficient PAH-contaminated hypersaline field remediation.

Development and characterization of nine polymorphic microsatellites for the small brown planthopper Laodelphax striatellus (Hemiptera: Delphacidae).

Nine microsatellite loci were isolated from the genome of Laodelphax striatellus (Homoptera: Delphacidae) by constructing (TC)(6)(AC)(5) and (AG)(6)(AC)(5) compound SSR-enriched libraries using suppression-PCR procedures. These loci were found to be highly polymorphic, with 13 to 30 alleles per locus in the three populations that we investigated (Jiangsu, Shandong and Zhejiang). The observed and expected heterozygosities ranged from 0.255 to 0.833 and 0.392 to 0.929, respectively. These microsatellite markers can be used for the study of population genetic structure and genetic diversity of L. striatellus.

The effect of candesartan on the pharmacokinetics of enalaprilat in nephrotic rats.

BACKGROUND AND OBJECTIVES: The adverse reactions in combination of angiotensin-converting enzyme inhibitors (ACEIs) and Ang II receptor blockers (ARBs) were severer than that in monotherapy for patients with nephropathy. The effect of candesartan on pharmacokinetics of enalaprilat in nephrotic rats was investigated to make references for the clinical therapy in patients with nephropathy to avoid related adverse effects. MATERIALS AND METHODS: Nephrotic rats were prepared by adriamycin injection. Control group and one nephrotic group received enalapril alone, another nephrotic group received enalapril and candesartan simultaneously. Blood samples were drawn at time points after a single oral administration. The concentration of enalaprilat was determined using LC-MS/MS. RESULTS: Compared with control group and nephrotic group received enalapril alone respectively, Tmax of enalaprilat in nephrotic group received both enalapril and candesartan cilexetil prolonged about 21.43% and 6.224%, respectively; AUC(0-t) increased by 185.3% and 60.63%, respectively; Cmax increased by 219.4% and 56.64%, respectively; t1/2 increased by 163.7% and 30.05%, respectively; CL/F reduced by 65.12% and 40.78%, respectively. There were no significant differences of the V1/F of enalaprilat between three groups. The CL/F and t1/2 of enalaprilat showed significant correlations with serum creatinine (Scr) respectively (r = -0.7502; r = 0.5626). DISCUSSION: The combination with candesartan in nephrotic rats significantly changed the pharmacokinetics of enalaprilat, showing increased accumulation and decreased elimination. In view of these findings, we should lower dosage and prolong dosing interval for nephrotic patients in the combination of enalapril and candesartan.

Prognostic role of epidermal growth factor-like domain 7 protein expression in laryngeal squamous cell carcinoma.

OBJECTIVE: This study aimed to retrospectively analyse the expression of epidermal growth factor-like domain 7 protein in cases of laryngeal squamous cell carcinoma. METHODS: We studied 116 patients retrospectively. Expression of epidermal growth factor-like domain 7 protein was determined in tumour and nontumour tissue samples, by immunohistochemistry. RESULTS: Expression levels were significantly increased in 94 cases. Increased expression levels correlated well with tumour stage (p = 0.001) and lymph node metastasis (p = 0.002). Log-rank survival testing showed a significant difference between patients with marked versus limited expression levels (p = 0.03). Multivariable Cox regression analysis showed that epidermal growth factor-like domain 7 protein expression level was an independent predictor of laryngeal squamous cell carcinoma prognosis. CONCLUSION: These findings provide evidence that increased epidermal growth factor-like domain 7 protein expression is associated with laryngeal squamous cell carcinoma stage, lymph node metastasis and poor survival. This suggests that this protein may be a potential marker for laryngeal squamous cell carcinoma.

Prospective study of sensorineural hearing loss following radiotherapy for nasopharyngeal carcinoma.

OBJECTIVES: To investigate the severity and incidence of sensorineural hearing loss in patients with nasopharyngeal carcinoma treated with radiotherapy. METHODS: Forty-two patients with nasopharyngeal carcinoma were treated with conventional radiotherapy. Audiological testing was performed to compare patients' hearing before and at varying stages after radiotherapy. RESULTS: At one month post-radiation, a significant hearing threshold increase was seen only for high frequencies. At 12, 24 and 60 months post-radiation, significant threshold increases were observed at speech frequencies (4.0 and 8.0 kHz), compared with pre-radiation data. The mean values of wave I, III and V latencies and of the I-V interpeak latency intervals were not significantly altered at one month post-radiation, but were significantly prolonged at 12, 24 and 60 months post-radiation, compared with pre-radiation data. CONCLUSION: In patients with nasopharyngeal carcinoma treated with radiotherapy, the severity and incidence of radiation-induced sensorineural hearing loss increased with time, especially at high frequencies. This hearing impairment may be due to changes in the cochlea and/or the retrocochlear auditory pathway.

Inhibitory efficacy of hypoxia-inducible factor 1alpha short hairpin RNA plasmid DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal neovascularization in a laser-induced rat model.

The aim of this study was to evaluate the possibility of poly (D, L-lactide-co-glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA) and to investigate its inhibitory efficacy on experimental choroidal neovascularization (CNV). We developed intravitreal administered, hypoxia-inducible factor 1alpha (HIF-1alpha) short hairpin RNA and green fluorescent protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1alpha NPs). CNV was induced by laser photocoagulation in 112 rats. The rats were then randomly assigned to be injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked pDNA, control pDNA NPs and pshHIF-1alpha NPs, respectively, and non-injection group was set as the control. Immunofluorescence staining, fluorescein fundus angiography and histologic analysis were performed to evaluate the inhibitory efficacy on CNV. The results showed that the expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks. The fluorescein leakage areas of CNV were significantly larger in the PBS, blank NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF-1alpha NPs group (P<0.01). The mean thickness of the CNV lesions in the intravitreally pshHIF-1alpha NPs-treated group was significantly smaller than other groups (P<0.01). No signs of functional or ultrastructural destruction in retina were detected. Therefore, pshHIF-1alpha NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV.

Cell growth suppression by thanatos-associated protein 11(THAP11) is mediated by transcriptional downregulation of c-Myc.

Thanatos-associated proteins (THAPs) are zinc-dependent, sequence-specific DNA-binding factors involved in cell proliferation, apoptosis, cell cycle, chromatin modification and transcriptional regulation. THAP11 is the most recently described member of this human protein family. In this study, we show that THAP11 is ubiquitously expressed in normal tissues and frequently downregulated in several human tumor tissues. Overexpression of THAP11 markedly inhibits growth of a number of different cells, including cancer cells and non-transformed cells. Silencing of THAP11 by RNA interference in HepG2 cells results in loss of cell growth repression. These results suggest that human THAP11 may be an endogenous physiologic regulator of cell proliferation. We also provide evidence that the function of THAP11 is mediated by its ability to repress transcription of c-Myc. Promoter reporter assays indicate a DNA binding-dependent c-Myc transcriptional repression. Chromatin immunoprecipitations and EMSA assay suggest that THAP11 directly binds to the c-Myc promoter. The findings that expression of c-Myc rescues significantly cells from THAP11-mediated cell growth suppression and that THAP11 expression only slightly inhibits c-Myc null fibroblasts cells growth reveal that THAP11 inhibits cell growth through downregulation of c-Myc expression. Taken together, these suggest that THAP11 functions as a cell growth suppressor by negatively regulating the expression of c-Myc.

Retraction of articles by H. Zhong et al.

A series of 41 papers by H. Zhong et al. are retracted.

Overexpression of HAb18G/CD147 promotes invasion and metastasis via alpha3beta1 integrin mediated FAK-paxillin and FAK-PI3K-Ca2+ pathways.

Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present study, we found that integrin alpha3beta1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147 on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin alpha3beta1 antibodies (p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin, and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147 reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca(2+) mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma cells via integrin alpha3beta1-mediated FAK-paxillin and FAKPI3K-Ca(2+) signal pathways.

High efficiency reconstitution of a human-mouse chimeric Fab of CAb-1 antibody specific to human colon cancer.

Monoclonal antibody (mAb) has been widely applied in the treatment of human diseases, especially in malignant tumours. However, most antibodies produced in mouse by hybridoma technology might induce severe human anti-mouse reactions. We had reported a murine mAb CAb-1 of therapeutic interest for its specifically binding to a cell surface glycoprotein of human colon cancer. Here, we attempted to generate a reconstituted human-mouse chimeric Fab (cFab) of CAb-1 in vitro to reduce its antigenicity and increase its capacity of penetration. First, the genes of heavy and light chain variable region (VH, VL) of CAb-1 were cloned. Then, the chimeric light chain (cL) and Fd (cFd) were constructed and expressed in Escherichia coli. Finally, the reconstituted cFab was obtained by gradient dialysis of the mixture of cFd and cL. SDS-PAGE and western blot analysis showed the reconstituted cFab with a recovery rate of 70.2% when the initial total concentration of cL and cFd proteins to be 100 microg/ml. The reconstituted cFab maintained the affinity and specificity to colon cancer cells compared with its parental antibody as determined by immunostaining analysis, FACS and ELISA. Our results established a foundation for further application of the cFab in diagnosis and treatment of colon cancer.

catena-Poly[[(1,10-phenanthroline-κN,N')praseodymium(III)]-di-µ-phenoxy-acetato-κO:O'-[(1,10-phenanthroline-κN,N')praseodymium(III)]-di-µ-phenoxy-acetato-κO:O'-di-µ-phenoxy-acetato-κO,O':O;κO:O,O'].

The title complex, [Pr(2)(C(8)H(7)O(3))(6)(C(12)H(8)N(2))(2)](n), which has an inversion centre midway between the two Pr(III) atoms of the structural unit, forms a one-dimensional polymer bridged alternately by either two bidentate, or two bidentate and two terdentate, phenoxy-acetate carboxyl-ate groups. Each Pr(III) atom is thus nine-coordinated by two N atoms of a 1,10-phenanthroline ligand and seven O atoms from six phenoxy-acetate ligands. The coordination geometry at the Pr(III) atom is distorted tricapped trigonal prismatic. One phenyl ring is disordered over two positions; the site occupancy factors are ca 0.6 and 0.4.