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Phosphoglycerate kinase 1 (PGK1) is an essential enzyme that catalyzes adenosine 5'-triphosphate (ATP) production in aerobic glycolysis. In addition to regulating cell metabolism, PGK1 is involved in multiple biological activities, including angiogenesis, mediated autophagy starting, binding of plasminogen, the DNA replication and repair, the proliferation and metastasis of tumor cells, cell invasion (a part of the flagellar axoneme and viral replication and it occurs mainly in protists), and is also associated with resistance to chemotherapy and prognosis of cancer patients. In this review, we focus on the basic functions of PGK1 and the relationship between PGK1 and different diseases, indicating that PGK1 has a broad application prospect to find a potential biomarker for tumor prognosis and an effective inhibitor.C-X-C motif chemokine 12 (CXCL12), also known as stromal cell-derived factor-1 (SDF-1), is produced by the bone marrow microenvironment. This chemokine binds and activates its cognate receptors C-X-C chemokine receptor type 4 (CXCR4) and C-X-C chemokine receptor type 7 (CXCR7) to widely regulate cell proliferation, survival, differentiation, as well as homing and mobilization of hematopoietic stem cells (HSCs) in specialized niches within the bone marrow. Given this key role in hematopoiesis, it comes as no surprise that any aberrancies in CXCL12/CXCR4 or CXCL12/CXCR7 pathways might lead to excessive proliferation of HSCs, an event that leads to the development of leukemia. So far, numerous therapeutic interventions have been developed to harness CXCL12/CXCR4 and CXCL12/CXCR7 axes in leukemic cells. Plerixafor, BKT140, LY2510924, PF-06747143, ulocuplumab, and NOX-A12 are among the most well-known CXCR4 and CXCL12 modulators that their therapeutic efficacies have been evaluated in different pre-clinical and clinical studies of hematologic malignancies. To have an overview of the importance of CXCL12/CXCR4 and CXCL12/CXCR7 axes in the pathogenesis of leukemia and to gather information about the latest advances as well as challenges in targeting these axes in clinical settings, the present review has begun with a discussion about how aberrant expression of CXCL12/CXCR4 and CXCL12/CXCR7 pathways might regulate leukemogenesis and ended by outlining the key news of preclinical and clinical investigations in leukemia treatment.Hepatocyte growth-promoting factor (pHGF) has a significant effect in promoting liver cell proliferation and restoring liver function. In this study, 815 short peptides of pHGF were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which 574 short peptides were assigned to 152 proteins related to hemoglobin subunits and some catalytic enzymes, indicating that pHGF might participate in the oxidation-reduction process by regulating reactive oxygen species (ROS) production. Proteomic analysis was used to identify the differentially expressed proteins (DEPs) in SMMC-7721 and L-02 cells after pHGF treatment, which suggested that pHGF had a significant impact on the JAK-STAT signaling pathway and the cell cycle of liver cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis revealed the mechanisms through which pHGF might activate the JAK2/STAT3/c-MYC pathway to up-regulate the expression of CDK4/6, thereby accelerating the G1/S transition to promote liver cell proliferation. These findings, for the first time, indicate the potential role of pHGF against the early or middle stages of acute, sub-acute, and chronic severe hepatitis. pHGF was also found to restore the reduced SOD1 and SOD2 protein levels that result from H2O2 exposure and significantly increase the HO-1 protein levels in L-02 cells, thus improving the viability of L-02 cells that have been damaged by H2O2 by reducing the ROS and lipid peroxidation levels.The closure of skin wounds is indispensable for resistance against pathogens, and fibroblast plays a critical role in skin wound healing. Our previous study demonstrates that the phosvitin-derived small peptide Pt5-1c not only possesses broad-spectrum antimicrobial activity but also exhibits synergistic effect and antibiofilm activity with traditional antibiotics against bacteria, including multi-drug resistant (MDR) strains. Here we provided the first evidence that Pt5-1c promoted the wound closure of surrogate scratch "wounds" of fibroblasts in vitro, and speeded up the healing and re-epithelialization of murine dermal wounds in vivo. We also showed that Pt5-1c activated migration of fibroblasts via a combined action of inducing migratory phenotype and trans-activating epidermal growth factor receptor (EGFR). Moreover, Pt5-1c accelerated attachment and proliferation of fibroblasts in vitro. Interestingly, Pt5-1c was able to promote collagen contraction through activation/differentiation of fibroblasts into myofibroblasts. These data together suggest that Pt5-1c is a promising candidate with therapeutic potential to promote wound healing.
High levels of circulating catecholamines are related to raise risk of cardiac arrhythmias. In addition, our recent studies have suggested that pinocembrin could decrease the susceptibility to arrhythmias in several rat models, including chronic ischemic heart failure, myocardial infarction and depression. In this research, the effects of pinocembrin on ventricular fibrillation (VF) susceptibility were investigated in rats treated with isoproterenol (ISO) and further explored the possible mechanism.
Cardiac remodeling was induced by intraperitoneally injection ISO (5mg/kg) 7 days. Simultaneously, Rats were received pinocembrin (5mg/kg) or saline by tail vein injection. The effects of pinocembrin were evaluated by electrocardiogram parameters, ventricular electrophysiological parameters, echocardiographic, western blot, ventricular histology, biochemical examinations. In vitro, we cultured H9C2 cardiomyocytes to further define the mechanisms.
Compared with ISO group, pinocembrin remarkably decreased VF inhibitor remarkably reduced the antioxidant effects of pinocembrin, which further demonstrated that the effect of pinocembrin was related to activation of Nrf2.
Our data demonstrate that pinocembrin decreases ventricular electrical remodeling, ion remodeling, ventricular fibrosis, hypertrophy and suppresses isoproterenol-induced oxidative stress. The findings shown that pinocembrin mediates antiarrhythmic effects in rats with isoproterenol-induced cardiac remodeling related to Nrf2/HO-1 pathway.
Our data demonstrate that pinocembrin decreases ventricular electrical remodeling, ion remodeling, ventricular fibrosis, hypertrophy and suppresses isoproterenol-induced oxidative stress. The findings shown that pinocembrin mediates antiarrhythmic effects in rats with isoproterenol-induced cardiac remodeling related to Nrf2/HO-1 pathway.Acute lymphoblastic leukemia (ALL) is a malignant hematologic tumor with highly aggressive characteristics, which is prone to relapse, has a poor prognosis and few clinically effective drugs. It is meaningful to gain a better understanding of its pathogenesis in order to discover and evaluate potential therapeutic drugs and new treatment targets. The goal of developing novel targeted drugs and treatment methods is to increase complete remission, reduce toxicity and morbidity, and that is also the most important prerequisite for modern leukemia treatment. However, the process of new drugs from research and development to clinical application is long and difficult. Many promising drugs were rejected by the USFoodandDrugAdministration(FDA) due to serious adverse drug reactions (ADR) in clinical phase I trials. Animal models provide us with an excellent tool to understand the complex pathological mechanisms of human diseases, to evaluate the potential of new targeted drugs and therapeutic approaches to treat ALL in vivo and, more importantly, to assess the potential ADR they may have on healthy organs. In this article we review ALL animal models' progression, their roles in revealing the pathogenesis of ALL and drug development. Selleckchem Wnt agonist 1 Additionally, we mainly focus on the mouse models, especially xenotransplantation and transgenic models that more closely reproduce the human phenotype. In conclusion, we summarize the advantages and limitations of each model, thereby facilitating further understanding the etiology of ALL, and eventually contributing to the effective management of the disease.
The influence of essential nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) on male fertility has been extensively studied. For reproductive health, adequate spermatogenesis, sperm maturation and motility, as well as optimal sperm function, these essential elements are required. Several pathologic and male infertility disorders have been linked to an imbalance of these elements.
The purpose of this study was to determine the relationship between essential and toxic elements, such as Ca, Cu, Fe, Mg Se, and Zn, as well as cadmium (Cd), lead (Pb), and mercury (Hg) in human biological samples, such as blood, serum, and seminal plasma, from 96 referent male adults aged 21 to 49years, who were further divided into three age groups. The biological samples of Eunuch people (n=37), ranging in age from 21 to 42years, were also analysed for comparison. The method of acid digestion was controlled by a microwave oven. The essential and toxic elements in the oxidised tial elemental deficiency and elevated levels of toxic heavy metals in all biological fluid samples may have significant negative effects on human reproductive health (sperm quality and function), leading to male infertility.
Since the COVID-19 pandemic began, a cohort of Multisystem inflammatory syndrome in children (MIS-C) patients has been described. Cardiac involvement is found in 80-85% patients, typically with cardiac dysfunction with or without cardiogenic shock. Here, three cardiac biomarkers, BNP, NT-proBNP and Galectin-3 were compared for the first time in MIS-C in a unique cohort of hospitalized French children.
Fourteen children with MIS-C hospitalized at Necker-Enfants Malades for cardiac management during the first three COVID-19 waves (March 2020-March 2021) were included. All had positive SARS-CoV-2 serology and proven cardiac involvement assessed by transthoracic echocardiography. NT-proBNP, BNP and Galectin-3 were measured at admission, discharge and first follow-up clinic.
All admission Galectin-3 measurements were comprised within the reference interval, both in patients with and without cardiogenic shock, and did not vary between admission, discharge and first follow-up clinic. Both median admission BNP and NT-proBNP were higher in children with cardiogenic shock than without. Median admission NT-proBNP was higher than its predictive positive value in heart failure in both groups of children, while median BNP was below its negative predictive value in children without cardiogenic shock but with cardiac dysfunction.
Galectin-3 does not seem affected by MIS-C. NT-proBNP seems to increase more precociously than BNP possibly making it a more sensitive marker for screening of heart failure in MIS-C.
Galectin-3 does not seem affected by MIS-C. NT-proBNP seems to increase more precociously than BNP possibly making it a more sensitive marker for screening of heart failure in MIS-C.