Publications by authors named "Min-Jeong Kim"

446 Publications

Anticancer Effects of JI017 on Two Prostate Cancer Cell Lines Involve Endoplasmic Reticulum Stress Mediated by Elevated Levels of Reactive Oxygen Species.

Front Pharmacol 2021 13;12:683575. Epub 2021 May 13.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

Prostate cancer is the second most commonly diagnosed cancer, and prostate cancer is the second most common cause of cancer death in United States men after lung cancer. Many therapies are used to treat prostate cancer, and chemotherapy is one of the most relevant treatments. However, chemotherapy has many side effects, and repeated administration of chemotherapeutic agents leads to acquired resistance. Thus, new drugs with few side effects are needed. We investigated the molecular mechanism of action of JI017 in human prostate cancer cells. We identified an endoplasmic reticulum (ER) stress pathway that depended on the reactive oxygen species (ROS) pathway and played a crucial role in JI017-induced apoptosis. We measured cell viability by the MTS assay to determine the effect of JI017. Analysis of apoptosis, mitochondrial dysfunction, and cell cycle features was performed by flow cytometry. We used western blot and RT-PCR to measure the levels of the proteins of the unfolded protein response (UPR) pathway and apoptosis markers. Immunoprecipitation assay and transfection were used to determine the expression levels of proteins interacting with the pathways influenced by JI017 in prostate cancer cells. The anticancer effects induced by JI017 were evaluated. JI017 induced cell death that regulated apoptotic molecules and caused cell cycle arrest that inhibited the proliferation of cancer cells. Moreover, JI017 generated ROS. Accumulation of ROS caused ER stress through the PERK-eIF2α-CHOP and IRE1α-CHOP pathways. Furthermore, persistent activation of the UPR pathway induced by JI017 treatment triggered mitochondrial dysfunction, including dissipation of mitochondrial membrane potential, which activated intrinsic apoptotic pathway in human prostate cancer cells. The data indicated that N-acetyl-L-cysteine diminished apoptosis. We demonstrated that JI017 induced ER stress and cell death. Anticancer properties of JI017 in prostate cancer cells and in a human prostate cancer model involved ROS-mediated ER stress. Thus, JI017 treatment provides a new strategy for chemotherapy of prostate cancer.
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http://dx.doi.org/10.3389/fphar.2021.683575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155384PMC
May 2021

Superconductivity emerging from a stripe charge order in IrTe nanoflakes.

Nat Commun 2021 May 26;12(1):3157. Epub 2021 May 26.

Center for Artificial Low Dimensional Electronic Systems, Institute for Basic Science, Pohang, Korea.

Superconductivity in the vicinity of a competing electronic order often manifests itself with a superconducting dome, centered at a presumed quantum critical point in the phase diagram. This common feature, found in many unconventional superconductors, has supported a prevalent scenario in which fluctuations or partial melting of a parent order are essential for inducing or enhancing superconductivity. Here we present a contrary example, found in IrTe nanoflakes of which the superconducting dome is identified well inside the parent stripe charge ordering phase in the thickness-dependent phase diagram. The coexisting stripe charge order in IrTe nanoflakes significantly increases the out-of-plane coherence length and the coupling strength of superconductivity, in contrast to the doped bulk IrTe. These findings clarify that the inherent instabilities of the parent stripe phase are sufficient to induce superconductivity in IrTe without its complete or partial melting. Our study highlights the thickness control as an effective means to unveil intrinsic phase diagrams of correlated van der Waals materials.
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http://dx.doi.org/10.1038/s41467-021-23310-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154908PMC
May 2021

Delta neutrophil index and symptomatic time are effective factors for predicting perforated appendicitis.

Medicine (Baltimore) 2021 May;100(20):e25935

Department of Surgery, Kangdong Sacred Heart Hospital.

Abstract: Appendicitis is a common intra-abdominal inflammatory disease, and morbidity increases with age when perforation occurs. Because, not all patients require emergency surgery, there have been numerous studies on factors for predicting perforated appendicitis. In this study, we aimed to confirm whether the delta neutrophil index (DNI) and the time from symptom onset to surgery are effective predictors for perforated appendicitis in different age groups.This was a retrospective study conducted on 542 appendicitis patients who underwent surgery at Kangdong Sacred Heart Hospital. The simple group consisted of 431 subjects, and the perforation group consisted of 111 subjects.Multiple logistic regression analyses demonstrated that age, neutrophil percentage, DNI, C-reactive protein (CRP), and symptomatic time were significant predictors of perforation. Analysis of the receiver-operating characteristic curve showed that the DNI was the most reliable predictive value. In the analyses according to age, the perforation rate was higher in the >65-year-age group; these patients also had a higher DNI, CRP, and symptomatic time. In the DNI analysis using receiver operating characteristic (ROC) analysis, the area under the curve was higher in the >65-year-age group than in other age groups. In addition, the cutoff values have been determined and perforation occurred significantly in the group with a DNI value of 2.1 or higher and a symptomatic time of 33 hours or longer.DNI is effective in predicting perforation in patients with appendicitis compared with other inflammatory factors. Furthermore, the simultaneous measurement of symptomatic time and DNI is helpful in predicting perforation and determining whether emergency surgery is necessary.
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http://dx.doi.org/10.1097/MD.0000000000025935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137091PMC
May 2021

Association between serum uric acid and left ventricular hypertrophy/left ventricular diastolic dysfunction in patients with chronic kidney disease.

PLoS One 2021 6;16(5):e0251333. Epub 2021 May 6.

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea.

Background: The level of serum uric acid (SUA) has been reported to be associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). However, this association remains unclear in patients with chronic kidney disease (CKD).

Methods: A total of 1025 patients with pre-dialysis CKD with preserved left ventricular systolic function were enrolled in this cross-sectional study. The LVH and LVDD were assessed using two-dimensional echocardiography and tissue Doppler imaging. The associations of LVH/LVDD with clinical and laboratory variables were investigated using univariable and multivariable logistic regression analyses.

Results: In a multivariable analysis, the SUA level was an independent predictor of LVH (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.31-1.50, P < 0.001). In addition, patient age, systolic blood pressure, intact parathyroid hormone levels, and left atrial volume index levels were independent predictors of LVH. The SUA level was also an independent predictor of LVDD (OR: 1.93, 95% CI: 1.53-2.43, P < 0.001). Furthermore, systolic blood pressure and left atrial volume index levels were an independent predictor of LVDD. Receiver-operating characteristic curve analysis showed that the best cutoff values of SUA levels for identifying LVH and LVDD were ≥ 7.5 mg/dL and ≥ 6.3 mg/dL, respectively.

Conclusion: The SUA level was an independent predictor of LVD and LVDD in patients with CKD, suggesting that SUA could be a biomarker for LVH and LVDD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251333PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101764PMC
May 2021

Bioinspired Adenosine Triphosphate as an "All-In-One" Green Flame Retardant via Extremely Intumescent Char Formation.

ACS Appl Mater Interfaces 2021 May 5;13(19):22935-22945. Epub 2021 May 5.

School of Advanced Materials Science and Engineering, Sungkyunkwan University (SKKU), Suwon 16419, South Korea.

The development of eco-friendly flame retardants is crucial due to the hazardous properties of most conventional flame retardants. Herein, adenosine triphosphate (ATP) is reported to be a highly efficient "all-in-one" green flame retardant as it consists of three essential groups, which lead to the formation of char with extreme intumescence, namely, three phosphate groups, providing an acid source; one ribose sugar, working as a char source; and one adenine, acting as a blowing agent. Polyurethane foam was used as a model flammable material to demonstrate the exceptional flame retardancy of ATP. The direct flammability tests have clearly shown that the ATP-coated polyurethane (PU) foam almost did not burn upon exposure to the torch flame. Importantly, ATP exhibits an extreme volume increase, whereas general phosphorus-based flame retardants show a negligible increase in volume. The PU foam coated with 30 wt % of ATP (PU-ATP 30 wt %) exhibits a significant reduction in the peak heat release rate (94.3%) with a significant increase in the ignition time, compared to bare PU. In addition, PU-ATP 30 wt % exhibits a high limiting oxygen index (LOI) value of 31% and HF-1 rating in the UL94 horizontal burning foamed material test. Additionally, we demonstrated that ATP's flame retardancy is sufficient for other types of matrices such as cotton, as confirmed from the results of the standardized ASTM D6413 test; cotton-ATP 30 wt % exhibits an LOI value of 32% and passes the vertical flame test. These results strongly suggest that ATP has great potential to be used as an "all-in-one" green flame retardant.
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http://dx.doi.org/10.1021/acsami.1c02021DOI Listing
May 2021

Antimicrobial activity of 405 nm light-emitting diode (LED) in the presence of riboflavin against on the surface of smoked salmon.

Food Sci Biotechnol 2021 Apr 12;30(4):609-618. Epub 2021 Mar 12.

Department of Food Science and Technology, Korea National University of Transportation, 61, Daehak-ro, Jeungpyeong-gun, Chungbuk, 27909 Republic of Korea.

This study investigated the antimicrobial activity of 405 nm light-emitting diode (LED) with and without riboflavin against in phosphate buffered saline (PBS) and on smoked salmon at different storage temperatures and evaluated its impact on food quality. The results show that riboflavin-mediated LED illumination in PBS 25 °C significantly inactivated cells by 6.2 log CFU/mL at 19.2 J/cm, while illumination alone reduced 1.9 log CFU/mL of populations at 57.6 J/cm. populations on illuminated smoked salmon decreased by 1.0-2.2 log CFU/cm at 1.27-2.76 kJ/cm at 4, 12, and 25 °C, regardless of the presence of riboflavin. Although illumination with and without riboflavin caused the lipid peroxidation and color change in smoked salmon, this study demonstrates the potential of a 405 nm LED to preserve the smoked salmon products, reducing the risk of listeriosis.
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http://dx.doi.org/10.1007/s10068-021-00895-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050274PMC
April 2021

Ameliorates Antibiotic-Associated Aggravation of DNCB-Induced Atopic Dermatitis by Restoring the Intestinal Microbiome Profile.

Nutrients 2021 Apr 18;13(4). Epub 2021 Apr 18.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome.
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http://dx.doi.org/10.3390/nu13041349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072552PMC
April 2021

Chorismate mutase peptide antibody enables specific detection of Acanthamoeba.

PLoS One 2021 23;16(4):e0250342. Epub 2021 Apr 23.

Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul, Korea.

Accurate and rapid diagnosis of Acanthamoeba keratitis (AK) is difficult. Although the diagnostic procedure for AK has improved, further development and effective diagnostic tool utilization for AK need to continue. Chorismate mutase is a key regulatory enzyme involved in the shikimate pathway, a metabolic pathway absent in mammals but central for amino acid biosynthesis in bacteria, fungi, algae, and plants. In this study, we describe the identification and production of a polyclonal peptide antibody targeting chorismate mutase secreted by A. castellanii, which could be used for AK diagnosis. Western blot was performed using the protein lysates and conditioned media of the human corneal epithelial (HCE) cells, non-pathogenic Acanthamoeba, pathogenic Acanthamoeba, clinical isolate of Acanthamoeba spp., and other causes of keratitis such as Fusarium solani, Pseudomonas aeruginosa, and Staphylococcus aureus. Polyclonal antibodies raised against A. castellanii chorismate mutase specifically interacted with lysates of Acanthamoeba origin and their culture media, while such interactions were not observed from other samples. Acanthamoeba-specificity of chorismate mutase was also confirmed using immunocytochemistry after co-culturing Acanthamoeba with HCE cells. Specific binding of the chorismate mutase antibody to Acanthamoeba was observed, which were absent in the case of HCE cells. These results indicate that the chorismate mutase antibody of Acanthamoeba may serve as a method for rapid and differential Acanthamoeba identification.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250342PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064552PMC
April 2021

Effects of the fermented in the amyloid β-induced Alzheimer's disease mouse model.

Nutr Res Pract 2021 Apr 25;15(2):173-186. Epub 2020 Sep 25.

Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.

Backgroud/objectives: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Due to the increased incidence of dementia, there is a corresponding increase concerning the importance of AD. In this study, we investigated the protective effects conferred by (Zj) and fermented by yeast (Zj-Y), on cognitive impairment in an AD mouse model.

Materials/methods: AD was induced by injecting amyloid beta (Aβ) in ICR mice, and subsequently 200 mg/kg Zj or Zj-Y was administered daily for 14 days. The cognitive ability of AD mice was observed through behavioral experiments in T-maze, novel object recognition, and Morris water maze tests. We subsequently measured the levels of malondialdehyde (MDA), nitric oxide (NO), aspartate aminotransferase, and alanine aminotransferase in either tissues or serum.

Results: In behavioral tests, deterioration was revealed in the short- and long-term learning and memory functions in the Aβ-injected control group compared to the normal group, indicating that Aβ injection impairs cognitive functions. However, administration of Zj and Zj-Y improved cognitive function in mice, as compared to the Aβ-injected control mice. In addition, the Aβ induced elevations of MDA and NO in the brain, kidney, and liver were suppressed after exposure to Zj and Zj-Y. Especially, Zj-Y showed stronger scavenging effect against MDA and NO, as compared to Zj.

Conclusions: Results of the present study indicate that Zj-Y exerts a protective effect on cognitive impairment and memory dysfunction, which is exerted by attenuating the oxidative stress induced by Aβ.
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http://dx.doi.org/10.4162/nrp.2021.15.2.173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007403PMC
April 2021

Exposure of Mesenchymal Stem Cells to an Alzheimer's Disease Environment Enhances Therapeutic Effects.

Stem Cells Int 2021 16;2021:6660186. Epub 2021 Mar 16.

Stem Cell Institute, ENCell Co. Ltd, Seoul 06072, Republic of Korea.

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer's disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an model reduced the expression of amyloid-beta 42 (A42) in the medium as well as the overexpression of amyloid-beta- (A-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of A and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and A levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF- induced primed-MSCs. Furthermore, treatment with TGF- reduced A expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.
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http://dx.doi.org/10.1155/2021/6660186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988745PMC
March 2021

Mineral-rich Jeju lava sea water suppresses lipid accumulation in 3T3-L1 adipocytes and ameliorates high-fat diet-induced obesity in C57BL/6 J mice.

Food Sci Biotechnol 2021 Feb 6;30(2):299-304. Epub 2021 Feb 6.

Department of Food Science and Technology, Seoul National University of Science and Technology, 232, Gongneung-ro, Nowon-gu, Seoul 01811 Republic of Korea.

This research aimed to evaluate the potential inhibitory effect of mineral-rich Jeju lava sea water (JLSW) on lipid accumulation. This study optimized the calcium (Ca): magnesium (Mg) ratio (5:1, 2.5:1, 1:1) of JLSW and evaluated the effect on lipid accumulation in 3T3-L1 cells using Oil Red O staining. JLSW with a high Ca:Mg ratio (5:1) suppressed lipid accumulation in 3T3-L1 adipocytes. Based on these results, the effects of JLSW on lipid accumulation were investigated in C57BL/6 J mice fed high-fat diets for 14 weeks. Epididymal adipose tissue weight was significantly decreased in mice that received JLSW with a hardness of 800 or 100 mg/L compared to HFD. Adipocyte size was significantly reduced in mice treated with JLSW with a hardness of 20 mg/L in comparison with HFD. Thus, long-term intake of JLSW may be expected to have anti-obesity effects due to the reduction of lipid accumulation.
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http://dx.doi.org/10.1007/s10068-020-00859-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914322PMC
February 2021

Identification of Nontuberculous Mycobacteria in Patients with Pulmonary Diseases in Gyeongnam, Korea, Using Multiplex PCR and Multigene Sequence-Based Analysis.

Can J Infect Dis Med Microbiol 2021 22;2021:8844306. Epub 2021 Feb 22.

Department of Microbiology, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.

Background: Nontuberculous mycobacteria (NTM) are widely present in environments, such as soil and water, and have recently been recognized as important pathogenic bacteria. The incidence of NTM-related infections is steadily increasing. As the diagnosis and treatment of NTM infection should be distinguished from tuberculosis, and the treatment should be specific to the species of NTM acquired, accurate species identification is required.

Methods: In this study, two-step multiplex PCR (mPCR) and multigene sequence-based analysis were used to accurately identify NTM species in 320 clinical isolates from Gyeongsang National University Hospital (GNUH). In particular, major mycobacterial strains with a high isolation frequency as well as coinfections with multiple species were diagnosed through two-step mPCR. Multigene sequencing was performed to accurately identify other NTM species not detected by mPCR. Variable regions of the genes 16S rRNA, , , and 16S-23S rRNA internal transcribed spacer were included in the analysis.

Results: Two-step mPCR identified 234 (73.1%) cases of . , 26 (8.1%) cases of . subsp. , and 13 (4.1%) cases of . subsp. infection. Additionally, 9 (2.8%) . , 9 (2.8%) . , 2 (0.6%) . , and 4 (1.2%) . isolates were identified. Coinfection was identified in 7 (2.2%) samples. The sixteen samples not classified by two-step mPCR included 6 (1.9%) cases of . , 4 (1.3%) . , 1 (0.3%) . , 1 (0.3%) . , and 1 (0.3%) . identified by sequence analysis.

Conclusions: The results of this study suggest a strategy for rapid detection and accurate identification of species using two-step mPCR and multigene sequence-based analysis. To the best of our knowledge, this study is the first to report the identification of NTM species isolated from patients in Gyeongnam/Korea.
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http://dx.doi.org/10.1155/2021/8844306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920741PMC
February 2021

Quercetin Induces Apoptosis in Glioblastoma Cells by Suppressing Axl/IL-6/STAT3 Signaling Pathway.

Am J Chin Med 2021 3;49(3):767-784. Epub 2021 Mar 3.

Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Gliomas are the mostly observed form of primary brain tumor, and glioblastoma multiforme (GBM) shows the highest incidence. The survival rate of GBM is fairly poor; thus, discovery of effective treatment options is required. Among several suggested targets for therapy, the Axl/IL-6/STAT3 signaling pathway has gained recent interest because of its important role within cancer microenvironment. Quercetin, a plant flavonoid, is well known for its anticancer action. However, the effect of quercetin on Axl has never been reported. Quercetin treatment significantly reduced cell viability in two GBM cell lines of U87MG and U373MG while keeping 85% of normal astrocytes alive. Further western blot assays suggested that quercetin induces apoptosis but does not affect Akt or mitogen-activated protein kinases, factors related to cell proliferation. Quercetin also decreased IL-6 release and phosphorylation of STAT3 in GBM cells. In addition, gene expression, protein expression, and half-life of synthesized Axl protein were all suppressed by quercetin. By applying shRNA for knockdown of Axl, we could confirm that the role of Axl was crucial in the apoptotic effect of quercetin on GBM cells. In conclusion, we suggest quercetin as a potential anticancer agent, which may improve cancer microenvironment of GBM via the Axl/IL-6/STAT3 pathway.
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http://dx.doi.org/10.1142/S0192415X21500361DOI Listing
March 2021

Dj1 deficiency protects against atherosclerosis with anti-inflammatory response in macrophages.

Sci Rep 2021 Feb 25;11(1):4723. Epub 2021 Feb 25.

Toronto General Hospital Research Institute, University Health Network, Toronto, ON, M5G 2C4, Canada.

Inflammation is a key contributor to atherosclerosis with macrophages playing a pivotal role through the induction of oxidative stress and cytokine/chemokine secretion. DJ1, an anti-oxidant protein, has shown to paradoxically protect against chronic and acute inflammation. However, the role of DJ1 in atherosclerosis remains elusive. To assess the role of Dj1 in atherogenesis, we generated whole-body Dj1-deficient atherosclerosis-prone Apoe null mice (Dj1Apoe). After 21 weeks of atherogenic diet, Dj1 Apoemice were protected against atherosclerosis with significantly reduced plaque macrophage content. To assess whether haematopoietic or parenchymal Dj1 contributed to atheroprotection in Dj1-deficient mice, we performed bone-marrow (BM) transplantation and show that Dj1-deficient BM contributed to their attenuation in atherosclerosis. To assess cell-autonomous role of macrophage Dj1 in atheroprotection, BM-derived macrophages from Dj1-deficient mice and Dj1-silenced macrophages were assessed in response to oxidized low-density lipoprotein (oxLDL). In both cases, there was an enhanced anti-inflammatory response which may have contributed to atheroprotection in Dj1-deficient mice. There was also an increased trend of plasma DJ-1 levels from individuals with ischemic heart disease compared to those without. Our findings indicate an atheropromoting role of Dj1 and suggests that targeting Dj1 may provide a novel therapeutic avenue for atherosclerosis treatment or prevention.
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http://dx.doi.org/10.1038/s41598-021-84063-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907332PMC
February 2021

Median nerve swelling is an independent risk factor of carpal tunnel syndrome in chronic hemodialysis patients.

Ther Apher Dial 2021 Feb 25. Epub 2021 Feb 25.

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea.

Carpal tunnel syndrome (CTS) has a wide variety of underlying causes and occurs in association with dialysis. Early diagnosis is essential to prevent permanent nerve damage and functional sequelae. We evaluated the association between CTS and cross-sectional area (CSA) of the median nerve in chronic hemodialysis (HD) patients. Patients with end-stage renal disease on maintenance HD via arteriovenous fistula were enrolled. We divided 43 patients into two groups; patients diagnosed with CTS (n = 19) and patients without CTS (n = 24). The median nerve CSA was measured at the wrist (CSA-W) and forearm (CSA-F) by ultrasonography. Median nerve swelling was assessed by the wrist-to-forearm ratio (WFR). There were no significant differences in the underlying causes of chronic kidney disease and adequacy of dialysis between the two groups (p = NS). The patients with CTS showed significantly higher WFR than the patients without CTS (p = 0.001). Univariate Cox regression analysis revealed that WFR >1.25 (odds ratio, 6.30; 95% confidence interval, 1.44-27.45; p = 0.014) was associated with CTS in HD patients. The factors traditionally associated with CTS such as age, sex, diabetes, vintage of HD, β2-MG, intact PTH, and Kt/V were not associated with CTS. After adjustment for age and sex, we found a strong correlation between CTS and the WFR >1.25 (odds ratio, 10.8; 95% confidence interval, 1.85-62.4; p = 0.008). High WFR was associated with the development of CTS, and median nerve swelling was an independent risk factor of CTS in chronic HD patients.
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http://dx.doi.org/10.1111/1744-9987.13636DOI Listing
February 2021

Distinct roles of UVRAG and EGFR signaling in skeletal muscle homeostasis.

Mol Metab 2021 May 6;47:101185. Epub 2021 Feb 6.

Toronto General Hospital Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, ON M5G 2C4, Canada. Electronic address:

Objective: Autophagy is a physiological self-eating process that can promote cell survival or activate cell death in eukaryotic cells. In skeletal muscle, it is important for maintaining muscle mass and function that is critical to sustain mobility and regulate metabolism. The UV radiation resistance-associated gene (UVRAG) regulates the early stages of autophagy and autophagosome maturation and plays a key role in endosomal trafficking. This study investigated the essential in vivo role of UVRAG in skeletal muscle biology.

Methods: To determine the role of UVRAG in skeletal muscle in vivo, we generated muscle-specific UVRAG knockout mice using the Cre-loxP system driven by Myf6 promoter that is exclusively expressed in skeletal muscle. Myf6-Cre UVRAG (M-UVRAG) mice were compared to littermate Myf6-Cre UVRAG (M-UVRAG) controls under basal conditions on a normal chow diet. Body composition, muscle function, and mitochondria morphology were assessed in muscles of the WT and KO mice at 24 weeks of age.

Results: M-UVRAG mice developed accelerated sarcopenia and impaired muscle function compared to M-UVRAG littermates at 24 weeks of age. Interestingly, these mice displayed improved glucose tolerance and increased energy expenditure likely related to upregulated Fgf21, a marker of muscle dysfunction. Skeletal muscle of the M-UVRAG mice showed altered mitochondrial morphology with increased mitochondrial fission and EGFR accumulation reflecting defects in endosomal trafficking. To determine whether increased EGFR signaling had a causal role in muscle dysfunction, the mice were treated with an EGFR inhibitor, gefitinib, which partially restored markers of muscle and mitochondrial deregulation. Conversely, constitutively active EGFR transgenic expression in UVRAG-deficient muscle led to further detrimental effects with non-overlapping distinct defects in muscle function, with EGFR activation affecting the muscle fiber type whereas UVRAG deficiency impaired mitochondrial homeostasis.

Conclusions: Our results show that both UVRAG and EGFR signaling are critical for maintaining muscle mass and function with distinct mechanisms in the differentiation pathway.
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http://dx.doi.org/10.1016/j.molmet.2021.101185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921879PMC
May 2021

Preparation of cellulose microfibril (CMF) from Gelidium amansii and feasibility of CMF as a cosmetic ingredient.

Carbohydr Polym 2021 Apr 5;257:117569. Epub 2021 Jan 5.

School of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea; Institute of Fermentation Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea. Electronic address:

Cellulose microfibrils (CMF) were successfully isolated from the red alga, Gelidium amansii. G. amansii was processed in two stages, microwave digestion and high-speed blending to remove agar and extract microfibrils, respectively. After pretreatment at 180 °C for 10 min, G. amansii containing 40.1 % glucan was microfibrillated through homogenization. Morphological analysis by SEM and FTIR, and analysis of the degree of fibrillation with water retention, sedimentation, and CtCBD3 protein binding of G. amansii-derived CMF were investigated. Functional analysis of CMF showed suppression of cyclooxygenase-2 expression in both in vitro and in vivo experiments. Additionally, suppression was evident in the: i) epidermal thickness of mice skin; ii) presence of proinflammatory cytokines; and iii) inhibition of JNK1/2 and p38 phosphorylation in human keratinocyte HaCaT cells. Such activity demonstrates its anti-inflammatory properties. The results in this study showed the possibility of using CMF derived from a red alga as an anti-inflammation material.
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http://dx.doi.org/10.1016/j.carbpol.2020.117569DOI Listing
April 2021

Root Protects against Aβ-Induced Cognitive Dysfunction and Pathology in Female Models of Alzheimer's Disease.

Antioxidants (Basel) 2021 Feb 1;10(2). Epub 2021 Feb 1.

Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon 35365, Korea.

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by irreversible cognitive dysfunction. Amyloid beta (Aβ) peptide is an important pathological factor that triggers the progression of AD through accumulation and aggregation, which leads to AD-related pathologies that consequently affect cognitive functions. Interestingly, several studies have reported that root extract (PGE), besides exhibiting other bioactive effects, displays neuroprotective, anti-neuroinflammatory, and cognitive-enhancing effects. However, to date, it is not clear whether PGE can affect AD-related cognitive dysfunction and pathogenesis. Therefore, to investigate whether PGE influences cognitive impairment in an animal model of AD, we conducted a Y-maze test using a 5XFAD mouse model. Oral administration of PGE for 3 weeks at a daily dose of 100 mg/kg significantly ameliorated cognitive impairment in 5XFAD mice. Moreover, to elucidate the neurohistological mechanisms underlying the PGE-mediated alleviative effect on cognitive dysfunction, we performed histological analysis of hippocampal formation in these mice. Histopathological analysis showed that PGE significantly alleviated AD-related pathologies such as Aβ accumulation, neurodegeneration, oxidative stress, and neuroinflammation. In addition, we observed a neuroprotective and antioxidant effect of PGE in mouse hippocampal neurons. Our findings suggest that administration of PGE might act as one of the therapeutic agents for AD by decreasing Aβ related pathology and ameliorating Aβ induced cognitive impairment.
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http://dx.doi.org/10.3390/antiox10020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912782PMC
February 2021

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

Taiwan J Obstet Gynecol 2021 Jan;60(1):36-40

Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Objective: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk.

Materials And Methods: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores.

Results: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043).

Conclusion: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.
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http://dx.doi.org/10.1016/j.tjog.2020.10.006DOI Listing
January 2021

Synthesis of [F]PS13 and Evaluation as a PET Radioligand for Cyclooxygenase-1 in Monkey.

ACS Chem Neurosci 2021 02 25;12(3):517-530. Epub 2021 Jan 25.

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, Bethesda, Maryland 20892-1003, United States.

Cyclooxygenase-1 (COX-1) and its isozyme COX-2 are key enzymes in the syntheses of prostanoids. Imaging of COX-1 and COX-2 selective radioligands with positron emission tomography (PET) may clarify how these enzymes are involved in inflammatory conditions and assist in the discovery of improved anti-inflammatory drugs. We have previously labeled the selective high-affinity COX-1 ligand, 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1-1,2,4-triazole (PS13), with carbon-11 ( = 20.4 min). This radioligand ([C]PS13) has been successful for PET imaging of COX-1 in monkey and human brain and in periphery. [C]PS13 is being used in clinical investigations. Alternative labeling of PS13 with fluorine-18 ( = 109.8 min) is desirable to provide a longer-lived radioligand in high activity that might be readily distributed among imaging centers. However, labeling of PS13 in its 1,1,1-trifluoroethoxy group is a radiochemical challenge. Here we assess two labeling approaches based on nucleophilic addition of cyclotron-produced [F]fluoride ion to -difluorovinyl precursors, either to label PS13 in one step or to produce [F]2,2,2-trifluoroethyl toluenesulfonate for labeling a hydroxyl precursor. From the latter two-step approach, we obtained [F]PS13 ready for intravenous injection in a decay-corrected radiochemical yield of 7.9% and with a molar activity of up to 7.9 GBq/μmol. PET imaging of monkey brain with [F]PS13 shows that this radioligand can specifically image and quantify COX-1 without radiodefluorination but with some radioactivity uptake in skull, ascribed to red bone marrow. The development of a new procedure for labeling PS13 with fluorine-18 at a higher molar activity is, however, desirable to suppress occupancy of COX-1 by carrier at baseline.
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http://dx.doi.org/10.1021/acschemneuro.0c00737DOI Listing
February 2021

Therapeutic effects of non-saponin fraction with rich polysaccharide from Korean red ginseng on aging and Alzheimer's disease.

Free Radic Biol Med 2021 Feb 8;164:233-248. Epub 2021 Jan 8.

Department of Biochemistry, College of Medicine, Konyang University, 158, Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea; Research Institute for Dementia Science, Konyang University, Daejeon, 35365, Republic of Korea. Electronic address:

Biological aging provokes morbidity and several functional declines, causing older adults more susceptible to a variety of diseases than younger adults. In particular, aging is a major risk factor contributing to non-communicable diseases, such as neurodegenerative disorders. Alzheimer's disease (AD) is an aging-related neurodegenerative disease that is characterized by cognitive deficits and the formation of amyloid plaques formed by the accumulation of amyloid-β (Aβ) peptides. Non-saponin fraction with rich polysaccharide (NFP) from red ginseng, the largest fraction of the components of red ginseng, perform many biological activities. However, it has not been clarified whether the NFP from Korean red ginseng (KRG) has beneficial effects in the aging and AD. First, proteomics analysis was performed in aged brain to identify the effect of NFP on protein changes, and we confirmed that NFP induced changes in proteins related to the neuroprotective- and neurogenic-effects. Next, we investigated (1) the effects of NFP on AD pathologies, such as Aβ deposition, neuroinflammation, neurodegeneration, mitochondrial dysfunction, and impaired adult hippocampal neurogenesis (AHN), in 5XFAD transgenic mouse model of AD using immunostaining; (2) the effect of NFP on Aβ-mediated mitochondrial respiration deficiency in HT22 mouse hippocampal neuronal cells (HT22) using Seahorse XFp analysis; (3) the effect of NFP on cell proliferation using WST-1 analysis; and (4) the effect of NFP on Aβ-induced cognitive dysfunction in 5XFAD mouse model of AD using Y-maze test. Histological analysis indicated that NFP significantly alleviated the accumulation of Aβ, neuroinflammation, neuronal loss, and mitochondrial dysfunction in the subiculum of 5XFAD mouse model of AD. In addition, NFP treatment ameliorated mitochondrial deficits in Aβ-treated HT22 cells. Moreover, NFP treatment significantly increased the AHN and neuritogenesis of neural stem cells in both healthy and AD brains. Furthermore, NFP significantly increased cell proliferation in the HT22 cells. Finally, NFP administration significantly enhanced and restored the cognitive function of healthy and AD mice, respectively. Taken together, NFP treatment demonstrated changes in proteins involved in central nervous system organization/maintenance in aged brain and ameliorates AD pathology. Collectively, our findings suggest that NFP from KRG could be a potential therapeutic candidate for aging and AD treatments.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.12.454DOI Listing
February 2021

A phase II study of gemcitabine, erlotinib and S-1 in patients with advanced pancreatic cancer.

J Cancer 2021 1;12(3):912-917. Epub 2021 Jan 1.

Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Gyeongigi-do, Korea.

We evaluated the efficacy and safety of gemcitabine in combination with erlotinib and S-1 for the treatment of advanced pancreatic cancer. Chemotherapy-naïve patients with pathologically-proven locally advanced, recurrent, or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine was administered at 1,000 mg/m intravenously on days 1 and 8, erlotinib was administered at 100 mg/day on days 1-21, and S-1 was administered at 60 mg/m on days 1-14 every 21 days and continued to a maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m was permitted from the second cycle for pre-defined tolerable patients. Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1-8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The confirmed overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and the disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer.
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http://dx.doi.org/10.7150/jca.50514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778528PMC
January 2021

Clinical performance of medical students in Korea in a whole-task emergency station in the objective structured clinical examination with a standardized patient complaining of palpitations

J Educ Eval Health Prof 2020 16;17:42. Epub 2020 Dec 16.

Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju, Korea

This study assessed the clinical performance of 150 third-year medicalstudents in Busan, Korea in a whole-task emergency objective structured clinical examination station that simulated a patient with palpitations visiting the emergency department. The examination was conducted from November 25 to 27, 2019. Clinical performance was assessed as the number and percentage of students who performed history-taking (HT), a physical examination (PE), an electrocardiography (ECG) study, patient education (Ed), and clinical reasoning (CR), which were items on the checklist. It was found that 18.0% of students checked the patient’s pulse, 51.3% completed an ECG study, and 57.9% explained the results to the patient. A sizable proportion (38.0%) of students did not even attempt an ECG study. In a whole-task emergency station, students showed good performance on HT and CR, but unsatisfactory results for PE, ECG study, and Ed. Clinical skills educational programs for subjected student should focus more on PE, timely diagnostic tests, and sufficient Ed.
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http://dx.doi.org/10.3352/jeehp.2020.17.42DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856094PMC
December 2020

Relationship between angiography timing and angiographic visualization of extravasation in patients with acute non-variceal gastrointestinal bleeding.

BMC Gastroenterol 2020 Dec 14;20(1):426. Epub 2020 Dec 14.

Department of Internal Medicine, University of Hallym College of Medicine, Hallym University Sacred Heart Hospital, 22 Gwanpyeong-ro 170-gil, Dongan-gu, Anyang, 431-796, Republic of Korea.

Background: Angiographic embolization is now considered the first-line therapy for acute gastrointestinal (GI) bleeding refractory to endoscopic therapy. The success of angiographic embolization depends on the detection of the bleeding site. This study aimed to identify the clinical and procedural predictors for the angiographic visualization of extravasation, including angiography timing, as well as analyze the outcomes of angiographic embolization according to the angiographic visualization of extravasation.

Methods: The clinical and procedural data of 138 consecutive patients (mean age, 66.5 years; 65.9% men) who underwent angiography with or without embolization for acute non-variceal GI bleeding between February 2008 and July 2018 were retrospectively analyzed.

Results: Of the 138 patients, 58 (42%) had active extravasation on initial angiography and 113 (81.9%) underwent embolization. The angiographic visualization of extravasation was significantly higher in patients with diabetes (p = 0.036), a low platelet count (p = 0.048), high maximum heart rate (p = 0.002) and AIMS65 score (p = 0.026), upper GI bleeding (p = 0.025), and short time-to-angiography (p = 0.031). The angiographic embolization was successful in all angiograms, with angiographic visualization of extravasation (100%). The clinical success of patients without angiographic visualization of extravasation (83.9%) was significantly higher than that of patients with angiographic visualization of extravasation (65.5%) (p = 0.004). In multivariate analysis, the time-to-angiography (odds ratio 0.373 [95% CI 0.154-0.903], p = 0.029) was the only significant predictor associated with the angiographic visualization of extravasation. The cutoff value of time-to-angiography was 5.0 h, with a sensitivity and specificity of 79.3% and 47.5%, respectively (p = 0.012).

Conclusions: Angiography timing is an important factor that is associated with the angiographic visualization of extravasation in patients with acute GI bleeding. Angiography should be performed early in the course of bleeding in critically ill patients.
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http://dx.doi.org/10.1186/s12876-020-01570-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737270PMC
December 2020

Clusterin Protects Lipotoxicity-Induced Apoptosis via Upregulation of Autophagy in Insulin-Secreting Cells.

Endocrinol Metab (Seoul) 2020 12 2;35(4):943-953. Epub 2020 Dec 2.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: There is a great need to discover factors that could protect pancreatic β-cells from apoptosis and thus prevent diabetes mellitus. Clusterin (CLU), a chaperone protein, plays an important role in cell protection in numerous cells and is involved in various cellular mechanisms, including autophagy. In the present study, we investigated the protective role of CLU through autophagy regulation in pancreatic β-cells.

Methods: To identify the protective role of CLU, mouse insulinoma 6 (MIN6) cells were incubated with CLU and/or free fatty acid (FFA) palmitate, and cellular apoptosis and autophagy were examined.

Results: Treatment with CLU remarkably upregulated microtubule-associated protein 1-light chain 3 (LC3)-II conversion in a doseand time-dependent manner with a significant increase in the autophagy-related 3 (Atg3) gene expression level, which is a mediator of LC3-II conversion. Moreover, co-immunoprecipitation and fluorescence microscopy experiments showed that the molecular interaction of LC3 with Atg3 and p62 was markedly increased by CLU. Stimulation of LC3-II conversion by CLU persisted in lipotoxic conditions, and FFA-induced apoptosis and dysfunction were simultaneously improved by CLU treatment. Finally, inhibition of LC3-II conversion by Atg3 gene knockdown markedly attenuated the cytoprotective effect of CLU.

Conclusion: Taken together, these findings suggest that CLU protects pancreatic β-cells against lipotoxicity-induced apoptosis via autophagy stimulation mediated by facilitating LC3-II conversion. Thus, CLU has therapeutic effects on FFA-induced pancreatic β-cell dysfunction.
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http://dx.doi.org/10.3803/EnM.2020.768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803614PMC
December 2020

Anthocyanins Derived from Contributes Anti-Cancer Effects by Suppressing NF-κB Pathways in Hep3B Human Hepatocellular Carcinoma Cells and In Vivo.

Molecules 2020 Nov 20;25(22). Epub 2020 Nov 20.

Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, 90 Chilam-dong, Jinju 660-702, Korea .

We previously demonstrated that anthocyanins from the fruits of (AIMs) induced the apoptosis of hepatocellular carcinoma cells. However, many researchers argued that the concentrations of AIMs were too high for in vivo experiments. Therefore, we performed in vitro at lower concentrations and in vivo experiments for the anti-cancer effects of AIMs. AIMs inhibited the cell proliferation of Hep3B cells in a dose-dependent manner with a maximum concentration of 100 µg/mL. AIMs also inhibited the invasion and migration at 100 µg/mL concentration with or without the presence of TNF-α. To establish the relevance between the in vitro and in vivo results, we validated their effects in a Xenograft model of Hep3B human hepatocellular carcinoma cells. In the in vivo test, AIMs inhibited the tumorigenicity of Hep3B cells in the xenograft mouse model without showing any clinical signs of toxicity or any changes in the body weight of mice. AIMs inhibited the activation NF-κB and suppressed the NF-κB-regulated proteins, intra-tumoral microvessel density (IMVD) and the Ki67 activity of Hep3B xenograft tumors in athymic nude mice. In conclusion, this study indicates that AIMs have anti-cancer effects (inhibition of proliferation, invasion, and angiogenesis) on human hepatocellular carcinoma xenograft through the inhibition of NF-κB and its target protein.
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http://dx.doi.org/10.3390/molecules25225445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699833PMC
November 2020

Analysis of treatment success with new inclusion criteria for antibiotic therapy for uncomplicated appendicitis: A multicentre cohort study.

Int J Clin Pract 2021 Apr 30;75(4):e13840. Epub 2020 Nov 30.

Center for Colorectal Cancer, National Cancer Center, Goyang, Republic of Korea.

Background: Conservative antibiotic treatment for uncomplicated appendicitis is debated because of the unproven criteria for use and relatively high failure rate. We developed inclusion criteria to optimize antibiotic therapy use and compared the success rate to that seen in previous literature.

Methods: Our antibiotic therapy inclusion criteria were developed based on clinical findings (symptom onset ≤48 hours and body temperature ≤38.3℃), laboratory parameters (white blood cell count ≤12000/mL) and radiologic findings (appendiceal diameter ≤12 mm and no appendicolith). Patients who met inclusion criteria were enrolled from three hospitals between 2016 and 2017. Treatment success was defined as a response to antibiotic therapy and no recurrent symptoms within 1 year. We compared our success rate with previous clinical trial success rates.

Results: There were 240 patients enrolled (116 men and 124 women) with a mean age of 38.7 years. After initial antibiotic treatment, 233 patients (97.1%) responded to therapy and were discharged. There were no post-treatment complications with Clavien-Dindo grade ≥III. During the 1-year follow-up period, the treatment success rate was 88.8% (213/240) and the recurrence rate was 8.6% (20/233; 15 underwent surgery and 5 received antibiotics again). In contrast, the combined treatment success rate for six previous clinical trials was 76.5% (573/749) and the recurrence rate was 21.6% (157/727).

Conclusions: The group enrolled with the new inclusion criteria showed an improved treatment success rate compared to previous studies. These criteria will aid in determining optimal conservative treatment use in patients with uncomplicated appendicitis.
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http://dx.doi.org/10.1111/ijcp.13840DOI Listing
April 2021

Amelioration effects of var. extract/fractions on amyloid beta-induced neurotoxicity in SH-SY5Y cells and identification of the main bioactive compound.

Food Funct 2020 Nov;11(11):9651-9661

Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea.

Amyloid beta (Aβ) is a neurotoxic peptide, and the accumulation of Aβ in the brain is the major characteristic of Alzheimer's disease (AD). Recently, the beneficial effects of Cirsium japonicum var. maackii (CJM) on brain health has attracted much attention. In the present study, we investigated the ability and protective mechanisms of CJM to attenuate neuronal toxicity caused by Aβ using SH-SY5Y cells. Aβ25-35 treatment decreased cell viability, whereas CJM extract/fractions increased cell viability in Aβ25-35-treated cells. We found that CJM treatment prevented the accumulation of reactive oxygen species observed in Aβ25-35-treated control cells. Furthermore, Aβ25-35-mediated production of inflammatory cytokines such as interleukin-1β was significantly suppressed by CJM. In addition, apoptotic factors were modulated in CJM-treated cells by downregulating B-cell lymphoma-2-associated X protein and upregulating B-cell lymphoma-2 protein expression. The assays showed that the ethyl acetate (EtOAc) fraction of CJM has greater neuroprotective bioactivities compared with the other extract/fractions. The main neuroprotective active compound from the EtOAc fraction of CJM was identified as pectolinarin using ultraperformance liquid chromatography-quadrupole time-of-flight-mass spectrometry. Collectively, this study not only describes the neuroprotective effect of CJM against Aβ25-35via the regulation of oxidative, inflammatory, and apoptotic signaling pathways, but also provides useful information for future studies on the mechanism of novel medicinal sources based on pectolinarin isolated from CJM.
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http://dx.doi.org/10.1039/d0fo01041cDOI Listing
November 2020

PET imaging of neuroinflammation in neurological disorders.

Lancet Neurol 2020 11;19(11):940-950

Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA. Electronic address:

A growing need exists for reliable in-vivo measurement of neuroinflammation to better characterise the inflammatory processes underlying various diseases and to inform the development of novel therapeutics that target deleterious glial activity. PET is well suited to quantify neuroinflammation and has the potential to discriminate components of the neuroimmune response. However, there are several obstacles to the reliable quantification of neuroinflammation by PET imaging. Despite these challenges, PET studies have consistently identified associations between neuroimmune responses and pathophysiology in brain disorders such as Alzheimer's disease. Tissue studies have also begun to clarify the meaning of changes in PET signal in some diseases. Furthermore, although PET imaging of neuroinflammation does not have an established clinical application, novel targets are under investigation and a small but growing number of studies have suggested that this imaging modality could have a role in drug development. Future studies are needed to further improve our knowledge of the cellular mechanisms that underlie changes in PET signal, how immune response contributes to neurological disease, and how it might be therapeutically modified.
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http://dx.doi.org/10.1016/S1474-4422(20)30346-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912433PMC
November 2020

Neuroinflammation in psychiatric disorders: PET imaging and promising new targets.

Lancet Psychiatry 2020 12 21;7(12):1064-1074. Epub 2020 Oct 21.

Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA. Electronic address:

Neuroinflammation is a multifaceted physiological and pathophysiological response of the brain to injury and disease. Given imaging findings of 18 kDa translocator protein (TSPO) and the development of radioligands for other inflammatory targets, PET imaging of neuroinflammation is at a particularly promising stage. This Review critically evaluates PET imaging results of inflammation in psychiatric disorders, including major depressive disorder, schizophrenia and psychosis disorders, substance use, and obsessive-compulsive disorder. We also consider promising new targets that can be measured in the brain, such as monoamine oxidase B, cyclooxygenase-1 and cyclooxygenase-2, colony stimulating factor 1 receptor, and the purinergic P2X7 receptor. Thus far, the most compelling TSPO imaging results have arguably been found in major depressive disorder, for which consistent increases have been observed, and in schizophrenia and psychosis, for which patients show reduced TSPO levels. This pattern highlights the importance of validating brain biomarkers of neuroinflammation for each condition separately before moving on to patient stratification and treatment monitoring trials.
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http://dx.doi.org/10.1016/S2215-0366(20)30255-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893630PMC
December 2020