ABSTRACT
Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS). To examine the role of PTPs in microglial activation and neuroinflammation, we used specific pharmacological inhibitors of PTPs. Inhibition of PTP1B, TC-PTP, SHP2, LYP, and RPTPβ suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPβ inhibitors downregulated microglial activation in an LPS-induced neuroinflammation model. Our results indicate that multiple PTPs are involved in regulating microglial activation and neuroinflammation, with different expression patterns and specific functions. Thus, PTP inhibitors can be exploited for therapeutic modulation of microglial activation in neuroinflammatory diseases.
Subject(s)
Brain , Microglia , Neuroglia , Nitric Oxide , Protein Tyrosine Phosphatase, Non-Receptor Type 2 , Protein Tyrosine PhosphatasesABSTRACT
Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues. In this review, we will explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy.
Subject(s)
Hypoxia , Homeostasis , Metabolic Networks and Pathways , Metabolism , Oxidation-Reduction , Oxidative Stress , Tumor MicroenvironmentABSTRACT
PURPOSE: Bacille Calmette-Guérin (BCG) lymphadenitis is a relatively frequent local adverse reactions after BCG vaccination. Its incidence rate is usually <1%. However, this rate may be different according to BCG strain, vaccination method or skill, etc. In the Republic of Korea, two BCG strains are used: intradermal Danish-1331 or percutaneous Tokyo-172. We surveyed the incidence rates of BCG lymphadenitis. METHODS: This survey was performed in total 25 centers (5 general hospitals, 20 private pediatric clinics). Immunized type of BCG strain in study subjects was verified by directly observing the scar. The occurrence of BCG lymphadenitis was asked to their parent. In cases of BCG lymphadenitis, location, diameter size, progression of suppuration, and treatment method were investigated, as well. RESULTS: The total number of study subjects was 3,342. Among these, the subjects suitable for enrollment criteria (total 3,222; Tokyo strain 2,501, Danish strain 721) were analyzed. BCG lymphadenitis regardless of its size developed in each five of subjects per strains, therefore, its incidence rate was 0.20% in Tokyo and 0.69% in Danish strain, respectively (P=0.086). However, when applying the WHO criteria - the development of lymph node swelling with diameter 1.5 cm or more, the incidence rate of BCG lymphadenitis was 0.16% (4 cases) in Tokyo and 0.42% (3 cases) in Danish strain, respectively. CONCLUSIONS: The incidence rate of lymphadenitis in two BCG types, percutaneous Tokyo and intradermal Danish strain BCG, is 0.20% and 0.69%, respectively. Both rates are acceptable.
Subject(s)
Humans , Cicatrix , Hospitals, General , Incidence , Lymph Nodes , Lymphadenitis , Mycobacterium bovis , Parents , Republic of Korea , Suppuration , VaccinationABSTRACT
PURPOSE: The purpose of this study was to identify the effects on cognitive function, depression, and activities of daily living of Silver-Care-Robot Program for institutionalized elders. METHODS: This study was a nonequivalent control group pretest-posttest design. The participants were 42 institutionalized elders (17 in the experimental group and 25 in the control group). The Silver-Care-Robot Program was provided as an intervention which was conducted twice a week for 5 weeks. The Silver-Care-Robot Program is an integrated entertainment program to help the mental, emotional, and physical health of elderly people. Pre-test was conducted on the two groups, and, in order to examine the effects of intervention, a post-test was conducted after 5 weeks. RESULTS: There were significant differences in cognitive function and ADL (activities of daily living) between two groups after the program. But the difference in depression in the institutionalized elders was not statistically significant between the two groups. CONCLUSION: The Silver-Care-Robot Program should be considered as a regular program for cognitive function and activities of daily living for institutionalized elders.