Complete genome of Phenylobacterium zucineum – a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562

<p>Abstract</p> <p>Background</p> <p><it>Phenylobacterium zucineum </it>is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, <it>P. zucineum </it>maintains a stable association with its host cell without affecting the growth and morphology of the latter.</p> <p>Results</p> <p>Here, we report the whole genome sequence of the type strain HLK1^T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to <it>Caulobacter crescentus</it>, a model species for cell cycle research. Notably, <it>P. zucineum </it>has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of <it>C. crescentus</it>, and most of the genes directly regulated by CtrA in the latter have orthologs in the former.</p> <p>Conclusion</p> <p>This work presents the first complete bacterial genome in the genus <it>Phenylobacterium</it>. Comparative genomic analysis indicated that the CtrA regulon is well conserved between <it>C. crescentus </it>and <it>P. zucineum</it>.</p

Molecular and Microenvironmental Determinants of Glioma Stem-Like Cell Survival and Invasion

Glioblastoma multiforme (GBM) is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC) subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence. GSCs are localized in a heterogeneous cellular niche, and cross talk between stromal cells and GSCs cultivates a fertile environment that promotes GSC invasion. Pro-migratory soluble factors from endothelial cells, astrocytes, macrophages, microglia, and non-stem-like tumor cells can stimulate peritumoral invasion of GSCs. Therefore, therapeutic efforts designed to target the invasive GSCs may enhance patient survival. In this review, we summarize the current understanding of extrinsic pathways and major stromal and immune players facilitating GSC maintenance and survival

Strength and Environmental Behaviours of Municipal Solid Waste Incineration Fly Ash for Cement-Stabilised Soil

Many sandy soil foundations need to be solidified during traffic construction in Guangxi, China. Because it has a similar chemical composition as cement, municipal solid waste incineration fly ash (MSWIFA) can strengthen sandy soil. However, the chloride ions and heavy metals in MSWIFA may have a negative influence on the solidification of sandy soil. Thus, FA resource use faces great challenges. This study evaluates the feasibility of using MSWIFA to solidify sandy soil. The acetic acid buffer solution method was used in the leaching test to simulate the weak acid groundwater environment in the Guangxi karst landform. The effects of the treatment methods (washing with ferrous sulphate solution, pre-treatment of organics via chelation, and adding sugarcane ash) on the strength and environmental characteristics of fly ash cement-stabilised soil (FACS) are discussed in detail. The results indicate that the FACS unconfined compressive strength (UCS) decreased by 24.82&ndash;46.64% when 5% cement was replaced with FA. Sugarcane ash effectively improved the strength of FACS by more than 10%. The leaching concentrations of Zn and Cu in the FACS meet the concentration limit set by GB 16889-2008. The leaching concentrations of Cr and Pb after washing with 6% ferrous sulphate solution were reduced by more than 30%. Meanwhile, the FACS strength developed faster. Organic chelating agents solidified most heavy metals

Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition

<div><h3>Background</h3><p>Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis.</p> <h3>Methodology</h3><p>BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed.</p> <h3>Principal Findings</h3><p>Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells.</p> <h3>Conclusions</h3><p>Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.</p> </div

Sch B does not inhibit lung metastasis of 4T1 cells using a tail vein injection or a delayed treatment model.

<p>(A) Tail vein injection model: mice (n = 10 for each group) were gavaged with Sch B (daily doses: 30 or 100 mg/kg body weight or vehicle) for 3 days prior to 4T1 cell inoculation. Then, each mouse was inoculated with 2×10⁵ 4T1 cells via tail vein injection, followed by treatment with Sch B (daily doses: gavaged with 30 or 100 mg/kg body weight or vehicle) for the next consecutive 7 days and sacrificed on day 18. (B) Delayed treatment model. Mice (n = 10 for each group) were inoculated with 5×10⁴ 4T1 cells <i>s.c</i>. into the second right mammary fat pad area, and the primary tumors were resected on day 10. Sch B (100 mg/kg body weight) or vehicle was given every day from day 13–19 for a total of 7 doses, and mice were sacrificed on day 30. The lung metastasis was scored by macroscopic metastatic nodule as described in Materials and Methods. *, P<0.05, Sch B versus control group.</p

Sch B prolongs mouse survival time in dose-dependent manner.

<p>Mice (n = 8 for each group) receiving Sch B (100, 30, 10 mg/kg body weight) or vehicle every day for total 7 doses, and primary tumors were resected on day 10. (A) Mouse survival time. (B) Mouse body weight. (C) Tumor weight resected on day 10. *, P<0.05, **, P<0.01, Sch B versus control group.</p

Sch B inhibits local invasion of 4T1 cells <i>in vivo</i>.

<p>Mice (n = 20 for each group) were treated with Sch B (100 mg/kg body weight) or vehicle intragastrically daily for 7 days. (A) Primary tumors and surrounding tissues were resected on day 15 for hematoxylin-eosin stain (upper, ×40, lower, ×100). (B) immunostaining of E-cadherin and vimentin.(×100).</p

An inflammation-based cumulative prognostic score system in patients with diffuse large B cell lymphoma in rituximab era

Abstract Background Systemic inflammatory parameters are associated with poor outcomes in malignant patients. Several inflammation-based cumulative prognostic score systems were established for various solid tumors. However, there is few inflammation based cumulative prognostic score system for patients with diffuse large B cell lymphoma (DLBCL). Methods We retrospectively reviewed 564 adult DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy between Nov 1 2006 and Dec 30 2013 and assessed the prognostic significance of six systemic inflammatory parameters evaluated in previous studies by univariate and multivariate analysis:C-reactive protein(CRP), albumin levels, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio(NLR), the platelet-lymphocyte ratio(PLR)and fibrinogen levels. Results Multivariate analysis identified CRP, albumin levels and the LMR are three independent prognostic parameters for overall survival (OS). Based on these three factors, we constructed a novel inflammation-based cumulative prognostic score (ICPS) system. Four risk groups were formed: group ICPS = 0, ICPS = 1, ICPS = 2 and ICPS = 3. Advanced multivariate analysis indicated that the ICPS model is a prognostic score system independent of International Prognostic Index (IPI) for both progression-free survival (PFS) (p < 0.001) and OS (p < 0.001). The 3-year OS for patients with ICPS =0, ICPS =1, ICPS =2 and ICPS =3 were 95.6, 88.2, 76.0 and 62.2%, respectively (p < 0.001). The 3-year PFS for patients with ICPS = 0–1, ICPS = 2 and ICPS = 3 were 84.8, 71.6 and 54.5%, respectively (p < 0.001). Conclusions The prognostic value of the ICPS model indicated that the degree of systemic inflammatory status was associated with clinical outcomes of patients with DLBCL in rituximab era. The ICPS model was shown to classify risk groups more accurately than any single inflammatory prognostic parameters. These findings may be useful for identifying candidates for further inflammation-related mechanism research or novel anti-inflammation target therapies

Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010–2011 and traced for SVD progression during 2016–2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (β = 2.694, standard error [SE] = 1.112, p  = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (β = −6.737, SE = 2.685, p  = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management

Patient needs in psoriasis treatment and their influencing factors: A nationwide multicentre cross-sectional study in China

Background: The management and treatment of psoriasis has rarely considered patient needs, which are numerous, multi-dimensional and are of great importance to improving treatment outcomes. Objectives: This study aimed to evaluate and compare the patients' needs for psoriasis treatment and identify factors predicting the need to make patient-centred decisions about treatment. Materials and Methods: This nationwide multicentre cross-sectional study included subjects between October 2020 and August 2021. The status quo of the needs in psoriasis treatment and their influencing factors were analysed mainly using the Chi-square test and binary logistic regression. Results: Information on sociodemographic and clinical characteristics were obtained. Factor analysis of a specially designed questionnaire showed that rapid skin clearance, reduced treatment expense and fewer hospital visits or treatment time were the first three patient needs in psoriasis treatment. Several influencing factors were important including the sociodemographic characteristics of gender, marital status, education level and family history, special location of skin lesions, dermatology life quality index (DLQI), Investigator's Global Assessment modified 2011 (IGA mod 2011), condition of the episode, clinical type of psoriasis, seasonal exacerbation and therapy. Conclusions: Patients with psoriasis pursued a wide range of treatment goals, with the most desired being rapid skin clearance, reduced treatment expense and time-saving. Paying attention to sex, marital status, education level, the special location of skin lesions and the DLQI will help dermatologists develop patient-centred treatment, meet the patient's needs and eventually improve the treatment outcomes