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61.
Saima M. Sidik Miryam A. Hortua Triana Aditya S. Paul Majida El Bakkouri Caroline G. Hackett Fanny Tran Nicholas J. Westwood Raymond Hui William J. Zuercher Manoj T. Duraisingh Silvia N. J. Moreno Sebastian Lourido 《The Journal of biological chemistry》2016,291(18):9566-9580
The life cycles of apicomplexan parasites progress in accordance with fluxes in cytosolic Ca2+. Such fluxes are necessary for events like motility and egress from host cells. We used genetically encoded Ca2+ indicators (GCaMPs) to develop a cell-based phenotypic screen for compounds that modulate Ca2+ signaling in the model apicomplexan Toxoplasma gondii. In doing so, we took advantage of the phosphodiesterase inhibitor zaprinast, which we show acts in part through cGMP-dependent protein kinase (protein kinase G; PKG) to raise levels of cytosolic Ca2+. We define the pool of Ca2+ regulated by PKG to be a neutral store distinct from the endoplasmic reticulum. Screening a library of 823 ATP mimetics, we identify both inhibitors and enhancers of Ca2+ signaling. Two such compounds constitute novel PKG inhibitors and prevent zaprinast from increasing cytosolic Ca2+. The enhancers identified are capable of releasing intracellular Ca2+ stores independently of zaprinast or PKG. One of these enhancers blocks parasite egress and invasion and shows strong antiparasitic activity against T. gondii. The same compound inhibits invasion of the most lethal malaria parasite, Plasmodium falciparum. Inhibition of Ca2+-related phenotypes in these two apicomplexan parasites suggests that depletion of intracellular Ca2+ stores by the enhancer may be an effective antiparasitic strategy. These results establish a powerful new strategy for identifying compounds that modulate the essential parasite signaling pathways regulated by Ca2+, underscoring the importance of these pathways and the therapeutic potential of their inhibition. 相似文献
62.
Habibul Bari Shozib Md. Mariful Islam Sultan Abu Saleh Mahmud Md. Nazmul Bari Nasima Akter Saima Jahan Shakir Hosen Mohammad Nazir Hossain A.H.M. Nurun Nabi Muhammad Ali Siddiquee Md. Manjurul Haque 《Saudi Journal of Biological Sciences》2021,28(12):7472-7480
BackgroundBlack pericarp rice has recently become popular among rice consumers for its diverse health benefits specially anti-cancer effect. Cyanidin-3-Glucosides (C3G), an prominant bioactive component of anthocyanins which is abundantly present in black pericarp rice.ObjectivesWe investigated, how effectively it can be used to fortify Cyanidin-3-Glucosides (C3G) content in red and white pericarp polished rice or rice based bakery products for more nutritional value.MethodIn the present study, we have characterized several black pericarp rice cultivars along with some red pericarp and white pericarp rice cultivars by physicochemical including mineral profiling, and quantified the C3G by UFLC and LCMS.ResultsC3G content was significantly reduced from raw rice to cooked rice condition. All the black pericarp rice cultivars synthesized C3G, while this content was not detected in red and white pericarp rice cultivars. However, when 25% of black pericarp rice were mixed with 75% red or white pericarp polished rice, C3G content was significantly retained in cooked rice conditions. Formulation of rice-based bakery food product using black pericarp rice powder was also remarkably retained the C3G content as compared to that of cooking. Black rice is harder in texture, difficult to digest and needs higher energy for cooking. Therefore, we tried to circumvent these challenges by fortifying 25% of black pericarp rice with white or red pericarp rice.ConclusionFortification of C3G enriched black rice (25%) with red or white pericarp rice (75%) might bring a better nutritional quality in both cooking and baking condition. This may lead a way to the effective management of the non-communicable disease such as cancer for common rice consuming population. 相似文献
63.
Mohammad Rehan Ajmal Nida Zaidi Parvez Alam Saima Nusrat Mohd Khursheed Siddiqi Gamal Badr 《Journal of biomolecular structure & dynamics》2017,35(1):46-57
The binding of clofazimine to human serum albumin (HSA) was investigated by applying optical spectroscopy and molecular docking methods. Fluorescence quenching data revealed that clofazimine binds to protein with binding constant in the order of 104 M?1, and with the increase in temperature, Stern–Volmer quenching constants gradually decreased indicating quenching mode to be static. The UV–visible spectra showed increase in absorbance upon interaction of HSA with clofazimine which further reveals formation of the drug–albumin complex. Thermodynamic parameters obtained from fluorescence data indicate that the process is exothermic and spontaneous. Forster distance (Ro) obtained from fluorescence resonance energy transfer is found to be 2.05 nm. Clofazimine impelled rise in α-helical structure in HSA as observed from far-UV CD spectra while there are minor alterations in tertiary structure of the protein. Clofazimine interacts strongly with HSA inducing secondary structure in the protein and slight alterations in protein topology as suggested by dynamic light scattering results. Moreover, docking results indicate that clofazimine binds to hydrophobic pocket near to the drug site II in HSA. 相似文献
64.
Lasioglossins LLIII affect the morphogenesis of Candida albicans and reduces the duration of experimental vaginal candidiasis in mice 下载免费PDF全文
Alena Vrablikova Lydie Czernekova Romana Cahlikova Zbynek Novy Milos Petrik Saima Imran Zdenek Novak Michal Krupka Vaclav Cerovsky Jaroslav Turanek Milan Raska 《Microbiology and immunology》2017,61(11):474-481
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66.
Protein tyrosine phosphatase 1B (PTP1B) is involved in the down-regulation of insulin signaling and is a well-validated therapeutic target for the treatment of diabetes and obesity. Key to the design of potent inhibitors of PTP1B is a moiety that effectively mimics the phosphate group of the natural phosphotyrosine substrate. Difluoromethylsulfonomethylphenylalanine (F(2)Smp) is one of the best monoanionic pTyr mimics reported to date. However, the difluoromethylenesulfonic acid (DFMS) group as a phosphate mimic has not been carefully evaluated in the context of a non-peptidyl platform. Here we present a careful examination of the DFMS group as a phosphate mimic. This was achieved by first constructing an analog of a previously reported high affinity, non-peptidyl PTP1B inhibitor (compound 2, IC(50)=8nM) in which a difluoromethylenephosphonic acid group is replaced with the DFMS moiety (compound 6). We also report the synthesis of its non-fluorinated methylenesulfonic analog (compound 7), as well as two other derivatives in which a distal sulfonamide moiety is replaced with a difluoromethylenesulfonamide group (compounds 8 and 9). Compounds 2 and 6-9 were examined as PTP1B inhibitors. Replacing the distal sulfonamide moiety with a difluoromethylenesulfonamide group had only a modest effect on inhibitor potency. However, compound 6 was approximately a 1000-fold poorer inhibitor than compound 2. Most significantly, inhibition studies with compound 7 and a peptide bearing sulfonomethylphenylalanine revealed that the fluorines have little effect on the potency of the DFMS-bearing inhibitors. This is in contrast to a previous assumption that the fluorines in DFMS-bearing inhibitors contributed significantly to their potency. This may in part explain the large difference in potency between the DFMS and DFMP-bearing compounds. These results also demonstrate that sulfonomethylphenylalanine, a pTyr mimic that is readily constructed, is a relatively good pTyr mimic in comparison to most others that have been reported when examined in the context of the DADE-X-LNH(2) peptide platform. 相似文献
67.
Muhammad Altaf Khan Saima Sadaf Muhammad Sajjad M. Waheed Akhtar 《Protein expression and purification》2009,68(1):85-89
This study describes comparison between IPTG and lactose induction on expression of caprine growth hormone (cGH), enhancing cell densities of Escherichia coli cultures and refolding the recombinant cGH, produced as inclusion bodies, to biologically active state. 2–3 times higher cell densities were obtained in shake flask cultures when induction was done with lactose showing almost same level of expression as in case of IPTG induction. With lactose induction highest cell densities were achieved in TB (OD600 16.3) and M9NG (OD600 16.1) media, producing 885 and 892 mg cGH per liter of the culture, respectively. Lactose induction done at mid-exponential stage resulted in a higher cell density and thus higher product yield. cGH over-expressed as inclusion bodies was solubilized in 50 mM Tris–Cl buffer (pH 12.5) containing 2 M urea, followed by dilution and lowering the pH in a step-wise manner to obtain the final solution in 50 mM Tris–Cl (pH 9.5). The cGH was purified by Q-Sepharose chromatography followed by gel filtration with a recovery yield of 39% on the basis of total cell proteins. The product thus obtained showed a single band by SDS–PAGE analysis. MALDI-TOF analysis showed a single peak with a mass of 21,851 dalton, which is very close to its calculated molecular weight. A bioassay based on proliferation of Nb2 rat lymphoma cells showed that the purified cGH was biologically active. 相似文献
68.
Khalid Mohammed Khan Momin Khan Muhammad Ali Muhammad Taha Saima Rasheed Shahnaz Perveen M. Iqbal Choudhary 《Bioorganic & medicinal chemistry》2009,17(22):7795-7801
Bis-Schiff bases 1–27 have been synthesized and their in vitro antiglycation potential has been evaluated. Compounds 21 (IC50 = 243.95 ± 4.59 μM), 20 (IC50 = 257.61 ± 5.63 μM), and 7 (IC50 = 291.14 ± 2.53 μM) showed an excellent antiglycation activity better than the standard (rutin, IC50 = 294.46 ± 1.50 μM). This study has identified a series of potential molecules as antiglycation agents. A structure–activity relationship has been studied, and all the compounds were characterized by spectroscopic techniques. 相似文献
69.
Oral administration of vanadate is an effective treatment for diabetes in animal models. However, vanadate exerts these effects at high doses and several toxic effects are produced. Low doses of vanadate are relatively safe but are unable to elicit any antidiabetic effect. The present study explored the prospect of using low doses of vanadate in combination with Trigonella seed powder (TSP) to evaluate their antidiabetic effect in alloxan-diabetic rats. Alloxan-diabetic rats were treated with insulin, vanadate, TSP and vanadate and TSP in combination for 3 weeks. The effect of these antidiabetic compounds was examined on general physiological parameters and distribution of glucose transporter (GLUT4) in skeletal muscle by immunoblotting and immunohistochemistry. Treatment of alloxan-diabetic rats with insulin, vanadate, TSP and vanadate in combination with TSP revived normoglycemia and restored the disturbances in the distribution of GLUT4 in skeletal muscle. TSP treatment was only partially effective in the restoration of diabetic alterations. The treatment of diabetic rats with combined doses of vanadate and TSP was most effective in the normalization of plasma glucose levels and correction of altered GLUT4 distribution. 相似文献
70.
A 67-year-old gentleman presented to Yale-New Haven Hospital (YNHH) for assessment of a supratherapeutic INR and sacral lesion. Hematologic workup revealed elevated ESR, PT, INR, PTT, and CRP, mixing studies that failed to correct, and a positive Russell Viper Venom Test (RVVT), which confirmed the presence of lupus anticoagulant (LA), a subtype of antiphospholipid syndrome (APA). Pathology of the patient's sacral lesion revealed diffuse large B-cell lymphoma. This case provides insight into the association between APA and lymphoid neoplasm. The patient's unique presentation is in marked contrast to other reports of APA and lymphoid malignancy, which are typically associated with elevated PTT, normal PT, minimal extranodal disease, and potential thrombotic complications. Further, treatment with Rituximab-CHOP chemotherapy led to excellent clinical response with tumor remission and normalization of PT and PTT. 相似文献