Synthesis and Antifungal Activities of Novel Griseofulvin Derivatives as Potential Anti-Phytopathogenic Fungi Agents.

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.

Characterization of Low-Loss Dielectric Materials for High-Speed and High-Frequency Applications.

In this study, the Df (dissipation factor or loss tangent) and Dk (dielectric constant or permittivity) of the low-loss dielectric material from three different vendors are measured by the Fabry-Perot open resonator (FPOR) technique. Emphasis is placed on the sample preparation, data collection, and the comparison with the data sheet values provided from vendors. A coplanar waveguide with ground (CPWG) test vehicle with one of these raw dielectric materials (vendor 1) is designed (through Polar and simulation) and fabricated. The impedance of the test vehicle is measured by TDR (time-domain reflectometer), and the effective Dk of the test vehicle is calculated by the real cross-section of the metal line width, spacing, and thickness of the test vehicle and a closed-form equation. In parallel, the insertion loss and return loss are measured with the VNA (vector network analyzer) of the test vehicle. Finally, the measurement and simulation results are correlated. Some recommendations on the low-loss dielectric materials of the Dk and Df are also provided.

Correlation between intraoperative mapping and monitoring and functional outcomes following supratentorial glioma surgery.

OBJECTIVES: Intraoperative neurophysiological monitoring (IONM) has long been regarded as the "gold standard" when resecting a supratentorial glioma, as it facilitates the goals of maximal tumor resection and preservation of sensorimotor function. The purpose of the present study was to evaluate the ability of motor evoked potentials (MEPs) monitoring or subcortical mapping (SCM), alone or in combination, to predict postoperative functional outcomes in glioma surgery. MATERIALS AND METHODS: We retrospectively reviewed patients with supratentorial glioma that underwent craniotomy for tumor removal with IONM. Statistical analyses were used to evaluate whether the following criteria correlated with postoperative functional outcomes: Reduced amplitude (>50% reduction) or disappearance of MEPs (criterion 1), SCM with a stimulation intensity threshold less than 3 mA (criterion 2), the presence of both two phenomena (criterion 3), or either one of the two phenomena (criterion 4). RESULTS: Ninety-two patients were included in this study, of whom 15 sustained new postoperative deficits, 4 experienced improved functional status, and 73 were unchanged. Postoperative functional status correlated significantly with all four criteria, and especially with criterion 3 (r = 0.647, P = 0.000). Sensitivity of IONM was better if using criteria 2 and 4, but specificity was better if using criteria 1 and 3. Criterion 3 had the most favorable overall results. CONCLUSION: Using statistical methodology, our study indicates that concomitant interpretation of MEPs and SCM is the most accurate predictor of functional outcomes following supratentorial glioma surgery. However, accurate interpretations of the monitoring results by experienced neurophysiologists are essential.

Cellular signaling pathways regulating ß-cell proliferation as a promising therapeutic target in the treatment of diabetes.

It is established that a decrease in ß-cell number and deficiency in the function of existing ß-cells contribute to type 1 and type 2 diabetes mellitus. Therefore, a major focus of current research is to identify novel methods of improving the number and function of ß-cells, so as to prevent and/or postpone the development of diabetes mellitus and potentially reverse diabetes mellitus. Based on prior knowledge of the above-mentioned causes, promising therapeutic approaches may include direct transplantation of islets, implantation and subsequent induced differentiation of progenitors/stem cells to ß-cells, replication of pre-existing ß-cells, or activation of endogenous ß-cell progenitors. More recently, with regards to cell replacement and regenerative treatment for diabetes patients, the identification of cellular signaling pathways with related genes or corresponding proteins involved in diabetes has become a topic of interest. However, the majority of pathways and molecules associated with ß-cells remain unresolved, and the specialized functions of known pathways remain unclear, particularly in humans. The current article has evaluated the progress of research on pivotal cellular signaling pathways involved with ß-cell proliferation and survival, and their validity for therapeutic adult ß-cell regeneration in diabetes. More efforts are required to elucidate the cellular events involved in human ß-cell proliferation in terms of the underlying mechanisms and functions.

Insulin-producing cells are bi-potential and differentiatorsprior to proliferation in early human development.

AIM: To investigate the differentiation and migration of endocrine cells to form the pancreatic islets of Langer-hans in early human development. METHODS: Embryonic pancreas of 6-14 wk gestation was observed using immunocytochemistry methods in early human development. RESULTS: Insulin and glucagon are expressed in the same epithelium cells in the pancreas. In addition, in-sulin-producing cells also secrete somatostatin in early human embryonic development and these insulin-pro-ducing cells also express nestin. CONCLUSION: Pancreatic duct epithelial cells that can produce insulin in early human development are pre-cursors and still have the potential to differentiate other endocrine cells. These progenitors have differen-tiated before migration from primary ductal epithelium to form the pancreatic islets.

[Role of Wnt/beta-catenin signaling transduction pathway in rat hepatocarcinogenesis].

AIM: To investigate the role of Wnt/beta-catenin signaling transduction pathway in rat hepatocarcinogenesis. METHODS: The mRNAs of Wnt1, beta-catenin, APC, cyclin D1 and c-myc genes were amplified by using of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) from normal rat livers, atypical hyperplasia livers and hepatoma tissues, respectively. Then the proteins expression of beta-catenin, APC and cyclin D1 was examined by immunohistochemical staining. RESULTS: In normal rat livers, the mRNAs of Wnt1, cyclin D1 and c-myc genes were not detected and only beta-catenin protein was observed to have low expression at cellular membrane. However, 14 weeks after cancer induction in atypical hyperplasia livers, beta-catenin protein and APC protein were accumulated in cytoplasm. Meanwhile, cyclin D1 protein was detected in cytoplasm and/or nucleus in some cells. 16 weeks after cancer induction in hepatoma tissues, the mRNAs and protein expression of beta-catenin, APC, cyclin D1 and c-myc genes were detected except Wnt1. CONCLUSION: The activation of Wnt/beta-catenin signaling transduction pathway might be one of the reasons for rat hepatocarcinogenesis.

Wnt/beta-catenin signaling pathway is active in pancreatic development of rat embryo.

AIM: To elucidate the role of Wnt/beta-catenin signaling pathway in pancreatic development of rat embryo. METHODS: The mRNAs of beta-catenin, APC, cyclin D1 genes were amplified by means of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) from embryonic pancreas in different periods and normal pancreas of rat, respectively. Protein expression of these genes in embryonic pancreas of E14.5-E18.5 was examined by immunohistochemical method. RESULTS: In embryonic pancreas of E14.5, the transcript amplification of beta-catenin and cyclinD1 genes was detected. In embryonic pancreas of E18.5, the transcription levels of beta-catenin and cyclinD1 genes became much higher than in other periods. But in adult rat pancreas the transcription of cyclinD1 gene could not be observed. Only until E18.5, the transcript amplification of mRNA of APC gene could be detected. Surprisingly, the transcription level of APC gene became much higher in adult rat pancreas than in embryonic pancreas. By means of immunohistochemical staining, identical results were obtained to the above by RP-PCR, except for beta-catenin protein in adult rat pancreas. CONCLUSION: Active Wnt/beta-catenin signaling occurs in rat embryonic pancreas and is probably important for pancreatic development and organ formation.

Islet formation and regeneration.

OBJECTIVE: To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration. METHODS: Human embryonic pancreatic tissue at 7-14 weeks of gestation was collected. Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin. Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues were observed by immunohistochemistry. RESULTS: At 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration. Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation. At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme. During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin. During pancreatic regeneration after damage, nestin expression of islet cells increased. CONCLUSION: In the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration. During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.

Role of beta-catenin in hepatocarcinogenesis of rats.

BACKGROUND: Beta-catenin has two distinct roles in E-cadherin mediated cell adhesion and carcinogenesis by activating the wnt/beta-catenin signaling pathway. One occurs at the cell-adhesion site, where cadherins are linked to the actin-based cytoskeleton. The other takes place in the cytoplasm and nuclei and is thought to regulate cell transformation. We studied the role of beta-catenin in hepatocarcinogenesis of rats. METHODS: Fresh liver specimens were obtained from normal rats, and atypical hyperplasia livers and hepatocarcinoma tissues from model rats. The changes of beta-catenin in gene expression levels were detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the different specimens separately. At the same time, their localization was observed immunohistochemically. RESULTS: In the normal liver specimens, beta-catenin staining was seen in the cell membrane. In liver specimens of atypical hyperplasia, beta-catenin staining occurred in the cell cytoplasm of some cells as well as in the cell membrane of others. Immunohistochemically cancerous tissues showed the presence of beta-catenin in the cytoplasm and nuclei. RT-PCR revealed that the gene expression levels of beta-catenin were same in all samples. CONCLUSIONS: The accumulation of beta-catenin in the cytoplasm and/or nuclei frequently occurs in hepatocarcinogenesis of rats. It may be an early event in the development of hepatocarcinoma of rats.

[The role of beta-catenin in rat embryonic development and tumorigenesis].

OBJECTIVE: To investigate the role of beta-catenin as a key element of Wnt/beta-catenin signaling pathway in the development of embryonic liver and liver tumorigenesis. METHODS: Immunohistochemical method was used to examined beta-catenin proteins in 12-day (E12), 16-day (E16) embryonic rat liver, neonate rat liver, and in adult rat liver as well as in rat hepatoma. Beta-catenin mRNA was amplified in the above-mentioned samples by means of semiquantitative RT-PCR. RESULTS: Beta-catenin proteins were found in cytoplasm of E12 and E16 embryonic liver as well as in hepatoma. The expression level of beta-catenin protein in E12 embryonic liver was higher than that in E16. There were much more positive cells in E12 embryonic liver than in E16. However, no positive cell was observed expressing beta-catenin proteins in neonate rat liver and adult rat liver. The quantity of beta-catenin mRNA was the same in all samples. CONCLUSION: Wnt/beta-catenin signaling pathway was open during the development of embryonic liver and hepatic tumorigenesis. The accumulation of beta-catenin proteins in cytoplasm of embryonic liver and rat hepatic carcinoma cells might be caused not by the elevation of transcription of beta-catenin gene but by the avoidance of degeneration of beta-catenin protein.

[Changes in the expression of vital cytokines for pancreatic development in early embryo].

OBJECTIVE: To clarify the changes in the expression of vital cytokines for pancreatic development in early embryo and hence provide preclinical data regarding embryonic pancreas transplanted for treatment, of diabetes mellitus. METHODS: Sample collection was conducted in accordance to the principle of informed consent. Histochemical S-ABC method was adopted in studying pancreas at 7-12 weeks of gestation, and analysis was made on vital cytokines expression as well as the differentiation and forming of pancreatic islets. RESULTS: It was found that the expression of Insulin, Glucagon, Somatostatin and Cytokeratin begins at 7 weeks, and the change is consistent with the differentiation and formation of pancreatic islets. IGF-I and F-VIII appear at 12 weeks. CONCLUSION: Insulin, Glucagon, Somatostatin, Cytokeratin, IGF-I and F-VIII play a regulatory role in the development of embryonic pancreas and are related to the differentiation and formation of endocrine and exocrine glands of pancreas. The pancreas after 12 weeks of gestation can be used as a donated graft for pancreas transplantation.