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Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

Cancer Drug Resistance 2022年第1期5卷 1-14页

作者： Lara Massai Damiano Cirri Tiziano Marzo Luigi Messori Department of Chemistry University of FlorenceSesto Fiorentino 50019Italy Department of Chemistry and Industrial Chemistry University of PisaPisa 56124Italy Department of Pharmacy University of PisaPisa 56126Italy CISUP-Centre for Instrumentation Sharing(Centro per l’Integrazione della Strumentazione Scientifica) University of PisaPisa 56126Italy University consortium for Research in the Chemistry of Metal ions in Biological Systems(CIRCMSB) Bari 70126Italy

Today colorectal cancer(CRC)is one of the leading causes of cancer death *** disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely *** drugs,oxaliplatin in particular,were reported to produce some significant benefit in CRC treatment,triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC *** this frame,gold compounds and,specifically,the established antiarthritic drug auranofin with its analogs,form a novel group of promising anticancer *** to its innovative mechanism of action and its favorable pharmacological profile,auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment,capable of overcoming resistance to platinum *** encouraging results in this direction have already been obtained.A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug *** perspectives of the research in this field are outlined.

关键词： Auranofin CRC colorectal cancer metallodrugs anticancer agents gold gold-based drugs

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Identification of speckle-type POZ protein somatic mutations in African American prostate cancer

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Asian Journal of Andrology 2014年第6期16卷 829-832页

作者： Eric Buckles Chiping Qian Andrew Tadros Sumana Majumdar Jennifer Cvitanovic Jovanny Zabaleta John Estrada John Wilson Wanguo Liu Department of Biology School of Science Technology Engineering and Mathematics Dillard University New Orleans LA USA New Orleans LA USA Department of Genetics Louisiana State University Health Sciences Center New Orleans LA USA Stanley S. Scott Cancer Center Louisiana State University Health Sciences Center New Orleans LA USA Biospecimen Core Laboratory Louisiana Cancer Research Consortium New Orleans LA USA Department of Pediatrics Louisiana State University Health Sciences Center New Orleans LA USA.

The speckle-type POZ protein （SPOP） is a tumor suppressor in prostate cancer （PCa）. SPOP somatic mutations have been reported in up to 15% of PCa of those of European descent. However, the genetic roles of SPOP in African American （AA）-PCa are currently unknown. We sequenced the SPOP gene to identify somatic mutations in 49 AA prostate tumors and identified three missense mutations （p.Y87C, p.F102S, and p.G111E） in five AA prostate tumors （10%） and one synonymous variant （p.11061） in one tumor. Intriguingly, all of mutations and variants clustered in exon six, and all of the mutations altered conserved amino acids. Moreover, two mutations （p.F102S and p.G111E） have only been identified in AA-PCa to date. Quantitative real-time polymerase chain reaction analysis showed a lower level of SPOP expression in tumors carrying SPOP mutations than their matched normal prostate tissues. In addition, SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa （P 〈 0.05）. Further studies with increased sample size are needed to validate the clinicopathological significance of these SPOP mutations in AA-PCa.

关键词： African American mutation analysis prostate cancer speckle-type POZ protein

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Estimation of the Mean of the Exponential Distribution Using Maximum Ranked Set Sampling with Unequal Samples

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Open Journal of Statistics 2014年第8期4卷 641-649页

作者： B. S. Biradar C. D. Santosha Department of studies in Statistics University of Mysore Mysore India All India Institute of Speech and Hearing Mysore India

In this paper maximum ranked set sampling procedure with unequal samples (MRSSU) is proposed. Maximum likelihood estimator and modified maximum likelihood estimator are obtained and their properties are studied under exponential distribution. These methods are studied under both perfect and imperfect ranking (with errors in ranking). These estimators are then compared with estimators based on simple random sampling (srs) and ranked set sampling (RSS) procedures. It is shown that relative efficiencies of the estimators based on MRSSU are better than those of the estimator based on srs. Simulation results show that efficiency of proposed estimator is better than estimator based on RSS under ranking error.

关键词： Efficiency Error in Ranking Maximum Likelihood Estimator Modified Maximum Likelihood Estimator Ranked Set Sampling

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Estimation of the Population Mean Using Paired Ranked Set Sampling

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Open Journal of Statistics 2015年第2期5卷 97-103页

作者： B. S. Biradar C. D. Santosha Department of studies in Statistics University of Mysore Mysore India All India Institute of Speech and Hearing Mysore India

In the situation where the sampling units in a study can be easily ranked than quantified, the ranked set sampling methods are found to be more efficient and cost effective as compared to srs. In this paper we propose an estimator of the population mean using paired ranked set sampling (RSS) method. The proposed estimator is an unbiased estimator of the population mean when the set size is even. In case of odd set size the estimator is unbiased when the underlying distribution is symmetric. It is shown that the proposed estimator is more efficient than its counterpart srs method for all distributions considered in this study.

关键词： Ranked Set Sampling Paired Ranked Set Sampling Population Mean Relative Efficiency Errors in Ranking

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Enhanced biological wastewater treatment using sodium alginate-immobilized microorganisms in a fluidized bed reactor

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Water Science and Engineering 2022年第2期15卷 125-133页

作者： Yaneth A.Bustos-Terrones Erick R.Bandala Gabriela E.Moeller-Chávez Victoria Bustos-Terrones Division of Graduate studies and Research CONACYT-TecNM-Technological Institute of CuliacánCuliacánSinaloa 80220Mexico Division of Hydrologic Sciences Desert Research InstituteLas VegasNV 89119-7363USA Academic Direction of Environmental Technology Engineering Polytechnic University of the State of MorelosJiutepecMorelos 62550Mexico

In this study,a microbial consortium isolated from an activated sludge tank of a conventional wastewater treatment plant was immobilized using sodium alginate(SA)as a support material for contaminant biodegradation in wastewater.A volume of 500 mL of activated sludge was immobilized in the SA beads(with a mass concentration of 25 g/L).The resulting SA beads were characterized,introduced into a fluidized bed reactor,fed with 1000 mL of the sample,and characterized again after the treatment *** SA-immobilized microorganisms were tested first for degradation of organic matter(expressed as chemical oxygen demand)and total phosphorous in domestic wastewater,achieving removal efficiencies of 71%and 93%,respectively,after 12 ***,the SA-immobilized microorganisms were tested for degradation of a basic blue 9(BB9)textile dye in a condition that simulated textile *** efficiency of the BB9 degradation was found to be as high as 99.5%after 2 *** to these results,SA-immobilized microorganisms were found to be an environmentally friendly and cost-effective alternative for treatment of municipal and industrial wastewater effluents.

关键词： Domestic wastewater Basic blue 9 Immobilized microorganisms Fluidized bed reactor Sodium alginate

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Tree diversity increases levels of herbivore damage in a subtropical forest canopy:evidence for dietary mixing by arthropods?

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Journal of Plant Ecology 2017年第1期10卷 13-27页

作者： Matteo Brezzi Bernhard Schmid Pascal A.Niklaus Andreas Schuldt Department of Evolutionary Biology and Environmental studies and Zürich-Basel Plant Science Center University of ZürichWinterthurerstr.190CH-8057 ZürichSwitzerland Institute of Ecology Animal Ecology GroupLeuphana University LueneburgScharnhorststr.1D-21335 LünebourgGermany

Aims Plant diversity has been linked to both increasing and decreasing levels of arthropod herbivore damage in different plant *** far,these links have mainly been studied in grasslands or in artificial tree plantations with low species ***,most studies provide results from newly established experimental plant communities where trophic links are not fully established or from stands of tree saplings that have not yet developed a ***,we test how tree diversity in a species-rich subtropical forest in China with fully developed tree canopy affects levels of herbivore damage caused by different arthropod feeding *** We established 27 plots of 30×30 m *** plots were selected randomly but with the constraint that they had to span a large range of tree diversity as required for comparative studies in contrast to sample *** recorded herbivore damage caused by arthropod feeding guilds(leaf chewers,leaf skeletonizers and sap feeders)on canopy leaves of all major tree *** Findings Levels of herbivore damage increased with tree species richness and tree phylogenetic *** effects were most pronounced for damage caused by leaf *** the two diversity measures were highly correlated,we additionally found a significant interaction between them,whereby species richness increased herbivory mostly at low levels of phylogenetic *** species with the lowest proportion of canopy leaf biomass in a plot tended to suffer the highest levels of herbivore damage,which is in contrast to expectations based on the resource concentration *** results are in agreement with expectations of the dietary mixing hypothesis where generalist herbivores with a broad spectrum of food plants benefit from increased resource diversity in tree species-rich forest patches.

关键词： arthropod herbivore damage feeding guilds forest canopy generalist herbivores leaf biomass resource dilution specialist herbivores tree species richness tree phylogenetic diversity

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Weibull-Bayesian Estimation Based on Maximum Ranked Set Sampling with Unequal Samples

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Open Journal of Statistics 2016年第6期6卷 1028-1036页

作者： B. S. Biradar B. K. Shivanna Department of studies in Statistics University of Mysore Mysuru India Department of Statistics Maharani’s Science College for Women Mysuru India

A modification of ranked set sampling (RSS) called maximum ranked set sampling with unequal sample (MRSSU) is considered for the Bayesian estimation of scale parameter α of the Weibull distribution. Under this method, we use Linex loss function, conjugate and Jeffreys prior distributions to derive the Bayesian estimate of α. In order to measure the efficiency of the obtained Bayesian estimates with respect to the Bayesian estimates of simple random sampling (srs), we compute the bias, mean squared error (MSE) and asymptotic relative efficiency of the obtained Bayesian estimates using simulation. It is shown that the proposed estimates are found to be more efficient than the corresponding one based on srs.

关键词： Bayesian Estimation Loss Function MRSSU srs RSS

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Determinants for adoption of physical soil and water conservation measures by smallholder farmers in Ethiopia

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International Soil and Water Conservation Research 2019年第4期7卷 354-361页

作者： Million Sileshi Reuben Kadigi Khamaldin Mutabazi Stefan Sieber School of Agricultural Economics and Business studies Sokoine University of AgricultureMorogoroTanzania Haramaya University Department of Rural Development and Agricultural ExtensionDire-dawaEthiopia Humboldt-University Berlin Department of Agricultural EconomicsBerlinGermany Leibniz Centre for Agricultural landscape Research(ZALF e.V.) Sustainable land Use in Developing CountriesMünchebergGermany

Adoption rates of soil and water conservation measures remain below the expected levels in Ethiopia despite the considerable investments in reducing land degradation and improving soil *** constitutes one of the key research agendas in the *** paper underscores the need for investigating the factors hindering or facilitating the adoption of soil and water conservation *** study results presented in this paper are based on cross-section data collected from 408 households in eastern Ethiopia,including field observations of 790 plots selected using a multi-stage sampling procedure.A multivariate probit model was employed to analyse the determinants of adoption of three soil and water conservation measures (stone bund,soil bund,and bench terracing) at the plot *** study findings reveal that household,socioeconomic,and institution characteristics were the key factors that influenced the adoption of soil bund,stone bund,and bench terracing conservation ***,there was a significant correlation among the three soil and water conservation measures,indicating that the adoption of these measures is *** particular,the results show that there was a positive correlation between stone bunds and soil ***,the correlations between bench terracing and stone bunds as well as bench terracing and soil bunds were negative (implying substitutability).These results imply that the Government and other relevant organizations that are responsible for reducing land degradation in order to increase agricultural production should support the establishment and strengthening of local institutions to facilitate the adoption of soil and water conservation measures.

关键词： Adoption Multiple soil and water conservation Multivariate probit Ethiopia

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Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang Miguel Garzon Sanz Oliver Smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BMLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy ***,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal *** best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well *** we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known *** results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator Healthy aging Drug discovery Bioisosteres Medicinal chemistry

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Dynamic Contrast-Enhanced MRI of Mouse Liver: A Feasibility Study Using a Dual-Input Two-Compartment Tracer Kinetic Model

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Journal of Biomedical Science and Engineering 2015年第2期8卷 90-97页

作者： Septian Hartono Choon Hua Thng Kai Hsiang Chuang Huynh Hung Tong San Koh School of Electrical & Electronic Engineering Nanyang Technological University Singapore City Singapore Department of Oncologic Imaging National Cancer Centre Singapore Singapore City Singapore Laboratory of Molecular Imaging Singapore Bioimaging Consortium Singapore City Singapore Laboratory of Molecular Endocrinology National Cancer Centre Singapore Singapore City Singapore

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been widely applied to evaluate microcirculatory parameters in clinical settings. However, pre-clinical studies involving DCE-MRI of small animals remain challenging with the requirement for high spatial and temporal resolution for quantitative tracer kinetic analysis. This study illustrates the feasibility of applying a high temporal resolution (2 s) protocol for liver imaging in mice by analyzing the DCE-MRI datasets of mice liver with a dual-input two-compartment tracer kinetic model. Phantom studies were performed to validate the T1 estimates derived by the proposed protocol before applying it in mice studies. The DCE-MRI datasets of mice liver were amendable to tracer kinetic analysis using a dual-input two-compartment model. Estimated micro-circulatory parameters were consistent with liver physiology, indicating viability of applying the technique for pre-clinical drug developments.

关键词： DCE-MRI Mouse Liver Imaging Preclinical Imaging

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