ABSTRACT
Recent advancements in various technologies have shed light on the critical role of metabolism in immune cells, paving the way for innovative disease treatment strategies through immunometabolism modulation. This review emphasizes the glucose metabolism of myeloid-derived suppressor cells (MDSCs), an emerging pivotal immunosuppressive factor especially within the tumor microenvironment. MDSCs, an immature and heterogeneous myeloid cell population, act as a double-edged sword by exacerbating tumors or mitigating inflammatory diseases through their immune-suppressive functions. Numerous recent studies have centered on glycolysis of MDSC, investigating the regulation of altered glycolytic pathways to manage diseases. However, the specific changes in MDSC glycolysis and their exact functions continue to be areas of ongoing discussion yet. In this paper, we review a range of current findings, including the latest research on the alteration of glycolysis in MDSCs, the consequential functional alterations in these cells, and the outcomes of attempts to modulate MDSC functions by regulating glycolysis. Ultimately, we will provide insights into whether these research efforts could be translated into clinical applications.
ABSTRACT
Background and Objectives@#This study aimed to evaluate the voice of patients with vocal cord palsy using the Praat compared to Speech tool.Materials and Method The medical record of the patients with vocal cord palsy from 2013 to 2021 was analyzed retrospectively to validate Praat as a voice evaluation modality compared to the speech tool. Total 60 patients were enrolled in this study. Thirty control and 30 vocal cord palsy patients were selected to undergo recording of voice samples. The voice samples, /a/ and “Sancheck” were evaluated both groups and cepstral peak prominence was analyzed with both modalities; Praat and speech tool. @*Results@#Statistically significant differences were observed between the control and vocal cord palsy groups in the speech tool and Praat. There was also a significant difference between pre- and post-treatment values in the vocal cord palsy group. A similar change in the voice value was observed using both methods. The Praat showed a lower value in 1st visit of patients with vocal cord palsy in the vowel test. The Praat vowel test may sensitively represent voice problems in patients with vocal cord palsy. This could contribute to decision-making regarding the treatment modality for vocal cord palsy. @*Conclusion@#Praat is open-access software that is freely available. It can be easily and sufficiently used for voice evaluation in patients with vocal cord palsy.
ABSTRACT
Background@#This study evaluated the effects of dexmedetomidine and propofol on brain-derived neurotrophic factor level in the cerebrospinal fluid (c-BDNF) and mechanical allodynia in a mild traumatic brain injury (TBI) rat model. @*Methods@#After fixing the rat’s skull on a stereotactic frame under general anesthesia, craniotomy was performed. After impact, 10 µl of drug was injected into the cisterna magna (group S: sham, group D: dexmedetomidine 5 μg/kg, group P: propofol 500 μg/kg, and group T: untreated TBI). The 50% mechanical withdrawal threshold (50% MWT) and c-BDNF level were measured on postoperative days (PODs) 1, 7, and 14. @*Results@#The 50% MWT measured on PODs 1, 7, and 14 was lower and the c-BDNF level on POD 1 was higher in group T than in group S. In group D, the c-BDNF level on POD 1 was lower than that in group T and was comparable with that in group S during the whole study period. The 50% MWT of group D was higher than that of group T throughout the postoperative period. In group P, there were no significant differences in the 50% MWT during the entire postoperative period compared with group T; the c-BDNF level was higher than that in group T on POD 1. @*Conclusions@#Intrathecal administration of dexmedetomidine may attenuate TBI-induced mechanical allodynia for up to two weeks post-injury through immediate suppression of c-BDNF in mild TBI rats. The inhibition of c-BDNF expression in the acute phase reduced the occurrence of TBI-induced chronic neuropathic pain.
ABSTRACT
Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.
ABSTRACT
BACKGROUND/OBJECTIVES@#Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription– polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. @*RESULTS@#TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. @*CONCLUSIONS@#Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.
ABSTRACT
Background and Objectives@#A lack of investigators for polysomnography has risen due to increased demand since health insurance started to cover the cost of the test. We examined the reliability of the automated scoring of polysomnography, which has been deployed to improve this imbalance.Subjects and Method We analyzed the data of 20 patients who underwent level 1 polysomnography from April 1 to July 27, 2019. The software from Noxturnal (Nox Medical) was used for the scoring of the Polysomnography data. Each of the polysomnographic data was scored both by the automated scoring system and by a skilled technician. @*Results@#Twenty patients were analyzed. There was no significant difference between automated scoring and manual scoring in sleep latency, apnea index, and rapid eye movement sleep stage ratio. However, the concordance rate of the sleep stage by epoch was 83.32%, and there was a significant difference with regards to apnea-hypoapnea index (AHI) and respiratory disturbance index (RDI). Two obvious errors were noted in the automated scoring that could be easily fixed; the failure to recognize wakefulness during sleep and the fragmentation of respiratory events. When two errors were corrected, many differences in polysomnography parameters, including AHI and RDI, were eliminated. @*Conclusion@#It showed 80% coincidence of epoch in the sleep stage between the automated scoring and manual scoring. However, there was no difference in AHI and RDI when the fragmented respiratory events of the automated scoring were adjusted. Therefore, automated scoring is considered to be useful if only a little modification could be made.
ABSTRACT
Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.
ABSTRACT
Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.
ABSTRACT
OBJECTIVE@#To investigate the effects of Korean Magnolia obovata crude extract (KME) on plateletderived growth factor (PDGF)-BB-induced proliferation and migration of vascular smooth muscle cells (VSMCs).@*METHODS@#KME composition was analyzed by high-performance liquid chromatography (HPLC). VSMCs were isolated from the aorta of a Sprague-Dawley rat, incubated in serum free-Dulbecco's modified Eagle's medium in the presence or absence of KME (10, 30, 100, and 300 μg/mL), then further treated with PDGF-BB (10 ng/mL). VSMC proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and VSMC migration was determined using the Boyden chamber and scratch wound healing assays. Western blot analysis was used to detect phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2), protein kinase B (p-Akt), and stress-activated protein kinase/c-Jun NH2-terminal kinase (p-SAPK/JNK). The antimigration and proliferation effects of KME were tested using aortic sprout outgrowth.@*RESULTS@#The HPLC analysis identified honokiol (0.45 mg/g) and magnolol (0.34 mg/g) as the major components of KME. KME (30, 100, and 300 μg/mL) significantly decreased the proliferation and migration of PDGF-BB-stimulated (10 ng/mL) VSMCs and the PDGF-BB-induced phosphorylation of EKR1/2, Akt, and SAPK/JNK (P<0.05). Furthermore, PDGF-BBinduced VSMCs treated with 300 μg/mL of KME showed reduction in aortic sprout outgrowth.@*CONCLUSION@#KME could inhibit abnormal proliferation and migration of VSMCs by down-regulating the phosphorylation of EKR1/2 and Akt. Thus, KME might be a functional food for preventing vascular disorders.
ABSTRACT
Central venous access devices (CVAD) provide hemophilic patients, particularly children, with prolonged reliable venous access to promote routine factor replacement therapy. However, one of the significant complications of CVAD use is infection. We report the case of a severe hemophilia B patient with an inhibitor who developed septic arthritis and infective endocarditis associated with methicillin-resistant Staphylococcus aureus infection originating from a CVAD. Our patient had an underlying condition of congenital heart disease, one of the risk factors for infective endocarditis. Unfortunately, the antibiotic therapy did not have a significant effect. An echocardiogram revealed vegetation on the right ventricular moderate band and surgery was determined to be the best course of action. Septic arthritis and endocarditis rarely occur in hemophilia patients, however, they must be taken into account in hemophiliacs with continuing bacteremia.