Role of NK Cell Subsets in Organ-Specific Murine Melanoma Metastasis

Tumor metastasis plays a major role in the morbidity and mortality of cancer patients. Among solid tumors that undergo metastasis, there is often a predilection to metastasize to a particular organ with, for example, prostate cancer preferentially metastasizing to bones and colon cancer preferentially metastasizing to the liver. Although many factors are thought to be important in establishing permissiveness for metastasis, the reasons for organ-specific predilection of each tumor are not understood. Using a B16 murine melanoma model, we tested the hypothesis that organ-specific NK cell subsets play a critical role in organ-specific metastasis of this tumor. Melanoma cells, given intravenously, readily colonized the lungs but not the liver. NK cell depletion (either iatrogenically or by using genetically targeted mice) resulted in substantial hepatic metastasis. Analysis of NK cell subsets, defined by the differential expression of a combination of CD27 and CD11b, indicated a significant difference in the distribution of NK cell subsets in the lung and liver with the mature subset being dominant in the lung and the immature subset being dominant in the liver. Several experimental approaches, including adoptive transfer, clearly indicated that the immature hepatic NK cell subset, CD27+ CD11b–, was protective against liver metastasis; this subset mediated its protection by a perforin-dependent cytotoxic mechanism. In contrast, the more mature NK cell subsets were more efficient at reducing pulmonary tumor load. These data indicate that organ-specific immune responses may play a pivotal role in determining the permissiveness of a given organ for the establishment of a metastatic niche.     

Effect of intralipid infusion on lecithin:cholesterol acyltransferase and lipoprotein lipase in young rats

We compared the effects of Intralipid and dextrose infusion on plasma lecithin:cholesterol acyltransferase (LCAT), plasma lipid profiles and lipolytic activity. We used 5-week-old male Sprague-Dawley rats which were given total parenteral nutrition (TPN) with either Intralipid (3 g/kg body weight) or an equicaloric amount of 25% dextrose in the presence or absence of heparin (1 or 10 IU/ml of TPN). 40 min after the end of 4 h of infusion, plasma LCAT activity was significantly decreased (P less than 0.001), while total cholesterol and free fatty acid levels were significantly (P less than 0.05) increased in rats given Intralipid as compared to those given dextrose. We found associations (P less than 0.005) between LCAT activity and total cholesterol and between LCAT and free fatty acid levels; the coefficients of negative correlation were 0.543 and 0.607, respectively. Concomitantly to the increment in plasma total cholesterol levels, there was a decrease in the high-density lipoprotein (HDL) cholesterol fraction; the latter, which was 40% of the total plasma cholesterol in control and dextrose-infused rats, declined to 9% in rats given Intralipid. Administration of heparin during Intralipid infusion, even up to 10 IU/ml of TPN, did not affect any of these changes. After dextrose infusion, the values of all three parameters were similar to those of the control group. Plasma lipolytic activity was not significantly different between rats given infusion (Intralipid or dextrose) and controls. However, in the presence of heparin, plasma lipolytic activity increased similarly in both infused groups. These data indicate that in young rats, Intralipid infusion leads to an increase in plasma total cholesterol and free fatty acid levels, which correlates with a decrease in LCAT activity; the concurrent decrease in HDL cholesterol levels might account, in part, for the loss of LCAT activity. The administration of heparin results in an elevation of plasma lipolytic activity; however, it does not prevent the hypercholesterolemia, nor the decline in LCAT activity associated with Intralipid infusion.     

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.     

Study of DYRK1B gene expression and its association with metabolic syndrome in a small cohort of Egyptians

Molecular Biology Reports - A cluster of many risk factors for type 2 diabetes and cardiovascular disease is used to describe the metabolic syndrome (MetS). Moreover, genetic differences associated...     

Hyaluronic acid optimises therapeutic effects of hydrogen peroxide‐induced oxidative stress on breast cancer

Distinguishing the multiple effects of reactive oxygen species (ROS) on cancer cells is important to understand their role in tumour biology. On one side, ROS can be oncogenic by promoting hypoxic conditions, genomic instability and tumorigenesis. Conversely, elevated levels of ROS‐induced oxidative stress can induce cancer cell death. This is evidenced by the conflicting results of research using antioxidant therapy, which in some cases promoted tumour growth and metastasis. However, some antioxidative or ROS‐mediated oxidative therapies have also yielded beneficial effects. To better define the effects of oxidative stress, in vitro experiments were conducted on 4T1 and splenic mononuclear cells (MNCs) under hypoxic and normoxic conditions. Furthermore, hydrogen peroxide (H₂O₂; 10–1,000 μM) was used as an ROS source alone or in combination with hyaluronic acid (HA), which is frequently used as drug delivery vehicle. Our result indicated that the treatment of cancer cells with H₂O₂ + HA was significantly more effective than H₂O₂ alone. In addition, treatment with H₂O₂ + HA led to increased apoptosis, decreased proliferation, and multiphase cell cycle arrest in 4T1 cells in a dose‐dependent manner under normoxic or hypoxic conditions. As a result, migratory tendency and the messenger RNA levels of vascular endothelial growth factor, matrix metalloproteinase‐2 (MMP‐2), and MMP‐9 were significantly decreased in 4T1 cells. Of note, HA treatment combined with 100–1,000 μM H₂O₂ caused more damage to MNCs as compared to treatment with lower concentrations (10–50 μM). Based on these results, we propose to administer high‐dose H₂O₂ + HA (100–1000 μM) for intratumoural injection and low doses for systemic administration. Intratumoural route could have toxic and inhibitory effects not only on the tumour but also on residential myeloid cells defending it, whereas systemic treatment could stimulate peripheral immune responses against the tumour. More in vivo research is required to confirm this hypothesis.     

Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design,synthesis, molecular docking studies and ADMET prediction

Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.     

Small and overlooked: Phylogeny of the genus Trigonodactylus (Squamata: Gekkonidae), with the first record of Trigonodactylus arabicus from Jordan

Geckos of the genus Trigonodactylus are widely distributed in the sand deserts of the Arabian Peninsula. Three species of this genus are currently recognized, with a fourth one, Stenodactylus pulcher, which placement within Trigonodactylus has been tentatively suggested, but not yet confirmed. We present a phylogenetic analysis of the genus Trigonodactylus with new specimens collected in central Saudi Arabia and southern Jordan. New genetic data has been generated from three mitochondrial markers to investigate the phylogenetic relationships of all species of the genus and to assess the putative generic assignment of S. pulcher. Our results confirm that S. pulcher indeed belongs within Trigonodactylus, branching as a sister lineage to all other species of the genus. The new samples cluster within Trigonodactylus arabicus, thus confirming the genetic homogeneity of the species across its large and seemingly inhospitable range. The new specimen collected in southern Jordan represents the first record for the country and a considerable range extension to the northwest from all previously reported localities. Our findings and discovery of a new species for Jordan highlight the need of more field surveys to be carried out in the underexplored parts of Jordan and northern Saudi Arabia, as these places still hold a potential for new discoveries and are crucial for understating the biogeography of the Arabian herpetofauna.     

Examining the reliability of the flexor carpi radialis V-wave at different levels of muscle contraction

This study examined the reliability and scaling of the flexor carpi radialis (FCR) V-wave during submaximal and maximal voluntary muscle contractions (MVC). 23 participants were tested on three separate sessions. For each session, participants performed isometric wrist flexions at five contraction levels (20, 40, 60, 80 and 100 %MVC). When the target contraction level was reached, a supramaximal electrical stimulus was applied to the median nerve in order to elicit an FCR V-wave. Across all participants, the FCR V-wave amplitude, normalized to its superimposed M-wave amplitude, increased from 0.030 ± 0.001 to 0.143 ± 0.015 (P < 0.001) as the muscle contraction increased from 20 to 100 %MVC. Contraction level did not influence the reliability of evoking the FCR V-wave, as the V-wave demonstrated both stability and consistency. With the exception of a single day main effect during the 20 %MVC condition, V:M_sup was not different across days or trials (P > 0.05) indicating measurement stability. High reliability co-efficients (0.827–0.913) at each contraction level signified measurement consistency. This study establishes that FCR V-waves can be reliably evoked during both submaximal and maximal muscle contractions and suggests the possibility for FCR V-wave recordings to be used to document neuromuscular adaptations associated with factors such as training or fatigue.