Korean Red Ginseng extract induces angiogenesis through activation of glucocorticoid receptor

Wai-Nam Sung,Hoi-Hin Kwok,Man-Hee Rhee,Patrick Ying-Kit Yue,Ricky Ngok-Shun Wong 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4

Background: Our previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA(miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes. The aim of this study was to determine the angiogenic properties of Korean Red Ginseng extract (KGE). Methods and Results: Combining in vitro and in vivo data, KGE at 500 mg/mL was found to induce angiogenesis. According to the miRNA sequencing, 484 differentially expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their corresponding angiogenic proteins were stimulated, including vascular endothelial growth factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array, proving that KGE could activate GR. Conclusion: KGE was found capable of inducing angiogenesis both in vivo and in vitro models through activating GR. This study provides a valuable insight into the angiogenic mechanisms depicted by KGE in relation to specific miRNAs.

IL10 and TNF variants and risk of non-Hodgkin lymphoma among three Asian populations

Hosgood III, H. Dean,Au, Wing-Yan,Kim, Hee Nam,Liu, Jie,Hu, Wei,Tse, Jovic,Song, Bao,Wong, Kit-fai,Lee, Je-Jung,Chanock, Stephen J.,Siu, L. P.,Purdue, Mark P.,Shin, Min-ho,Yu, Jinming,Liang, Raymond,K Springer-Verlag 2013 International journal of hematology Vol.97 No.6

<P>Genetic variation in immune-related genes, such as IL10 and TNF, have been associated with the development of non-Hodgkin lymphoma (NHL) in Caucasian populations. To test the hypothesis that IL10 and TNF polymorphisms may be associated with NHL risk in Asian populations, we genotyped 20 single nucleotide polymorphisms (SNPs) within the IL10 and TNF/LTA loci in three independent case-control studies (2635 cases and 4234 controls). IL10 rs1800871, rs1800872, and rs1800896 were genotyped in all three studies, while 5 of the remaining SNPs were genotyped in two studies, and 12 in a single study. IL10 rs1800896 was associated with B cell lymphoma [per-allele odds ratio (OR)?=?1.25, 95?% confidence interval (CI)?1.08-1.45; p trend?=?0.003], specifically diffuse large B cell lymphoma (DLBCL) (per-allele OR?=?1.29, 95?% CI?1.08-1.53; p trend?=?0.004), as well as T cell lymphoma (per-allele OR?=?1.44, 95?% CI?1.13-1.82; p trend?=?0.003). TNF rs1800629, which was genotyped in only two of our studies, was also associated with B cell lymphoma (per-allele OR?=?0.77, 95?% CI?0.64-0.91; p trend?=?0.003), specifically DLBCL (per-allele OR?=?0.69, 95?% CI?0.55-0.86; p trend?=?0.001). Our findings suggest that genetic variation in IL10 and TNF may also play a role in lymphomagenesis in Asian populations.</P>

A Computed Tomography Analysis of the Success of Spinal Fusion Using Ultra-Low Dose (0.7 mg per Facet) of Recombinant Human Bone Morphogenetic Protein 2 in Multilevel Adult Degenerative Spinal Deformity Surgery

Gabriel Liu,Jun Hao Tan,Changwei Yang,John Ruiz,Hee-Kit Wong 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.6

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28–72 years) were examined. Each patient received a total dose of 12 mg with an average dose of 0.69±0.2 mg (0.42–1 mg) per single FF and 1.38±0.44 mg (0.85–2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (κ=0.95) and 100% vs. 100% IBF, respectively (κ=1). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (κ=0.96). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1–2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of 32.8±6.3, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of 4.7±2.1, and physical component summary improved by an average of 10.5±2.1. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%–98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

Korean Red Ginseng extract induces angiogenesis through activation of glucocorticoid receptor

Sung, Wai-Nam,Kwok, Hoi-Hin,Rhee, Man-Hee,Yue, Patrick Ying-Kit,Wong, Ricky Ngok-Shun The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4

Background: Our previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes. The aim of this study was to determine the angiogenic properties of Korean Red Ginseng extract (KGE). Methods and Results: Combining in vitro and in vivo data, KGE at $500{\mu}g/mL$ was found to induce angiogenesis. According to the miRNA sequencing, 484 differentially expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their corresponding angiogenic proteins were stimulated, including vascular endothelial growth factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array, proving that KGE could activate GR. Conclusion: KGE was found capable of inducing angiogenesis both in vivo and in vitro models through activating GR. This study provides a valuable insight into the angiogenic mechanisms depicted by KGE in relation to specific miRNAs.

Making a Traditional Spine Surgery Clinic Telemedicine-Ready in the “New Normal” of Coronavirus Disease 2019

Liu Ka-Po Gabriel,Tan Wei Loong Barry,Yip Wei Luen James,Tan Jun-Hao,Wong Hee-Kit 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.2

Study Design: An original article describing a comprehensive methodology for making a traditional spine surgery clinic telemedicineready in terms of logistical considerations and workflow.Purpose: The aim of this study is to promote the use of telemedicine via videoconferencing to reduce human exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reduce the risk of coronavirus disease 2019 (COVID-19) transmission at outpatient clinics.Overview of Literature: The COVID-19 pandemic is the biggest healthcare crisis in the 21st century. Until a vaccine is developed or herd immunity against SARS-CoV-2 is achieved, social distancing to avoid crowding is an important strategy to reduce disease transmission and resurgence. Telemedicine has already been applied in the field of orthopedics with encouraging results.Methods: We reviewed the evidence behind telemedicine and described our clinical protocol, patient selection criteria, and workflow for telemedicine. We discussed a simple methodology to convert pre-existing traditional clinic resources into telemedicine tools, along with future challenges.Results: Our methodology was successfully and easily applied in our clinical practice, with a streamlined workflow allowing our spine surgery service to implement telemedicine as a consultation modality in line with the national recommendations of social distancing.Conclusions: Telemedicine was well incorporated into our outpatient practice using the above workflow. We believe that the use of telemedicine via videoconferencing can become part of the new normal and a safe strategy for healthcare systems as both a medical and an economic countermeasure against COVID-19.

Sagittal Radiographic Parameters of the Spine in Three Physiological Postures Characterized Using a Slot Scanner and Their Potential Implications on Spinal Weight-Bearing Properties

Hey Hwee Weng Dennis,Ng Nathaniel Li-Wen,Loh Khin Yee Sammy,Tan Yong Hong,Tan Kimberly-Anne,Moorthy Vikaesh,Lau Eugene Tze Chun,Liu Gabriel Ka-Po,Wong Hee-Kit 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.1

Study Design: Prospective radiographic comparative study.Purpose: To compare and understand the load-bearing properties of each functional spinal unit (FSU) using three commonly assumed, physiological, spinal postures, namely, the flexed (slump sitting), erect (standing) and extended (backward bending) postures. Overview of Literature: Sagittal spinal alignment is posture-dependent and influences the load-bearing properties of the spine. The routine placement of intervertebral cages “as anterior as possible” to correct deformity may compromise the load-bearing capabilities of the spine, leading to complications.Methods: We recruited young patients with nonspecific low back pain for <3 months, who were otherwise healthy. Each patient had EOS images taken in the flexed, erect and extended positions, in random order, as well as magnetic resonance imaging to assess for disk degeneration. Angular and disk height measurements were performed and compared in all three postures using paired t-tests. Changes in disk height relative to the erect posture were caclulated to determine the alignment-specific load-bearing area of each FSU.Results: Eighty-three patients (415 lumbar intervertebral disks) were studied. Significant alignment changes were found between all three postures at L1/2, and only between erect and flexion at the other FSUs. Disk height measurements showed that the neutral axis of the spine, marked by zones where disk heights did not change, varied between postures and was level specific. The load-bearing areas were also found to be more anterior in flexion and more posterior in extension, with the erect spine resembling the extended spine to a greater extent.Conclusions: Load-bearing areas of the lumbar spine are sagittal alignment-specific and level-specific. This may imply that, depending on the surgical realignment strategy, attention should be paid not just to placing an intervertebral cage “as anterior as possible” for generating lordosis, but also on optimizing load-bearing in the lumbar spine.

Symptomatic Construct Failure after Metastatic Spine Tumor Surgery

Kumar Naresh,Patel Ravish,Tan Jiong Hao,Song Joshua,Pandita Naveen,Hey Dennis Hwee Weng,Lau Leok Lim,Liu Gabriel Ka-Po,Thambiah Joseph,Wong Hee-Kit 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.4

Study Design: Retrospective cohort study.Purpose: To evaluate the incidence and presentation of symptomatic failures (SFs) after metastatic spine tumor surgery (MSTS). To identify the associated risk factors. To categorize SFs based on the management in these patients.Overview of Literature: Few studies have reported on the incidence (1.9%–16%) and risk factors of SF after MSTS. It is unclear whether all SFs, occurring in MSTS-patients, result in revision surgery.Methods: We conducted a retrospective analysis on 288 patients (246 for final analysis) who underwent MSTS between 2005–2015. Data collected were demographics and peri/postoperative clinical and radiological features. Early and late radiological SF were defined as presentation before and after 3 months from index surgery, respectively. Univariate and multivariate models of competing risk regression analysis were designed to determine the risk factors for SF with death as a competing event.Results: We observed 14 SFs (5.7%) in 246 patients; 10 (4.1%) underwent revision surgery. Median survival was 13.4 months. The mean age was 58.8 years (range, 21–87 years); 48.4% were women. The median time to failure was 5 months (range, 1–60 months). Patients with SF were categorized into three groups: (1) SF when the primary implant was revised (n=5, 35.7%); (2) peri-construct progression of disease requiring extension (n=5, 35.7%); and (3) SFs that did not warrant revision (n=4, 28.5%). Four patients (28.5%) presented with early failure. SF commonly occurred at the implant-bone interface (9/14) and all patients had a spinal instability neoplastic score (SINS) >7. Thirteen patients (92.8%) who developed failure had fixation spanning junctional regions. Multivariate competing risk regression showed that preoperative Eastern Cooperative Oncology Group score was a significant risk factor for implant failure (adjusted sub-hazard ratio, 7.0; 95% confidence interval, 1.63–30.07; p<0.0009).Conclusions: The incidence of SF (5.7%) was low in patients undergoing MSTS although these patients did not undergo spinal fusion. Preoperative ambulators involved a 7 times higher risk of failure than non-ambulators. Preoperative SINS >7 and fixations spanning junctional regions were associated with SF. Majority of construct failures occurred at the implant-bone interface.

Cervical Inclination Angle: Normative Values in an Adult Multiethnic Asymptomatic Population

Jean Charles Le Huec,Zeeshan M. Sardar,Emanuele Quarto,Meghan Cerpa,Michael P. Kelly,Kazuhiro Hasegawa,Hwee Weng Dennis Hey,Hee-Kit Wong,Hend Riahi,Lawrence G. Lenke,Stéphane Bourret,MEANS study group 대한척추신경외과학회 2022 Neurospine Vol.19 No.4

Objective: The role of the craniocervical complex in spinal sagittal alignment has rarely been analyzed but it may play a fundamental role in postoperative mechanical complications. The aim of the study is to analyze the normative value of the cervical inclination angle (CIA) in an adult asymptomatic multiethnic population. Methods: Standing full-spine EOS of adult asymptomatic volunteers from 5 different countries were analyzed. The CIA was analyzed globally and then in each decade of life. Different ethnicities were compared. Comparisons between different groups was performed using a t-test and statistical significance was considered with a p-value < 0.05. Results: EOS of 468 volunteers were analyzed. The global mean CIA was 80.2° with a maximum difference of 9° between T1 and T12 (p < 0.001). The CIA remains constant until 60 years old then decreases significantly passing from a mean value before 20 years old of 82.25° to 73.65° after 70 years old. A statistically significant difference was found between the Arabics and other ethnicities with the formers having an inferior CIA: this was related to a mean older age (p < 0.05) and higher body mass index (p < 0.05) in the Arabics. Conclusion: The CIA remains constant until 60 years old and then reduces slightly but never under 70°. This angle is helpful to evaluate the lever arm at the upper instrumented vertebra after an adult spinal deformity surgery and could predict the occurrence of a proximal junctional kyphosis when its value is lower than normal. Further clinical studies must confirm this theory.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment

Paul J. Park,Fthimnir M. Hassan,Xavier E. Ferrer,Cole Morrissette,Nathan J. Lee,Meghan Cerpa,Zeeshan M. Sardar,Michael P. Kelly,Stephane Bourret,Kazuhiro Hasegawa,Hee-Kit Wong,Gabriel Liu,Hwee Weng De 대한척추신경외과학회 2023 Neurospine Vol.20 No.3

Objective: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. Methods: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20–79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). Results: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7–S1 sagittal vertical axis (SVA) (p < 0.001), C2–7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). Conclusion: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2–7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.