Publications by authors named "Ji Soo Yoon"

9 Publications

  • Page 1 of 1

Role of myeloid cell leptin signaling in the regulation of glucose metabolism.

Sci Rep 2021 Sep 15;11(1):18394. Epub 2021 Sep 15.

Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Although innate immunity is linked to metabolic health, the effect of leptin signaling in cells from the innate immune system on glucose homeostasis has not been thoroughly investigated. We generated two mouse models using Cre-lox methodology to determine the effect of myeloid cell-specific leptin receptor (Lepr) reconstitution and Lepr knockdown on in vivo glucose metabolism. Male mice with myeloid cell-specific Lepr reconstitution (Lyz2CreLepr) had better glycemic control as they aged compared to male mice with whole-body transcriptional blockade of Lepr (Lyz2CreLepr). In contrast, Lyz2CreLepr females only had a trend for diminished hyperglycemia after a prolonged fast. During glucose tolerance tests, Lyz2CreLepr males had a mildly improved plasma glucose profile compared to Cre controls while Lyz2CreLepr females had a similar glucose excursion to their Cre controls. Myeloid cell-specific Lepr knockdown (Lyz2CreLepr) did not significantly alter body weight, blood glucose, insulin sensitivity, or glucose tolerance in males or females. Expression of the cytokine interleukin 10 (anti-inflammatory) tended to be higher in adipose tissue of male Lyz2CreLepr mice (p = 0.0774) while interleukin 6 (pro-inflammatory) was lower in male Lyz2CreLepr mice (p < 0.05) vs. their respective controls. In conclusion, reconstitution of Lepr in cells of myeloid lineage has beneficial effects on glucose metabolism in male mice.
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September 2021

Patients' perspectives on the conventional synthetic cast a newly developed open cast for ankle sprains.

World J Orthop 2020 Nov 18;11(11):492-498. Epub 2020 Nov 18.

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam 463-707, Gyeonggi, South Korea.

Background: Orthopedic physicians typically apply a cast to immobilize a body part that has been injured. There have been no significant structural changes or advances in synthetic casts since the development of the modern cast. The Opencast is a recently developed type of cast that allows ventilation and direct visual inspection of the skin to avoid cast-related complications. Although this novel cast appears to have more benefits than the conventional synthetic cast, its clinical efficacy and advantages have not been established.

Aim: To investigate the clinical efficacy and advantages of the newly developed Opencast based on patients' perspectives in those with ankle inversion injury.

Methods: A specifically designed questionnaire consisting of 19 items was used to compare patients' opinions and concerns of the Opencast and the conventional synthetic cast. The items were focused on subjective patient satisfaction, discomfort, and adverse effects while wearing the cast. Patients with an ankle inversion injury diagnosed as a high-grade ankle sprain were enrolled. The subjects were randomized and instructed to fill the questionnaire after wearing a synthetic cast or an Opencast for 2 wk. They were then required to fill the questionnaire again, after switching to the alternative type of cast for 2 more weeks.

Results: A total of 22 subjects participated in the study. The synthetic cast appeared to be more rigid and stable than the Opencast, but there was no significant difference in the amount of pain relief. The likelihood of adverse effects when wearing the synthetic cast was significantly higher. Patient satisfaction tended to be rated higher after wearing the Opencast. Opencast showed more subjective vulnerability than the synthetic cast, but there was no significant difference in the redo rate. Patients were more anxious about removal of the synthetic cast than of the Opencast.

Conclusion: The results indicate that the Opencast could replace the conventional synthetic cast as it offers increased patient satisfaction, which would in turn increase compliance to treatment.
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November 2020

Are There Harmful Effects of Preoperative Mild Lateral or Patellofemoral Degeneration on the Outcomes of Open Wedge High Tibial Osteotomy for Medial Compartmental Osteoarthritis?

Orthop J Sports Med 2020 Jun 23;8(6):2325967120927481. Epub 2020 Jun 23.

Department of Orthopedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Background: Early osteoarthritis of the knee joint mostly affects the medial compartment, making osteotomy a rational approach to slow the progression of the disease. However, some patients show asymptomatic mild degeneration in the lateral or patellofemoral compartment.

Purpose: To evaluate the effect of asymptomatic mild lateral or patellofemoral degeneration on the outcomes of medial open wedge high tibial osteotomy (OWHTO) by assessing the outcomes according to the preoperative status of the lateral or patellofemoral degenerative changes.

Study Design: Cohort study; Level of evidence, 3.

Methods: A total of 114 patients (121 knees) who underwent biplanar OWHTO with second-look arthroscopic surgery and postoperative magnetic resonance imaging (MRI) were retrospectively enrolled. Patients were categorized into 4 groups according to the Osteoarthritis Research Society International (OARSI) and MRI Osteoarthritis Knee Score (MOAKS) classification systems. The International Cartilage Repair Society (ICRS) grade was used to evaluate the preoperative and postoperative cartilage status. Clinical outcomes were assessed by the American Knee Society (AKS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short Form Health Survey (SF-36).

Results: No degenerative changes in the lateral and patellofemoral compartments of knees (group I) were identified in 51.2% of cases (62 knees). Asymptomatic degenerative changes only in the lateral compartment (group II: OARSI grades 1-3 and MOAKS grades 1-3) were identified in 15.7% of cases (19 knees), changes only in the patellofemoral compartment (group III: OARSI grades 1-3 and MOAKS grades 1-3) were identified in 10.7% of cases (13 knees), and changes in both the lateral and the patellofemoral compartments (group IV) were identified in 22.3% of cases (27 knees). In the medial compartment, there was no significant difference in the improvement of MOAKS and ICRS grades among all groups ( = .813 and .985, respectively). In the lateral and patellofemoral compartments, there was no significant difference in the decline of MOAKS ( = .649 and .421, respectively) and ICRS grades ( = .927 and .676, respectively) among all groups.

Conclusion: The presence of mild lateral or patellofemoral degenerative changes did not affect the MRI, arthroscopic, and clinical outcomes of OWHTO. However, long-term observations are necessary to draw definitive conclusions as to whether OWHTO can be indicated in such patients without harmful effects.
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June 2020

Standardized Seed Extract of (HU-033) Attenuates Testosterone Propionate-Induced Benign Prostatic Hyperplasia α1-Adrenergic Receptors and Androgen/Estrogen Signaling.

Prev Nutr Food Sci 2019 Dec 31;24(4):492-497. Epub 2019 Dec 31.

HUONS Research Center, Gyeonggi 15588, Korea.

Benign prostatic hyperplasia (BPH) is an age-related disease characterized by prostatic enlargement and is the most common urologic symptoms in elderly men 60 years of age and older. Previously, we documented that 70% ethanol (EtOH) seed extract of (QI) attenuates pathological condition of testosterone propionate (TP)-induced BPH rat model modulation of proliferation and apoptosis of prostate cells. Based on this potential of QI, we produced standardized seed extract of QI (HU-033) in order to prove further mechanisms. In this study, we aimed to suggest further mechanisms underlying the relationship between BPH and HU-033. Through not only cellular and nuclear receptor functional assays, but TP-mediated BPH rat model treated with HU-033, we demonstrated that HU-033 exerted antagonist effect on α1- and α1-adrenergic receptors and inhibitory effect on protein expression of androgen receptor and estrogen receptor alpha . Taken together, these results suggest that HU-033 is a novel candidate for the management of BPH.
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December 2019

Effects of walking speed and slope on pedobarographic findings in young healthy adults.

PLoS One 2019 24;14(7):e0220073. Epub 2019 Jul 24.

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Kyungki, Korea.

Background: This study aimed to investigate the effects of walking speed and slope on foot pressure changes in young healthy adults.

Methods: Twenty young healthy adults (mean age 22.4 years, SD 1.2 years; 10 male and 10 female) participated in the study. Dynamic pedobarographic data during treadmill walking were obtained for combinations of three different walking speeds (3.2 km/hr, 4.3 km/hr, and 5.4 km/hr) and 5 different slopes (downhill 8 degrees, downhill 4 degrees, ground walking (0 degree), uphill 4 degrees, and uphill 8 degrees). Pedobarographic data such as the peak pressure and pressure-time integral were measured on five plantar segments: medial forefoot (MFF), lateral forefoot (LFF), medial midfoot (MMF), lateral midfoot (LMF), and heel. Maximum ankle dorsiflexion was also recorded using the Plug in Gait marker set.

Results: All participants maintained heel-toe gait in all walking conditions. The peak pressure on the MFF during downhill slope walking was lower than that during ground and uphill walking, whereas the peak pressure on the MFF during uphill slope walking was similar to that during ground walking at each walking speed. The peak pressures on the heel were similar for different walking slopes at each walking speed. The peak pressures on the MFF and heel increased with an increase in walking speed. The pressure-time integral of the MFF did not show significant changes at different walking speeds and slopes. The pressure-time integral of the heel increased with an increase in walking slope and decrease in walking speed.

Conclusions: Different walking speeds and slopes affected the pedobarographic characteristics of young healthy adults. Downhill walking with slower speed appeared to be beneficial to reduce or optimize MFF pressures, while downhill walking at a comfortable speed would be helpful to reduce or optimize heel pressures. The findings of this study have clinical implications in recommending activities to patients with foot pressure-related symptoms and disorders.
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February 2020

Metabolic effects of leptin receptor knockdown or reconstitution in adipose tissues.

Sci Rep 2019 03 1;9(1):3307. Epub 2019 Mar 1.

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.

The relative contribution of peripheral and central leptin signalling to the regulation of metabolism and the mechanisms through which leptin affects glucose homeostasis have not been fully elucidated. We generated complementary lines of mice with either leptin receptor (Lepr) knockdown or reconstitution in adipose tissues using Cre-lox methodology. Lepr knockdown mice were modestly lighter and had lower plasma insulin concentrations following an oral glucose challenge compared to controls, despite similar insulin sensitivity. We rendered male mice diabetic using streptozotocin (STZ) and found that upon prolonged leptin therapy, Lepr knockdown mice had an accelerated decrease in blood glucose compared to controls that was associated with higher plasma concentrations of leptin and leptin receptor. Mice with transcriptional blockade of Lepr (Lepr) were obese and hyperglycemic and reconstitution of Lepr in adipose tissues of Lepr mice resulted in males reaching a higher maximal body weight. Although mice with adipose tissue Lepr reconstitution had lower blood glucose levels at several ages, their plasma insulin concentrations during an oral glucose test were elevated. Thus, attenuation or restoration of Lepr in adipocytes alters the plasma insulin profile following glucose ingestion, modifies the glucose-lowering effect of prolonged leptin therapy in insulin-deficient diabetes, and may modulate weight gain.
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March 2019

Benzothiophenone Derivatives Targeting Mutant Forms of Estrogen Receptor-α in Hormone-Resistant Breast Cancers.

Int J Mol Sci 2018 Feb 15;19(2). Epub 2018 Feb 15.

Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.

Estrogen receptor-α positive (ERα⁺) breast cancers represent 75% of all invasive breast cancer cases, while de novo or acquired resistance to ER-directed therapy is also on the rise. Numerous factors contribute to this phenomenon including the recently-reported ESR1 gene mutations such as Y537S, which amplifies co-activator interactions with ERα and promotes constitutive activation of ERα function. Herein, we propose that direct targeting of the activation function-2 (AF2) site on ERα represents a promising alternative therapeutic strategy to overcome mutation-driven resistance in breast cancer. A systematic computer-guided drug discovery approach was employed to develop a potent ERα inhibitor that was extensively evaluated by a series of experiments to confirm its AF2-specific activity. We demonstrate that the developed small-molecule inhibitor effectively prevents ERα-coactivator interactions and exhibits a strong anti-proliferative effect against tamoxifen-resistant cells, as well as downregulates ERα-dependent genes and effectively diminishes the receptor binding to chromatin. Notably, the identified lead compound successfully inhibits known constitutively-active, resistance-associated mutant forms of ERα observed in clinical settings. Overall, this study reports the development of a novel class of ERα AF2 inhibitors, which have the potential to effectively inhibit ERα activity by a unique mechanism and to circumvent the issue of mutation-driven resistance in breast cancer.
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February 2018

Neuronal PAS Domain Protein 4 Suppression of Oxygen Sensing Optimizes Metabolism during Excitation of Neuroendocrine Cells.

Cell Rep 2018 01;22(1):163-174

Diabetes Research Group, BC Children's Hospital Research Institute, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada. Electronic address:

Depolarization of neuroendocrine cells results in calcium influx, which induces vesicle exocytosis and alters gene expression. These processes, along with the restoration of resting membrane potential, are energy intensive. We hypothesized that cellular mechanisms exist to maximize energy production during excitation. Here, we demonstrate that NPAS4, an immediate early basic helix-loop-helix (bHLH)-PAS transcription factor, acts to maximize energy production by suppressing hypoxia-inducible factor 1α (HIF1α). As such, knockout of Npas4 from insulin-producing β cells results in reduced OXPHOS, loss of insulin secretion, β cell dedifferentiation, and type 2 diabetes. NPAS4 plays a similar role in the nutrient-sensing cells of the hypothalamus. Its knockout here results in increased food intake, reduced locomotor activity, and elevated peripheral glucose production. In conclusion, NPAS4 is critical for the coordination of metabolism during the stimulation of electrically excitable cells; its loss leads to the defects in cellular metabolism that underlie the cellular dysfunction that occurs in metabolic disease.
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January 2018