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PLC zeta

Joseph George, Irene K Yan, Tushar Patel
Hepatocellular carcinoma is highly resistant to chemotherapy. Here we evaluated the use and efficacy of milk-derived nanovesicles (MNV) as an approach to improve delivery of anticancer agents into HCC cells and intrahepatic tumors. We developed a protocol for isolation of MNVs from skim milk using ultracentrifugation, and characterized using nanoparticle tracking analysis (NTA) and electron microscopy. MNVs were loaded with doxorubicin (dox-MNV) or miR221 antisense oligonucleotides (anti-miR221-MNV), and further evaluated using spectrophotometry, NTA, and zeta potential measurements...
May 10, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Michail Nomikos, Junaid Kashir, F Anthony Lai
At mammalian fertilisation, the fundamental stimulus that triggers oocyte (egg) activation and initiation of early embryonic development is an acute rise of the intracellular-free calcium (Ca2+ ) concentration inside the egg cytoplasm. This essential Ca2+ increase comprises a characteristic series of repetitive Ca2+ oscillations, starting soon after sperm-egg fusion. Over the last 15 years, accumulating scientific and clinical evidence supports the notion that the physiological stimulus that precedes the cytosolic Ca2+ oscillations is a novel, testis-specific phospholipase C (PLC) isoform, known as PLC-zeta (PLCζ)...
October 23, 2017: Biochemical Journal
Panagiotis Ntostis, Deborah Carter, David Iles, J D Huntriss, Maria Tzetis, David Miller
Paternal contributions to the zygote are thought to extend beyond delivery of the genome and paternal RNAs have been linked to epigenetic transgenerational inheritance in different species. In addition, sperm-egg fusion activates several downstream processes that contribute to zygote formation, including PLC zeta-mediated egg activation and maternal RNA clearance. Since a third of the preimplantation developmental period in the mouse occurs prior to the first cleavage stage, there is ample time for paternal RNAs or their encoded proteins potentially to interact and participate in early zygotic activities...
September 15, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
Eva Bilkova, Roman Pleskot, Sami Rissanen, Simou Sun, Aleksander Czogalla, Lukasz Cwiklik, Tomasz Róg, Ilpo Vattulainen, Paul S Cremer, Pavel Jungwirth, Ünal Coskun
The orchestrated recognition of phosphoinositides and concomitant intracellular release of Ca(2+) is pivotal to almost every aspect of cellular processes, including membrane homeostasis, cell division and growth, vesicle trafficking, as well as secretion. Although Ca(2+) is known to directly impact phosphoinositide clustering, little is known about the molecular basis for this or its significance in cellular signaling. Here, we study the direct interaction of Ca(2+) with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), the main lipid marker of the plasma membrane...
March 22, 2017: Journal of the American Chemical Society
Ahmed Alaa Kassem, Sameh Hosam Abd El-Alim, Mona Basha, Abeer Salama
To enhance the oral antidiabetic effect of repaglinide (RG), a newly emerging approach, based on the combination of phospholipid complexation and micelle techniques, was employed. Repaglinide-phospholipid complex (RG-PLC) was prepared by the solvent-evaporation method then characterized using Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XPRD). The results revealed obvious disappearance of the characteristic peaks of the prepared RG-PLCs confirming the formation of drug-phospholipid complex...
March 1, 2017: European Journal of Pharmaceutical Sciences
Lígia N M Ribeiro, Michelle Franz-Montan, Márcia C Breitkreitz, Ana C S Alcântara, Simone R Castro, Viviane A Guilherme, Raquel M Barbosa, Eneida de Paula
In dental practice, local anesthesia causes pain, fear, and stress, and is frequently the reason that patients abandon treatment. Topical anesthetics are applied in order to minimize the discomfort caused by needle insertion and injection, and to reduce the symptoms of superficial trauma at the oral mucosa, but there are still no efficient commercially available formulations. Factorial design is a multivariate data analysis procedure that can be used to optimize the manufacturing processes of lipid nanocarriers, providing valuable information and minimizing development time...
October 10, 2016: European Journal of Pharmaceutical Sciences
Jahahreeh Finley
In all mammalian species studied to date, the initiation of oocyte activation is orchestrated through alterations in intracellular calcium (Ca(2+)) signaling. Upon sperm binding to the oocyte plasma membrane, a sperm-associated phospholipase C (PLC) isoform, PLC zeta (PLCζ), is released into the oocyte cytoplasm. PLCζ hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol 1,4,5-trisphosphate (IP3), which induces the release of Ca(2+) from endoplasmic reticulum (ER) Ca(2+) stores...
August 2016: Medical Hypotheses
Huqiang Yi, Peng Liu, Nan Sheng, Ping Gong, Yifan Ma, Lintao Cai
Smart tumor-targeted drug delivery is crucial for improving the effect of chemotherapy and reducing the adverse effects. Here, we synthesized a smart polypeptide copolymer based on n-butylamine-poly(L-lysine)-b-poly(L-cysteine) (PLL-PLC) with functionalization of folic acid (FA) and 1,2-dicarboxylic-cyclohexene anhydride (DCA) for multistage responsive tumor-targeted drug delivery. The copolymers (FA-PLL(DCA)-PLC) spontaneously crosslinked in situ to form redox and pH dual responsive FA-PLL(DCA)-PLC nanoparticles (FD-NPs), which had a reversible zeta potential around -30 mV at pH 7...
March 21, 2016: Nanoscale
Siti Nornadhirah Amdani, Marc Yeste, Celine Jones, Kevin Coward
The development of a mammalian embryo is initiated by a sequence of molecular events collectively referred to as 'oocyte activation' and regulated by the release of intracellular calcium in the ooplasm. Over the last decade, phospholipase C zeta (PLCζ), a sperm protein introduced into the oocyte upon gamete fusion, has gained almost universal acceptance as the protein factor responsible for initiating oocyte activation. A large body of consistent and reproducible evidence, from both biochemical and clinical settings, confers support for the role of PLCζ in this fundamental biological context, which has significant ramifications for the management of human male infertility...
May 2016: Advances in Biological Regulation
Karl Swann, F Anthony Lai
The most fundamental unresolved issue of fertilization is to define how the sperm activates the egg to begin embryo development. Egg activation at fertilization in all species thus far examined is caused by some form of transient increase in the cytoplasmic free Ca(2+) concentration. What has not been clear, however, is precisely how the sperm triggers the large changes in Ca(2+) observed within the egg cytoplasm. Here, we review the studies indicating that the fertilizing sperm stimulates a cytosolic Ca(2+) increase in the egg specifically by delivering a soluble factor that diffuses into the cytosolic space of the egg upon gamete membrane fusion...
January 2016: Physiological Reviews
Lu Wang, Yafang Wang, Xueqing Wang, Lin Sun, Zhengzheng Zhou, Jinjian Lu, Ying Zheng
CONTEXT: PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release. OBJECTIVE: This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. MATERIALS AND METHODS: DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method...
February 2016: Journal of Microencapsulation
Geeta Goswami, Sarabjeet Singh, M Gouri Devi
Spermatids are the earliest male germ cells with haploid set of chromosomes. Spermatid injection was introduced in human assisted reproduction for the treatment of men with non-obstructive azoospermia. Spermatozoa can be recovered in half of patients with nonobstructive azoospermia. The use of spermatids for intracytoplasmic injection (ICSI) has been proposed for cases in which no spermatozoa can be retrieved. However, there are low pregnancy rates following ICSI using round spermatids from men with no elongated spermatids or spermatozoa in their testes...
July 2015: Journal of Human Reproductive Sciences
Maria Luisa Bondì, Angela Scala, Giuseppe Sortino, Erika Amore, Chiara Botto, Antonina Azzolina, Daniele Balasus, Melchiorre Cervello, Antonino Mazzaglia
Sorafenib (Sor), an effective chemiotherapeutic drug utilized against hepatocellular carcinoma (HCC), robustly interacts with nonionic amphiphilic cyclodextrin (aCD, SC6OH), forming, in aqueous solution, supramolecular complexes that behave as building blocks of highly water-dispersible colloidal nanoassemblies. SC6OH/Sor complex has been characterized by complementary spectroscopic techniques, such as UV-vis, steady-state fluorescence and anisotropy, resonance light scattering and (1)H NMR. The spectroscopic evidences and experiments carried out in the presence of an adamantane derivative, which competes with drug for CD cavity, agree with the entrapment of Sor in aCD, pointing out the role of the aCD cavity in the interaction between drug and amphiphile...
December 14, 2015: Biomacromolecules
Zoltan Machaty
Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations are the result of repeated release and re-uptake of Ca(2+) stored in the smooth endoplasmic reticulum. Ca(2+) release is primarily mediated by the phosphoinositide signaling system of the oocyte. The system is stimulated when the sperm causes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG); IP3 then binds its receptor on the surface of the endoplasmic reticulum that induces Ca(2+) release...
January 2016: Cell and Tissue Research
L Chansel-Debordeaux, S Dandieu, S Bechoua, C Jimenez
Infertility affects approximately 15% of couples in reproductive age. Male infertility is estimated to represent about 20% of the etiologies. Among them, a rare type of teratozoospermia known as globozoospermia leads to disappointing pregnancy outcomes. Morphological, physiological and genetic aspects of this severe disorder have been described. We undertook a complete review of the available data on the reproductive outcomes in globozoospermic patients. To this end, a literature review in both English and French, over a 20-year time period using PubMed/Medline, ScienceDirect, and Scopus was performed...
November 2015: Andrology
James D M Nicopoullos, E Whitney, V Wells, S Batha, R Faris, H Abdalla
PURPOSE: Total fertilisation failure (TFF), even with intracytoplasmic sperm injection (ICSI), occurs in approximately 3 % of cycles, can be recurrent and the exact cause is difficult to elucidate. Differentiation between oocyte and sperm-related cause of TFF is possible using mouse oocyte-activation techniques, but is not an option within most clinical settings. Therefore, the management of these couples is clinically driven, and the endpoint, if recurrent, is often the use of donor gametes...
November 2015: Journal of Assisted Reproduction and Genetics
Marc Yeste, Celine Jones, Siti Nornadhirah Amdani, Sheena Patel, Kevin Coward
BACKGROUND: Infertility affects between 10 and 16% of couples worldwide. Twenty to 30% of cases of infertility are due to a male factor, 20-35% to a female factor, and 25-40% are due to both male and female factors. In ∼10-25% of cases, the precise underlying cause remains unclear. IVF or ICSI followed by embryo transfer can be very appropriate treatment options in cases of female tubal damage, ovulatory failure or male-factor infertility. While the use of IVF has been reported to be suitable for many infertile couples, normal IVF cycles can fail in some cases...
January 2016: Human Reproduction Update
Wei Lin, Yuanzhen Suo, Yuting Deng, Zhichao Fan, Yijie Zheng, Xunbin Wei, Yiwei Chu
BACKGROUND: The changes in T-cell morphology during immunological synapse (IS) formation are essential for T-cell activation. Previous researches have shown that T cell changed from spherical to elongated and/or flattened during in contact with B cell. As most powerful antigen presenting cell, dendritic cell (DC) has a strong ability to activate T cells. However, the morphological change of T cell which contacts DC and the relationship between morphological change and T-cell activation are not very clear...
2015: BMC Immunology
Zahabiya H Chithiwala, Hoi Chang Lee, David L Hill, Teru Jellerette-Nolan, Rafael Fissore, Daniel Grow, Daniel A Dumesic
PURPOSE: The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca(2+)) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro. METHODS: An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca(2+) release...
September 2015: Journal of Assisted Reproduction and Genetics
Michail Nomikos, Jessica R Sanders, Junaid Kashir, Randa Sanusi, Luke Buntwal, Daniel Love, Peter Ashley, David Sanders, Paul Knaggs, Adnan Bunkheila, Karl Swann, F Anthony Lai
Mammalian oocyte activation is mediated by cytosolic calcium (Ca(2+)) oscillations initiated upon delivery of a putative 'sperm factor' by the fertilizing sperm. Previous studies suggest the identity of this sperm factor as the testis-specific phospholipase C-zeta (PLCζ). Recently, a post-acrosomal sheath WW domain-binding protein (PAWP) has been proposed as an alternative sperm factor candidate, following a report that human PAWP protein and cRNA elicited Ca(2+) oscillations in mouse and human oocytes. Those Ca(2+) oscillations were inhibited by a PAWP-derived peptide corresponding to a functional PPGY binding motif...
September 2015: Molecular Human Reproduction
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