Inhibitory effect of Taraxacum officinale L (Compositae) aqueous root extract on spermatogenesis

Purpose: To investigate if T. officinale root aqueous extract has anti-spermatogenic activity similar to that of the whole plant which was shown previously to inhibit spermatogenesis.Methods: T. officinale aqueous extract was prepared by soaking 100 g of dried materials in 1 L distilled water for two days at 45 oC. Fifty adult male rats were divided into five groups and treated for 60 days. Four groups were gavaged with the whole plant or root aqueous extract in low or high doses. The male rat rats were allowed to mate with female rats. The control group received distilled water. Sperm count, motility and morphology as well as chromatin integrity were evaluated.Results: Serum testosterone level, sperm parameters, pregnancy rate and average number of fetuses per pregnant females decreased significantly in the treated groups compared to control and in the rootreceiving rats compared to the whole plant-receiving rats. Female rats which were mated with high dose root-receiving males did not deliver fetuses. Cross sections of seminiferous tubules of T. officinale treated rats showed lesions and disorganized germinal epithelium. Late spermatogenesis maturation arrest (spermatid stage) was observed in all of the treated groups except the high dose root-receiving group which showed early maturation arrest (spermatocyte stage). In addition, the mRNA level of two spermatogonial stem cell markers responsible for self-renewal and proliferation of spermatogonia increased in high dose-receiving rats.Conclusion: T. officinale root aqueous extract has inhibitory effects on spermatogenesis. Further studies are required to identify specific ingredient(s) in T. officinale that may be useful as male contraceptive(s).Keywords: Taraxacum officinale, Dandelion, GDNF family receptor alpha 1, Macrophage Colony- Stimulating Factor, Promyelocytic Leukaemia Zinc-Finger, Testosterone, Sperm coun

Novel palladium(II) and platinum(II) complexes with a fluoropiperazinyl based ligand exhibiting high cytotoxicity and anticancer activity in vitro

cis-Dichloro-palladium(II) and cis-dichloro-platinum(II) complexes (2, 4) of the general formula [M(N-N)Cl2] (M=Pd(II) and Pt(II), N-N= 1,2-diamino-4-fluoro-5-(4-methyl-1-piperazinyl) benzene, (DFMPB)) and the dicationic palladium(II) complex [Pd(N-N)(CH3CN)2](BF4)2 (3) have been prepared and characterized by elemental analysis, 1H-NMR-, mass spectroscopy, and IR spectroscopy. The cytotoxic effect of these complexes against MDA-231 and MCF-7 human breast cancer cell lines and K562 human leukemia cell line has been studied. The influence was dose dependent and varies with cell type. The palladium(II) complex (2) showed superior cytotoxic effect compared with the corresponding platinum(II) complex and the standard, cisplatin, when tested against all the above cell lines. 2016 Kayed A. Abu-Safieh et al.Scopu

Synthesis, docking study, and structure activity relationship of novel anti-tumor 1, 2, 4 triazole derivatives incorporating 2-(2, 3- dimethyl aminobenzoic acid) moiety

A series of 1,2,4 triazole derivatives (H7-12) have been synthesized by reacting an excess of hydrazine hydrate with carbothioamide derivatives (H1-6). The final compounds (HB1-HB6) were synthesized by reacting the triazole derivatives with mefenamic acid using DCC as a coupling agent. The chemical structures were confirmed by FT-IR, 1H, and 13C-NMR spectra, and some physicochemical properties were determined. The cytotoxicity of the different compounds (HB1-HB6) was evaluated by the MTT assay against two human epithelial cancer cell lines, A549 lung carcinoma and Hep G2 hepatocyte carcinoma, and one normal human cell line WI-38 lung fibroblasts. The mode of cell killing (apoptosis versus necrosis), as well as the effect on cell cycle phases were evaluated via flow cytometry. Additionally, EGFR tyrosine kinase inhibition assay was performed. The results presented in the current study indicate that the six tested compounds exhibited cytotoxicity against both cancer cell lines, and the lowest IC50 was achieved with compound HB5 against Hep G2 cancer cells which was found to be highly selective against cancer cells. HB5-treated Hep G2 cells were arrested at the S and G2/M cell cycle phases. Compound HB5 caused cell killing via apoptosis rather than necrosis, and this was achieved by inhibiting EGFR tyrosine kinase activity needed for cell proliferation, and cell cycle progression. In silico pre-ADMET studies confirmed all final compounds don’t cause CNS side effects, with little liver dysfunction effect

Synthesis, docking study, and structure activity relationship of novel anti-tumor 1, 2, 4 triazole derivatives incorporating 2-(2, 3- dimethyl aminobenzoic acid) moiety

A series of 1,2,4 triazole derivatives (H7-12) have been synthesized by reacting an excess of hydrazine hydrate with carbothioamide derivatives (H1-6). The final compounds (HB1-HB6) were synthesized by reacting the triazole derivatives with mefenamic acid using DCC as a coupling agent. The chemical structures were confirmed by FT-IR, 1H, and 13C-NMR spectra, and some physicochemical properties were determined. The cytotoxicity of the different compounds (HB1-HB6) was evaluated by the MTT assay against two human epithelial cancer cell lines, A549 lung carcinoma and Hep G2 hepatocyte carcinoma, and one normal human cell line WI-38 lung fibroblasts. The mode of cell killing (apoptosis versus necrosis), as well as the effect on cell cycle phases were evaluated via flow cytometry. Additionally, EGFR tyrosine kinase inhibition assay was performed. The results presented in the current study indicate that the six tested compounds exhibited cytotoxicity against both cancer cell lines, and the lowest IC50 was achieved with compound HB5 against Hep G2 cancer cells which was found to be highly selective against cancer cells. HB5-treated Hep G2 cells were arrested at the S and G2/M cell cycle phases. Compound HB5 caused cell killing via apoptosis rather than necrosis, and this was achieved by inhibiting EGFR tyrosine kinase activity needed for cell proliferation, and cell cycle progression. In silico pre-ADMET studies confirmed all final compounds don’t cause CNS side effects, with little liver dysfunction effect

Discovery of new fenamate-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in silico study

VEGFR-2 is a critical target for the treatment of solid tumors. This work represents synthetic approaches to a new class of fenamate-based derivatives with essential pharmacophoric properties comparable to VEGFR-2 inhibitors. The reaction of tolfenamic acid hydrazide with substituted phenacyl bromide, and phenylisothiocynate derivatives produced novel tolfenamic acid (TA) derivatives (compounds 4 and 5). The target molecules were validated using spectroscopic techniques such as FT-IR and 1HNMR. Docking tests were performed to determine how the synthesized chemicals bind to the putative molecular target, VEGFR-2. The docking results demonstrated that the synthesized compounds could bind VEGFR-2 correctly. Finally, computational physicochemical analysis of the most active candidates revealed that they have favorable assets and reasonable drug-likeness reports

FEASIBILITY OF COLLECTING UMBILICAL CORD BLOOD IN JORDAN AND THE EFFECT OF MATERNAL AND NEONATAL FACTORS ON HEMATOPOIETIC STEM CELL CONTENT

Abstract Background: Cord blood transplant is an accepted treatment for many malignant and non-malignant diseases. We sought to determine the feasibility of collecting cord blood in Jordan and the effect of maternal and fetal factors on the quality of the cord blood units. Methods: A total of 124 cord blood units were collected and 75 (60%) cord blood units were included in this analysis. Cord blood volume, total nucleated cell (TNC) count, cell viability and CD34+ content were measured, and clonogenic assay was performed. Results: The mean volume of the collected units was 68.9 ml (range 40-115) with mean nucleated cell count of 6.5 x 108 (range 1-23.0). Our results showed a positive correlation between the volume of cord blood and TNC count (p=0.008), cell viability (p=0.001), CD34+ content (p=0.034) and the length of the umbilical cord (p=0.011). In addition, our results showed an inverse relation between the Colony Forming Unit-Granulocyte Macrophage (CFU-GM) concentration and the gestation duration (p=0.038). Conclusion: We conclude that it is feasible to collect cord blood units in Jordan with excellent TNC and CD34+ cell content. The volume of cord blood collected was associated with higher TNC count and CD34+ count. Efforts toward establishing public cord blood banks in our area are warranted

Characterization of a Human Neuronal Culture System for the Study of Cofilin–Actin Rod Pathology

Cofilactin rod pathology, which can initiate synapse loss, has been extensively studied in rodent neurons, hippocampal slices, and in vivo mouse models of human neurodegenerative diseases such as Alzheimer’s disease (AD). In these systems, rod formation induced by disease-associated factors, such as soluble oligomers of Amyloid-β (Aβ) in AD, utilizes a pathway requiring cellular prion protein (PrPC), NADPH oxidase (NOX), and cytokine/chemokine receptors (CCR5 and/or CXCR4). However, rod pathways have not been systematically assessed in a human neuronal model. Here, we characterize glutamatergic neurons differentiated from human-induced pluripotent stem cells (iPSCs) for the formation of rods in response to activators of the PrPC-dependent pathway. Optimization of substratum, cell density, and use of glial-conditioned medium yielded a robust system for studying the development of Aβ-induced rods in the absence of glia, suggesting a cell-autonomous pathway. Rod induction in younger neurons requires ectopic expression of PrPC, but this dependency disappears by Day 55. The quantification of proteins within the rod-inducing pathway suggests that increased PrPC and CXCR4 expression may be factors in the doubling of the rod response to Aβ between Days 35 and 55. FDA-approved antagonists to CXCR4 and CCR5 inhibit the rod response. Rods were predominantly observed in dendrites, although severe cytoskeletal disruptions prevented the assignment of over 40% of the rods to either an axon or dendrite. In the absence of glia, a condition in which rods are more readily observed, neurons mature and fire action potentials but do not form functional synapses. However, PSD95-containing dendritic spines associate with axonal regions of pre-synaptic vesicles containing the glutamate transporter, VGLUT1. Thus, our results identified stem cell-derived neurons as a robust model for studying cofilactin rod formation in a human cellular environment and for developing effective therapeutic strategies for the treatment of dementias arising from multiple proteinopathies with different rod initiators

Human chorionic gonadotropin cutoff value determined by receiver operating characteristic curve analysis is useful but not absolute for determining pregnancy outcomes

Objective: To assess the clinical value of a single early human chorionic gonadotropin (HCG) assay (day 14 post embryo transfer) in assisted reproductive technology (ART) pregnancies. Design: Retrospective study. Settings: The Assisted Reproductive Unit at Jordan University Hospital, Amman, Jordan. Patients: During 2009–2011, a total of 248 embryo transfer cycles resulting in pregnancy, defined as serum HCG concentration of ⩾10 IU/l, were included. Interventions: None. Materials and methods: Pregnancies were classified as viable (live fetus at 24 weeks gestation) or non-viable (biochemical pregnancy, miscarriage, ectopic pregnancy). Receiver operating characteristic (ROC) curve analysis was used to evaluate the cutoff value of HCG with maximal sensitivity and specificity to differentiate between viable and non-viable pregnancies. Results: The median HCG concentration was 264 IU/l in viable pregnancies and 120 IU/l in non-viable pregnancies (p < 0.001). The median HCG concentration was 222 IU/l in singleton pregnancies, 389 IU/l in twin pregnancies and 809 IU/l in triplet pregnancies (p < 0.001). An HCG value of 145 IU/l emerged as the most suitable cutoff point to predict viable pregnancy. Conclusion: HCG cutoff values determined by a ROC curve analysis are useful but not absolute for discriminating between viable and non-viable pregnancy outcomes on day 14 after embryo transfer. So it is important to continue routine monitoring of ART pregnancy outcomes