| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Chen, Yan-Ting, et al.
(författare)
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Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:27, s. 32967-32983
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Tidskriftsartikel (refereegranskat)abstract
- Due to the mortality associated with thrombosis and its highrecurrence rate, there is a need to investigate antithrombotic approaches.Noninvasive site-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targeting efficiency, poorability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms,and risk of thrombus recurrence that is comparable to that of traditionalpharmacological thrombolysis agents. Therefore, it is vital to develop an alternativetechnique that can overcome the aforementioned limitations. To this end, a cottonball-shaped platelet (PLT)-mimetic self-assembly framework engineered with aphototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has beendeveloped. This platform is capable of delivering a synthetic peptide derived fromhirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors fornoninvasive site-specific thrombolysis, effective anticoagulation, and vascularrestoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequentlyrupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability ofthe P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancingbioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination cansignificantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultantphototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLTnanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.
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| 3. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 5. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 6. |
- Chen, Min-Wei, et al.
(författare)
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H3K9 histone methyltransferase G9a promotes lung cancer invasion and metastasis by silencing the cell adhesion molecule Ep-CAM
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:20, s. 7830-7840
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Tidskriftsartikel (refereegranskat)abstract
- G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression.
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| 7. |
- Chien, Ming-Hsien, et al.
(författare)
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Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway.
- 2009
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 30:12, s. 2005-13
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF)-C is recognized as a tumor lymphangiogenic factor based on the effects of activated VEGF-R3 on lymphatic endothelial cells. Many tumor cells express VEGF-R3 but the function of this receptor in tumor cells is largely unknown. It has been reported that the VEGF-C/VEGF-R3 axis is activated in subsets of leukemia patients. Herein, we have shown that VEGF-C induces angiogenic activity in the tube formation assay invitro and Matrigel plug assay in vivo by upregulating an angiogenic factor, cyclooxygenase-2 (COX-2), through VEGF-R3 in the human acute myeloid leukemia (AML) cell line, THP-1. COX-2 induction by VEGF-C was also observed in other VEGF-R3(+) human AML cell lines (U937 and HL60). Moreover, immunohistochemical analysis of bone marrow specimens of 37 patients diagnosed with AML revealed that VEGF-C expression in specimens was associated with the expression of COX-2 (P < 0.001). The manner by which signaling pathways transduced by VEGF-C is responsible for COX-2 upregulation was further investigated. Blocking the p42/44 mitogen-activated protein kinase (MAPK) pathway with the MAPK kinase inhibitor, PD 98059, failed to inhibit VEGF-C-mediated COX-2 expression. However, VEGF-C-induced COX-2 upregulation was effectively abolished by overexpression of dominant-negative c-Jun N-terminal kinase (JNK) or treatment with the JNK inhibitor, SP 600125. VEGF-C induced JNK-dependent nuclear translocation of c-Jun. Furthermore, chromatin immunoprecipitation and reporter assays revealed that VEGF-C enhanced c-Jun binding to the cyclic adenosine 3',5'-monophosphate-response element of the COX-2 promoter and induced COX-2 expression. In sum, the data herein highlight the pathogenic role of VEGF-C in leukemia via regulation of angiogenesis through upregulation of COX-2.
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| 8. |
- Dumitrescu, Adrian, et al.
(författare)
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Finding Small Complete Subgraphs Efficiently
- 2023
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Ingår i: Combinatorial Algorithms - 34th International Workshop, IWOCA 2023, Proceedings. - 1611-3349 .- 0302-9743. - 9783031343469 ; 13889 LNCS, s. 185-196
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Konferensbidrag (refereegranskat)abstract
- (I) We revisit the algorithmic problem of finding all triangles in a graph G= (V, E) with n vertices and m edges. According to a result of Chiba and Nishizeki (1985), this task can be achieved by a combinatorial algorithm running in O(mα) = O(m3 / 2) time, where α= α(G) is the graph arboricity. We provide a new very simple combinatorial algorithm for finding all triangles in a graph and show that is amenable to the same running time analysis. We derive these worst-case bounds from first principles and with very simple proofs that do not rely on classic results due to Nash-Williams from the 1960s. (II) We extend our arguments to the problem of finding all small complete subgraphs of a given fixed size. We show that the dependency on m and α in the running time O(αℓ-2· m) of the algorithm of Chiba and Nishizeki for listing all copies of Kℓ, where ℓ≥ 3, is asymptotically tight. (III) We give improved arboricity-sensitive running times for counting and/or detection of copies of Kℓ, for small ℓ≥ 4. A key ingredient in our algorithms is, once again, the algorithm of Chiba and Nishizeki. Our new algorithms are faster than all previous algorithms in certain high-range arboricity intervals for every ℓ≥ 7.
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| 9. |
- Hashemzehi, Mojgan, et al.
(författare)
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Modelling and optimization of main independent parameters for biodiesel production over a Cu0.4Zn0.6Al2O4 catalyst using an RSM method
- 2021
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Ingår i: Journal of chemical technology and biotechnology (1986). - : John Wiley & Sons. - 0268-2575 .- 1097-4660. ; 97:1, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- In this research, the modeling of Cu0.4Zn0.6Al2O4 catalysts performance and optimizing of esterification reactions were considered by the central composite design (RSM) response method. The main independent parameters of temperature, the ratio of alcohol to oil, the amount of catalyst and time duration have been considered for setting the esterification process. To access the maximum activity in the esterification process, the optimum conditions are estimated at 10.42 the molar ratio of alcohol to oil, 2.98 wt.% for the amount of catalyst at the temperature of 163.37 degrees C and within 4.15 hrs. Under these conditions, the conversion will be above 97.94%. These conditions have been applied to adjust the process of transesterification of waste cooking oil. The reusability of the Cu0.4Zn0.6Al2O4 nanocatalyst in the esterification reaction was investigated in this study. Employed statistical techniques and developed models can be employed as a useful tool for design, prediction, and optimization of the biodiesel production process with effective performance for various industrial applications. (c) 2021 Society of Chemical Industry (SCI).
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| 10. |
- Hsieh, Yves S-Y, et al.
(författare)
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Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 16:11, s. 6054-68
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Tidskriftsartikel (refereegranskat)abstract
- Detailed structures of the active polysaccharides extracted from the leaf and stem cell walls and mucilage of Dendrobium huoshanense are determined by using various techniques, including chromatographic, spectroscopic, chemical, and enzymatic methods. The mucilage polysaccharide exhibits specific functions in activating murine splenocytes to produce several cytokines including IFN-gamma, IL-10, IL-6, and IL-1alpha, as well as hematopoietic growth factors GM-CSF and G-CSF. However, the deacetylated mucilage obtained from an alkaline treatment fails to induce cytokine production. The structure and bioactivity of mucilage components are validated by further fractionation. This is the first study that provides clear evidence for the structure and activity relationship of the polysaccharide in D. huoshanense.
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