ACE2 Deficiency Enhances Angiotensin II-Mediated Aortic Profilin-1 Expression, Inflammation and Peroxynitrite Production

Inflammation and oxidative stress play a crucial role in angiotensin (Ang) II-mediated vascular injury. Angiotensin-converting enzyme 2 (ACE2) has recently been identified as a specific Ang II-degrading enzyme but its role in vascular biology remains elusive. We hypothesized that loss of ACE2 would facilitate Ang II-mediated vascular inflammation and peroxynitrite production. 10-week wildtype (WT, Ace2+/y) and ACE2 knockout (ACE2KO, Ace2−/y) mice received with mini-osmotic pumps with Ang II (1.5 mg.kg−1.d−1) or saline for 2 weeks. Aortic ACE2 protein was obviously reduced in WT mice in response to Ang II related to increases in profilin-1 protein and plasma levels of Ang II and Ang-(1–7). Loss of ACE2 resulted in greater increases in Ang II-induced mRNA expressions of inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, and IL-6 without affecting tumor necrosis factor-α in aortas of ACE2KO mice. Furthermore, ACE2 deficiency led to greater increases in Ang II-mediated profilin-1 expression, NADPH oxidase activity, and superoxide and peroxynitrite production in the aortas of ACE2KO mice associated with enhanced phosphorylated levels of Akt, p70S6 kinase, extracellular signal-regulated kinases (ERK1/2) and endothelial nitric oxide synthase (eNOS). Interestingly, daily treatment with AT1 receptor blocker irbesartan (50 mg/kg) significantly prevented Ang II-mediated aortic profilin-1 expression, inflammation, and peroxynitrite production in WT mice with enhanced ACE2 levels and the suppression of the Akt-ERK-eNOS signaling pathways. Our findings reveal that ACE2 deficiency worsens Ang II-mediated aortic inflammation and peroxynitrite production associated with the augmentation of profilin-1 expression and the activation of the Akt-ERK-eNOS signaling, suggesting potential therapeutic approaches by enhancing ACE2 action for patients with vascular diseases

Oral cancer knowledge, attitudes, and practices among dentists in Khartoum State, Sudan

The dental professions hold an important responsibility in the control of oral cancer and the early diagnosis highly depends on their knowledge. The present study was developed to assess the knowledge, attitude, and practice of dentists in Khartoum State regarding oral cancer prevention and early detection. An administered questionnaire was structured and sent to all licensed 130 dentists working in public dental clinics in Khartoum State. Responses to the questionnaire were analyzed using descriptive and analytical statistics. Although the majority of the dentists were knowledgeable about the major risk factors of oral cancer, more than half of the dentists reported they do not carry out any special examination to detect oral cancer in age 40 and above in asymptomatic patients. Dentists indicated their lack of training as the main barrier for conducting a comprehensive oral cancer examination. Interestingly, the vast majority of the dentists express their interest to have further oral cancer educational and training sessions. The findings of the present study suggested strongly that educational and training interventions are necessary to enhance preventive measures which may lead to reduce mortality and morbidity from oral cancer

Characterisation of the cancer-associated glucocorticoid system:key role of 11β-hydroxysteroid dehydrogenase type 2

Background:Recent studies have shown that production of cortisol not only takes place in several non-adrenal peripheral tissues such as epithelial cells but, also, the local inter-conversion between cortisone and cortisol is regulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). However, little is known about the activity of this non-adrenal glucocorticoid system in cancers.Methods:The presence of a functioning glucocorticoid system was assessed in human skin squamous cell carcinoma (SCC) and melanoma and further, in 16 epithelial cell lines from 8 different tissue types using ELISA, western blotting and immunofluorescence. 11β-HSD2 was inhibited both pharmacologically and by siRNA technology. Naïve CD8 + T cells were used to test the paracrine effects of cancer-derived cortisol on the immune system in vitro. Functional assays included cell-cell adhesion and cohesion in two-and three-dimensional models. Immunohistochemical data of 11β-HSD expression were generated using tissue microarrays of 40 cases of human SCCs as well as a database featuring 315 cancer cases from 15 different tissues.Results:We show that cortisol production is a common feature of malignant cells and has paracrine functions. Cortisol production correlated with the magnitude of glucocorticoid receptor (GR)-dependent inhibition of tumour-specific CD8 + T cells in vitro. 11β-HSDs were detectable in human skin SCCs and melanoma. Analyses of publicly available protein expression data of 11β-HSDs demonstrated that 11β-HSD1 and-HSD2 were dysregulated in the majority (73%) of malignancies. Pharmacological manipulation of 11β-HSD2 activity by 18β-glycyrrhetinic acid (GA) and silencing by specific siRNAs modulated the bioavailability of cortisol. Cortisol also acted in an autocrine manner and promoted cell invasion in vitro and cell-cell adhesion and cohesion in two-and three-dimensional models. Immunohistochemical analyses using tissue microarrays showed that expression of 11β-HSD2 was significantly reduced in human SCCs of the skin.Conclusions:The results demonstrate evidence of a cancer-associated glucocorticoid system and show for the first time, the functional significance of cancer-derived cortisol in tumour progression

Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

Assessment of multi-strain PGPRs biofertilization as compared to sole-strain or mineral n-fertilization on wheat plants grown in clayey soil in Egypt

A field experiment was performed at Malawi Station, Agric. Res. Center (ARC), Minia, Egypt during 2004-2005 and 2005-2006 winter seasons, to investigate the response of bread wheat (Triticum aestivum L.) cv. Sids 1, grown in clayey soil to inoculation with plant-growth promoting rhizobacteria (PGPRs) such as cyanobacteria spp; Serratia sp; Rhizobium leguminosarum bv. viciae and Bacillus polymyxa either solely or in combinations in comparison to mineral N-fertilization, Full N-dose; 75 Kg N/fed. Results revealed the superiority of Bacillus polymyxa for increasing wheat growth and productivity followed by Serratia, Cyanobacteria, and Rhizobium inoculation. Concerning combined inoculations, tetras combination treatment caused the highest increases in wheat parameters, triple combinations were the second, dual combinations were the third and the sole inoculation caused lower increases but still higher than control treatment. On the other hand, full dose of N-fertilizers recorded increases ranged between those of tetras and those of triple combinations. Also, results confirmed the necessity of combined applications with N2-fixers and its superiority on mineral N-fertilizations for wheat productivity.Egyptian Journal of Biotechnology Vol. 25 (1) 2007: pp. 27-4

CASSAVA AS NEW ANIMAL FEED IN EGYPT 3 - PELLETED COMPLETE CASSAVA FEED FOR GROWING RABBITS

[EN] Forty New Zealand White rabbits (20 males and 20 females) aged 5 weeks, of 735g in average weight, were divided into two groups on basis of weight and sex. A pelleted complete rabbit feed containing 45 % cassava products (CCF diet) as 30 % root meal + 15 % leaf meal, was formulated to be fed in comparison with a commercial feed (AF diet ; Atmida Cº) during the 15 weeks of experiment, divided in 3 stages of 5 weeks. 1 % urea was added to the CCF diet in arder to increase the N-content. The results indicated that CP digestibility and N-balance of CCF were significantly (P<0.05) lower than that in AF diet in the first 5 weeks after weaning (1st stage). But the CP digestibility and N-balance were not significantly different between two Qroups fed CCF and AF diets at 15 weeks after weaning (3rá stage). The CF digestibility was not significantly affected by type of feed and it was improved by advance in age of rabbits fed CCF or AF diets. In contrast N-balance was decreased with advancing of age of two groups of growing rabbits. No significant effect of sex was observed on digestibility or N-balance. The feed intake was significantly (P<0.01) lower with CCF diet than that with AF diet in 1 st and 2nd stages. Daily body gain was significantly (P<0.01) lower with rabbits fed CCF than those fed AF diets in 1 st stage but it was nearly similar between two groups at 2nd and 3rd stages. Feed conversion (feed/gain) was more efficient with rabbits fed AF than those fed CCF diets at 1 st stage but opposite trend was observed in 2nd and 3rd stages of growth. Slaughter and carcass traits showed no significant differences between the two groups fed CCF and AF diets. There were no significant differences in feed intake, feed conversion and daily body gain between male and female rabbits. Conclusively, it could be appear that cassava products (roots and leaves) can be used satisfactorily as the partial substitute for traditional energy and protein supplements to formulating pelleted diet for growing rabbits.[FR] Quarante lapins Néo-zélandais Blancs (20 males et 20 feme/les) agés de 5 semaines, pesant en moyenne 735g ont été divisés en deux groupes compte tenu de leur sexe et de leur poids. lis ont rer;u au cours des 15 semaines d'expérience, soit un aliment granulé complet (CCF) contenant 45 % de manioc (30 % de farine de racines et 15 % de farine de feuilles) soit un aliment complet (Atmida CJe) du commerce (AF). 1 % d'urée a été ajouté au régime CCF afin d'augmenter la teneur en azote. Les résultats indiquent que la digestibilité des PB et le bilan azoté du régime CCF etaient significativement plus bas que ceux du régime AF dans les 5 premiares semaines apres le sevrage (1 ere période). Mais la digestibilité des PB et le bilan azoté n'étaient pas significativement différents entre les deux groupes (CCF et AF) 15 semaines apres le sevrage (3eme période). La digestibilité de la cellulose brute n'était pas affectée par le régime, par contre, elle s'est améliorée avec l'age. A l'inverse, le bilan azoté s'est dégradé avec l'age, au sein des deux lots. Aucun effet de sexe n'a été observé pour la digestibilité ou le bilan azoté. La consommation était significativement plus basse (P<0.01) avec le régime CCF qu'avec le régime AF au cours des 1 ere et 2eme périodes. Le gain de poids journalier était significativement plus bas avec l'aliment CCF qu'avec l'aliment AF au cours de la premiare période mais il était presque identique dans les deux groupes au cours des 2eme et 3eme périodes. L'efficacité alimentaire était supérieure avec l'aliment AF comparé a l'aliment CCF pendant la premiare période, mais une tendance contraire a été observée durant la 2eme et 3eme périodes de croissance. Les caractéristiques d'abattage et de carcasse ne présentaient pas de différences significatives entre les deux groupes. 11 n'y avait pas de différences significatives entre males et feme/les concernant la consommation, /'indice de consommation et le gain de poids journalier. En conclusion il apparait que le manioc (feuilles et racines) peut etre utilisé de maniere satisfaisante comme substitut partiel des composants traditionnels énergétiques et azotés dans des formules d'aliments granulés pour lapins en croissance.Abd El-Baki, S.; Nowar, M.; Bassuny, S.; Hassona, E.; Soliman, E. (1993). CASSAVA AS NEW ANIMAL FEED IN EGYPT 3 - PELLETED COMPLETE CASSAVA FEED FOR GROWING RABBITS. World Rabbit Science. 1(4). doi:10.4995/wrs.1993.207SWORD1

No Association Between Ct Value and COVID-19 Severity and Mortality in Qatar.

The association between the cycle threshold (Ct) which reflects the SARS-CoV-2 viral load and the severity of COVID-19 is still not clear. We investigated the association between Ct values, symptoms and the risk of ICU admission and mortality from COVID-19 in Qatar. This case-control study used data of hospitalized individuals with confirmed COVID-19 during the period March to September 2020. Cases were defined as individuals with confirmed COVID-19 who were admitted to the intensive care unit (ICU) or died and controls as those who were not admitted to the ICU. The association between Ct value, symptoms, ICU admission and mortality was investigated using Ct value as a categorical variable (below and above 25) in multivariable regression models and adjusted for relevant confounders. A total of 622 participants with median age 53 (IQR: 53-63), of which 69% were males, were included. There were 236 ICU admissions and 111 deaths. When categorized, Ct value (<25 vs ≥25) had no association with the odds of ICU admission (OR 0.85, 95% CI 0.56 to 1.29) or odds of mortality (OR 1.21, 95% CI 0.71 to 2.08). Respiratory (OR 2.95, 95% CI 1.57 to 5.56) and gastrointestinal symptoms (OR 1.99, 95% CI 1.18 to 3.35) were associated with higher odds of ICU admission. Similarly, respiratory (OR 4.96, 95% CI 1.10 to 22.43) and gastrointestinal symptoms (OR 3.17, 95% CI 1.29 to 7.84) were associated with higher odds of mortality. Although RT-PCR Ct has good diagnostic value, its prognostic value appears to be unreliable. Respiratory and gastrointestinal symptoms are associated with COVID-19 criticality and mortality in this setting.Open access funding provided by the Qatar National Library

Radioactivity concentrations and their radiological significance in sediments of the Tema Harbour (Greater Accra, Ghana)

Studies on environmental radioactivity in tropical Africa are scarce. Therefore, a baseline study of natural (238U, 210Pb, 226Ra, 232Th, 228Ra, 228Th, 40K) and anthropogenic (137Cs) radionuclides was carried out on Tema Harbour (Greater Accra, Ghana) surface sediments and on their radiological significance. Grab surface sediment samples were collected from 21 stations within the Tema Harbour and their radioactivity concentrations measured by gamma spectrometry. The mean sediment radioactivity concentrations (Bq kg−1 dw) were 34 for 238U, 210 for 210Pb, 14 for 226Ra, 30 for 232Th, 29 for 228Ra, 31 for 228Th, 320 for 40K, and 1.5 for 137Cs. Large 238U/226Ra disequilibria were observed in the harbour sediments and a complex dynamics of several mixed sources of sediments within the Tema Harbour can be inferred from the spatial variations in the radioactivity concentrations. The estimated total absorbed dose rate in air (D), radium equivalent activity (Raeq), external hazard index (Hex), annual gonadal dose equivalent (AGDE) and annual effective dose equivalent (AEDE) indicated no significant radiological risks from the sediment radioactivity concentrations. Application of the Environmental Risk from Ionising Contaminants Assessment and Management tool (ERICA) confirmed that the potential dose rates to biota from the sediment radioactivity concentrations are unlikely to pose appreciable ecological risks. The radioactivity levels are compared with levels reported in sediments from other coastal areas of the world