• Journal of Dental Anesthesia and Pain Medicine
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• v.24 no.2
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• pp.129-135
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• 2024

Concomitant chemoradiotherapy (CCRT) treated patients experience various complications. We present a rare case of post-CCRT Bell's palsy and describe its various possible causes, so as to increase awareness among clinicians about Bell's palsy being a CCRT-associated adverse effect. The patient was a 48-year-old man diagnosed with squamous cell carcinoma who presented with post-CCRT Bell's palsy. After radiotherapy for 6 weeks (overall 67.5 Gy) and four rounds of cisplatin chemotherapy, he complained of paralysis of the entire left face. A test was performed 33 days after the last CCRT session to differentiate Bell's palsy from other causative factors. Based on magnetic resonance imaging findings, facial nerve invasion due to tumor size increase was determined to not cause Bell's palsy. Inflammation of the left Eustachian tube was observed. Hence, steroids and famciclovir were administered, which markedly improved the facial paralysis symptoms within 56 days after facial paralysis development. In conclusion, patients can develop Bell's palsy owing to complex effects of various CCRT mechanisms. Although the exact cause of Bell's palsy has not been identified and the effectiveness of drug treatment was questionable in this case, unlikely causative factors should be excluded through various tests and appropriate and timely measures must be adopted.

• Journal of Korean Medicine Rehabilitation
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• v.34 no.3
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• pp.89-96
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• 2024

Objectives This study is designed to evaluated the safety of peony root extract tablet in healthy male volunteers. Methods 12 healthy male volunteers were recruited, and this study was conducted by a single center. The safety was evaluated by collecting laboratory test and vital signs of volunteers. As the registration process, 12 subjects were assigned by serial number. To evaluate safety, vital signs were checked and blood samples were collected 4 times during the screening period, pre & post-administration (after 8 hours) and post-administration (after 7 days). The difference in variables was summarized by the mean±standard deviation. The normality test was carried out using the Shapiro-Wilk test and Kolmogorov-Smirnov test. When normality is fulfilled, a paired t-test is applied and the significance level was p<0.05. And the incidence of all adverse effects and serious adverse effects are shown in percentage. Results In the case of vital sign, body temperature (BT) (℃) was 0.06±0.05 ℃ (p=0.008), and there was a statistically significant difference in before and after administration. However, clinical symptoms were not occurred and BT (℃) of all subjects before and after administration showed values within the normal reference value. There was no significant difference from the control group in all other vital signs and laboratory test data. And no side-effects associated to clinical trial drugs were followed. Conclusions The peony root extract tablet was considered to be safe for healthy male volunteers.

• Dementia and Neurocognitive Disorders
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• v.21 no.2
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• pp.45-58
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• 2022

Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer's dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD's diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

• International Journal of Oncology
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• v.56 no.6
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• pp.1540-1550
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• 2020

The epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR-TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib-resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti-apoptotic proteins, Mcl-1 and Bcl-2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR-TKI therapy, in EGFR-TKI-resistant cancers.

• Journal of Life Science
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• v.34 no.8
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• pp.588-593
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• 2024

An extensive analysis of 3,490 metabolic pathways in 471 archaebacterial species was conducted using the MetaCyc database. The number of metabolic pathways in these species varied significantly, ranging from 13 to 184 per species. Notably, no single metabolic pathway was found to be common in all archaebacteria. However, the "UTP and CTP de novo biosynthesis" and "tRNA charging" pathways were present in the 470 species. Among the top 12 most prevalent metabolic pathways in archaebacteria, five were associated with nucleic acids and five with proteins. The remaining pathways included the "synthetic pathway of S-adenosyl-L-methionine (SAM)," a critical cofactor in various bioreactions, and "phosphopantothenate biosynthesis III (archaea)," which is required for essential post-translational modifications. These findings underscore the importance of nucleic acids and protein metabolism in archaeal biology. When the average and standard deviation of the distance values obtained from the phylogenetic tree of metabolic pathways, each class of archaebacteria was divided into main two groups and the others, showing that the distribution of metabolic pathways was diverse. This study's insights hold potential applications in both foundational science and drug development.

• Oncology Letters
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• v.18 no.5
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• pp.4858-4864
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• 2019

XAV939, a tankyrase inhibitor, exerts an anticancer effect in 3-dimensional (3D) cultured SW480 cells, however this is not exhibited in 2-dimensional (2D) cultured SW480 cells. In the current study, XAV939 induced a 3.7-fold increase in cellular apoptosis in 3D culture but not in the 2D culture. However, no significant changes were indicated in cell cycle distribution in the 2D or 3D culture. Based on the observation that protein expression, which was associated with the glycolytic pathway, was increased in the 3D culture, the effect of XAV939 on the patterns of glycolytic protein expression was assessed. XAV939 was revealed to decrease lactose dehydrogenase A (LDHA) expression in 3D cultured SW480 cells, but only exerted a small effect in the 2D culture. The coadministration of XAV939 with the LDHA inhibitor FX11 decreased proliferation in 3D cultured SW480 cells compared with the single administration of FX11, while there was no additive effect in the 2D culture. The lactate assay also indicated that XAV939 decreased lactate secretion in the 3D cell culture but not in the 2D culture. These results suggest that XAV939 exerts an anticancer effect through inhibition of LDHA in the 3D culture.

• Oncology Letters
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• v.17 no.3
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• pp.3589-3598
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• 2019

Colorectal cancer (CRC) is a complex disease involving numerous genetic abnormalities. One of the major characteristics of CRC is enhanced Wnt signaling caused by loss-of-function mutations in the adenomatous polyposis coli (APC) gene. Previously, it has been demonstrated that the majority of malignant phenotypes following APC deletion in adult murine small intestines could be rescued when Myc, a downstream target of the Wnt pathway, was deleted. This indicated that Myc is a critical regulator of CRC development following APC loss. Previous studies reported that cyclic adenosine 3',5'-monophosphate (cAMP) can influence the AKT/mammalian target of rapamycin (mTOR) survival pathway in cancer and Myc is a critical downstream molecule of AKT/mTOR signaling. Phosphodiesterase 4D (PDE4D), a member of the cAMP-specific PDE4 family, has been associated with drug resistance in CRC. However, the association between PDE4D and Myc remains unclear. To investigate the potential role of PDE4D in Myc regulation in CRC, the present study evaluated the expression levels of PDE4 subtypes in DLD-1 CRC cells. Additionally, the effects of PDE4 inhibitors on Myc expression and oncogenic properties were analyzed by western blot analysis, reverse transcription-quantitative polymerase chain reaction, colony formation and soft agar assays. It was demonstrated that cAMP/PDE4D signals serve a critical role in regulating Myc expression in DLD-1 CRC cells. Furthermore, PDE4D was identified to be a main hydrolyzer of cAMP and suppression of PDE4D using selective inhibitors of PDE4 increased intracellular cAMP levels, which resulted in a marked decrease in the oncogenic properties of DLD-1 cells, including colony formation, cell proliferation and anchorage-independent growth. Notably, the current data imply that cAMP represses Myc expression via the downregulation of AKT/mTOR signaling, which was abolished by high PDE4D activities in DLD-1 cells. Additionally, a natural polyphenol resveratrol in combination with forskolin elevated the concentration of cAMP and enhanced the expression of Myc and the malignant phenotype of DLD-1 cells, reproducing the effect of known chemical inhibitors of PDE4. In conclusion, the present study identified that cAMP/PDE4D signaling is a critical regulator of Myc expression in DLD-1 and possibly other CRC cells.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.479-491
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• 2024

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

• Biomolecules & Therapeutics
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• v.32 no.5
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• pp.627-634
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• 2024

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

• The Korean journal of internal medicine
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• v.39 no.4
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• pp.668-679
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• 2024

Background/Aims: This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES). Methods: Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis. Results: Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60-0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use. Conclusions: The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.