Search

Cadmium (Cd) has become a critical problem in freshwater ecosystems because of both increasing levels and high toxicity. Hence, this study aimed to investigate the effects of dietary supplementation of turmeric powder (TP) alone or in combination with black pepper powder (BPP) on the Cd-induced growth and health disturbances in the African catfish (Clarias gariepinus). A total of 180 healthy fish were divided into six groups in triplicate. The first, second, and third groups were fed on a non-supplemented basal diet, a basal diet supplemented with TP (0.5%), and a basal diet supplemented with TP (0.5%) + BPP (0.1%), respectively. The fourth group was exposed to Cd (0.8 mg/L water) only. The fifth and sixth groups were exposed to Cd and fed on diets supplemented with TP or TP + BPP. The growth performance indicators, somatic indices, whole chemical composition, and Cd residues were evaluated. The liver and kidney function indicators, reproductive hormones, oxidative stress, lipid peroxidation, and adenosine triphosphate (ATP) content were estimated. A histopathological investigation and immunohistochemical detection of the apoptotic marker, caspase 3 of hepatic, renal, and testicular tissues were performed. The results showed that Cd reduced growth, crude lipid, protein, ash contents, and hepatosomatic and gonadosomatic indexes. Moreover, considerably elevated levels of alanine transaminase, alkaline phosphatase, lactate dehydrogenase, urea, creatinine, potassium, and malondialdehyde were recorded. However, a considerable depletion of lysozyme activity, immunoglobulin M, testosterone, estradiol, catalase, and superoxide dismutase in addition to ATP content was evident. The highest amount of Cd was detected in the liver compared with that in the muscles. Moreover, the impairment of hepatic, renal, and testicular tissues architecture with high expression of caspase 3 was prominent. However, the addition of TP and TP + BPP in the diet of Cd-intoxicated fish restored the disturbances in most of the indicators. Notably, the combined TP + BPP supplementation achieved the highest recovery. Overall, TP + BPP mixture can be added in C. gariepinus diet to enhance growth and ameliorate the hepatotoxic, nephrotoxic, and reprotoxic effects of Cd.

Application of herbal immune-stimulants for modulation of fish growth and immune response has received great interest during the past decades. With several pharmacological properties, Doum palm, Hyphaene thebaica (Mart.) is known to be a beneficial medicinal plant. The objective of this study was to investigate the effects of the dietary addition of doum palm fruit powder (DPFP) on growth performance, non-specific immune response, and antioxidant parameters of African catfish, Clarias gariepinus (B.). A total of 120 fish (average initial weight 60.50 &plusmn, 0.04 g) were randomly allocated to four groups (three replicates/group, 10 fish/aquarium), a basal diet without DPFP supplementation was used as a control, and three other diets were prepared by supplementing 5, 10, or 15 g kg&minus, 1 DPFP for a ten-week feeding period. Following ten weeks of feeding, the fish were challenged with Aeromonas hydrophila (as an immune challenge test), and mortalities were recorded. In comparison to the control diet, dietary DPFP significantly improved growth parameters, including final body weight, body weight gain (WG), specific growth rate (SGR), feed conversion ratio (FCR), and protein efficiency ratio (PER), along with an increase in the content of dry matter of the whole body, in a concentration-dependent manner. Moreover, the heights of intestinal villi, numbers of goblet cells, and intraepithelial lymphocytes (IEL) exhibited marked escalation in all parts of the intestine by increasing the level of DPFP, except for numbers of IEL in the proximal part. The decline in serum glucose, cholesterol, and triglyceride levels was prominent in DPFP10 and DPFP15 groups respective to the DPFP0 group. Furthermore, DPFP boosted the hepatic level of catalase (CAT) in the fish, in a dose-dependent manner, meanwhile, the activity of superoxide dismutase (SOD) and reduced glutathione (GSH) content were also augmented in DPFP10 and DPFP15 groups respective to the DPFP0 group. Dietary DPFP (DPFP15 followed by DPFP10 then DPFP5) led to a pronounced enhancement in the innate immune response (phagocytic percent and index, lysozyme activity, nitric oxide (NO) production, and sialoglycans, namely &alpha, 2,3-sialyltransferase and &alpha, 2,6-sialyltransferase content), however, the myeloperoxidase (MPO) activity was reduced. Significantly higher relative percentage survival (RPS, 88.56%) of the fish, following the A. hydrophila challenge, was observed for the DPFP15 group. We can suggest that DPFP can beneficially influence fish growth, intestinal histomorphology, hepatic levels of catalase (CAT), superoxide dismutase (SOD) activity and glutathione (GSH) content, immune response, and disease resistance against A. hydrophila challenge.

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15 min, 2.46 nM nanomagnetolectin significantly promoted apoptosis (~12-fold, p value

Abnormal cell surface display of sialic acids - a family of unusual 9-carbon sugars - is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an "Achilles' heel" that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural monosaccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer "sialome" they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.

In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platform to measure and compare the binding affinity of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor (VEGFR) and VEGF to bevacizumab. Results have shown that bevacizumab binds VEGF with a higher association rate and affinity compared to VEGFR. Further, this platform has been employed to mimic the in vivo condition of the VEGF–VEGFR angiogenic switch. Competitive binding to VEGF between VEGFR and bevacizumab was monitored in real-time using this platform. Results demonstrated a significant blockage of VEGF–VEGFR binding by bevacizumab. From the results, it is evident that the proposed strategy is simple and highly sensitive for the direct and real-time measurements of bevacizumab drug efficacy to the VEGF–VEGFR angiogenic switch in living SKOV-3 cells.

The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approaching maturity, but their different glycosylation compositions relevant to early diagnosis still remain practically unexplored at the sub-glycoproteome scale. Lectins generally exhibit strong binding to specific sub-glycoproteome components and this property has been quite poorly addressed as the basis for the early diagnosis methods. Here, we discuss some glycoproteome issues that make tackling the glycoproteome particularly challenging in the cancer biomarkers field and include a brief view for next generation technologies.

The terminal monosaccharide of glycoconjugates on a eukaryotic cell surface is typically a sialic acid (Neu5Ac). Increased sialylation usually indicates progression and poor prognosis of most carcinomas. Here, we utilize two human mammary epithelial cell lines, HB4A (breast normal cells) and T47D (breast cancer cells) as a model system to demonstrate differential surface glycans when treated with sialic acid under nutrient deprivation. Under a starved condition, sialic acid treatment of both cells resulted in increased activities of α2→3/6 sialyltransferases as demonstrated by solid phase assay using lectin binding. However, a very strong MAL-I (Maackia amurensis agglutinin I) staining on the membrane of sialic acid treated T47D cells was observed, indicating an increase of Neu5Acα2→3Gal on the cell surface. To our knowledge, this is a first report showing the utility of lectins, particularly MAL-I, as a means to discriminate between normal and cancer cells after sialic acid treatment under nutrient deprivation. This method is sensitive and allows selectively detection of glycan sialylation on a cancer cell surface.

A plant lectin isolated in its pure state from the Egyptian seeds of Pisum sativum (PSL) produced two bands in SDS–PAGE (5.53 and 19.3 kDa; i.e. α and β chain) but one peak by gel filtration chromatography on Sephadex G-100, corresponding to 50 kDa, i.e., a dimeric structure of two monomers, each consisting of one α and one β subunit. PSL is a glycoprotein bound with glucose (2 mol/mol of protein) and stabilized by 2 atoms of each of Ca 2+ and Mn 2+ per molecule of protein. It highly agglutinated human, rabbit and rat erythrocytes but weakly agglutinated chicken erythrocytes, while no agglutination occurred with sheep erythrocytes. Hemagglutination was markedly affected by acidic pH, but was heat stable below 60 °C for 30 min. Among the various tested sugars, PSL agglutination was most inhibited by mannose. PSL is rich in hydroxyl amino acids while totally lacking sulfur amino acids. PSL inhibited the growth of Aspergillus flavus, Trichoderma viride and Fusarium oxysporum .

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools.

To determine the outcome of infants born to diabetic mothers at Security Forces Hospital, Riyadh, Saudi Arabia, and compare the complications seen in these infants with infants of non-diabetic mothers.This is a concurrent prospective cohort study of a population of newborn infants delivered at Security Forces Hospital, Riyadh, Saudi Arabia for diabetic mothers between January 2011 and November 2011.A total of 601 infants were enrolled in the study consisting of 319 infants of non-diabetic mothers, and 282 infants of diabetic mothers. Infants of diabetic mothers showed significantly higher rates of associated complications and prolonged hospital stay reflected in their admission to the neonatal intensive care when compared with infants of non-diabetic mothers. There was no difference in rate of complications between infants of gestational diabetics and pre-gestational diabetics.Our study showed that diabetic pregnancies are associated with an increased incidence of neonatal complications. These seem to be related to the degree of maternal glycemic control. The higher rates of complications among our infants of diabetic mothers, particularly major congenital malformations call for those involved in the care of diabetic mothers to consolidate their efforts to facilitate early booking in specialist clinics.