1.Dietary glucosinolates inhibit splenic inflammation in high fat/cholesterol diet-fed C57BL/6 mice
HyunJi GU ; Min-Hee GWON ; Sang-Min KIM ; Jung-Mi YUN
Nutrition Research and Practice 2021;15(6):798-806
BACKGROUND/OBJECTIVES:
Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity.Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3′-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the antiinflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/ cholesterol diet (HFCD)-fed C57BL/6 mice.MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/ day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/ day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate proinflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue.
RESULTS:
Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements.
CONCLUSIONS
PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.
2.Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells
Aeri LEE ; HyunJi GU ; Min-Hee GWON ; Jung-Mi YUN
Nutrition Research and Practice 2021;15(5):591-603
BACKGROUND/OBJECTIVES:
Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions.MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 μM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses.
RESULTS:
Hesperetin (0–100 μM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment.
CONCLUSIONS
Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.
3.Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells
Aeri LEE ; HyunJi GU ; Min-Hee GWON ; Jung-Mi YUN
Nutrition Research and Practice 2021;15(5):591-603
BACKGROUND/OBJECTIVES:
Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions.MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 μM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses.
RESULTS:
Hesperetin (0–100 μM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment.
CONCLUSIONS
Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.
4.Predicting Vascularized Bone Graft Viability Using 1-Week Postoperative Bone SPECT/CT After Maxillofacial Reconstructive Surgery
Hyunji KIM ; Koeun LEE ; Sejin HA ; Eonwoo SHIN ; Kang-Min AHN ; Jee-Ho LEE ; Jin-Sook RYU
Korean Journal of Nuclear Medicine 2020;54(6):292-298
Purpose:
We aimed to evaluate the performance of hybrid bone single-photon emission computed tomography (SPECT)/computed tomography (CT) in predicting bone graft viability after maxillary or mandibular reconstructive surgery with vascularized bone grafts.
Methods:
We retrospectively reviewed 46 bone planar scintigraphy and SPECT/CT images of 45 adult patients taken at 1 week (5–8 days) after maxillary or mandibular reconstructive surgery with vascularized bone grafts. By visual analysis, two nuclear medicine physicians scored the uptake degrees of each bone graft segment compared with the calvarium uptake on planar bone scintigraphy and SPECT/CT, respectively (0 = absence of uptake, 1 = less uptake, 2 = similar uptake, and 3 = more uptake). The imaging results were compared with clinical follow-up for assessing bone graft viability.
Results:
During follow-up, five bone graft segments were surgically removed and confirmed as nonviable—one had a score of 0, although the other four had a score of 1–3 on planar bone scintigraphy. All five bone graft segments were scored 0 on SPECT/CT and eventually confirmed as nonviable. All other graft segments with a score of > 1 on SPECT/CT were viable and uneventful.The anatomical CT information on SPECT/CT images was helpful in discriminating bone graft uptake from adjacent bone or soft tissue uptake.
Conclusions
The absence of tracer uptake by the vascularized bone graft on bone SPECT/CT at 1 week after maxillary or mandibular reconstructive surgery can predict graft failure. Bone SPECT/CT can be used to predict vascularized bone graft viability postoperatively.
5.Successful Localization Using â¶â¸Ga-DOTATOC PET/CT of a Phosphaturic Mesenchymal Tumor Causing Osteomalacia in a Patient with Concurrent Follicular Lymphoma
Sejin HA ; Sujin PARK ; Hyunji KIM ; Heounjeong GO ; Seung Hun LEE ; Ji Yoon CHOI ; Jung Yong HONG ; Jin Sook RYU
Korean Journal of Nuclear Medicine 2018;52(6):462-467
Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of â¶â¸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹â¸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. â¶â¸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.
6.Successful Localization Using ⁶⁸Ga-DOTATOC PET/CT of a Phosphaturic Mesenchymal Tumor Causing Osteomalacia in a Patient with Concurrent Follicular Lymphoma
Sejin HA ; Sujin PARK ; Hyunji KIM ; Heounjeong GO ; Seung Hun LEE ; Ji Yoon CHOI ; Jung Yong HONG ; Jin Sook RYU
Korean Journal of Nuclear Medicine 2018;52(6):462-467
Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.
Alkaline Phosphatase
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Biopsy, Large-Core Needle
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Diagnosis
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Drug Therapy
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Humans
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Hypophosphatemia
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Lymph Nodes
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Lymphoma
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Lymphoma, Follicular
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Middle Aged
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Osteomalacia
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Phosphorus
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Positron-Emission Tomography and Computed Tomography
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Vitamins