P-selectin glycoprotein ligand 1 promotes T cell lymphoma development and dissemination

P-selectin glycoprotein ligand-1 (PSGL-1) is a membrane-bound glycoprotein expressed in lymphoid and myeloid cells. It is a ligand of P-, E- and L-selectin and is involved in T cell trafficking and homing to lymphoid tissues, among other functions. PSGL-1 expression has been implicated in different lymphoid malignancies, so here we aimed to evaluate the involvement of PSGL-1 in T cell lymphomagenesis and dissemination. PSGL-1 was highly expressed at the surface of human and mouse T cell leukemia and lymphoma cell lines. To assess its impact on T cell malignancies, we stably expressed human PSGL-1 (hPSGL-1) in a mouse thymic lymphoma cell line, which expresses low levels of endogenous PSGL-1 at the cell surface. hPSGL-1-expressing lymphoma cells developed subcutaneous tumors in athymic nude mice recipients faster than control empty vector or parental cells. Moreover, the kidneys, lungs and liver of tumor-bearing mice were infiltrated by hPSGL-1-expressing malignant T cells. To evaluate the role of PSGL-1 in lymphoma cell dissemination, we injected intravenously control and hPSGL-1-expressing lymphoma cells in athymic mice. Strikingly, PSGL-1 expression facilitated disease infiltration of the kidneys, as determined by histological analysis and anti-CD3 immunohistochemistry. Together, these results indicate that PSGL-1 expression promotes T cell lymphoma development and dissemination to different organs.We thank Roger McEver, José M Almendral, Hind Medyouf, João T Barata and Neil D Perkins for providing reagents and cells, André Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Fundação para a Ciência e a Tecnologia (Portugal), European Social Fund , European Regional Development Fund ( PTDC/SAU-OBD/103336/2008 , PTDC/MED-ONC/32592/2017 , UID/BIM/04773/2013 , NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead GÉNESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ). We thank Roger McEver, Jos? M Almendral, Hind Medyouf, Jo?o T Barata and Neil D Perkins for providing reagents and cells, Andr? Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Funda??o para a Ci?ncia e a Tecnologia (Portugal), European Social Fund, European Regional Development Fund (PTDC/SAU-OBD/103336/2008, PTDC/MED-ONC/32592/2017, UID/BIM/04773/2013, NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead G?NESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122)

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Could giardiasis be a risk factor for low zinc status in schoolchildren from northwestern Mexico? A cross-sectional study with longitudinal follow-up

<p>Abstract</p> <p>Background</p> <p>Both giardiasis and zinc deficiency are serious health problems worldwide. In Mexico, the prevalence of <it>G. intestinalis </it>was estimated at 32% in 1994. It remains a health problem in northwestern Mexico. Recent surveys (1987, 1995, and 1999) reported zinc deficiency in the Mexican population. The association of giardiasis and malabsorption of micronutrients has been well documented, although the association with zinc remains controversial. This study investigated the association between giardiasis and zinc deficiency in schoolchildren from northwestern Mexico.</p> <p>Methods</p> <p>We combined a cross-sectional design with a longitudinal follow-up six months after parasite treatment. The baseline sample consisted of 114 schoolchildren (mean age 8.8 yr) from seven suburban public schools, grouped as <it>Giardia</it>-free (<it>n </it>= 65, 57%) and <it>Giardia</it>-infected (<it>n </it>= 49, 43%). Three stool analyses per child were done using Faust's method. Children with giardiasis received secnidazole. Serum zinc was determined by atomic absorption spectrophotometry. Height and weight were measured. Socioeconomic information was obtained in an oral questionnaire, and daily zinc intake was assessed using 24 hour-recalls. Pearson's correlation and ANCOVA and paired t-test analyses were used to determine the association between giardiasis and zinc status.</p> <p>Results</p> <p>Longitudinal analysis demonstrated a significant increase of the mean serum zinc levels in the <it>Giardia</it>-infected group six months after treatment (13.78 vs. 19.24 μmol/L μmol/L; p = 0.001), although no difference was found between the <it>Giardia</it>-free and the <it>Giardia</it>-infected groups (p = 0.86) in the baseline analysis. Z scores for W/A and H/A were lower in the <it>Giardia</it>-infected than in the <it>Giardia</it>-free group (p < 0.05). No difference was observed in the socioeconomic characteristics and mean daily intakes of zinc between the groups (p > 0.05).</p> <p>Conclusions</p> <p>Giardiasis may be a risk factor for zinc deficiency in schoolchildren from northwestern Mexico.</p

Laxative effects of partially defatted flaxseed meal on normal and experimental constipated mice

<p>Abstract</p> <p>Background</p> <p>Constipation is a very common health problem in the world. Intake of sufficient amount of dietary fibers is a cornerstone in the prevention and treatment of constipation. As a traditional medicine, flaxseed has been used to treat constipation for centuries, but the controlled trials are rare. The purpose of the present study was to assess that whether partially defatted flaxseed meal (PDFM) has the potential role to facilitate fecal output in normal and experimental constipated mice.</p> <p>Methods</p> <p>After supplemented with 2.5%, 5% and 10% (w/w) PDFM (L-, M- and H -PDFM) for 14 days, the constipation models of mice were induced by atropine-diphenoxylate. The small intestinal transit rates, start time of defecation, amount of defecation and wet weight of feces were researched in normal and constipation model mice.</p> <p>Results</p> <p>M- and H-PDFM significantly increase small intestinal transit rates in constipation model mice. All dose of PDFM markedly shortened the start time of defecation and M- and H-PDFM significantly increase stool frequency and weight in both normal and constipation model mice.</p> <p>Conclusions</p> <p>PDFM may be a useful laxative to facilitate fecal output in normal and constipation conditions.</p

Constitutive modelling of skin ageing

The objective of this chapter is to review the main biomechanical and structural aspects associated with both intrinsic and extrinsic skin ageing, and to present potential research avenues to account for these effects in mathematical and computational models of the skin. This will be illustrated through recent work of the authors which provides a basis to those interested in developing mechanistic constitutive models capturing the mechanobiology of skin across the life course

The emerging role of magnetic resonance imaging and multidetector computed tomography in the diagnosis of dilated cardiomyopathy

Magnetic resonance imaging and multidetector computed tomography are new imaging methods that have much to offer clinicians caring for patients with dilated cardiomyopathy. In this article we briefly describe the clinical, pathophysiological and histological aspects of dilated cardiomyopathy. Then we discuss in detail the use of both imaging methods for measurement of chamber size, global and regional function, for myocardial tissue characterisation, including myocardial viability assessment, and determination of arrhythmogenic substrate, and their emerging role in cardiac resynchronisation therapy