Chonnam Medical Journal最新文献

N-acetylcysteine (NAC) has been used as an antioxidant to prevent oxidative cell death. However, we found NAC itself to induce neuronal death in mouse cortical cultures. Therefore, the current study was performed to investigate the mechanism of neuronal death caused by NAC. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media after 24-48 h exposure to NAC. NAC (0.1-10 mM) induced neuronal death in a concentration- and exposure time-dependent manner. However, NAC did not injure astrocytes even at a concentration of 10 mM. Also, 10 mM NAC markedly attenuated oxidative astrocyte death induced by 0.5 mM diethyl maleate or 0.25 mM H₂O₂. The NMDA receptor antagonist MK-801 (10 µM) markedly attenuated the neuronal death caused by 10 mM NAC, while NBQX did not affect the neuronal death. Cycloheximide (a protein synthesis inhibitor, 0.1 µg/mL) and z-VAD-FMK (a caspase inhibitor, 100 µM) also significantly attenuated neuronal death. Apoptotic features such as chromatin condensation, nuclear fragmentation, and caspase 3 activation were observed 1 h after the NAC treatment. The neuronal death induced by 1 or 10 mM NAC was significantly attenuated by the treatment with 100 µM Trolox or 1 mM ascorbic acid. NAC induced the generation of intracellular reactive oxygen species (ROS), as measured by the fluorescent dye 2',7'-dichlorofluorescein diacetate. The ROS generation was almost completely abolished by treatment with Trolox or ascorbic acid. These findings demonstrate that NAC can cause oxidative, apoptotic, and excitotoxic neuronal death in mouse neuronal cultures.

Although nivolumab shows survival benefits for patients with advanced gastric cancer (AGC), predictive biomarkers for nivolumab treatment in AGC remain unclear, especially in the case of peritoneal metastases. This study investigated the clinical significance of the prognostic nutrition index (PNI), reflecting the host nutritional status and immunity, in AGC patients undergoing nivolumab monotherapy. This study retrospectively analyzed 53 AGC patients who received nivolumab between October 2017 and February 2021. Among them, 35 patients with peritoneal metastases were reviewed to investigate the relationship between the PNI and oncological outcomes. The PNI was calculated as 10×serum albumin level (g/dl)+0.005×total lymphocyte count (per mm³) at the first administration of nivolumab. With a median follow-up duration of 2.0 (0.3-13.5) months, the median overall survival (OS) was 2.0 months. The overall response and disease-control rates were 0.0% and 20.0%, respectively. Among the 35 patients, 13 patients were identified as a high-PNI group. In the univariate analysis, the high-PNI group showed a significantly longer PFS and OS than the low-PNI group. In the multivariate analysis, the high-PNI was independently associated with a longer PFS (p=0.021) and OS (p=0.022). The PNI can be useful for predicting PFS and OS in AGC patients with peritoneal metastases. However, further studies are required to validate these results in AGC and new strategies are needed to improve the outcome for AGC patients with peritoneal metastases.

To investigate differences of tear neuromediators between subjects with and without dry eye (DE) depending on the ocular sensitivity. Thirty-one subjects with DE and 29 subjects without DE were recruited in this study. The eyes were stimulated by exposure to an irritating product applied to the periocular region. Both DE and non-DE subjects were divided into the high sensitivity and low sensitivity groups based on the degree of ocular sensitivity to ocular irritation. Baseline tear film break-up time (TBUT) and corneal staining score were examined, and tear samples were collected. The concentrations of the tear neuromediators, including nerve growth factor (NGF), serotonin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide Y, and vasoactive intestinal peptide were measured using the enzyme-linked immune sorbent assay. The baseline neuromediator concentrations were compared between subjects with and without DE based on ocular sensitivity. In both DE and non-DE subjects, baseline TBUT was significantly lower in the high sensitivity group than in the low sensitivity group. In the high sensitivity group, baseline tear NGF levels were higher in subjects with DE than in those without DE. In the low sensitivity group, baseline levels of tear CGRP were lower in subjects with DE than in those without DE. Tear neuromediators associated with DE had differences in their concentrations depending on ocular sensitivity. In patients with DE, tear NGF levels increased with high ocular sensitivity to ocular irritation, whereas tear CGRP levels decreased with low ocular sensitivity.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by -1.13% in all patients (p<0.001), and by -1.36 and -0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of -2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

The use of herbal medicine to manage chronic conditions including diabetes has become a recent global trend. Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia. The present review is aimed to analyze the antidiabetic activity of N. sativa as many type 2 diabetic patients use it as a complementary therapy along with their modern allopathic medications or as an alternative therapy. The literature was reviewed in databases like Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, Web of science, EMBASE, Directory of open access journals (DOAJ), and reference lists to identify relevant articles supporting the use of N. sativa in diabetes management. Numerous clinical and animal studies have demonstrated the antidiabetic efficacy of black seeds (N. sativa) and its major bioactive constituent thymoquinone. Based on these findings patients with diabetes may use N. sativa as an adjuvant therapy, which may help to reduce the dose and incidence of adverse effects of modern antidiabetic medicines.

Acer mono is known to contain bioactive substances that exhibit beneficial effects in osteoporosis, gastric ulcers, hepatic damage, and pathologic angiogenesis. The current study aimed to investigate the effects of Acer mono extract on the invasive activities and cell-cycle progression of human fibrosarcoma cells. Cytotoxicity of Acer mono extract was assessed by MTT assay, in-vitro invasiveness of HT1080 fibrosarcoma cells was measured using matrigel assay, expression of invasion- and cell-cycle-related proteins was analyzed by western blot analysis, and that of E2F target genes was quantified using qRT-PCR. Acer mono extract did not show distinct cytotoxicity in the experimental concentrations used. Invasiveness of HT1080 fibrosarcoma cells and expression of cyclin D1 and CDK4 in them were significantly reduced in a dose-dependent manner after treatment with Acer mono extract. Acer mono extract showed inhibitory effects on the G1/S transition during cell-cycle progression; the active phosphorylated Rb protein level was decreased, and expression of E2F target genes was downregulated by the Acer mono extract. Our data collectively demonstrated that Acer mono extract exerts inhibitory effects on the invasiveness and cell-cycle progression of HT1080 human fibrosarcoma cells.

Potent antiplatelet therapy after primary percutaneous coronary intervention (PCI) has the potential to reduce infarct size. This study analyzed the association between on-treatment platelet reactivity and myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. In this single-center, retrospective study, 253 patients who underwent primary PCI for STEMI were divided into two groups according to platelet reactivity measurements (53 patients in the high platelet reactivity [HPR] group and 200 in the non-HPR group). Technetium Tc-99m tetrofosmin single-photon emission computed tomography (SPECT) was performed before hospital discharge. We measured the infarct size using SPECT imaging and serial cardiac biomarker levels, and compared the infarct sizes of each group. The patients with HPR were older (65.5±13.2 vs. 60.6±12.1 years, p=0.011) than the patients with non-HPR. On the other hand, the non-HPR group had a higher incidence of smoking (26.4% vs. 51.0%, p=0.001) than the HPR group. Infarct size was similar between the two groups (22.6±17.3% vs. 24.8±17.7%, p=0.416). Multivariate analysis revealed that onset to balloon time >240 min (odds ratio [OR]=1.92; 95% confidence interval [CI]=1.08-3.40; p=0.025) and anterior infarction (OR=5.28; 95% CI=3.05-9.14; p<0.001) were independent predictors of large (>22%) infarct size. HPR was not a predictor of infarct size assessed by SPECT. The two groups also showed analogous cumulative creatinine kinase-myocardial band and troponin T levels. In conclusion, compared to non-HPR, HPR showed no significant association with myocardial infarct size measured by SPECT imaging in early phase of MI.