Growth Inhibition of Human Gynecologic and Colon Cancer Cells by Phyllanthus watsonii through Apoptosis Induction

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC50 values of ≤ 20.0 µg/mL. Hexane extract of P. watsonii was further subjected to bioassay-guided fractionation and yielded 10 fractions (PW-1→PW-10). PW-4→PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1→PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC50 values ranged from 0.66 – 0.83 µg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs

Conidiation Color Mutants of Aspergillus fumigatus Are Highly Pathogenic to the Heterologous Insect Host Galleria mellonella

The greater wax moth Galleria mellonella has been widely used as a heterologous host for a number of fungal pathogens including Candida albicans and Cryptococcus neoformans. A positive correlation in pathogenicity of these yeasts in this insect model and animal models has been observed. However, very few studies have evaluated the possibility of applying this heterologous insect model to investigate virulence traits of the filamentous fungal pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Here, we have examined the impact of mutations in genes involved in melanin biosynthesis on the pathogenicity of A. fumigatus in the G. mellonella model. Melanization in A. fumigatus confers bluish-grey color to conidia and is a known virulence factor in mammal models. Surprisingly, conidial color mutants in B5233 background that have deletions in the defined six-gene cluster required for DHN-melanin biosynthesis caused enhanced insect mortality compared to the parent strain. To further examine and confirm the relationship between melanization defects and enhanced virulence in the wax moth model, we performed random insertional mutagenesis in the Af293 genetic background to isolate mutants producing altered conidia colors. Strains producing conidia of previously identified colors and of novel colors were isolated. Interestingly, these color mutants displayed a higher level of pathogenicity in the insect model compared to the wild type. Although some of the more virulent color mutants showed increased resistance to hydrogen peroxide, overall phenotypic characterizations including secondary metabolite production, metalloproteinase activity, and germination rate did not reveal a general mechanism accountable for the enhanced virulence of these color mutants observed in the insect model. Our observations indicate instead, that exacerbated immune response of the wax moth induced by increased exposure of PAMPs (pathogen-associated molecular patterns) may cause self-damage that results in increased mortality of larvae infected with the color mutants. The current study underscores the limitations of using this insect model for inferring the pathogenic potential of A. fumigatus strains in mammals, but also points to the importance of understanding the innate immunity of the insect host in providing insights into the pathogenicity level of different fungal strains in this model. Additionally, our observations that melanization defective color mutants demonstrate increased virulence in the insect wax moth, suggest the potential of using melanization defective mutants of native insect fungal pathogens in the biological control of insect populations

Design science research for the humanities. The case of prosopography

International audienceThe humanities focus on understanding human beings and cultures. They include such disciplines as history, literature, and the arts. Digital humanities, defined as the application of IT to research and teaching in the humanities, is well established as a field in its own right. More particularly, research in the humanities is in demand of innovative and useful IT artifacts. This makes it a relevant application area for design science research (DSR). This also raises specific challenges to DSR researchers, due to the specific stakeholders and knowledge domains that come into play in the digital humanities. This paper focuses on prosopography, a branch of digital humanities that represents and interprets historical data, sourced from texts describing historical person's life. Starting from typical issues addressed by prosopographical researchers, we identify relevant IT artifacts to address these issues, making DSR relevant for prosopographical research. We adapt and instantiate Hevner's DSR framework to the specific case of prosopography, as a first step towards defining a DSR framework for the humanities more generally. Based on this adapted and instantiated DSR framework, we propose two artifacts: requirements and a methodology for prosopography. We demonstrate the methodology on a prosopography scenario

A randomized clinical trial of oral steroids for ulnar neuropathy in type 1 and type 2 leprosy reactions Ensaio clínico sobre o tratamento com esteróides via oral da neuropatia ulnar em reação tipo 1 e tipo 2 da hanseníase

BACKGROUND: Steroids regimens in leprosy neuropathies are still controversial in botth types of reactions. METHOD: For this trial, 21 patients with ulnar neuropathy were selected from 163 leprosy patients, 12 with type 1 reaction (T1R) and nine with type 2 (T2R). One experimental group started with prednisone 2 mg/kg/day and the control group with 1 mg/kg/day. A clinical score based on tests for spontaneous pain, nerve palpation, sensory and muscle function was used. Neurophysiological evaluation consisted on the motor nerve conduction of the ulnar nerve in three segments. Student "t" test for statistical analysis was applied on the results: before treatment, first week, first month and sixth month, between each regimen and types of reaction. CONCLUSION: In both reactions during the first month higher doses of steroids produced better results but, earlier treatment with lower dose was as effective. Short periods of steroid, 1 mg/Kg/day at the beginning and,tapering to 0,5 mg/Kg/day or less in one month turned out to be efficient in T2R.<br>INTRODUÇÃO: O tratamento da neuropatia da hanseníase com esteróides é ainda controverso nos dois tipos de reações. MÉTODO: Neste ensaio, de 163 pacientes foram selecionados 21 com neuropatia ulnar, 12 com reação tipo 1 e 9 com tipo 2. Um grupo experimental iniciou com 2 mg/kg/dia e o grupo controle com 1 mg/kg/dia. Foi composto um escore clínico pela avaliação da sensação dolorosa espontânea, palpação de nervos e funções sensitiva e motora. Realizou-se a condução nervosa motora do nervo ulnar em três segmentos. Aplicaram-se os estudos estatísticos com o teste t de Student nos resultados: antes do tratamento, primeira semana, primeiro mês e sexto mês. CONCLUSÃO: Em ambas as reações dosagens mais elevadas iniciais produziram melhores resultados, mas a dose menor quando administrada precocemente foi igualmente efetiva. Períodos curtos com doses efetivas, 1 mg/Kg/dia no início e reduzindo-se para 0,5 mg/Kg/dia ou menos em um mês foram eficientes na reação tipo 2