• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.3
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• pp.185-194
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• 2023

Purpose : This study aimed to investigate the relationship between the characteristics of hemodialysis patients and the occurrence of sarcopenia through a comprehensive literature review. Methods : A systematic literature search was conducted to identify eligible studies in the Cochrane library, PubMed and Embase. In this review, we included all papers published since the initiative's inception and summarized results as of december 2022. Studies that investigated association between sarcopenia diagnosis and hemodialysis patients (aged≥18 years) were included. Ultimately, 16 studies met our selection criteria. The risk of bias was assessed using the Newcastle-Ottawa scale. Results : Fourteen of the sixteen studies (88 %) reported that significant association between sarcopenia diagnosis and hemodialysis patients. However, two studies reported no association between sarcopenia diagnosis and hemodialysis patients. As a factor statistically related to sarcopenia in hemodialysis patients, Mortality (6 studies, 38 %), age (5 studies, 31 %), body composition (4 studies, 25 %), physical activity (2 studies, 13 %), diabetes (2 studies, 13 %), cardiovascular abnormalities (1 studies, 6 %), nutritional status (3 studies, 19 %), and gender (3 studies, 19 %). Conclusion : Our findings highlight the necessity of developing a physical therapy program that accurately reflects the health status of hemodialysis patients. To further investigate the association between the diagnosis of sarcopenia and hemodialysis patients, it is recommended to conduct large-scale longitudinal studies using standardized diagnostic criteria and evaluation methods, as well as analyze potential risk factors. Consequently, this study emphasizes the importance and potential of developing physical therapy programs that effectively address the health consequences associated with hemodialysis. The significance of this research lies in its ability to provide valuable insights and lay the foundation for future studies focused on developing preventive and therapeutic interventions targeting muscle wasting syndrome resulting from hemodialysis.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.289-302
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• 2023

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

• BMB Reports
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• v.56 no.5
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• pp.308-313
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• 2023

Phenotypic features such as ataxia and loss of motor function, which are characteristics of Parkinson's disease (PD), are expected to be very closely related to cerebellum function. However, few studies have reported the function of the cerebellum. Since the cerebellum, like the cerebrum, is known to undergo functional and morphological changes due to neuroinflammatory processes, elucidating key functional factors that regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed PD patients and MPTP-induced PD mouse model to find cytokines involved in cerebellar neuroinflammation in PD and to examine changes in cell function by regulating related genes. Along with the establishment of a PD mouse model, abnormal shapes such as arrangement and number of Purkinje cells in the cerebellum were confirmed based on histological finding, consistent with those of cerebellums of PD patients. As a result of proteome profiling for neuroinflammation using PD mouse cerebellar tissues, fetuin-A, a type of cytokine, was found to be significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, neurons isolated from cerebellums of embryos (E18) were treated with fetuin-A siRNA. We uncovered that not only the population of neuronal cells, but also their morphological appearances were significantly different. In this study, we found a functional gene called fetuin-A in the PD model's cerebellum, which was closely related to the role of cerebellar Purkinje cells of mouse and human PD. In conclusion, morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with a decrease of fetuin-A, suggesting that diagnosis and treatment of cerebellar functions of PD patients might be possible through regulation of fetuin-A.

• BMB Reports
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• v.56 no.5
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• pp.265-274
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• 2023

Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.191-202
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• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

• Korean Journal of Clinical Pharmacy
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• v.33 no.4
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• pp.254-260
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• 2023

Background: Adherence to antiretroviral treatment (ART) is crucial for maintaining the HIV-RNA suppression in patients living with HIV/AIDS. This study aims to analyze the risk factors contributing to low medication adherence among individuals with HIV/AIDS by analyzing data from the Korean HIV/AIDS cohort study. Methods: The dependent variable is ART medication adherence. The depressive symptom and anxiety scores were collected as main independence variables. Covariates included gender, age, transmission route, alcohol and smoking information, and antiviral treatment regimen details. To predict the relationship between ordinal dependent variables and independent variables, an ordered logistic regression analysis was conducted, and odds ratios (OR) were calculated. Results: The results of the ordered logistic regression analysis showed that female was associated with a higher risk of low medication adherence (OR=2.91, 95% CI=1.08, 7.83). Among the subjects who were non-smokers and non-drinkers, the risk of low medication adherence was lower (OR=0.36, 95% CI=0.18, 0.70). Depending on the ART treatment group, individuals taking integrase inhibitor had a lower risk of medication adherence (OR=0.31, 95% CI=0.13, 0.76), and those experiencing depressive symptoms were related with a higher risk of low medication adherence (OR=1.97, 95% CI=1.12, 3.46). Conclusions: The encouragement and emotional support of healthcare professionals are essential for patients living with HIV/AIDS who experience depressive symptoms to maintain ART adherence. Additionally, further research is needed to ensure that HIV/AIDS infected female with concurrent depressive symptoms can achieve appropriate ART therapeutic effect.

• Journal of Cerebrovascular and Endovascular Neurosurgery
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• v.25 no.3
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• pp.288-296
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• 2023

Objective: Cerebral collateral circulation may affect subarachnoid hemorrhage (SAH) induced cerebral vasospasm and delayed cerebral ischemia. In this study our aim was to investigate the relationship between collateral status, vasospasm and delayed cerebral ischemia (DCI) in both aneurysmal and nonaneurysmal SAH. Methods: Patients diagnosed as SAH with and without aneurysm were included and their data investigated retrospectively. After the patients diagnosed as SAH according to cerebral computed tomography (CT)/magnetic resonance imaging (MRI), they underwent cerebral angiography to check for cerebral aneurysm. The diagnosis of DCI was made according to the neurological examination and control CT/MRI. All the patients had their control cerebral angiography on days 7 to 10 in order to assess vasospasm and also collateral circulation. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) Collateral Flow Grading System was modified to measure collateral circulation. Results: A total of 59 patients data were analyzed. Patients with aneurysmal SAH had higher Fisher scores and DCI was more common. Although there was no statistically significant difference between the patients with and without DCI in terms of demographics and mortality, patients with DCI had worse collateral circulation and more severe vasospasm. These patients had higher Fisher scores and more cerebral aneurysm overall. Conclusions: According to our data, patients with higher Fisher scores, more severe vasospasm, and poor cerebral collateral circulation may experience DCI more frequently. Additionally aneurysmal SAH had higher Fisher scores and DCI was seen more common. To improve the clinical results for SAH patients, we believe that physicians should be aware of the DCI risk factors.

• Therapeutic Science for Rehabilitation
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• v.13 no.3
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• pp.9-21
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• 2024

Objective : This study investigated the effects of depression on online and offline social interactions among middle-aged and older adults with the aim of enhancing their social connectivity and mental well-being. Methods : Utilizing the Patient Health Questionnaire-9 and the Lubben Social Network Scale-6, this study assessed depression and social relationships in 429 middle-aged adults. We explored the mediation effects of offline relationships on online interactions using path analysis and the Sobel test. Results : Significant links were found between depression and social relationships in a cohort of educated males averaging 63 years of age. Offline interactions mediated 32% of the influence of depression on online relationships, with strong model fit indices emphasizing the importance of offline social interactions. Conclusion : This study highlights the role of active engagement in online and offline networks in improving mental health and managing the impact of depression on social activity among older adults, helping prevent isolation.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.96-105
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• 2001

Objective : Lithium inhibits the action of inositol monophosphatase(IMPase) in phosphoinositide(PI) signal transduction system at therapeutically relevant concentration. The depletion of inositol by lithium itself cannot explain the lithium's therapeutic effect. However, attention has focused on the abnormality of PI signal transduction system as the pathophysiology of bipolar affective disorder(BPD). We investigated whether IMPase mRNA levels of lymphocytes would be different between BPD patients(n=16) and age, sex-matched normal controls(n=16). We also investigated the change of IMPase mRNA level by lithium during 4 weeks to probe the possibility that IMPase mRNA levels could predict the therapeutic response to lithium and clinical course. Method : Relative IMPase mRNA levels in lymphocyte were quantified by reverse transcriptase(RT)-PCR in sixteen drug-free BPD patients and sex, age-matched normal controls. The psychopathology of patients were measured using YMRS (Young Mania Rating Scale) and CGI(Clinical Global Impression). Results : There was no significant difference in IMPase mRNA levels between BPD patients and normal controls. And the IMPase mRNA levels were not significantly changed by 4 week treatment with lithium. However, the basal IMPase mRNA levels were negatively correlated with the changes of CGI after 4 weeks. Furthermore, the patients with relatively high basal IMPase mRNA levels showed much more improvement during 4 weeks. Conclusions : BPD patients and normal controls were not distinguished by lymphocyte IMPase mRNA level. Although we do not support the hypothesis that lymphocyte IMPase activity would be related with the pathogenesis of BPD and the action of lithium, these data raise the possibility that lymphocyte IMPase mRNA levels could function as a predictor of therapeutic response and clinical course of BPD.