Influence of the dimensions of spheroniser plate protuberances on the production of pellets by extrusion-spheronisation

This study systematically investigated the influence of the dimensions of square-patterned pyramidal protuberances on a spheronisation plate on pellet yield, size and shape distributions, surface tensile strength and surface morphology was investigated using a 45 wt% microcrystalline cellulose/ water paste. Tests were conducted using four different extrudate diameters (1.0, 1.5, 2.0 and 2.5 mm) generated by screen extrusion and seven plate geometries, including a flat plate as a control, allowing the relative size of extrudate to protuberance feature to be studied. Geometrical analyses of the protuberance shapes provide some insight into the observed differences, with protuberance angle being significant in many cases. Sharper protuberances reduced yield (promoting breakage and attrition) but tended to give narrower size distributions and more uneven pellet surface. Pellet yield for 1 mm extrudates was also subject to losses caused by fragments passing through the 1.0 mm gap between the plate and spheroniser wall. Pellet tensile strength was noticeably greater for 1.0 mm diameter extrudates, which is attributed to the greater extensional strain imparted on the paste during the extrusion step. For some geometries there is an optimal ratio of extrudate to protuberance dimensions

PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma

Background Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. Methods We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Results Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Conclusions Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer

Bear bile: dilemma of traditional medicinal use and animal protection

Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future

Network Topologies and Dynamics Leading to Endotoxin Tolerance and Priming in Innate Immune Cells

The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.Comment: 15 pages, 8 figures, submitte

Maternal characteristics and obstetrical complications impact neonatal outcomes in Indonesia: a prospective study

Abstract Background We investigated associations between maternal characteristics, access to care, and obstetrical complications including near miss status on admission or during hospitalization on perinatal outcomes among Indonesian singletons. Methods We prospectively collected data on inborn singletons at two hospitals in East Java. Data included socio-demographics, reproductive, obstetric and neonatal variables. Reduced multivariable models were constructed. Outcomes of interest included low and very low birthweight (LBW/VLBW), asphyxia and death. Results Referral from a care facility was associated with a reduced risk of LBW and VLBW [AOR = 0.28, 95% CI = 0.11–0.69, AOR = 0.18, 95% CI = 0.04–0.75, respectively], stillbirth [AOR = 0.41, 95% CI = 0.18–0.95], and neonatal death [AOR = 0.2, 95% CI = 0.05–0.81]. Mothers age <20 years increased the risk of VLBW [AOR = 6.39, 95% CI = 1.82–22.35] and neonatal death [AOR = 4.10, 95% CI = 1.29–13.02]. Malpresentation on admission increased the risk of asphyxia [AOR = 4.65, 95% CI = 2.23–9.70], stillbirth [AOR = 3.96, 95% CI = 1.41–11.15], and perinatal death [AOR = 3.89 95% CI = 1.42–10.64], as did poor prenatal care (PNC) [AOR = 11.67, 95%CI = 2.71–16.62]. Near-miss on admission increased the risk of neonatal [AOR = 11.67, 95% CI = 2.08–65.65] and perinatal death [AOR = 13.08 95% CI = 3.77–45.37]. Conclusions Mothers in labor should be encouraged to seek care early and taught to identify early danger signs. Adequate PNC significantly reduced perinatal deaths. Improved hospital management of malpresentation may significantly reduce perinatal morbidity and mortality. The importance of hospital-based prospective studies helps evaluate specific areas of need in training of obstetrical care providers

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The role of CD147 expression in prostate cancer: a systematic review and meta-analysis

Yun Ye,1,2,* Su-Liang Li,2,* Yao Wang,2 Yang Yao,2 Juan Wang,1 Yue-Yun Ma,1 Xiao-Ke Hao1 1Department of Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, 2Department of Clinical Laboratory, The First Affiliated Hospital of Xi&rsquo;an Medical University, Xi&rsquo;an, Shaanxi, People&rsquo;s Republic of&nbsp;China *These authors contributed equally to&nbsp;this work Background: There are a number of studies which show that expression of CD147 is increased significantly in prostate cancer (PCa). However, conflicting conclusions have also been reported by other researchers lately. In order to arrive at a clear conclusion, a meta-analysis of eligible studies was conducted.Materials and methods: We searched PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases to identify all the published case&ndash;control studies on the relationship between the expression of CD147 and PCa until February 2016. In the end, a total of 930 patients in eight studies were included in the meta-analysis.Results: CD147 expression in the PCa patients increased significantly (odds ratio [OR], 4.65; 95% confidence interval [CI], 3.52&ndash;6.14; Z=10.79; P&lt;0.05), but there was obvious heterogeneity between studies (I2=92.9%, P&lt;0.05). Subgroup analysis showed that positive expression of CD147 was associated with PCa among the Asian population (OR, 21.01; 95% CI, 12.88&ndash;34.28; Z=12.19; P&lt;0.05). Furthermore, it was significantly related to TNM stage (OR, 0.24; 95% CI, 0.17&ndash;0.35; Z=7.74; P&lt;0.05), Gleason score (OR, 0.41; 95% CI, 0.31&ndash;0.56; Z=5.62; P&lt;0.05), differentiation grade (OR, 0.27; 95% CI, 0.13&ndash;0.56; Z=3.47; P&lt;0.05), and pretreatment serum prostate-specific antigen level (OR, 0.07; 95% CI, 0.03&ndash;0.16; Z=6.47; P&lt;0.05).Conclusion: Positive expression of CD147 was related to PCa, significant heterogeneity was not found between Asian studies, and the result became more significant. The positive expression of CD147 was significantly related to the clinicopathological characteristics of PCa. This suggests that CD147 plays an essential role in poor prognosis and recurrence prediction. Keywords: CD147, prostate cancer, meta-analysi

pH-dependent and cathepsin B activable CaCO3 nanoprobe for targeted in vivo tumor imaging

201907 bcrcVersion of RecordPublishe