Stokholmbrown2215
Cancer patients have problems coping with new circumstances. They need support and help to understand and accept their situation.
Cancer patients have problems coping with new circumstances. They need support and help to understand and accept their situation.Correction to European Review for Medical and Pharmacological Sciences 2018; 22 (15) 4861-4868-DOI 10.26355/eurrev_201808_15622-PMID 30070317, published online 15 August 2018. After publication, the authors found some mistakes in the article. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. learn more https//www.europeanreview.org/article/15622.Ischemic stroke leads to substantial mortality and morbidity worldwide. Door-to-CT time, door-to-needle time (DNT), and door-to-groin time (DGT) are important quality indicators of stroke care. However, patient characteristics remain important determinants of outcome as well. In this single-center study, we investigated the interaction between these quality indicators and stroke severity regarding long-term functional outcome. All consecutive stroke patients treated at the ZOL stroke center, Genk, Belgium, between 2017 and 2020 were included in this retrospective observational study. Stroke severity was graded as "mild" if National Institutes of Health Stroke Scale (NIHSS) was equal to or lower than 8, "moderate" if NIHSS was between 9 and 15, and "severe" if NIHSS was higher than 16. Modified Rankin Scale (mRS) scores were collected before and 3 months after stroke. Ordinal regression analysis with correction for patient characteristics of functional outcome was done. link2 A total of 1255 patients were included, of which 84% suffered an ischemic CVA (n = 1052) and 16% a TIA (n = 203). The proportion of patients treated conservatively or with thrombolysis, thrombectomy, or the combination of both differed according to stroke severity (p less then 0.0001). Door-to-CT time was longer in mild and moderate stroke (p less then 0.0001). Median DNT also differed between stroke categories 46 (IQR 31-70) min for mild vs. 36 (25-56) min for moderate vs. 30 (21-45) min for severe stroke (p = 0.0002). Median DGT did not differ between stroke severity categories (p = 0.15). NIHSS on admission and pre-stroke mRS were independently associated with mRS at 90 days. Operational performance, reflected in door-to-CT time and DNT, was worse in patients with mild and moderate stroke severity. DNT was also associated with functional outcome in our center, along with pre-stroke mRS, NIHSS on admission and age.In many countries, Sinophobia or discrimination against Chinese has taken place amid the Covid-19 pandemic. While this wave of Sinophobia is popularly understood to be based on a stereotypical association of Chinese with coronavirus, I argue that at a time of international tensions surrounding China, political antipathy toward China and Chinese matters as well. Thus, there is a phenomenon of "triple conflation" in which the health, racial, and political/national statuses of Chinese people become intermingled. In this study, I examine this triple conflation based on dozens of select cases covering Sinophobic actions of governments, politicians, media, businesses and lay persons in North America, Australia, New Zealand, and Western Europe. My study consists of three parts using three respective interdisciplinary approaches. First, using a sociological approach, I argue that the racial and national statuses of Chinese are both, and sometimes interchangeably, used as identity markers for implementing containment, a public health measure that easily leads to stigmatization. Second, using a discursive approach, I examine how political claims unfavorable to China/Chinese are constructed in discussions of the pandemic. Third, using an interpretive approach, I analyze how Covid bio-political metaphors present certain imaginaries depicting Chinese as suspicious bio-political subjects. These three parts are unified in my analysis of the geopolitics of belonging, in which Chinese people's rights to certain social and physical spaces are contested sometimes thorough administrative means (such as travel restriction) and sometimes through mental representations (such as the imagination of Chinese as alien).
Cancer stem cells represent a cancer cell subpopulation that has been found to be associated with metastasis and chemoresistance. Therefore, it is vital to identify mechanisms regulating cancer stemness. Previously, we have shown that the atypical cyclin P (CCNP), also known as CNTD2, is upregulated in lung and colorectal cancers and is associated with a worse clinical prognosis. Given that other cyclins have been implicated in pluripotency regulation, we hypothesized that CCNP may also play a role in cancer stemness.
Cell line-derived spheroids, ex vivo intestinal organoid cultures and induced-pluripotent stem cells (iPSCs) were used to investigate the role of CCNP in stemness. The effects of CCNP on cancer cell stemness and the expression of pluripotency markers and ATP-binding cassette (ABC) transporters were evaluated using Western blotting and RT-qPCR assays. Cell viability was assessed using a MTT assay. The effects of CCNP on WNT targets were monitored by RNA-seq analysis. Data from publicly available web-based resources were also analyzed.
We found that CCNP increases spheroid formation in breast, lung and colorectal cancers, and upregulates the expression of stemness (CD44, CD133) and pluripotency (SOX2, OCT4, NANOG) markers. In addition, we found that CCNP promotes resistance to anticancer drugs and induces the expression of multidrug resistance ABC transporters. Our RNA-seq data indicate that CCNP activates the WNT pathway, and that inhibition of this pathway abrogates the increase in spheroid formation promoted by CCNP. Finally, we found that CCNP knockout decreases OCT4 expression in iPSCs, further supporting the notion that CCNP is involved in stemness regulation.
Our results reveal CCNP as a novel player in stemness and as a potential therapeutic target in cancer.
Our results reveal CCNP as a novel player in stemness and as a potential therapeutic target in cancer.Sepsis is life-threatening organ dysfunction caused by a dysregulated inflammatory and immune response to infection. Sepsis involves the combination of exaggerated inflammation and immune suppression. During systemic infection and sepsis, the liver works as a lymphoid organ with key functions in regulating the immune response. Extracellular nucleotides are considered damage-associated molecular patterns and are involved in the control of inflammation. Their levels are finely tuned by the membrane-associated ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) enzyme family. Although previous studies have addressed the role of NTPDase1 (CD39), the role of the other extracellular NTPDases, NTPDase2, -3, and -8, in sepsis is unclear. In the present studies we identified NTPDase8 as a top downregulated gene in the liver of mice submitted to cecal ligation-induced sepsis. Immunohistochemical analysis confirmed the decrease of NTPDase8 expression at the protein level. In vitro mechanistic studies using HepG2 hepatoma cells demonstrated that IL-6 but not TNF, IL-1β, bacteria, or lipopolysaccharide are able to suppress NTPDase8 gene expression. NTPDase8, as well as NTPDase2 and NTPDase3 mRNA was downregulated, whereas NTPDase1 (CD39) mRNA was upregulated in polymorphonuclear leukocytes from both inflamed and septic patients compared to healthy controls. Although the host's inflammatory response of polymicrobial septic NTPDase8 deficient mice was no different from that of wild-type mice, IL-6 levels in NTPDase8 deficient mice were higher than IL-6 levels in wild-type mice with pneumonia. Altogether, the present data indicate that extracellular NTPDases are differentially regulated during sepsis.High-fat diets lead to accumulation of body fat that is associated with the onset of insulin resistance and type II diabetes mellitus. link3 On the other hand, photobiomodulation (PBM) is an electrophysical resource that interacts with cells, stimulating mitochondrial respiration, increasing ATP production, reducing key inflammatory mediators, inhibiting apoptosis, and stimulating angiogenesis. However, little is known about its therapeutic effectiveness on the development of diabetes in diet-induced obese mice. Thus, our aim was to evaluate the effect of PBM applied single point over the pancreas area on glucose homeostasis, insulin expression, and pancreatic morphometric parameters of mice submitted to high-fat diet for 12 weeks. Male mice C57BL6/J were divided into three groups control group (C), diabetic group (D), and diabetic + PBM (D + PBM). The treatment with PBM started at 9th week and ended in the 12th week, applied 3 × /week. Body mass, fast blood glucose, and glucose and insulin tolerance were evaluated. Immunohistochemistry to detect insulin expression and pancreatic morphometry were also performed. At the end of 12th week, both groups submitted to high-fat diet showed an increase in body mass, adiposity, disturbances on glucose homeostasis, and high insulin expression when compared to the control group. However, mice treated with PBM had more discrete impairments on glucose homeostasis during the glucose tolerance test when compared to untreated D animals. Despite modest, the results were positive and encourage future investigations to explore different doses and duration of PBM to better elucidate its role in obesity-associated type 2 diabetes development.In cutaneous leishmaniasis, infection of dendritic cells (DC) is essential for generation of T cell-dependent protective immunity. DC acquires Leishmania major through Fc receptor (FcR)-mediated uptake of complexes comprising antibodies bound to parasites. We now assessed the development of the initial B cell and DC response to the parasite itself and if natural IgG play a role. L. major parasites display large numbers of phospholipids on their surface. Parasites were opsonized with normal mouse serum (NMS), or serum containing anti-phospholipid IgG (PL). We found that L. major bound to PL which significantly enhanced parasite phagocytosis by DC as compared to NMS. Similar results were obtained with cross-reactive human PL antibodies using myeloid primary human DC. In addition, mice infected with PL-opsonized parasites showed significantly improved disease outcome compared to mice infected with NMS-opsonized parasites. Finally, IgMi mice, which produce membrane-bound IgM only and no secreted antibodies, displayed increased susceptibility to infection as compared to wild types. Interestingly, once NMS was administered to IgMi mice, their phenotype was normalized to that of wild types. Upon incubation with IgG-opsonized parasite (IgG derived from infected mice or using PL antibodies), also the IgMi mice were able to show superior immunity. Our findings suggest that "natural" cross-reactive antibodies (e.g., anti-PL Ab) in NMS bind to pathogens to facilitate phagocytosis, which leads to induction of protective immunity via preferential DC infection. Prior L. major-specific B cell-priming does not seem to be absolutely required to facilitate clearance of this important human pathogen in vivo. KEY MESSAGES We found that anti-phospholipid (anti-PL) antibodies enhance phagocytosis of L. major by DCs. We also found that normal mouse sera have natural antibodies that can imitate PL specific antibodies. Using different genetically modified mice, we found that these antibodies can be IgG, not only IgM.