• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.390-398
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• 2024

FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1's roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID-3CO6) using the Glide module of the Schrödinger suite. In silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9985-9996
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• 2014

Background and Aim: Laparoscopic and open rectum surgery for rectal cancer remains controversial. This systematic review compared the short-term and long-term efficiency and complications associated with laparoscopic and open resection for rectal cancer. Materials and Methods: We searched PubMed, Embase, Cochrane Library, ISI Web of Knowledge and the China Biology Medicine Database to identify potential randomized controlled trials from their inception to March 31, 2014 without language restriction. Additional articles were identified from searching bibliographies of retrieved articles. Two reviewers independently assessed the full-text articles according to the pre-specified inclusion and exclusion criteria as well as the methodological quality of included trials. The meta-analysis was performed using RevMan 5.2. Results: A total of 16 randomized controlled trials involving 3,045 participants (laparoscopic group, 1,804 cases; open group, 1,241 cases) were reviewed. Laparoscopic surgery was associated with significantly lower intraoperative blood loss, earlier return of bowel movement and reduced length of hospital stay as compared to open surgery, although with increased operative time. It also showed an obvious advantage for minimizing late complications of adhesion-related bowel obstruction. Importantly, there were no significant differences in other postoperative complications, oncological clearance, 3-year and 5-year or 10 year recurrence and survival rates between two procedures. Conclusions: On the basis of this meta-analysis we conclude that laparoscopic surgery has advantages of earlier postoperative recovery, less blood loss and lower rates of adhesion-related bowel obstruction. In addition, oncological outcome is comparable after laparoscopic and open resection for rectal cancer.

• BMB Reports
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• v.51 no.5
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• pp.236-241
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• 2018

Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic $Ca^{2+}$ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by $Ca^{2+}$ and heat remain more elusive. To investigate critical amino acid residues for modulation of $Ca^{2+}$ and heat sensing, we constructed a randomized mutant library for ANO1. Among 695 random mutants, reduced $Ca^{2+}$ sensitivity was observed in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced sensitivity to $Ca^{2+}$ but not to high temperatures, whereas the E705V mutant exhibited reduced sensitivity to both $Ca^{2+}$ and noxious heat. These results suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical for modulation of $Ca^{2+}$ and/or heat responses. Furthermore, these findings help to provide a better understanding of the $Ca^{2+}$-mediated activation and heat-sensing mechanism of ANO1.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.361-375
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• 2018

We aimed to compare the efficacy and safety of long-acting injectable (LAI) and oral second-generation antipsychotics (SGAs) in treating schizophrenia by performing a systematic review and meta-analysis. MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library, as well as five Korean databases, were systemically searched to identify studies published from 2000 to 16 April 2015, which compared the efficacy and safety of LAI and oral SGAs. Using data from randomized controlled trials (RCTs), meta-analyses were conducted. In addition, the GRADE (the Grading of Recommendations, Assessment, Development and Evaluation) approach was applied to explicitly assess the quality of the evidence. A total of 30 studies including 17 RCTs and 13 observational studies were selected. The group treated with LAI SGAs was characterized by significantly lower relapse rates, longer times to relapse and fewer hospital days, but also by a higher occurrence of extrapyramidal syndrome and prolactin-related symptoms than that in the group treated with oral SGAs. Our findings demonstrate that there is moderate to high level of evidence suggesting that in the treatment of schizophrenia, LAI SGAs have higher efficacy and are associated with higher rates of extrapyramidal syndrome and prolactin-related symptoms. Additionally, the use of LAI SGAs should be combined with appropriate measures to reduce dopamine $D_2$ antagonism-related symptoms.

• Korean Journal of Radiology
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• v.21 no.7
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• pp.812-828
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• 2020

Objective: To provide an evidence-based guide for the MRI interpretation of complete tumor response after neoadjuvant chemoradiation therapy (CRT) for rectal cancer using visual assessment on T2-weighted imaging (T2) and diffusion-weighted imaging (DWI). Materials and Methods: PubMed MEDLINE, EMBASE, and Cochrane Library were searched on November 28, 2019 to identify articles on the following issues: 1) sensitivity and specificity of T2 or DWI for diagnosing pathologic complete response (pCR) and the criteria for MRI diagnosis; 2) MRI alone vs. MRI combined with other test(s) in sensitivity and specificity for pCR; and 3) tests to select patients for the watch-and-wait management. Eligible articles were selected according to meticulous criteria and were synthesized. Results: Of 1615 article candidates, 55 eligible articles (for all three issues combined) were identified. Combined T2 and DWI performed better than T2 alone, with a meta-analytic summary sensitivity of 0.62 (95% confidence interval [CI], 0.43-0.77; I² = 80.60) and summary specificity of 0.89 (95% CI, 0.80-0.94; I² = 92.61) for diagnosing pCR. The criteria for the complete response on T2 in most studies had the commonality of remarkable tumor decrease to the absence of mass-like or nodular intermediate signal, although somewhat varied, as follows: (near) normalization of the wall; regular, thin, hypointense scar in the luminal side with (near) normal-appearance or homogeneous intermediate signal in the underlying wall; and hypointense thickening of the wall. The criteria on DWI were the absence of a hyperintense signal at high b-value (≥ 800 sec/mm²) in most studies. The specific algorithm to combine T2 and DWI was obscure in half of the studies. MRI combined with endoscopy was the most utilized means to select patients for the watch-and-wait management despite a lack of strong evidence to guide and support a multi-test approach. Conclusion: This systematic review and meta-analysis provide an evidence-based practical guide for MRI assessment of complete tumor response after CRT for rectal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3419-3424
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• 2014

Background: Our aim was to conduct a meta-analysis to compare the efficacy and safety of pemetrexed and docetaxel for non-small cell lung cancer (NSCLC). Materials and Methods: We systematically searched the Cochrane Library, PubMed, Embase, China Biology Medicine Database for randomized controlled trials (RCTs) comparing the efficacy and toxicities of pemetrexed versus docetaxel as a treatment for advanced NSCLC. We limited the languages to English and Chinese. Two reviewers independently screened articles to identify eligible trials according to the inclusion and exclusion criteria and assessed the methodological quality of included trials, and then extracted data. The meta-analysis was performed using STATA12.0. Results: Six RCTs involving 1,414 patients were identified. We found that there was no statistically significant differences in overall response rate, survival time, progression-free survival, disease control rate, and 1-2yr survival rate (p>0.050) but it is worthy of mention that patients in the pemetrexed arms had significantly higher 3-yr survival rate (P=0.002). With regard to the grade 3 or 4 hematological toxicity, compared with docetaxel, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, and leukocyts toxicity (p<0.001). There was no significant difference in anemia between the two arms (p=0.08). In addition, pemetrexed led to higher rate of grade 3-4 thrombocytopenia toxicity (p=0.03). As for the non-hematological toxicities, compared with docetaxel, pemetrexed group had lower rate of grade 3-4 diarrhea and alopecia. Conclusions: Pemetrexed was almost as effective as docetaxel in patients with advanced NSCLC. At the same time, pemetrexed might increase the 3-yr survival rate. As for safety, pemetrexed led to lower rate of grade 3-4 febrile neutropenia, neutropenia, leukocytes, diarrhea and alopecia toxicity. However, it was associated with a higher rate of grade 3-4 thrombocytopenia.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.3
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• pp.60-79
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• 2020

Objectives: This review plans to assess the efficacy and effectiveness of oriental medicine for the treatment of Ovarian Hyperstimulation Syndrome (OHSS) through literature research and overview. Methods: Database searching was conducted to identify relevant randomized controlled trials (RCTs) on oriental medicine for the treatment of Ovarian Hyperstimulation Syndrome. Studies were searched from Journal of Korean Obstetrics and Gynecology, Korean Medical Database, Korean studies Information Service System, China National Knowledge Infrastructure, Cochrane library, PubMed and EmBase up to 21^st May, 2020. Results: Seventeen studies were finally selected. Fifteen studies intervened with oral Chinese herb medicine, two studies intervened with acupuncture and moxibustion. Nine studies concluded that intervention with oriental medicine significantly relieved OHSS symptoms. Three studies reporting ovary diameter, four studies reporting abdominal circumference and other four studies reporting pelvic effusion showed significant reduction compared to control groups. Six studies showed significantly shorter duration for hospitalization in intervention groups. Only one study showed significantly higher pregnancy rate. Factors related with vascular permeability and blood cell coagulation were significantly lowered in intervention groups in general. Conclusions: From seventeen studies, oriental medicine relieved OHSS symptoms and showed treatment effectiveness. Further strictly designed studies and long-term observed studies are needed to establish evidences.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.3
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• pp.80-94
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• 2020

Objectives: The purpose of this review is to analyze the domestic study trends of clinical use of Digital Infrared Thermal Imaging (DITI) as a diagnosis instrument on obstetrics and gynecological diseases in Korean literature. Methods: We searched for clinical studies using DITI in the journal of Korean obstetrics & gynecology, National Digital Science Library, Research Information Sharing Service, Korean Medical Database up to May 2020. After searching studies, we selected studies and analyzed according to disease. Results: 18 clinical studies were published in two kinds of academic journals. There were 4 studies about dysmenorrhea and menopausal symptoms, 2 studies about postpartum disease and hypercryalgesia, 1 study about amenorrhea, premenstrual syndrome, leukorrhea, infertility, polycystic ovary syndrome and hot flush. Conception vessel was frequently used for DITI measurement, followed by stomach meridian. The temperatures of abdomen (CV4, CV12), face (HN3), upper and lower limb (PC8, LU4, LR3, ST32) were commonly measured. Conclusions: This study shows that DITI could be one of effective diagnosis instrument for obstetrics and gynecological diseases. More well-designed clinical studies using DITI will be needed.

• Journal of Acupuncture Research
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• v.28 no.1
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• pp.15-28
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• 2011

Objectives : To understand the strength and weakness of traditional warm needle acupuncture based on existing research outcomes in Korea mostly and to suggest how to build the desirable warm needle acupuncture apparatus by overcoming demerits of traditional and currently existing ones. Methods : We searched warm needle relating papers in Korean with the key words of '온침, 화침, 열자극' by using DBpia, Journal of Korean Oriental Medical Society, Journal of Korean Acupuncture & Moxibustion Society and Journal of Society for Meridian and Acupoint. Degree dissertations in Korean were also searched with the same words through the search engine of Library of Kyung Hee University. We also searched with words of 'warm, thermal, heat, needle, acupuncture, temperature' via Pubmed and found a small number of English written papers and large number of Chinese written ones. To find english translated version of those papers, we googled with the same words with no success. Results : About 20 papers on warm needle acupuncture written in Korean were found and analyzed with respect to experimental factors that affected the thermal properties or the amount of heat stimulus of the acupuncture. More rigorous descriptions seemed to be required on the insertion depth, duration and manipulation of warm needle treatment. A basic heat transfer model was presented for the clarification of heat loss through the needle of warm needle acupuncture. Environmental factors such as air flow on the properties seems to be considered for the warm needle acupuncture. Conclusions : Papers on warm needle acupuncture were reviewed and analyzed based on their thermal properties and tools such as needles and moxa cones. Several suggestions were made on the descriptions relating the properties. Necessary specifications were introduced to aim modernized warm needle systems.

• Journal of the Korean Magnetic Resonance Society
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• v.6 no.1
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• pp.54-68
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• 2002

PEBP2/CBF (Polyomavirus Enhancer-core Binding Protein 2/Core Binding Factor), represents a new family of heterodimeric transcription factor. Those members play important roles in hematopoiesis and osteogenesis in mouse and human. PEBP2/CBF is a sequence-specific DNA binding protein. Each member of the PEBP2/CBF family of transcription factors is composed of two subunits, ${\alpha}$ and ${\beta}$. The evolutionarily conserved 128 amino acid region in ${\alpha}$ subunit has been called the Runt domain, which harbors two different activities, the ability to bind DNA and interact with the ${\beta}$ subunit. Recently, cDNA clones encoding the C. elegans Runt domain were isolated by screening a cDNA library. This gene was referred to run (Runt homologous gene). In this study, the basic experiments for the structural characterization of RUN protein were performed using spectroscopic methods. We have identified the structural properties of RUN using bioinformatics, CD and NMR. The limit temperature of the structural stability was up to 60$^{\circ}C$ with irreversible thermal process, and the structure of RUN seems to adopt ${\alpha}$ helices and one or more ${\beta}$ sheet or turn. The degree of NMR peak dispersion and intensity was increased by addition of glycine. Therefore, glycine could be used to alleviate the aggregation property of RUN in NMR experiment.