Gold(III)-Dithiocarbamato Peptidomimetics in the Forefront of the Targeted Anticancer Therapy: Preclinical Studies against Human Breast Neoplasia

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. 53% inhibition of breast tumor growth in mice was observed after 27 days of treatment at 1.0 mg kgSUP−1 dSUP−1, compared to control. Remarkably, if only the most responsive mice are taken into account, 85% growth inhibition, with some animals showing tumor shrinkage, was observed after 13 days. These results led us to file an international patent, recognizing this class of gold(III) peptidomimetics as suitable candidates for entering phase I clinical trials

Pengaruh Implementasi Kebijakan Tambahan Penghasilan Terhadap Motivasi Kerja Pegawai Dinas Kesehatan Provinsi Sulawesi Tengah

This study was conducted to determine how much influence the implementation of additional policies on work motivation income civil servants in Central Sulawesi province. This study uses the theory of Van Meter and Van Horn with standard dimensions and policy objectives, resources, communication between the implementing agency, the implementing body characteristics, social, economic and political, disposition / attitude implementers. The method used in the study is survay analytic using cross sectional design of a study to study the dynamics of the correlation between risk factors by means of observation or data collection approach as well. The results showed that the magnitude of the effect of the implementation of additional policies on work motivation of employees earning the provincial health bureau in Central Sulawesi was the degree of correlation moderate to very low-level relations with the interval of the correlation coefficient between 0.172 up to 0.457

Transcriptome sequencing and phylogenomic resolution within Spalacidae (Rodentia)

BACKGROUND: Subterranean mammals have been of great interest for evolutionary biologists because of their highly specialized traits for the life underground. Owing to the convergence of morphological traits and the incongruence of molecular evidence, the phylogenetic relationships among three subfamilies Myospalacinae (zokors), Spalacinae (blind mole rats) and Rhizomyinae (bamboo rats) within the family Spalacidae remain unresolved. Here, we performed de novo transcriptome sequencing of four RNA-seq libraries prepared from brain and liver tissues of a plateau zokor (Eospalax baileyi) and a hoary bamboo rat (Rhizomys pruinosus), and analyzed the transcriptome sequences alongside a published transcriptome of the Middle East blind mole rat (Spalax galili). We characterize the transcriptome assemblies of the two spalacids, and recover the phylogeny of the three subfamilies using a phylogenomic approach. RESULTS: Approximately 50.3 million clean reads from the zokor and 140.8 million clean reads from the bamboo ratwere generated by Illumina paired-end RNA-seq technology. All clean reads were assembled into 138,872 (the zokor) and 157,167 (the bamboo rat) unigenes, which were annotated by the public databases: the Swiss-prot, Trembl, NCBI non-redundant protein (NR), NCBI nucleotide sequence (NT), Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 5,116 nuclear orthologous genes were identified in the three spalacids and mouse, which was used as an outgroup. Phylogenetic analysis revealed a sister group relationship between the zokor and the bamboo rat, which is supported by the majority of gene trees inferred from individual orthologous genes, suggesting subfamily Myospalacinae is more closely related to subfamily Rhizomyinae. The same topology was recovered from concatenated sequences of 5,116 nuclear genes, fourfold degenerate sites of the 5,116 nuclear genes and concatenated sequences of 13 protein coding mitochondrial genes. CONCLUSIONS: This is the first report of transcriptome sequencing in zokors and bamboo rats, representing a valuable resource for future studies of comparative genomics in subterranean mammals. Phylogenomic analysis provides a conclusive resolution of interrelationships of the three subfamilies within the family Spalacidae, and highlights the power of phylogenomic approach to dissect the evolutionary history of rapid radiations in the tree of life

Cancer-induced bone pain sequentially activates the ERK/MAPK pathway in different cell types in the rat spinal cord

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrates that, after nerve injury, extracellular signal-regulated protein kinase (ERK) activation in the spinal cord-initially in neurons, then microglia, and finally astrocytes. In addition, phosphorylation of ERK (p-ERK) contributes to nociceptive responses following inflammation and/or nerve injury. However, the role of spinal cells and the ERK/MAPK pathway in cancer-induced bone pain (CIBP) remains poorly understood. The present study analyzed activation of spinal cells and the ERK/MAPK pathway in a rat model of bone cancer pain.</p> <p>Results</p> <p>A Sprague Dawley rat model of bone cancer pain was established and the model was evaluated by a series of tests. Moreover, fluorocitrate (reversible glial metabolic inhibitor) and U0126 (a MEK inhibitor) was administered intrathecally. Western blots and double immunofluorescence were used to detect the expression and location of phosphorylation of ERK (p-ERK). Our studies on pain behavior show that the time between day 6 and day 18 is a reasonable period ("time window" as the remaining stages) to investigate bone cancer pain mechanisms and to research analgesic drugs. Double-labeling immunofluorescence revealed that p-ERK was sequentially expressed in neurons, microglia, and astrocytes in the L4-5 superficial spinal cord following inoculation of Walker 256 cells. Phosphorylation of ERK (p-ERK) and the transcription factor cAMP response element-binding protein (p-CREB) increased in the spinal cord of CIBP rats, which was attenuated by intrathecal injection of fluorocitrate or U0126.</p> <p>Conclusions</p> <p>The ERK inhibitors could have a useful role in CIBP management, because the same target is expressed in various cells at different times.</p

Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution

<p>Abstract</p> <p>Background</p> <p>The subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China.</p> <p>Methods</p> <p>Lymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification.</p> <p>Results</p> <p>From January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin.</p> <p>Conclusions</p> <p>The lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.</p

Analysis of influencing factors for the determination of ammonia nitrogen in water by spectrophotometry

The research is supported by a Project Funded by the brand professional project form Yancheng teachers college (2016) and the teaching reform and practice of medicinal chemistry (2018YCTUJGY006) and the innovation and entrepreneurship training program for college students in jiangsu province（201910324016Z） Abstract The content of ammonia nitrogen in water was determined by national standard method - nessler's reagent spectrophotometry. Through comparison, it was found that the method of reagent configuration, the amount of reagent, the detection wavelength, the color development time and the temperature had an impact on the analysis results in the ammonia nitrogen measurement in water by the reagent spectrophotometry. Based on the experimental results, the factors influencing the determination of ammonia nitrogen by spectrophotometry with nessler's reagent were discussed. Keywords Nessler's reagent spectrophotometry, Ammonia nitrogen, Influencing factors, Blank value, ABS value, Correlation coefficient. DOI: 10.7176/JEP/10-31-08 Publication date: November 30th 201