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Article ; Online: Dual Function of Secreted APE1/Ref-1 in TNBC Tumorigenesis

Sunga Choi / Yu-Ran Lee / Ki-Mo Kim / Euna Choi / Byeong-Hwa Jeon

International Journal of Molecular Sciences, Vol 23, Iss 16, p

An Apoptotic Initiator and a Regulator of Chronic Inflammatory Signaling

2022 Volume 9021

Abstract: The simultaneous regulation of cancer cells and inflammatory immune cells in the tumor microenvironment (TME) can be an effective strategy in treating aggressive breast cancer types, such as triple-negative breast cancer (TNBC). Apurinic/apyrimidinic ... ...

Abstract	The simultaneous regulation of cancer cells and inflammatory immune cells in the tumor microenvironment (TME) can be an effective strategy in treating aggressive breast cancer types, such as triple-negative breast cancer (TNBC). Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multi-functional nuclear protein that can be stimulated and then secreted. The extracellular APE1/Ref-1 causes a reduction in disulfide bonds in cytokine receptors, resulting in their conformational changes, thereby inhibiting inflammatory signaling. Furthermore, the secreted APE1/Ref-1 in response to acetylation has been shown to bind to a receptor for the advanced glycation end product (RAGE), initiating the apoptotic cell death of TNBC in vitro and in vivo. This study used PPTLS-APE1/Ref-1 in an adenovirus vector (Ad-PPTLS-APE1/Ref-1) for the constant expression of extracellular APE1/Ref-1, and our results demonstrated its dual function as an apoptotic initiator and inflammation regulator. Injecting MDA-MB 231 orthotopic xenografts with the Ad-PPTLS-APE1/Ref-1 inhibited tumor growth and development in response to acetylation. Moreover, Ad-PPTLS-APE1/Ref-1 generated reactive oxygen species (ROS), and tumor tissues derived from these xenografts exhibited apoptotic bodies. Compared to normal mice, a comparable ratio of anti- and pro-inflammatory cytokines was observed in the plasma of Ad-PPTLS-APE1/Ref-1-injected mice. Mechanistically, the disturbed cytokine receptor by reducing activity of PPTLS-APE1/Ref-1 inhibited inflammatory signaling leading to the inactivation of the p21-activated kinase 1-mediated signal transducer and activator of transcription 3/nuclear factor-κB axis in tumor tissues. These results suggest that the regulation of inflammatory signaling with adenoviral-mediated PPTLS-APE1/Ref-1 in tumors modulates the secretion of pro-inflammatory cytokines in TME, thereby inhibiting aggressive cancer cell progression, and could be considered as a promising and safe therapeutic strategy for treating ...
Keywords	TNBC ; PPTLS-APE1/Ref-1 ; apoptosis ; tumor microenvironment ; cytokines ; anti-inflammatory signaling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Veronica persica

Shim, Ki-Shuk / Park, Musun / Yang, Won-Kyung / Lee, Hanbyeol / Kim, Seung-Hyung / Choo, Byung-Kil / Chae, Sungwook / Kim, Ho-Kyoung / Kim, Taesoo / Kim, Ki-Mo

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 6

Abstract: Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. ...

Abstract	Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation.
Language	English
Publishing date	2023-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12061267
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Article ; Online: Functional outcomes of residual varus alignment versus mechanical alignment in total knee arthroplasty for varus osteoarthritis: A preferred reporting items for systematic reviews and meta-analyses-compliant meta-analysis.

Han, Seung-Beom / Jang, Ki-Mo / Kim, Jun-Hyun / Kim, Sang-Bum / Shin, Kyun-Ho

Journal of orthopaedic surgery (Hong Kong)

2022 Volume 30, Issue 2, Page(s) 10225536221115273

Abstract: Background: One in five patients with mechanical alignment (MA) after total knee arthroplasty (TKA) was reportedly dissatisfied. As constitutional varus knees are common, restoring the patients' natural residual varus (RV) alignment is as an appealing ... ...

Abstract	Background: One in five patients with mechanical alignment (MA) after total knee arthroplasty (TKA) was reportedly dissatisfied. As constitutional varus knees are common, restoring the patients' natural residual varus (RV) alignment is as an appealing alternative to neutral MA. This meta-analysis aimed to evaluate the effects of RV alignment on the functional outcomes compared with those of MA in TKA for the knees with varus osteoarthritis. Methods: The MEDLINE/PubMed, Cochrane Library, and EMBASE databases were comprehensively searched for papers comparing the effects of RV alignment and MA on the functional outcomes from the time of inception of the databases to July 2020. Studies comparing the functional outcomes in the knees subjected to TKA with RV alignment (case group) and MA (control group) were included. The Knee Society knee and functional scores (KSKS and KSFS, respectively), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Oxford knee score (OKS), and forgotten joint score (FJS) were compared. Results: Seven studies were finally included; all studies showed a low risk of selection bias and provided detailed demographic data. The pooled mean difference in the KSKS (0.06, 95% confidence interval [CI]: -0.14 to 0.27; Conclusion: The beneficial effects of RV alignment on the functional outcomes are limited compared to those of MA in TKA for varus osteoarthritis to date. Currently, TKA with neutral MA should be considered as the gold standard.
MeSH term(s)	Arthroplasty, Replacement, Knee ; Humans ; Knee/surgery ; Knee Joint/surgery ; Knee Prosthesis ; Osteoarthritis, Knee/surgery
Language	English
Publishing date	2022-07-11
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	1493368-8
ISSN	2309-4990 ; 1022-5536
ISSN (online)	2309-4990
ISSN	1022-5536
DOI	10.1177/10225536221115273
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Article: Particulated Costal Allocartilage With Microfracture Versus Microfracture Alone for Knee Cartilage Defects: A Multicenter, Prospective, Randomized, Participant- and Rater-Blinded Study.

Chung, Kwangho / Jung, Min / Jang, Ki-Mo / Park, Sang-Hoon / Nam, Bum Joon / Kim, Hyungjun / Kim, Sung-Hwan

Orthopaedic journal of sports medicine

2023 Volume 11, Issue 7, Page(s) 23259671231185570

Abstract: Background: Microfracture is the first-line treatment for cartilage defects; however, the suboptimal quality of the repaired cartilage remains an issue.: Purpose/hypothesis: The aim of this first in-human study was to compare the clinical efficacy ... ...

Abstract	Background: Microfracture is the first-line treatment for cartilage defects; however, the suboptimal quality of the repaired cartilage remains an issue. Purpose/hypothesis: The aim of this first in-human study was to compare the clinical efficacy and safety of a combination of particulated costal allocartilage and microfracture versus microfracture alone in treating knee cartilage defects. We hypothesized that the particulated costal allocartilage with microfracture would result in superior cartilage repair quality and better clinical outcomes at 48 weeks postoperatively. Study design: Randomized controlled trial; Level of evidence, 1. Methods: Patients with cartilage defects were allocated randomly to the treatment group (particulated costal allocartilage with microfracture) and control group (microfracture alone). Magnetic resonance imaging (MRI) outcomes of cartilage repair (the primary outcome measure) were evaluated at the 48-week follow-up using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported clinical outcomes (visual analog scale [VAS] pain score, Knee injury and Osteoarthritis Outcome Score [KOOS], and International Knee Documentation Committee score) and adverse events were evaluated at 12, 24, and 48 weeks postoperatively. Results: Overall, 88 patients were included (44 patients each in the treatment and control groups). The total MOCART score at 48 weeks postoperatively was significantly higher in the treatment group than in the control group ( Conclusion: Microfracture augmented with particulated costal allocartilage resulted in superior cartilage repair quality compared with microfracture alone in terms of MRI evaluation of the knee joint cartilage defect at the 48-week follow-up. Functional outcomes were favorable for both treatments at final follow-up. Registration: KCT0004936 (Clinical Research Information Service [CRiS] of the Republic of Korea).
Language	English
Publishing date	2023-07-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2706251-X
ISSN	2325-9671
ISSN	2325-9671
DOI	10.1177/23259671231185570
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Article ; Online: Veronica persica Ethanol Extract Ameliorates Dinitrochlorobenzene-Induced Atopic Dermatitis-like Skin Inflammation in Mice, Likely by Inducing Nrf2/HO-1 Signaling

Shim, Ki-Shuk / Park, Musun / Yang, Won-Kyung / Lee, Hanbyeol / Kim, Seung-Hyung / Choo, Byung-Kil / Chae, Sungwook / Kim, Ho-Kyoung / Kim, Taesoo / Kim, Ki-Mo

Antioxidants. 2023 June 13, v. 12, no. 6

2023

Abstract: Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. Veronica persica has pharmacological activity that prevents asthmatic inflammation by ameliorating inflammatory cell activation. However, the potential effects of ... ...

Abstract	Atopic dermatitis (AD) is chronic allergic contact dermatitis with immune dysregulation. Veronica persica has pharmacological activity that prevents asthmatic inflammation by ameliorating inflammatory cell activation. However, the potential effects of the ethanol extract of V. persica (EEVP) on AD remain elusive. This study evaluated the activity and underlying molecular pathway of EEVP in two AD models: dinitrochlorobenzene (DNCB)-induced mice and interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated human HaCaT keratinocytes. EEVP attenuated the DNCB-induced increase in serum immunoglobulin E and histamine levels, mast cell counts in toluidine-blue-stained dorsal skin, inflammatory cytokine (IFN-γ, interleukin [IL]-4, IL-5, and IL-13) levels in cultured splenocytes, and the mRNA expression of IL6, IL13, IL31 receptor, CCR-3, and TNFα in dorsal tissue. Additionally, EEVP inhibited the IFN-γ/TNF-α-induced mRNA expression of IL6, IL13, and CXCL10 in HaCaT cells. Furthermore, EEVP restored the IFN-γ/TNF-α-induced downregulation of heme oxygenase (HO)-1 in HaCaT cells by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) expression. A molecular docking analysis demonstrated that EEVP components have a strong affinity to the Kelch-like ECH-associated protein 1 Kelch domain. In summary, EEVP inhibits inflammatory AD by attenuating immune cell activation and inducing the Nrf2/HO-1 signaling pathway in skin keratinocytes.
Keywords	Kelch repeats ; Veronica persica ; atopic dermatitis ; blood serum ; contact dermatitis ; ethanol ; gene expression ; heme oxygenase (biliverdin-producing) ; histamine ; humans ; immunoglobulin E ; inflammation ; interferons ; interleukin-13 ; interleukin-5 ; interleukin-6 ; keratinocytes ; mast cells ; medicinal properties ; necrosis ; splenocytes
Language	English
Dates of publication	2023-0613
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12061267
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Article ; Online: Dual Function of Secreted APE1/Ref-1 in TNBC Tumorigenesis: An Apoptotic Initiator and a Regulator of Chronic Inflammatory Signaling.

Choi, Sunga / Lee, Yu-Ran / Kim, Ki-Mo / Choi, Euna / Jeon, Byeong-Hwa

International journal of molecular sciences

2022 Volume 23, Issue 16

Abstract	The simultaneous regulation of cancer cells and inflammatory immune cells in the tumor microenvironment (TME) can be an effective strategy in treating aggressive breast cancer types, such as triple-negative breast cancer (TNBC). Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multi-functional nuclear protein that can be stimulated and then secreted. The extracellular APE1/Ref-1 causes a reduction in disulfide bonds in cytokine receptors, resulting in their conformational changes, thereby inhibiting inflammatory signaling. Furthermore, the secreted APE1/Ref-1 in response to acetylation has been shown to bind to a receptor for the advanced glycation end product (RAGE), initiating the apoptotic cell death of TNBC in vitro and in vivo. This study used PPTLS-APE1/Ref-1 in an adenovirus vector (Ad-PPTLS-APE1/Ref-1) for the constant expression of extracellular APE1/Ref-1, and our results demonstrated its dual function as an apoptotic initiator and inflammation regulator. Injecting MDA-MB 231 orthotopic xenografts with the Ad-PPTLS-APE1/Ref-1 inhibited tumor growth and development in response to acetylation. Moreover, Ad-PPTLS-APE1/Ref-1 generated reactive oxygen species (ROS), and tumor tissues derived from these xenografts exhibited apoptotic bodies. Compared to normal mice, a comparable ratio of anti- and pro-inflammatory cytokines was observed in the plasma of Ad-PPTLS-APE1/Ref-1-injected mice. Mechanistically, the disturbed cytokine receptor by reducing activity of PPTLS-APE1/Ref-1 inhibited inflammatory signaling leading to the inactivation of the p21-activated kinase 1-mediated signal transducer and activator of transcription 3/nuclear factor-κB axis in tumor tissues. These results suggest that the regulation of inflammatory signaling with adenoviral-mediated PPTLS-APE1/Ref-1 in tumors modulates the secretion of pro-inflammatory cytokines in TME, thereby inhibiting aggressive cancer cell progression, and could be considered as a promising and safe therapeutic strategy for treating TNBCs.
MeSH term(s)	Animals ; Apoptosis ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; Cytokines/metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics ; DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism ; Humans ; Inflammation/pathology ; Mice ; Oxidation-Reduction ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Tumor Microenvironment
Chemical Substances	Cytokines ; APEX1 protein, human (EC 4.2.99.18) ; DNA-(Apurinic or Apyrimidinic Site) Lyase (EC 4.2.99.18)
Language	English
Publishing date	2022-08-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23169021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Adjustable-Loop Cortical Suspensory Fixation Results in Greater Tibial Tunnel Widening Compared to Interference Screw Fixation in Primary Anterior Cruciate Ligament Reconstruction.

Lee, Tae-Jin / Jang, Ki-Mo / Kim, Tae-Jin / Lee, Sang-Min / Bae, Ji-Hoon

Medicina (Kaunas, Lithuania)

2022 Volume 58, Issue 9

Abstract: Background: Although the use of adjustable-loop suspensory fixation has increased in recent years, the influence of the shortcomings of suspensory fixation, such as the bungee-cord or windshield-wiper effects, on tunnel widening remains to be clarified. ... ...

Abstract	Background: Although the use of adjustable-loop suspensory fixation has increased in recent years, the influence of the shortcomings of suspensory fixation, such as the bungee-cord or windshield-wiper effects, on tunnel widening remains to be clarified. Hypothesis/Purpose: The purpose of this study was to compare adjustable-loop femoral cortical suspensory fixation and interference screw fixation in terms of tunnel widening and clinical outcomes after anterior cruciate ligament reconstruction (ACLR). We hypothesized that tunnel widening in the adjustable-loop femoral cortical suspensory fixation (AL) group would be comparable to that in the interference screw fixation (IF) group. Methods: This study evaluated patients who underwent primary ACLR at our institution between March 2015 and June 2019. The femoral and tibial tunnel diameters were measured using plain radiographs in the immediate postoperative period and 2 years after ACLR. Tunnel widening and clinical outcomes (Lysholm score, 2000 International Knee Documentation Committee subjective score, and Tegner activity level) were compared between the two groups. Results: There were 48 patients (mean age, 29.8 ± 12.0 years) in the AL group and 44 patients (mean age, 26.0 ± 9.5 years) in the IF group. Tunnel widening was significantly greater in the AL group than that in the IF group at the tibia anteroposterior (AP) middle (2.03 mm vs. 1.32 mm, p = 0.017), tibia AP distal (1.52 mm vs. 0.84 mm, p = 0.012), tibia lateral proximal (1.85 mm vs. 1.00 mm, p = 0.001), tibia lateral middle (2.36 mm vs. 1.03 mm, p < 0.001), and tibia lateral distal (2.34 mm vs. 0.85 mm, p < 0.001) levels. There were no significant differences between the two groups with respect to femoral tunnel widening and clinical outcomes. Conclusions: Tibial tunnel widening was significantly greater in the AL group than in the IF group at 2 years after primary ACLR. However, the clinical outcomes in the two groups were comparable at 2 years.
MeSH term(s)	Adolescent ; Adult ; Anterior Cruciate Ligament/surgery ; Anterior Cruciate Ligament Injuries/surgery ; Anterior Cruciate Ligament Reconstruction/methods ; Bone Screws ; Femur/surgery ; Humans ; Knee Joint/surgery ; Tibia/surgery ; Young Adult
Language	English
Publishing date	2022-09-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58091193
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Article ; Online: Detection of Lateral Hinge Fractures After Medial Closing Wedge Distal Femoral Osteotomy: Computed Tomography Versus Plain Radiography.

Nha, Kyung Wook / Kim, Kun Woo / Bae, Ji Hoon / Jang, Ki-Mo / Kim, Sang-Gyun

The American journal of sports medicine

2021 Volume 49, Issue 12, Page(s) 3350–3356

Abstract: Background: Limited evidence exists in the literature regarding the detection rates of lateral hinge fracture (LHF) on computed tomography (CT) after medial closing wedge distal femoral osteotomy (MCDFO). Moreover, the effect of LHF on bone healing ... ...

Abstract	Background: Limited evidence exists in the literature regarding the detection rates of lateral hinge fracture (LHF) on computed tomography (CT) after medial closing wedge distal femoral osteotomy (MCDFO). Moreover, the effect of LHF on bone healing after MCDFO remains unclear. Hypothesis: The detection rates of LHF after MCDFO would be higher on CT than on plain radiography. The incidence of problematic bone healing would be higher in the knees with LHF than in those without LHF. Study design: Cohort study (diagnosis), Level of evidence, 3. Methods: Patients who underwent MCDFO between May 2009 and July 2019 were retrospectively evaluated. The presence of LHF was evaluated using immediate postoperative plain radiography and CT. The detection rates of LHF on plain radiography and CT were compared. The incidence of problematic bone healing (nonunion, delayed union, and loss of correction) was also compared between the knees with LHF and those without LHF. Results: A total of 55 knees of 43 patients (mean age, 37.7 ± 16.7 years) were included in the study. Although 33 LHFs were detected on CT, only 19 LHFs were detected on plain radiography. The detection rate of LHF was significantly higher on CT than on plain radiography (60% vs 34.5%; Conclusion: LHF can be detected better on CT than on plain radiography and has a negative effect on bone healing after MCDFO. For patients with LHF detected on either plain radiography or CT, careful rehabilitation with close follow-up is recommended.
MeSH term(s)	Adult ; Cohort Studies ; Humans ; Middle Aged ; Osteoarthritis, Knee/diagnostic imaging ; Osteotomy/adverse effects ; Radiography ; Retrospective Studies ; Tibia ; Tomography, X-Ray Computed ; Young Adult
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	197482-8
ISSN	1552-3365 ; 0363-5465
ISSN (online)	1552-3365
ISSN	0363-5465
DOI	10.1177/03635465211031434
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Article ; Online: Static and Dynamic Quadriceps Stretching Exercises in Patients With Patellofemoral Pain: A Randomized Controlled Trial.

Lee, Jin Hyuck / Jang, Ki-Mo / Kim, Eunseon / Rhim, Hye Chang / Kim, Hyeong-Dong

Sports health

2021 Volume 13, Issue 5, Page(s) 482–489

Abstract: Background: Limited data are available on the effect of stretching exercise in patients with patellofemoral pain (PFP) who have inflexible quadriceps, which is one of the various causes of PFP syndrome. This study compares quadriceps flexibility, ... ...

Abstract	Background: Limited data are available on the effect of stretching exercise in patients with patellofemoral pain (PFP) who have inflexible quadriceps, which is one of the various causes of PFP syndrome. This study compares quadriceps flexibility, strength, muscle activation time, and patient-reported outcomes after static and dynamic quadriceps stretching exercises in patients with PFP who had inflexible quadriceps. Hypothesis: Quadriceps flexibility and strength, muscle activation time, and patient-reported outcomes would improve with dynamic quadriceps stretching as compared with static quadriceps stretching exercises. Study design: Randomized controlled trial. Level of evidence: Level 2. Methods: Of the 44 patients included in the study, 20 performed static stretching and 24 performed dynamic stretching. Quadriceps flexibility was assessed by measuring the knee flexion angle during knee flexion in the prone position (the Ely test). Muscle strength and muscle activation time were measured using an isokinetic device. The patient-reported outcomes were evaluated using the visual analogue scale for pain and anterior knee pain scale. Results: No significant differences in quadriceps flexibility and strength, muscle activation time, and patient-reported outcomes in the involved knees were found between the 2 groups ( Conclusion: Quadriceps flexibility and strength, muscle activation time, and patient-reported outcomes in patients with PFP who had inflexible quadriceps showed no significant differences between the static and dynamic quadriceps stretching exercise groups. Clinical relevance: Both static and dynamic stretching exercises may be effective for improving pain and function in patients with PFP who have inflexible quadriceps.
MeSH term(s)	Adult ; Female ; Humans ; Male ; Muscle Strength/physiology ; Muscle Stretching Exercises ; Pain Measurement ; Patellofemoral Pain Syndrome/physiopathology ; Patellofemoral Pain Syndrome/therapy ; Prospective Studies ; Quadriceps Muscle/physiopathology
Language	English
Publishing date	2021-02-20
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2508802-6
ISSN	1941-0921 ; 1941-7381
ISSN (online)	1941-0921
ISSN	1941-7381
DOI	10.1177/1941738121993777
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Article ; Online: Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and blood lactate levels: A systematic review and meta-analysis.

Rhim, Hye Chang / Kim, Sung Jong / Park, Jewel / Jang, Ki-Mo

Journal of sport and health science

2020 Volume 9, Issue 6, Page(s) 553–561

Abstract: Background: Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements ...

Abstract	Background: Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels. Methods: A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies. Results: The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17). Conclusion: Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.
MeSH term(s)	Citrulline/administration & dosage ; Citrulline/adverse effects ; Citrulline/analogs & derivatives ; Dietary Supplements ; Fruit and Vegetable Juices ; Humans ; Lactic Acid/blood ; Malates/administration & dosage ; Malates/adverse effects ; Myalgia/prevention & control ; Perception/physiology ; Physical Exertion/physiology ; Resistance Training
Chemical Substances	Malates ; Citrulline (29VT07BGDA) ; Lactic Acid (33X04XA5AT) ; citrulline malate (PAB4036KHO)
Language	English
Publishing date	2020-02-08
Publishing country	China
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2673028-5
ISSN	2213-2961 ; 2095-2546
ISSN (online)	2213-2961
ISSN	2095-2546
DOI	10.1016/j.jshs.2020.02.003
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