Re-Evaluation of Chemotherapeutic Potential of Pyoktanin Blue.
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ABSTRACT:
SUBMITTER: Sakagami H
PROVIDER: S-EPMC8305689 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionThe use of administrative data to capture 30-day readmission rates in end-stage renal disease is challenging since Medicare combines claims from acute care, inpatient rehabilitation (IRF), and long-term care hospital stays into a single "Inpatient" file. For data prior to 2012, the United States Renal Data System does not contain the variables necessary to easily identify different facility types, making it likely that prior studies have inaccurately estimated 30-day readmission rates.MethodsFor this report, we developed two methods (a "simple method" and a "rehabilitation-adjusted method") to identify acute care, IRF, and long-term care hospital stays from United States Renal Data System claims data, and compared them to methods used in previously published reports.FindingsWe found that prior methods overestimated 30-day readmission rates by up to 12.3% and overestimated average 30-day readmission costs by up to 11%. In contrast, the simple and rehabilitation-adjusted methods overestimated 30-day readmission rates by 0.1% and average 30-day readmission costs by 1.8%. The rehabilitation-adjusted method also accurately identified 96.8% of IRF stays.DiscussionPrior research has likely provided inaccurate estimates of 30-day readmissions in patients undergoing dialysis. In the absence of data on specific facility types particularly when using data prior to 2012, future researchers could employ our method to more accurately characterize 30-day readmission rates and associated outcomes in patients with end-stage renal disease.
| S-EPMC5398945 | biostudies-literature
Project description:Erythrocytes possess an unusual programmed cell death mechanism termed eryptosis, and several compounds have been previously claimed to induce eryptosis in vitro. Malaria parasites (genus Plasmodium) reside in erythrocytes during the pathogenic part of their life cycle, and the potential of several eryptosis inducers to act as antimalarials has been tested in recent years. However, the eryptosis-inducing capacity of these compounds varies significantly between eryptosis-focused studies and malaria investigations. Here, we investigated the reasons for these discrepancies, we developed a protocol to investigate eryptosis in malaria cultures and we re-evaluated the potential of eryptosis inducers as antimalarials. First, we showed that eryptosis read-out in vitro is dependent on culture conditions. Indeed, conditions that have consistently been used to study eryptosis do not support P. falciparum growth and prime erythrocytes for eryptosis. Next, we defined culture conditions that allow the detection of eryptosis while supporting P. falciparum survival. Finally, we selected six eryptosis-inducers based on their clinical use, molecular target and antimalarial activities, and re-evaluated their eryptosis inducing capacities and their potential as antimalarials. We demonstrate that none of these compounds affect the viability of naïve or P. falciparum-infected erythrocytes in vitro. Nevertheless, three of these compounds impair parasite development, although through a mechanism unrelated to eryptosis and yet to be elucidated. We conclude that careful consideration of experimental set up is key for the accurate assessment of the eryptosis-inducing potential of compounds and their evaluation as potential antimalarials.
| S-EPMC7994622 | biostudies-literature
Project description:BackgroundThe chemotherapy of schistosomiasis currently depends on the use of a single drug, praziquantel. In order to develop novel chemotherapeutic agents we are investigating enzymes involved in the epigenetic modification of chromatin. Sirtuins are NAD+ dependent lysine deacetylases that are involved in a wide variety of cellular processes including histone deacetylation, and have been demonstrated to be therapeutic targets in various pathologies, including cancer.Methodology principal findingsIn order to determine whether Schistosoma mansoni sirtuins are potential therapeutic targets we first identified and characterized their protein sequences. Five sirtuins (SmSirt) are encoded in the S. mansoni genome and phylogenetic analysis showed that they are orthologues of mammalian Sirt1, Sirt2, Sirt5, Sirt6 and Sirt7. Both SmSirt1 and SmSirt7 have large insertion in the catalytic domain compared to their mammalian orthologues. SmSirt5 is the only mitochondrial sirtuin encoded in the parasite genome (orthologues of Sirt3 and Sirt4 are absent) and transcripts corresponding to at least five splicing isoforms were identified. All five sirtuins are expressed throughout the parasite life-cycle, but with distinct patterns of expression. Sirtuin inhibitors were used to treat both schistosomula and adult worms maintained in culture. Three inhibitors in particular, Sirtinol, Salermide and MS3 induced apoptosis and death of schistosomula, the separation of adult worm pairs, and a reduction in egg laying. Moreover, Salermide treatment led to a marked disruption of the morphology of ovaries and testes. Transcriptional knockdown of SmSirt1 by RNA interference in adult worms led to morphological changes in the ovaries characterized by a marked increase in mature oocytes, reiterating the effects of sirtuin inhibitors and suggesting that SmSirt1 is their principal target.Conclusion significanceOur data demonstrate the potential of schistosome sirtuins as therapeutic targets and validate screening for selective sirtuin inhibitors as a strategy for developing new drugs against schistosomiasis.
| S-EPMC3772001 | biostudies-literature
Project description:Although the genus Arthrinium (sexual morph Apiospora) is commonly isolated as an endophyte from a range of substrates, and is extremely interesting for the pharmaceutical industry, its molecular phylogeny has never been resolved. Based on morphology and DNA sequence data of the large subunit nuclear ribosomal RNA gene (LSU, 28S) and the internal transcribed spacers (ITS) and 5.8S rRNA gene of the nrDNA operon, the genus Arthrinium is shown to belong to Apiosporaceae in Xylariales. Arthrinium is morphologically and phylogenetically circumscribed, and the sexual genus Apiospora treated as synonym on the basis that Arthinium is older, more commonly encountered, and more frequently used in literature. An epitype is designated for Arthrinium pterospermum, and several well-known species are redefined based on their morphology and sequence data of the translation elongation factor 1-alpha (TEF), beta-tubulin (TUB) and internal transcribed spacer (ITS1, 5.8S, ITS2) gene regions. Newly described are A. hydei on Bambusa tuldoides from Hong Kong, A. kogelbergense on dead culms of Restionaceae from South Africa, A. malaysianum on Macaranga hullettii from Malaysia, A. ovatum on Arundinaria hindsii from Hong Kong, A. phragmites on Phragmites australis from Italy, A. pseudospegazzinii on Macaranga hullettii from Malaysia, A. pseudosinense on bamboo from The Netherlands, and A. xenocordella from soil in Zimbabwe. Furthermore, the genera Pteroconium and Cordella are also reduced to synonymy, rejecting spore shape and the presence of setae as characters of generic significance separating them from Arthrinium.
| S-EPMC3719201 | biostudies-literature
Project description:Abstract Sympoventuriaceae (Venturiales, Dothideomycetes) comprises genera including saprophytes, endophytes, plant pathogens, as well as important animal or human opportunistic pathogens with diverse ecologies and wide geographical distributions. Although the taxonomy of Sympoventuriaceae has been well studied, generic boundaries within the family remain poorly resolved due to the lack of type materials and molecular data. To address this issue and establish a more stable and reliable classification system in Sympoventuriaceae, we performed multi-locus phylogenetic analyses using sequence data of seven genes (SSU, ITS, LSU, act1, tub2, tef1 and rpb2) with increased taxon sampling and morphological analysis. The molecular data combined with detailed morphological studies of 143 taxa resolved 22 genera within the family, including one new genus, eight new species, five new combinations and one new name. Finally, we further investigated the evolutionary history of Sympoventuriaceae by reconstructing patterns of lifestyle diversification, indicating the ancestral state to be saprophytic, with transitions to endophytic, animal or human opportunistic and plant pathogens. Citation: Wei TP, Zhang H, Zeng XY, et al. 2022. Re-evaluation of Sympoventuriaceae. Persoonia 48: 219-260. https://doi.org/10.3767/persoonia.2022.48.07.. Effectively published online: 17 June 2022 [Received: 2 February 2022; Accepted: 27 April 2022].
| S-EPMC10792283 | biostudies-literature
Project description:A series of organometallic ruthenium(II) complexes containing iminophosphorane ligands have been synthesized and characterized. Cationic compounds with chloride as counterion are soluble in water (70-100 mg/mL). Most compounds (especially highly water-soluble 2) are more cytotoxic to a number of human cancer cell lines than cisplatin. Initial mechanistic studies indicate that the cell death type for these compounds is mainly through canonical or caspase-dependent apoptosis, nondependent on p53, and that the compounds do not interact with DNA or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (shrinkage) of 56% after 28 days of treatment (14 doses of 5 mg/kg every other day) with low systemic toxicity. Pharmacokinetic studies showed a quick absorption of 2 in plasma with preferential accumulation in the breast tumor tissues when compared to kidney and liver, which may explain its high efficacy in vivo.
| S-EPMC4266334 | biostudies-literature
Project description:Liver stem/progenitor cells (LPCs) are defined as cells that supply two types of liver epithelial cells, hepatocytes and cholangiocytes, during development, cellular turnover, and regeneration. Hepatoblasts, which are fetal LPCs derived from endoderm stem cells, robustly proliferate and differentiate into hepatocytes and cholangiocytes during fetal life. Between mid-gestation and the neonatal period, some cholangiocytes function as LPCs. Although LPCs in adult livers can be enriched in cells positive for cholangiocyte markers, their tissue localization and functions in cellular turnover remain obscure. On the other hand, it is well known that liver regeneration under conditions suppressing hepatocyte proliferation is supported by LPCs, though their origin has not been clearly identified. Recently many groups took advantage of new techniques including prospective isolation of LPCs by fluorescence-activated cell sorting and genetic lineage tracing to facilitate our understanding of epithelial supply in normal and injured livers. Those works suggest that, in normal livers, the turnover of hepatocytes mostly depends on duplication of hepatocytes. It is also demonstrated that liver epithelial cells as well as LPCs have great plasticity and flexible differentiation capability to respond to various types of injuries by protecting or repairing liver tissues.
| S-EPMC4154955 | biostudies-literature
Project description:UNLABELLED:Phyllosticta is a geographically widespread genus of plant pathogenic fungi with a diverse host range. This study redefines Phyllosticta, and shows that it clusters sister to the Botryosphaeriaceae (Botryosphaeriales, Dothideomycetes), for which the older family name Phyllostictaceae is resurrected. In moving to a unit nomenclature for fungi, the generic name Phyllosticta was chosen over Guignardia in previous studies, an approach that we support here. We use a multigene DNA dataset of the ITS, LSU, ACT, TEF and GPDH gene regions to investigate 129 isolates of Phyllosticta, representing about 170 species names, many of which are shown to be synonyms of the ubiquitous endophyte P. capitalensis. Based on the data generated here, 12 new species are introduced, while epitype and neotype specimens are designated for a further seven species. One species of interest is P. citrimaxima associated with tan spot of Citrus maxima fruit in Thailand, which adds a fifth species to the citrus black spot complex. Previous morphological studies lumped many taxa under single names that represent complexes. In spite of this Phyllosticta is a species-rich genus, and many of these taxa need to be recollected in order to resolve their phylogeny and taxonomy. TAXONOMIC NOVELTIES:New species - Phyllosticta abieticola Wikee & Crous, P. aloeicola Wikee & Crous, P. citrimaxima Wikee, Crous, K.D. Hyde & McKenzie, P. leucothoicola Wikee, Motohashi & Crous, P. mangifera-indica Wikee, Crous, K.D. Hyde & McKenzie, P. neopyrolae Wikee, Motohashi, Crous, K.D. Hyde & McKenzie, P. pachysandricola Wikee, Motohashi & Crous, P. paxistimae Wikee & Crous, P. podocarpicola Wikee, Crous, K.D. Hyde & McKenzie, P. rhaphiolepidis Wikee, C. Nakash. & Crous, P. rubra Wikee & Crous, P. vacciniicola Wikee, Crous, K.D. Hyde & McKenzie; New combinations - P. foliorum (Sacc.) Wikee & Crous, P. philoprina (Berk. & M.A. Curtis) Wikee & Crous; Epitypifications (basionyms) - P. concentrica Sacc., P. cussoniae Cejp, P. owaniana G. Winter; Neotypifications (basionyms) - Phyllosticta cordylinophila P.A. Young, Physalospora gregaria var. foliorum Sacc., Sphaeropsis hypoglossi Mont., Sphaeropsis minima Berk. & M.A. Curtis.
| S-EPMC3825230 | biostudies-literature
Project description:Sentiment quantification is the task of training, by means of supervised learning, estimators of the relative frequency (also called "prevalence") of sentiment-related classes (such as Positive, Neutral, Negative) in a sample of unlabelled texts. This task is especially important when these texts are tweets, since the final goal of most sentiment classification efforts carried out on Twitter data is actually quantification (and not the classification of individual tweets). It is well-known that solving quantification by means of "classify and count" (i.e., by classifying all unlabelled items by means of a standard classifier and counting the items that have been assigned to a given class) is less than optimal in terms of accuracy, and that more accurate quantification methods exist. Gao and Sebastiani 2016 carried out a systematic comparison of quantification methods on the task of tweet sentiment quantification. In hindsight, we observe that the experimentation carried out in that work was weak, and that the reliability of the conclusions that were drawn from the results is thus questionable. We here re-evaluate those quantification methods (plus a few more modern ones) on exactly the same datasets, this time following a now consolidated and robust experimental protocol (which also involves simulating the presence, in the test data, of class prevalence values very different from those of the training set). This experimental protocol (even without counting the newly added methods) involves a number of experiments 5,775 times larger than that of the original study. Due to the above-mentioned presence, in the test data, of samples characterised by class prevalence values very different from those of the training set, the results of our experiments are dramatically different from those obtained by Gao and Sebastiani, and provide a different, much more solid understanding of the relative strengths and weaknesses of different sentiment quantification methods.
| S-EPMC9481048 | biostudies-literature
Project description:Protein kinase D (PKD) signaling plays a critical role in the regulation of DNA synthesis, proliferation, cell survival, adhesion, invasion/migration, motility, and angiogenesis. To date, relatively little is known about the potential role of PKD in the development and/or progression of human colorectal cancer. We evaluated the expression of different PKD isoforms in colorectal cancer and investigated the antitumor activity of PKD inhibitors against human colorectal cancer. PKD2 was the dominant isoform expressed in human colon cancer cells. PKD3 expression was also observed but PKD1 expression, at both the RNA and protein levels, was not detected. Suppression of PKD using the small molecule inhibitors CRT0066101 and kb-NB142-70 resulted in low micromolar in vitro antiproliferative activity against multiple human colorectal cancer cell lines. Drug treatment was associated with dose-dependent suppression of PKD2 activation. Incubation with CRT0066101 resulted in G(2)-M phase arrest and induction of apoptosis in human colorectal cancer cells. Further studies showed that CRT0066101 treatment gave rise to a dose-dependent increase in expression of cleaved PARP and activated caspase-3, in addition to inhibition of AKT and ERK signaling, and suppression of NF-?B activity. Transfection of PKD2-targeted siRNAs resulted in similar effects on downstream pathways as observed with small molecule inhibitors. Daily administration of CRT0066101 resulted in significant inhibition of tumor growth in HCT116 xenograft nude mice. Taken together, our studies show that PKD plays a significant role in mediating growth signaling in colorectal cancer and may represent a novel chemotherapeutic target for the treatment of colorectal cancer.
| S-EPMC4019967 | biostudies-literature