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Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-β1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP3) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10−7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10−9–10−5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC β1 inhibitor (U73122) and IP3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca2+/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC β1, which in turn liberates IP3, which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is a primary malignancy of the central nervous system that is classified by the WHO as a grade IV astrocytoma. Despite decades of research, several aspects about the biology of GB are still unclear. Its pathogenesis and resistance mechanisms are poorly understood, and methods to optimize patient diagnosis and prognosis remain a bottle neck owing to the heterogeneity of the malignancy. The field of omics has recently gained traction, as it can aid in understanding the dynamic spatiotemporal regulatory network of enzymes and metabolites that allows cancer cells to adjust to their surroundings to promote tumor development. In combination with other omics techniques, proteomic and metabolomic investigations, which are a potent means for examining a variety of metabolic enzymes as well as intermediate metabolites, might offer crucial information in this area. Therefore, this review intends to stress the major contribution these tools have made in GB clinical and preclinical research and highlights the crucial impacts made by the integrative "omics" approach in reducing some of the therapeutic challenges associated with GB research and treatment. Thus, our study can purvey the use of these powerful tools in research by serving as a hub that particularly summarizes studies employing metabolomics and proteomics in the realm of GB diagnosis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Calcium-sensing receptor (CaSR) has been associated with breast cancer metastasis to the bone. Targeting chemoattractant factors, such as calcium, that are released in response to bone resorption could prevent metastasis and induce apoptosis of cancer cells. In the present study, we investigated the potential caspase 3/7 activation following treatment with a CaSR antagonist, NPS-2143, in breast cancer cells. In addition, the effects of NPS-2143 on breast cancer cell proliferation, migration and invasion were assessed. Methods: Colorimetric MTT assay was used to evaluate cell viability. Apo-one homogeneous caspase-3/7 assay was used to measure caspase 3/7 activities in breast cancer cells. Cell migration and invasion were assessed using scratch wound assay and matrigel invasion chambers, respectively. The protein expressions of p-ERK1/2, integrin β1 and Bcl-2 were evaluated using western blotting. Results: Our study revealed that NPS-2143 significantly reduced cell proliferation with half maximal (50%) inhibitory concentration (IC50) values of 4.08 and 5.71 µM in MDA-MB-231 and MCF-7 cells, respectively. NPS-2143 induced caspase 3/7 activation in MDA-MB-231 breast cancer cells which was accompanied with a remarkable reduction in the expression of Bcl-2 antiapoptotic protein. NPS-2143 suppressed migratory and invasive abilities of MDA-MB-231 cells with a significant reduction in the expression of p-ERK1/2 and integrin β1 proteins. Conclusion: Our study confirms the ability NPS-2143 to suppress proliferative, migratory and invasive effects of breast cancer cells which was accompanied by caspase 3/7 activation and suggests the potential of NPS-2143 as a promising anti-cancer molecule in breast cancer. [ABSTRACT FROM AUTHOR]

Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis, which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders. [ABSTRACT FROM AUTHOR]

The study aimed to figure out the impact of the employee engagement on the continuous improvement through the innovative behavior as a mediating variable in the public sector in the Hashemite Kingdom of Jordan. The study adopted the descriptive, analytical approach. To achieve the objectives of the study, the researchers distributed a questionnaire to (411) members of the study population. After analyzing the data using the (AMOS), the study concluded a statistically significant impact at sig. (α≤0.05) for the employee engagement on the continuous improvement of the employees in light of the innovative behavior as a mediating variable. [ABSTRACT FROM AUTHOR]