[Inhibitory effect of Streptococcus mutans antisense vicK RNA regulating the cariogenicity of oral streptococci multi-species biofilm].

Objective: To investigate the regulative effects of Streptococcus mutans (Sm) antisense vicK RNA (ASvicK) on the multi-species biofilm formed by three common oral streptococci (Sm, Streptococcus sanguinis, and Streptococcus gordonii) (Sm+Ss+Sg). Methods: ASvicK over-expression strain was constructed by using a recombinant plasmid, and three-species biofilm UA159+Ss+Sg and ASvicK+Ss+Sg were cultured. The phenotypes of biofilms were detected by scanning electron microscopy (SEM). Crystal violet (CV) assay was used to detect biofilm biomass. Lactate kit and anthrone-sulfuric acid colorimetric assay were used to determine the abilities of lactic acid and exopolysaccharides production, respectively. The proportions of three-species and expression levels of the cariogenic-related genes in biofilms were detected by TaqMan fluorescence quantitative PCR and real-time fluorescence quantitative PCR. A biofilm demineralization model of human enamel slabs was further constructed, and the hardness of enamel surface was detected. Results: Compared to UA159+Ss+Sg, over-expression of ASvicK could inhibit biofilm formation and lactic acid production in ASvicK+Ss+Sg biofilm significantly decreased by 78.93% (P<0.001) and 62.23% (P<0.001), respectively. With ASvicK over-expression, the amounts of water-insoluble and-soluble glucoses in ASvicK+Ss+Sg biofilm were reduced respectively by 39.13% (P<0.001) and 68.00% (P<0.001). Compared to the UA159+Ss+Sg Group, the proportion of Sm, the cariogenic bacteria, showed 33.00% reduction (P<0.01) in Sm+Ss+Sg biofilm, and the gene expressions of cariogenic-relative genes vicK/X, gtfB/C/D, and ftf significantly decreased (P<0.05). The micro-hardness value of enamel slabs after demineralization by ASvicK+Ss+Sg biofilm was significantly increased to 183.84% (P<0.001). Conclusions: ASvicK over-expression could reduce the Sm proportion and weaken the cariogenicity of oral Streptococcus biofilm, thereby possibly slowing down the progression of caries.

[Standardized nomenclature of oral microorganisms in Chinese: the 2023 update].

Oral microbial community, as an important part of human microbial community, is closely related to oral and general health. Oral microbiological research has become the forefront of international microbiological research. Standardized and unified nomenclature for oral microorganisms in Chinese is of great significance to support the development of oral medicine research. Standardized translation of microbial names is the basis for writing canonical and authoritative professional textbooks and reference books, which helps students to accurately acquire the characteristics and classifications of oral microbes. Unified translation of oral microorganisms is also conducive to academic communication and cooperation, and plays an important role in oral health education and science popularization, which enables oral microbiology knowledge to be accurately disseminated to the public. Therefore, in order to standardize the words in scientific research, funding application, publications, academic exchanges and science popularization within the field of oral medicine, we have fully discussed and revised the Chinese names of oral microorganisms in 2017 edition and ones of newly discovered oral microbes, finally reaching a consensus to form the 2023 edition of Chinese names of oral microorganisms.

Trichinella spiralis: RNAi-mediated silencing of serine protease results in reduction of intrusion, development and fecundity.

In previous studies, a Trichinella spiralis serine protease (TsSP) was identified in excretion/secretion (ES) products from intestinal infective L1 larvae (IIL1) using immunoproteomics. The complete cDNA sequence of TsSP gene was 1372 bp, which encoded 429 amino acids with 47.55 kDa. The TsSP was transcribed and expressed at all T. spiralis life cycle phases, as well as mainly located at the cuticle and stichosome of the parasitic nematode. Recombinant TsSP bind to intestinal epithelial cells (IEC) and promoted larva invasion, however, its exact function in invasion, development and reproduction are still unknown. The aim of this study was to confirm the biological function of TsSP during T. spiralis invasion and growth using RNA interference (RNAi) technology. The results showed that on 1 day after electroporation using 2.5 µM siRNA156, TsSP mRNA and protein expression of muscle larvae (ML) was suppressed by 48.35 and 59.98%, respectively. Meanwhile, silencing of TsSP gene by RNAi resulted in a 61.38% decrease of serine protease activity of ML ES proteins, and a significant reduction of the in vitro and in vivo invasive capacity of IIL1 to intrude into the IEC monolayer and intestinal mucosa. When mice were infected with siRNA 156-transfected larvae, adult worm and muscle larva burdens were decreased by 58.85 and 60.48%, respectively. Moreover, intestinal worm growth and female fecundity were evidently inhibited after TsSP gene was knockdown, it was demonstrated that intestinal adults became smaller and the in vitro newborn larval yield of females obviously declined compared with the control siRNA group. The results indicated that knockdown of TsSP gene by RNAi significantly reduced the TsSP expression and enzymatic activity, impaired larvae intrusion and growth, and lowered the female reproductive capacity, further verified that TsSP might participate in diverse processes of T. spiralis life cycle, it will be a new prospective candidate molecular target of anti-Trichinella vaccines.

Functional analysis of Trichinella spiralis serine protease 1.2 by siRNA mediated RNA interference.

A T. spiralis serine protease 1.2 (TsSP1.2) was identified in the muscle larvae (ML) and intestinal larvae surface/excretory-secretory (ES) proteins by immunoproteomics. The aim of this study was to determine the TsSP1.2 function in the process of T. spiralis intrusion, growth and reproduction by using RNA interference (RNAi). RNAi was used to silence the expression of TsSP1.2 mRNA and protein in the nematode. On 2 days after the ML were electroporated with 2 µM of TsSP1.2-specific siRNA 534, TsSP1.2 mRNA and protein expression declined in 56.44 and 84.48%, respectively, compared with untreated ML. Although TsSP1.2 silencing did not impair worm viability, larval intrusion of intestinal epithelium cells (IEC) was suppressed by 57.18% (P < 0.01) and the suppression was siRNA-dose dependent (r = 0.976). Infection of mice with siRNA 534 transfected ML produced a 57.16% reduction of enteral adult burden and 71.46% reduction of muscle larva burden (P < 0.05). Moreover, silencing of TsSP1.2 gene in ML resulted in worm development impediment and reduction of female fertility. The results showed that silencing of TsSP1.2 by RNAi inhibited larval intrusion and development, and reduced female fecundity. TsSP1.2 plays a crucial role for worm invasion and development in T. spiralis life cycle, and is a potential vaccine/drug target against Trichinella infection.

[Dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of dedifferentiated liposarcoma (DDLPS) with inflammatory myofibroblastic tumor (IMT)-like features. Methods: Five cases of DDLPS with IMT-like features were collected from the First Affiliated Hospital of Nanjing Medical University, the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and the First People's Hospital of Qinzhou between 2013 and 2018. EnVision method and fluorescence in situ hybridization (FISH) were used to detect the immunophenotype of the tumor cells and the profile of MDM2 gene amplification respectively. Results: All five cases were male and the median age was 61 (range 53 to 65) years. The clinical symptoms were mainly related to the space-occupying lesions. The tumors were located in duodenal mesentery (two cases), intestinal wall (one case), retroperitoneum (one case), and spermatic cord (one case). Grossly, the tumors were not well encapsulated, ranging from 3 to 13 cm (median 6.7 cm) in diameter, with tan to gray and firm cut surface. Histologically, the dedifferentiated component closely resembled inflammatory myofibroblastic tumor (IMT), with spindle/polygonal/stellate-shaped cells arranged in storiform, sheet-like, or random pattern, with varying degrees of chronic inflammation and fibrosis. All three major patterns seen in IMT (myxoid, cellular and hypocellular fibrous) were observed, the hypocellular fibrous pattern was the most common. Well-differentiated liposarcomatous component was found in the peripheral areas of all the tumors. One case had high grade dedifferentiated component. Four cases were strongly positive for MDM2 and p16. Two cases were positive for SMA, and one case was focally positive for desmin and one for CD34. None of the cases stained for ALK-1. FISH demonstrated MDM2 gene amplification in all five cases. Clinical follow-ups were available in all five cases and the interval ranged from 3 to 66 months (median 23 months). Two patients developed recurrences and one patient had metastasis. The remaining two patients were alive with no evidence of tumor recurrence at 3 and 14 months after surgery respectively. Conclusions: DDLPS with IMT-like features is a more aggressive neoplasm than its histological mimic (IMT), and should not be misdiagnosed as other intermediate or low-grade malignant tumors, such as IMT, sclerosing liposarcoma, inflammatory liposarcoma, aggressive fibromatosis, solitary fibrous tumors, low-grade myofibroblastic sarcoma, and low-grade fibrosarcoma.

Effects of Astragalus glycoprotein on Th17/Treg cells in mice with collagen-induced arthritis.

In this study of Th17/Treg cells, the therapeutic effect of Astragalus glycoprotein on collagen-induced arthritis in mice (CIA) was explored, and a basis for the clinical treatment of rheumatoid arthritis is provided. Sixty mice were selected for the establishment of a CIA mouse model, and were then randomly divided into a CIA model group, a hydrocortisone control group, a low, medium, and high dose group of Astragalus glycoprotein, respectively. The same number of control groups with same number of mice was established and after basic immunization, intraperitoneal injections were given once daily for two weeks in the treatment. At the end of the treatment, the mice in each group were selected and the proportion of Th17/Treg cells was detected by flow cytometry. The expression and positive expression of RORt, Foxp3, P-STAT3 and P-STAT5 protein were detected by Western blot and immunohistochemistry. Astragalus glycoprotein was shown to potentially improve the diet and mental state, reduce the arthritis index score and improve the pathological state of synovial membranes in the mice. Moreover, flow cytometry results showed that, compared with the CIA model group, the proportion of Th17 cells in the four other groups of mice decreased, while the proportion of Treg cells increased. This difference was statistically significant (P less than 0.05). From the experiment, the following conclusions were drawn: Astragalus glycoprotein can reduce Th17 cells and their transcription factors in the peripheral blood of CIA mice, up-regulate Treg cells and their transcription factors, and correct the balance of Th17/Treg cells so as to achieve an effective of treatment for CIA mice.

Metagenomic analysis of oral microbiome in young children aged 6-8 years living in a rural isolated Chinese province.

BACKGROUND: The mixed dentition is an important transition period from primary teeth to permanent teeth. However, the caries prevalence of first permanent molar in mixed dentitions was about 30%, which almost represent the caries rate of permanent teeth in this period of time. Therefore, we assessed the oral bacterial profiles in young children (age 6-8) with mixed dentition with or without first molar caries for providing the research basis of caries etiology. METHODS: We collected samples of supragingival plaque and saliva from the children living in Guizhou, a rural isolated province in China. Then, we performed DNA extraction and purification followed by 454 pyrosequencing of the V1-V3 hypervariable regions of the 16S rRNA and compared our results with those of previous research. RESULTS: (i) We analyzed 48,320 unique sequences that represented 18 phyla, 29 classes, 44 orders, 74 families, 129 genera, 15,003 species-level OUT in plaque and saliva samples; (ii) longitudinally, there was the "healthy core microbiome" between healthy deciduous dentition and early mixed dentition, for example, Neisseria, Porphyromonas, Selenomonas etc.; (iii) horizontally, there also existed the "healthy core microbiome" in early mixed dentition, for example, Neisseria, Streptococcus, Prevotella etc.; (iv) the dominant bacteria detected by Lefse in caries group including Actinomycetaceae, Streptobacillus (p < 0.05) and those in caries-free group including Gammaproteobacteria, Pasteurellaceae, Aggregatibacter, Chloroflexi, (p < 0.05). CONCLUSIONS: The oral cavity is a highly heterogeneous ecosystem with the "healthy core microbiome" in children, although microbial composition shifts along with aging. In addition, the abundance and diversity of microbiota vary between caries and caries-free groups verify the ecological plaque hypothesis.

Low miR-34c expression is associated with poor outcome in de novo acute myeloid leukemia.

INTRODUCTION: MicroRNA-34c (miR-34c) has been found to play important roles in tumorigenesis. However, little is known about miR-34c expression and the impact on prognosis in acute myeloid leukemia (AML). METHODS: Real-time quantitative PCR (qRT-PCR) was performed to analyze the status of miR-34c expression in 122 patients with de novo AML and 62 normal controls. RESULTS: MiR-34c expression in AML was significantly downregulated compared to controls (P < 0.001). Receiver operating characteristic curves (ROC) indicated the distinguishing value of miR-34c for discriminating whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML) patients from healthy controls. No significant differences were found between low miR-34c-expressing and high miR-34c-expressing patients in age, sex, hemoglobin, platelet count, percentage of blasts in bone marrow (BM), WHO classifications, karyotypes, and eight gene mutations, but low miR-34c cases had higher white blood cells (WBC) than high miR-34c cases (P = 0.035). MiR-34c low-expressed patients had similar rates of complete remission (CR) as miR-34c high-expressed patients in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.347, 0.314 and 0.167, respectively). Kaplan-Meier analysis indicated that patients with low miR-34c level had markedly shorter overall survival (OS) time in whole-cohort AML, non-M3 AML, and CN-AML patients (P = 0.033, 0.024 and 0.001, respectively). Furthermore, multivariate analysis confirmed that low miR-34c expression was an independent risk factor not only in whole-cohort AML (P = 0.040) but also in non-M3 AML (P = 0.015) and CN-AML patients (P = 0.021). CONCLUSIONS: Our findings indicate that low miR-34c level is a novel promising biomarker in predicting prognosis in patients with de novo AML.

[Cloning and expression analysis of two pro-inflammatory cytokines, IL-1ß and its receptor, IL-1R2, in the Asian swamp eel Monopterus albus].

Interleukin-1ß (IL-1ß) is the prototypic pro-inflammatory cytokine, whose functions are mediated through interaction with its receptors (IL-1R1 and IL-1R2). Herein, we cloned the full-length cDNA and genomic DNA of IL-1ß and IL-1R2 in the Asian swamp eel (Monopterus albus). The eel IL-1ß cDNA encodes a putative polypeptide of 246 amino acids. The protein sequence includes a typical IL-1 family signature, but lacked an interleukin-converting enzyme cleavage site. The genomic DNA of eel IL-1ß was 2520 bp and comprised five exons and four introns. The eel IL-1R2 cDNA encoded a putative propeptide of 423 amino acid residues, comprising a signal peptide, a transmembrane region and two Ig-like domains in the extracellular region. Similar to other vertebrates, the genomic DNA of the eel IL-1R2 has nine exons and eight introns. Real-time PCR analysis indicated that IL-1ß and IL-1R2 were constitutively expressed in all tissues, especially in the liver and immune-related organs. After infection with Aeromonas hydrophila, the transcript levels of IL-1ß and IL-1R2 were induced in the head kidney and spleen, reaching their highest levels at 6 h post injection. In vitro, IL-1ß and IL-1R2 mRNA levels were also upregulated rapidly at 1h post infection with A. hydrophila. Furthermore, acanthocephalan Pallisentis (Neosentis) celatus could induce the expression of both genes in the head kidney and intestine. In infected intestines, the transcript levels of IL-1ß and IL-1R2 were increased by 21.4-fold and 20.8-fold, respectively, relative to the control. The present study indicated that IL-1ß and IL-1R2 play an important role in inflammation and host defense, especially in the antiacanthocephalan response.

Effect of multilayer structure, stacking order and external electric field on the electrical properties of few-layer boron-phosphide.

Development of nanoelectronics requires two-dimensional (2D) systems with both direct-bandgap and tunable electronic properties as they act in response to the external electric field (E-field). Here, we present a detailed theoretical investigation to predict the effect of atomic structure, stacking order and external electric field on the electrical properties of few-layer boron-phosphide (BP). We demonstrate that the splitting of bands and bandgap of BP depends on the number of layers and the stacking order. The values for the bandgap show a monotonically decreasing relationship with increasing layer number. We also show that AB-stacking BP has a direct-bandgap, while ABA-stacking BP has an indirect-bandgap when the number of layers n > 2. In addition, for a bilayer and a trilayer, the bandgap increases (decreases) as the electric field increases along the positive direction of the external electric field (E-field) (negative direction). In the case of four-layer BP, the bandgap exhibits a nonlinearly decreasing behavior as the increase in the electric field is independent of the electric field direction. The tunable mechanism of the bandgap can be attributed to a giant Stark effect. Interestingly, the investigation also shows that a semiconductor-to-metal transition may occur for the four-layer case or more layers beyond the critical electric field. Our findings may inspire more efforts in fabricating new nanoelectronics devices based on few-layer BP.

[Comparative study of total hip arthroplasty with subtrochanteric osteotomy for treating Hartofilakidis types C1 and C2 developmental dysplasia of the hip].

OBJECTIVE: To compare efficacies and complications of total hip arthroplasty (THA) with subtrochanteric osteotomy for treating patients with Hartofilakidis types C1 and C2 developmental dysplasia of the hip (DDH). METHODS: Retrospective analysis was performed in 32 patients with DDH who underwent THA. These patients were divided into two groups according to Hartofilakidis classification, 17 patients in type C1 and 15 in type C2. Their HSS and WOMAC scores, leg length discrepancy (LLD), hip joint image data and complications were evaluated. RESULTS: HSS scores in type C1 was changed from preoperative 43.7±4.6 to postoperative 87.2±7.1 (P<0.001), together with WOMAC scores 43.6±4.3 to 87.5±6.7 (P<0.001). HSS scores in type C2 was changed from preoperative 44.4±5.4 to postoperative 86.5±8.0 (P<0.001), together with WOMAC scores 44.1±4.1 to 86.7±8.1 (P<0.001). Four cases in type C2 and one case in type C1 presented intraoperative fracture which all healed during the postoperative follow-up. The postoperative X-ray films showed that the joint prosthesis location was satisfactory, the surrounding bone was not dissolved and the bone at femur osteotomy site healed with no infection. CONCLUSION: For unilateral high dislocation DDH patients, THA with femur osteotomy can be effective and safe. No significant differences were found between types C1 and C2, however intraoperative fracture in type C2 should be paid attention to.

Effect of Tanshinone IIA intrathecal injections on pain and spinal inflammation in mice with bone tumors.

The study aimed to investigate the effect of intrathecal injections of Tanshinone IIA on thermal hyperalgesia in a mouse model of bone cancer-pain. Spinal IL-1ß, IL-6, TNF-α expression levels were analyzed. C3H/HeNCrlVr male mice were assigned to groups that either received dose-dependent injections of Tanshinone IIA, or the DMSO + Sham, Tanshinone IIA + Sham, DMSO + Tumor, and Control groups. Paw withdrawal thermal latency (PWTL) was measured with a radiant heat stimulus and mRNA expression levels were determined using real-time PCR. Fourteen days post-injection, PWTL in the DMSO + Tumor group was lower than that in the controls (P < 0.05). Twenty-one days post-injection, compared with the Control group, there was no significant difference in PWTL and IL-1ß, IL-6, and TNF-α expression levels between the Tanshinone IIA + Sham and DMSO + Sham groups (P > 0.05). PWTL in the DMSO + Tumor group was significantly lower than the Control group (P < 0.05), while the expression levels of IL-1ß, IL-6, and TNF-α were significantly higher than controls. Compared with the DMSO + Tumor group, PWTLs were higher in the Tanshinone IIA - 20-µg and 40-µg groups, while expression levels of IL-1ß, IL-6, and TNF-α were significantly lower (P < 0.05). These measures were not significantly different between the Tanshinone IIA 10 µg and the DMSO + Tumor groups (P > 0.05). In conclusion, Tanshinone IIA may inhibit the release of inflammatory cytokines, such as, IL-1 ß, IL-6 α, TNF-α.

Effect of calcitonin on anastrozole-induced bone pain during aromatase inhibitor therapy for breast cancer.

This study aimed to investigate calcitonin as an effective therapy for osteoporosis in patients with bone pain during the anastrozole treatment of breast cancer. Ninety-one patients, who were on anastrozole treatment for breast cancer and also suffered anastrozole-induced bone pain, were randomly divided into two groups: the calcitonin group received salmon calcitonin and Caltrate D, and the control group received Caltrate D. All patients were evaluated by the visual analogue scale (VAS) and underwent the dual energy x-ray absorptiometry test for bone mineral density (BMD), and serum osteocalcin (BGP), alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were measured at three months before and after the treatment. Significant differences in serum Ca, P, BGP, and ALP were found in each group between before and after treatment (P < 0.05), while no differences between the calcitonin and control groups were found. No difference was observed in femur BMD between the two groups, or between before and after treatment in each group. There was a significant difference in spine BMD between before and after treatment in the control group (P < 0.05) but not in the calcitonin group, while no difference was found between the calcitonin and control groups. Futhermore, VAS score significantly declined in each group after treatment (P < 0.05), but much more in the calcitonin group than the control group (P < 0.05). Our finding suggests that calcitonin may alleviate bone pain during the anastrozole treatment of breast cancer but has no effect on bone loss during cancer treatment.

Microbial diversity in the oral cavity of healthy Chinese Han children.

OBJECTIVE: This study aimed to identify the oral microbial diversity of healthy Chinese Han children. METHODS: Dental plaques were sampled from the oral cavity of ten healthy Chinese Han children. The oral microbiome was examined using the 16S rRNA-based Human Oral Microbe Identification Microarray. The microbial diversity and similarity were analyzed using the Chao-Jaccard similarity index. RESULTS: A total of 112 species, which belonged to nine bacterial phyla and 41 genera, were detected. Each individual harbored an average of 54.1 microbial species (ranging from 37 to 69) and 26.2 genera (ranging from 21 to 31), with interindividual variations both at the species and genus level. Thirteen genera were conserved among all individuals. The Chao-Jaccard similarity index averages, at the genus and species level, were 0.642 (ranging from 0.485 to 0.871) and 0.506 (ranging from 0.338 to 0.676), respectively, suggesting that the healthy oral community was more conserved at the genus level than at the species level. CONCLUSION: Although there was interindividual variation in the oral microflora, some bacterial genera were conserved among individuals, supporting the existence of a core microbiome in the oral cavity of healthy Chinese Han children.

Microbial profiles in saliva from children with and without caries in mixed dentition.

OBJECTIVE: The purpose of this study was to determine the bacterial profiles in saliva of the isolated children for studying caries etiology. MATERIALS AND METHODS: Samples were collected from isolated children from 6 to 8years old including 20 caries-free (dmfs=0) (healthy) and 30 caries-active individuals (dmfs>8) (patients). 16S rRNA genes were amplified by PCR from bacterial DNA of saliva sample and labeled via incorporation of Cy3-dCTP in second nested PCR. After hybridization of labeled amplicons on HOMIM, the microarray slides were scanned and original data acquired from professional software. RESULTS: Collectively, 94 bacterial species or clusters representing six bacterial phyla and 30 genera were detected. A higher bacterial diversity was observed in patients than in healthy samples. Statistical analyses revealed eight species or clusters were detected more frequently in diseased patients than in healthy samples, while six different species were detected more frequently in healthy as compared to diseased patients. CONCLUSION: The diversity of microbe within saliva derived from isolated population increased in caries-active status, and there are some bacteria in salivary flora can be as candidate biomarkers for caries prognosis in mixed dentition. The imbalances in the resident microflora may be the ultimate mechanism of dental caries.

An innovative approach to synthesize highly-ordered TiO2 nanotubes.

An innovative route to prepare highly-ordered and dimensionally controlled TiO2 nanotubes has been proposed using a mild sonication method. The nanotube arrays were prepared by the anodization of titanium in an electrolyte containing 3% NH4F and 5% H2O in glycerol. It is demonstrated that the TiO2 nanostructures has two layers: the top layer is TiO2 nanowire and underneath is well-ordered TiO2 nanotubes. The top layer can easily fall off and form nanowires bundles by implementing a mild sonication after a short annealing time. We found that the dimensions of the TiO2 nanotubes were only dependent on the anodizing condition. The proposed technique may be extended to fabricate reproducible well-ordered TiO2 nanotubes with large area on other metals.

Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated oncolytic adenovirus armed with TRAIL gene.

Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated Ad·AFP·E1A·E1B (Δ55) (Ad·AFP·D55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/α-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. Ad·AFP·D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into Ad·AFP·D55. Ad·AFP·D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad·AFP·D55-TRAIL can induce both autophagy owing to the Ad·AFP·D55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, Ad·AFP·D55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis.

Study of a hydrogen-bombardment process for molecular cross-linking within thin films.

A low-energy hydrogen bombardment method, without using any chemical additives, has been designed for fine tuning both physical and chemical properties of molecular thin films through selectively cleaving C-H bonds and keeping other bonds intact. In the hydrogen bombardment process, carbon radicals are generated during collisions between C-H bonds and hydrogen molecules carrying ∼10 eV kinetic energy. These carbon radicals induce cross-linking of neighboring molecular chains. In this work, we focus on the effect of hydrogen bombardment on dotriacontane (C(32)H(66)) thin films as growing on native SiO(2) surfaces. After the hydrogen bombardment, XPS results indirectly explain that cross-linking has occurred among C(32)H(66) molecules, where the major chemical elements have been preserved even though the bombarded thin film is washed by organic solution such as hexane. AFM results show the height of the perpendicular phase in the thin film decreases due to the bombardment. Intriguingly, Young's modulus of the bombarded thin films can be increased up to ∼6.5 GPa, about five times of elasticity of the virgin films. The surface roughness of the thin films can be kept as smooth as the virgin film surface after thorough bombardment. Therefore, the hydrogen bombardment method shows a great potential in the modification of morphological, mechanical, and tribological properties of organic thin films for a broad range of applications, especially in an aggressive environment.

LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in prostate tumor cells.

LYRIC/AEG-1 is a unique protein that has been shown to promote tumor cell migration and invasion through activation of the transcription factor NF-kappaB. We performed yeast two-hybrid screening to detect LYRIC/AEG-1 associated proteins, and identified BCCIP, a CDKN1A and BRCA2-associated protein involved in cell cycle regulation and DNA repair. Here, we demonstrate association between LYRIC/AEG-1 and BCCIP in mammalian cells, and define the region of interaction. Co-expression of the two proteins resulted in decreased levels of BCCIPalpha, an effect partially abrogated by proteasome inhibition. A truncated LYRIC/AEG-1 construct lacking the interaction region did not alter BCCIPalpha protein levels. Coincidentally, it was observed that overexpression of BCCIPalpha in DU145 prostate tumor cells induced an apparent neuroendocrine differentiation. In summary, our data suggest LYRIC/AEG-1 is a negative regulator of BCCIPalpha, promoting proteasomal degradation either through direct interaction, or potentially through an indirect mechanism involving downstream effects of the NF-kappaB signaling pathway.