A new ant species of the genus Tapinoma (Hymenoptera, Formicidae) from Saudi Arabia with a key to the Arabian species

Tapinoma wilsonisp. n. is described and illustrated from Saudi Arabia based on the worker caste collected from Al Baha, Saudi Arabia. It closely resembles Tapinoma lugubre Santschi 1917, from Zimbabwe in body measurements but can be distinguished from the latter species by the yellowish brown color; the yellowish pubescence, the two pairs of hairs present on the anterior part of the head; and the distinctly concave anterior clypeal margin. Biological and ecological notes of the new species are presented. An identification key to the workers of the Arabian species of the genus Tapinoma is given.     

Synthesis,potential antitumor activity,cell cycle analysis,and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study

Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4–24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59–14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI₅₀) of 0.26 µM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC₅₀) of 2.97 and 6.94 μM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC₅₀ = 0.2 and 0.19 μM, respectively) and HER2 (IC₅₀ = 0.13 and 0.07 μM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity.     

CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290

Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD are included in the rapidly expanding group of disorders called ciliopathies, because all six gene products implicated in JSRD (NPHP1, AHI1, CEP290, RPGRIP1L, TMEM67, and ARL13B) function in the primary cilium/basal body organelle. By using homozygosity mapping in consanguineous families, we identify loss-of-function mutations in CC2D2A in JSRD patients with and without retinal, kidney, and liver disease. CC2D2A is expressed in all fetal and adult tissues tested. In ciliated cells, we observe localization of recombinant CC2D2A at the basal body and colocalization with CEP290, whose cognate gene is mutated in multiple hereditary ciliopathies. In addition, the proteins can physically interact in vitro, as shown by yeast two-hybrid and GST pull-down experiments. A nonsense mutation in the zebrafish CC2D2A ortholog (sentinel) results in pronephric cysts, a hallmark of ciliary dysfunction analogous to human cystic kidney disease. Knockdown of cep290 function in sentinel fish results in a synergistic pronephric cyst phenotype, revealing a genetic interaction between CC2D2A and CEP290 and implicating CC2D2A in cilium/basal body function. These observations extend the genetic spectrum of JSRD and provide a model system for studying extragenic modifiers in JSRD and other ciliopathies.     

Synthesis,anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies

A new series of quinazolinone compounds 16–34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC₅₀: 10.38–38.67?μM and 9.91–15.77?μM, respectively); the comparative IC₅₀ values for 5-fluorouracil and erlotinib in these cells lines were 70.28?μM, 22.24?μM and 15.23?μM, 25.31?μM respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10?μM, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone.

Graphical Abstract: Compound 31 showed potent antitumor activity and efficient inhibitory effect against EGFR-TK and induced apoptosis of MDA-MB-231 cells at a concentration of 10?μM.     

Relationship Between IL-2, IL-17 Concentrations,and Serum Creatinine Levels in Men with Chronic Kidney Diseases

Background:Chronic kidney disease (CKD), is a major public health challenge worldwide. It is more prevalent in developed countries compared with the rest of the world, due to the higher rates of life expectancy and unhealthy lifestyle related factors. This aim of the current study is to evaluate the relationship between interleukins IL-2 and IL-17 concentrations and kidney function markers in men with CKD.Methods:Forty-five men with CKD and seventy controls were enrolled in the current study to assess the relationship between interleukin-2 (IL-2), interleukin-17 (IL-17), and CKD parameters. Fasting blood samples were collected from patients with CKD and their controls at same time. Serum IL-2, and IL-17 were measured in patients with CKD and their controls, and then the relationship between these interleukins and serum creatinine, serum urea, serum uric acid and urine albumin were evaluated.Results:A significant relationship was detected between IL-2 (p< 0.001), IL-17 (p< 0.001) levels and serum creatinine concentrations. The significant increase of IL-2 and IL-17 levels were also paralleled with a significant increase in serum urea (p< 0.001), and urine albumin (p< 0.001) concentrations respectively.Conclusion:IL-2 and IL-17 may play a critical role in the pathophysiology of CKD. The significant increase of IL-2 and IL-17 is associated with significantly high concentrations of creatinine, serum urea and urine albumin suggesting that these interleukins may be used as targets for future biomarkers and molecular therapy. However, due to limited sample size of the current study, larger prospective cohorts are needed to confirm these observations.Key Words: Chronic kidney disease, Interleukins, Serum creatinine, Serum urea, Urine albumin     

Hypoxia,a dynamic tool to amplify the gingival mesenchymal stem cells potential for neurotrophic factor secretion

Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC’s had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation.     

Ribosylation of bovine serum albumin induces ROS accumulation and cell death in cancer line (MCF-7)

Formation of advanced glycation end products (AGE) is crucially involved in the several pathophysiologies associated with ageing and diabetes, for example arthritis, atherosclerosis, chronic renal insufficiency, Alzheimer’s disease, nephropathy, neuropathy, and cataracts. Because of devastating effects of AGE and the significance of bovine serum albumin (BSA) as a transport protein, this study was designed to investigate glycation-induced structural modifications in BSA and their functional consequences in breast cancer cell line (MCF-7). We incubated d-ribose with BSA and monitored formation of d-ribose-glycated BSA by observing changes in the intensity of fluorescence at 410 nm. NBT (nitro blue tetrazolium) assay was performed to confirm formation of keto-amine during glycation. Absorbance at 540 nm (fructosamine) increased markedly with time. Furthermore, intrinsic protein and 8-anilino-1-naphthalenesulfonate (ANS) fluorescence revealed marked conformational changes in BSA upon ribosylation. In addition, a fluorescence assay with thioflavin T (ThT) revealed a remarkable increase in fluorescence at 485 nm in the presence of glycated BSA. This suggests that glycation with d-ribose induced aggregation of BSA into amyloid-like deposits. Circular dichroism (CD) study of native and ribosylated BSA revealed molten globule formation in the glycation pathway of BSA. Functional consequences of ribosylated BSA on cancer cell line, MCF-7 was studied by MTT assay and ROS estimation. The results revealed cytotoxicity of ribosylated BSA on MCF-7 cells.     

Platyphylloside,a potential inhibitor from epicarp of B. aegyptiaca against CYP450 protein in T. rubrum – In vitro and in silico approaches

Trichophyton rubrum is one of the major disease causing pathogens in human; mainly it causes tinea pedis, tinea cruris and tinea corporis. Cytochrome P450 which considered to be an important protein that can impact ergosterol biosynthesis pathway. B. aegyptiaca is rich source of secondary metabolites with tremendous medicinal values and it has sweet pulp, leaves with spine, strong seed and oily kernel. The epicarp of the fruit was taken for this study to inhibit T. rubrum using in vitro and in silico techniques. The epicarp portion was extracted using various solvents and water. The anti-dermatophytic activity on T. rubrum of these extracts was assessed utilizing poison plate technique with 5 individual concentrations. The fractioned chloroform extract of epicarp had fully inhibited the growth of T. rubrum at 3 mg/ml. Further, the chloroform extract was subjected to LC-MS analysis, in total, 40 compounds were elucidated. Then, the derived compounds were included for predicting ADMETox properties using Qikprop module. From the analysis 40 compounds were identified to be eligible for docking process. Then the desirable compounds, drug Ketoconazole were subjected to docking analysis using Glide module of Schrödinger. It shows that Platyphylloside has better docking result than other compounds and drug Ketoconazole. Further, MD simulation was carried out for Ketoconazole-Cyp450 and Platyphylloside-CYP450 complexes using Desmond, Schrödinger. MD simulation study also confirmed that the Platyphylloside-CYP450 complex more stable. This study suggests that Platyphylloside may act as potential inhibitor and it could be further subjected to experimental analysis to inhibit the T. rubrum growth.     

Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS)

Abstract Asymptomatic infection due to Bordetella pertussis has been suggested to be one cause of sudden infant death syndrome (SIDS). We examined developmental and environmental factors previously found to affect binding of another toxigenic species, Staphylococcus aureus , to human epithelial cells: expression of the Lewis^a antigen; infection with respiratory syncytial virus (RSV); exposure to cigarette smoke; and the inhibitory effect of breast milk on bacterial binding. Binding of two strains of B. pertussis (8002 and 250825) to buccal epithelial cells was significantly reduced by treating the cells with monoclonal antibodies to Lewis^a ( P < 0.05) and Lewis^x ( P < 0.01) antigens. Both strains bound in significantly greater numbers to cells from smokers compared with cells from non-smokers ( P < 0.05). HEp-2 cells infected with RSV subtypes A or B had higher binding indices for both 8002 ( P < 0.001) and 250825 ( P < 0.01). On RSV-infected cells, there was significantly enhanced binding of monoclonal antibodies to Lewis^x ( P < 0.05), CD14 ( P < 0.001) and CD18 ( P < 0.01); and pre-treatment of cells with anti-CD14 or CD18 also significantly reduced binding of both strains of B. pertussis . Pre-treatment of the bacteria with human milk significantly reduced their binding to epithelial cells. The results are discussed in relation to our three-year survey of bacterial carriage among 253 healthy infants, their mothers and local SIDS cases between 1993–1995 and in relation to the change to an earlier immunisation schedule for infants and the recent decline in SIDS in Britain.     

Sodium louroyl sarcosinate (sarkosyl) modulate amyloid fibril formation in hen egg white lysozyme (HEWL) at alkaline pH: a molecular insight study

Amyloid fibril formation is responsible for several neurodegenerative diseases and are formed when native proteins misfold and stick together with different interactive forces. In the present study, we have determined the mode of interaction of the anionic surfactant sarkosyl with hen egg white lysozyme (HEWL) [EC No. 3.2.1.17] at two pHs (9.0 and 13.0) and investigated its impact on fibrillogenesis. Our data suggested that sarkosyl is promoting amyloid fibril formation in HEWL at the concentration range between 0.9 and 3.0 mM and no amyloid fibril formation was observed in the concentration range of 3.0–20.0 mM at pH 9.0. The results were confirmed by several biophysical and computational techniques, such as turbidity measurement, dynamic light scattering, Raleigh scattering, ThT fluorescence, intrinsic fluorescence, far-UV CD and atomic force microscopy. Sarkosyl was unable to induce aggregation in HEWL at pH 13.0 as confirmed by turbidity and RLS measurements. HEWL forms larger amyloid fibrils in the presence of 1.6 mM of sarkosyl. The spectroscopic, microscopic and molecular docking data suggest that the negatively charged carboxylate group and 12-carbon hydrophobic tail of sarkosyl stimulate amyloid fibril formation in HEWL via electrostatic and hydrophobic interaction. This study leads to new insight into the process of suppression of fibrillogenesis in HEWL which can be prevented by designing ligands that can retard the electrostatic and hydrophobic interaction between sarkosyl and HEWL.