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Over the past 20 years, granulocyte colony-stimulating factor (G-CSF) has driven the attention of researchers as a therapeutic agent for curing patients suffering from neutropenia. Despite the successful use of G-CSF, it currently requires daily injections, which are inconvenient, expensive, and distressing for children. Therefore, an alternative strategy for using G-CSF for treatment is needed. Understanding the G-CSF structure, expression, mechanism of action, and how it induces neutrophils mobilization is crucial to producing promising cancer therapy. The ability of G-CSF to mobilize hematopoietic stem cells from the bone marrow into the blood circulation was consequently exploited and altered the practice of hematopoietic stem cell transplantation. This is the motivation for the current review, which sheds light on the history of G-CSF and then focuses on the mechanism of action upon binding to its receptor (G-CSFR) and how that had led to the stimulation of neutrophils mobilization. The findings of this review show new insight into the mechanism of G-CSF that induces neutrophils mobilization. Thus, Understanding the G-CSF will provide a more effective treatment for all neutropenia patients.

There are many approaches to assessing platelet reactivity and many uses for such measurements. Initially, measurements were based on the ability of platelets separated from other blood cells to aggregate together following activation with an appropriate 'aggregating agent'. Later, measurements of platelet aggregation in blood itself were performed, and this led to a point-of-care approach to platelet function testing. Measurement of secretory activity through the appearance of the activation marker Pselectin on platelets now provides an alternative approach, which enables remote testing. Measurement of vasodilator-stimulated phosphoprotein phosphorylation is also moving toward application in situations remote from the testing laboratory. Here we provide an overview of the various approaches that are now available, assess their advantages and disadvantages, and describe some of the clinical situations in which they are being used. Keywordsaspirin, flow cytometry, light transmission aggregometry (LTA), multiplate electrode aggregometry (MEA), P-selectin, P2Y12 antagonists, platelet aggregation, platelet reactivity, VASP phosphorylation, VerifyNow Platelet reactivity is a broad term indicating the degree of the response of blood platelets to an external stimulus, usually an 'aggregating agent'. Platelet reactivity can be measured in many different ways and the purpose of this review is to summarize the approaches, with an emphasis on the newer approaches that are becoming available.Platelets play an important role in the hemostatic process [1,2]. They contribute to the formation of a hemostatic plug that serves to prevent blood loss from injured blood vessels. The hemostatic plug contains thousands of platelets that have aggregated together within a network of fibrin. However, platelets also contribute to the generation of a thrombotic mass in a coronary or cerebral artery or in an artificial stent leading to blockage and resulting in conditions such as heart attack, stroke and stent thrombosis [3,4]. A thrombus is also composed of platelet aggregates within a fibrin network. So thrombus formation can thus be considered to be hemostasis in the wrong place.

Multiple sclerosis (MS) is an immune-mediated inflammatory disease that leads to demyelination and neuronal loss in the central nervous system. Immune cells of lymphoid and myeloid origin play a significant role in the initiation and amplification of neuronal inflammation in MS. STAT3 signaling plays a pivotal role in both myeloid and lymphoid immune cells, such as neutrophils and CD4+ T cells, through regulation of their inflammatory potential. Dysregulation in STAT3 signaling in myeloid and lymphoid cell compartments has been reported in MS. In this report, we attempted to investigate the effect of a small molecular inhibitor of STAT3, i.e., Stattic, in a relapsing–remitting (RR) model of experimental autoimmune encephalomyelitis (EAE). The effect of Stattic was investigated for clinical features, oxidative stress parameters, and Th17-related signaling in both the periphery and brain of SJL/J mice. Our data report that p-STAT3 expression is elevated in granulocytes, CD4+ T cells, and brain tissue in myelin proteolipid protein (PLP)-immunized SJL/J mice, which is associated with the presence of clinical symptoms and upregulation of inflammatory markers in these cells/tissues. Treatment with Stattic leads to the amelioration of disease symptoms and attenuation of inflammatory markers in neutrophils (iNOS/nitrotyrosine/IL-1β), CD4+ T cells (IL-17A/IL-23R), and brain tissue (IL-17A/iNOS/IL-1β/MPO activity/lipid peroxides) in mice with EAE. These data suggest that the blockade of STAT3 signaling in cells of lymphoid and myeloid origin may cause the attenuation of systemic and neuronal inflammation, which could be responsible for the amelioration of disease symptoms in an RR model of EAE. Therefore, pharmacological inhibition of STAT3 in RRMS could be a potential therapeutic strategy.

Sepsis affects millions of people worldwide and is associated with multiorgan dysfunction that is a major cause of increased morbidity and mortality. Sepsis is associated with several morbidities, such as lung, liver, and central nervous system (CNS) dysfunction. Sepsis-associated CNS dysfunction usually leads to several mental problems including depression. IL-17A is one of the crucial cytokines that is expressed and secreted by Th17 cells. Th17 cells are reported to be involved in the pathogenesis of depression and anxiety in humans and animals. One of the protein tyrosine kinases that plays a key role in controlling the development/differentiation of Th17 cells is ITK. However, the role of ITK in sepsis-associated neuroinflammation and depression-like symptoms in mice has not been investigated earlier. Therefore, this study investigated the efficacy of the ITK inhibitor, BMS 509744, in sepsis-linked neuroinflammation (ITK, IL-17A, NFkB, iNOS, MPO, lipid peroxides, IL-6, MCP-1, IL-17A) and a battery of depression-like behavioral tests, such as sucrose preference, tail suspension, and the marble burying test. Further, the effect of the ITK inhibitor on anti-inflammatory signaling (Foxp3, IL-10, Nrf2, HO-1, SOD-2) was assessed in the CNS. Our data show that sepsis causes increased ITK protein expression, IL-17A signaling, and neuroinflammatory mediators in the CNS that are associated with a depression-like state in mice. ITK inhibitor-treated mice with sepsis show attenuated IL-17A signaling, which is associated with the upregulation of IL-10/Nrf2 signaling and the amelioration of depression-like symptoms in mice. Our data show, for the first time, that the ITK inhibition strategy may counteract sepsis-mediated depression through a reduction in IL-17A signaling in the CNS.

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Monosodium glutamate (MSG), a commonly used avor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 mg/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for seven days. Results showed that MSG augmented the hepatic (AST and ALT) and renal (urea and creatinine) functions markers as well as glucose, triglycerides, total cholesterol and LDL levels. Moreover, marked increases in MDA levels accompanied by declines in GSH levels and notable decreases in the activities of SOD, CAT, GPx, and GR were observed in MSG-treated group. The MSG-mediated oxidative stress was further con rmed by down-regulation of Nfe2l2 gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal in ammatory response as witnessed by increased in ammatory cytokines (IL-1b and TNF-α) and elevated NF-κB levels in both tissues. Further, signi cant increases in Bax (proapoptotic biomarker) levels together with decreases in Bcl-2 (anti-apoptotic marker) levels were observed in MSG administration. Hepatic and renal histopathological screening supported the biochemical and molecular ndings. On the contrary, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of in ammatory mediators and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatic and renal injurious effects through modulation of oxidative, in ammatory and apoptotic alterations.