Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression

Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1

BCL-W is dispensable for the sustained survival of select Burkitt lymphoma and diffuse large B-cell lymphoma cell lines

Dysregulated expression of BCL-2 family proteins allows cancer cells to escape apoptosis. To counter this, BH3-mimetic drugs that target and inhibit select BCL-2 prosurvival proteins to induce apoptosis have been developed for cancer therapy. Venetoclax, which targets BCL-2, has been effective as therapy for patients with chronic lymphocytic leukemia, and MCL-1-targeting BH3-mimetic drugs have been extensively evaluated in preclinical studies for a range of blood cancers. Recently, BCL-W, a relatively understudied prosurvival member of the BCL-2 protein family, has been reported to be abnormally upregulated in Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and Hodgkin lymphoma patient samples. Therefore, to determine if BCL-W would be a promising therapeutic target for B-cell lymphomas, we have examined the role of BCL-W in the sustained growth of human BL- and DLBCL-derived cell lines. We found that CRISPR/CAS9-mediated loss or short hairpin RNA-mediated knockdown of BCL-W expression in selected BL and DLBCL cell lines did not lead to spontaneous apoptosis and had no effect on their sensitivity to a range of BH3-mimetic drugs targeting other BCL-2 prosurvival proteins. Our results suggest that BCL-W is not universally required for the sustained growth and survival of human BL and DLBCL cell lines. Thus, targeting BCL-W in this subset of B-cell lymphomas may not be of broad therapeutic benefit

Nation, Migration, Identity: Learning from the Cross-Strait Context

It has been argued that globalisation, with its flexible landscapes of production, consumption and mobility, has favoured the emergence of new forms of belonging and identity that are not necessarily built on such principles of the nation state. In this paper, we argue that this process is more likely to happen when movements occur between states that are not in conflictual relations with each other. When the relations between two nations are shaped by conflicts, for instance due to disputes about sovereignty over a territory, nationalism may remain a crucial factor shaping identification and belonging of those who move between the two territories. In this paper, by taking the case of migrants moving between the People’s Republic of China and Taiwan, we will shed light on how the issue of “unresolved sovereignty” may eventually lead these actors to reinforce nationalist ideals and identities in their daily narratives and practices, instead of favouring the generation of hybrid identities

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)

The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants

Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.

Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases

Analysis of COVID-19 Guideline Quality and Change of Recommendations: A Systematic Review.

Background Hundreds of coronavirus disease 2019 (COVID-19) clinical practice guidelines (CPGs) and expert consensus statements have been developed and published since the outbreak of the epidemic. However, these CPGs are of widely variable quality. So, this review is aimed at systematically evaluating the methodological and reporting qualities of COVID-19 CPGs, exploring factors that may influence their quality, and analyzing the change of recommendations in CPGs with evidence published. Methods We searched five electronic databases and five websites from 1 January to 31 December 2020 to retrieve all COVID-19 CPGs. The assessment of the methodological and reporting qualities of CPGs was performed using the AGREE II instrument and RIGHT checklist. Recommendations and evidence used to make recommendations in the CPGs regarding some treatments for COVID-19 (remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir) were also systematically assessed. And the statistical inference was performed to identify factors associated with the quality of CPGs. Results We included a total of 92 COVID-19 CPGs developed by 19 countries. Overall, the RIGHT checklist reporting rate of COVID-19 CPGs was 33.0%, and the AGREE II domain score was 30.4%. The overall methodological and reporting qualities of COVID-19 CPGs gradually improved during the year 2020. Factors associated with high methodological and reporting qualities included the evidence-based development process, management of conflicts of interest, and use of established rating systems to assess the quality of evidence and strength of recommendations. The recommendations of only seven (7.6%) CPGs were informed by a systematic review of evidence, and these seven CPGs have relatively high methodological and reporting qualities, in which six of them fully meet the Institute of Medicine (IOM) criteria of guidelines. Besides, a rapid advice CPG developed by the World Health Organization (WHO) of the seven CPGs got the highest overall scores in methodological (72.8%) and reporting qualities (83.8%). Many CPGs covered the same clinical questions (it refers to the clinical questions on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir in COVID-19 patients) and were published by different countries or organizations. Although randomized controlled trials and systematic reviews on the effectiveness of treatments of remdesivir, glucocorticoids, hydroxychloroquine/chloroquine, interferon, and lopinavir-ritonavir for patients with COVID-19 have been published, the recommendations on those treatments still varied greatly across COVID-19 CPGs published in different countries or regions, which may suggest that the CPGs do not make sufficient use of the latest evidence. Conclusions Both the methodological and reporting qualities of COVID-19 CPGs increased over time, but there is still room for further improvement. The lack of effective use of available evidence and management of conflicts of interest were the main reasons for the low quality of the CPGs. The use of formal rating systems for the quality of evidence and strength of recommendations may help to improve the quality of CPGs in the context of the COVID-19 pandemic. During the pandemic, we suggest developing a living guideline of which recommendations are supported by a systematic review for it can facilitate the timely translation of the latest research findings to clinical practice. We also suggest that CPG developers should register the guidelines in a registration platform at the beginning for it can reduce duplication development of guidelines on the same clinical question, increase the transparency of the development process, and promote cooperation among guideline developers all over the world. Since the International Practice Guideline Registry Platform has been created, developers could register guidelines prospectively and internationally on this platform

Promoting Effect of Layered Titanium Phosphate on the Electrochemical and Photovoltaic Performance of Dye-Sensitized Solar Cells

We reported a composite electrolyte prepared by incorporating layered α-titanium phosphate (α-TiP) into an iodide-based electrolyte using 1-ethyl-3-methylimidazolium tetrafluoroborate(EmimBF4) ionic liquid as solvent. The obtained composite electrolyte exhibited excellent electrochemical and photovoltaic properties compared to pure ionic liquid electrolyte. Both the diffusion coefficient of triiodide (I3−) in the electrolyte and the charge-transfer reaction at the electrode/electrolyte interface were improved markedly. The mechanism for the enhanced electrochemical properties of the composite electrolyte was discussed. The highest conversion efficiency of dye-sensitized solar cell (DSSC) was obtained for the composite electrolyte containing 1wt% α-TiP, with an improvement of 58% in the conversion efficiency than the blank one, which offered a broad prospect for the fabrication of stable DSSCs with a high conversion efficiency

Caregiver awareness of reproductive health issues for women with intellectual disabilities

<p>Abstract</p> <p>Background</p> <p>Limited attention has been paid to the issue of reproductive health as it affects women with intellectual disabilities, despite reproductive health being a vital issue in public health policy for women in the general population. This paper describes caregiver awareness of reproductive health issues relative to women with intellectual disabilities who are being cared for in welfare institutions in Taiwan.</p> <p>Methods</p> <p>The study employed a cross-sectional, questionnaire-based study which recruited 1,152 caregivers (response rate = 71.87%) from 32 registered disability welfare institutions in Taiwan. We classified their understanding/awareness of reproductive health issues into four domains: menstrual (1) and menopause (2) issues, sex education (3), and reproductive health services (4). Each domain had five associated yes/no questions and the total score for the four domains was out of a maximum of 20. Data were analyzed using SPSS 15.0 software.</p> <p>Results</p> <p>We found that most of the caregivers were familiar with matters concerning sex education, menopause, and reproductive health services, but they lacked adequate understanding of issues associated with menstruation in women with ID. Many aspects of reproductive health such as "menstrual pain", "age at menarche", "masturbation", "diet during perimenopause", and "publicly available reproductive health services" were issues in which caregivers lacked adequate knowledge and required further instruction. Logistic regression analysis revealed that female caregivers with a university degree, and those who had experience assisting with reproductive health care were more inclined to have higher reproductive health awareness scores than their counterparts.</p> <p>Conclusions</p> <p>This study highlights that service providers should offer appropriate reproductive health education to institutional caregivers, and that more attention be focused on the personal experiences and concerns of intellectually disabled women in future research.</p