A Novel Human BTB-kelch Protein KLHL31, Strongly Expressed in Muscle and Heart, Inhibits Transcriptional Activities of TRE and SRE

Weishi Yu,Yuequn Wang,Yongqing Li,Yun Deng,Zequn Wang,Wuzhou Yuan,Dali Li,Chuanbing Zhu,Xueying Zhao,Xiaoyang Mo,Wen Huang,Na Luo,Yan Yan,Karen Ocorr,Rolf Bodmer,Xiushan Wu 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.5

The Bric-a-brac, Tramtrack, Broad-complex (BTB) domain is a protein-protein interaction domain that is found in many zinc finger transcription factors. BTB containing proteins play important roles in a variety of cellular functions including regulation of transcription, regulation of the cytoskeleton, protein ubiquitination, angiogenesis, and apoptosis. Here, we report the cloning and characterization of a novel human gene, KLHL31, from a human embryonic heart cDNA library. The cDNA of KLHL31 is 5743 bp long, encoding a protein product of 634 amino acids containing a BTB domain. The protein is highly conserved across different species. Western blot analysis indicates that the KLHL31 protein is abundantly expressed in both embryonic skeletal and heart tissue. In COS-7 cells, KLHL31 proteins are localized to both the nucleus and the cytoplasm. In primary cultures of nascent mouse cardiomyocytes, the majority of endogenous KLHL31 proteins are localized to the cytoplasm. KLHL31 acts as a transcription repressor when fused to GAL4 DNA-binding domain and deletion analysis indicates that the BTB domain is the main region responsible for this repression. Overexpression of KLHL31 in COS-7 cells inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). KLHL31 also significantly reduces JNK activation leading to decreased phosphorylation and protein levels of the JNK target c-Jun in both COS-7 and Hela cells. These results suggest that KLHL31 protein may act as a new transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions.

Evaluating the Reproducibility of the Walking Test for Intermittent Claudication Associated with Lumbar Spinal Stenosis

Tanishima Shinji,Weishi Li,Jianzhong Hu,Jie Zhao,Huilin Yang,Nagashima Hideki 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.3

Study Design: This is a multicenter, prospective study.Purpose: This study aimed to evaluate the reproducibility of the walking test for patients with lumbar spinal stenosis (LSS).Overview of Literature: Walking test is one of the useful procedures to investigate cauda equina syndrome with lumbar spinal stenosis. One the other hands, there were few studies to investigate the reproducibility of this test.Methods: In this study, we prospectively examined 70 LSS patients with intermittent claudication symptoms at a multicenter outpatient clinic. A walking test was administered at baseline and week 4 to assess patients’ walking distance and lower limb pain and numbness. Immediately after the walking test, patients were asked to use the Visual Analog Scale (VAS) to rate their pain and numbness in the front, back, outside, inside, and hip of the lower legs. The reproducibility of the walking test was evaluated using Cohen’s κ analysis and intraclass correlation coefficients (ICCs). Meanwhile, the Swiss Spinal Stenosis (SSS) Questionnaire was used to evaluate the severity of the stenosis.Results: The walking distance ICC at baseline and at week 4 remained unchanged at 0.7, with acceptable interobserver reliabilities for lower limb pain and numbness in both legs. The average VAS score for lower leg pain was 23.2±25.2 mm at baseline and 27.4±28.8 mm at week 4, while the corresponding average VAS score for numbness was 23.4±26.7 mm at baseline and 24.8±25.2 mm at week 4. The ICC score was 0.7 for leg pain and 0.7 for numbness. The mean SSS was 30.2±5.5 at baseline and 29.2±5.2 at week 4, and there was no significant difference in the severity.Conclusions: The walking test for LSS has acceptable reproducibility.

Taint Inference for Cross-Site Scripting in Context of URL Rewriting and HTML Sanitization

Jinkun Pan,Xiaoguang Mao,Weishi Li 한국전자통신연구원 2016 ETRI Journal Vol.38 No.2

Currently, web applications are gaining in prevalence. In a web application, an input may not be appropriately validated, making the web application susceptible to cross-site scripting (XSS), which poses serious security problems for Internet users and websites to whom such trusted web pages belong. A taint inference is a type of information flow analysis technique that is useful in detecting XSS on the client side. However, in existing techniques, two current practical issues have yet to be handled properly. One is URL rewriting, which transforms a standard URL into a clearer and more manageable form. Another is HTML sanitization, which filters an input against blacklists or whitelists of HTML tags or attributes. In this paper, we make an analogy between the taint inference problem and the molecule sequence alignment problem in bioinformatics, and transfer two techniques related to the latter over to the former to solve the aforementioned yet-to-be-handled-properly practical issues. In particular, in our method, URL rewriting is addressed using local sequence alignment and HTML sanitization is modeled by introducing a removal gap penalty. Empirical results demonstrate the effectiveness and efficiency of our method.

Analysis of Global Sagittal Postural Patterns in Asymptomatic Chinese Adults

Panpan Hu,Miao Yu,Zhuoran Sun,Weishi Li,Liang Jiang,Feng Wei,Xiaoguang Liu,Zhongqiang Chen,Zhongjun Liu 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.2

Study Design: A prospective imaging study. Purpose: To characterize the distribution of the global sagittal postural patterns in asymptomatic Chinese adults using Roussouly classification. Overview of Literature: The norms of sagittal parameters in asymptomatic Chinese population have been previously described, but no report described their global sagittal postural patterns as characterized by Roussouly classification. Methods: A cohort of 272 asymptomatic Chinese adults was recruited. Data was assimilated by reviewing the films for each subject. Sagittal parameters were measured and sagittal postural patterns were then determined according to Roussouly classification. The pattern distributions were compared across genders within the study cohort. We also compared the data across different ethnicities from our study and a previous study to further characterize Chinese sagittal postures. Results: The cohort included 161 males and 111 females, with mean age of 23.2±4.4 years. The average descriptive results were as below: pelvic incidence (PI) 46.4°±9.6°, thoracic kyphosis (TK) 24.2°±9.0°, lumbar lordosis (LL) 50.6°±10.6°, sacral slope (SS) 37.2°±7.6°, pelvic tilt (PT) 9.4°±6.8°, spinosacral angle (SSA) 131.1°±7.5° and sagittal vertical axis (SVA) 17.24±32.36 mm. Despite a significant difference between two genders in LL, PI, SSA, and SVA, no difference was found in the distribution of Roussouly types among them. 47.8% of our cohort belonged to Roussouly type 3, while type 1, 2 and 4 comprised 23.2%, 14.0% and 15.1% of the subjects, respectively. Roussouly classification was capable of categorizing sagittal parameters except for the PT. This study also found that 4.4% of the recruited subjects belonged to the C7-anterior subgroup. Conclusions: From a characterization of the sagittal postural patterns of asymptomatic Chinese adults using Roussouly classification, the distribution was similar between Chinese males and females; however, from a cross-study comparison, it was different between asymptomatic Chinese and Caucasian adults, with a higher proportion of Roussouly type 3 in Chinese adults.

Polymicrobial and Monomicrobial Infections after Spinal Surgery: A Retrospective Study to Determine which Infection is more Severe

Shaoqiang Liu,Qiang Qi,Zhongqiang Chen,Ning Liu,Zhaoqing Guo,Chuiguo Sun,Weishi Li,Yan Zeng,Zhongjun Liu 대한척추외과학회 2017 Asian Spine Journal Vol.11 No.3

Study Design: A retrospective clinical review. Purpose: To investigate the difference in clinical manifestations and severity between polymicrobial and monomicrobial infections after spinal surgery. Overview of Literature: Surgical site infections (SSIs) after spinal surgery are a major diagnostic and therapeutic challenge for spinal surgeons. Polymicrobial infections after spinal surgery seem to result in poorer outcomes than monomicrobial infections because of complementary resistance to antibiotics. However, comparison of the clinical manifestations and severity between polymicrobial and monomicrobial infections are limited. Methods: Sixty-seven patients with SSIs after spinal surgery were studied: 20 patients with polymicrobial infections and 47 with monomicrobial infections. Pathogenic bacteria identified were counted and classified. Age, sex, and body mass index were compared between the two groups to identify homogeneity. The groups were compared for clinical manifestations by surgical site, postoperative time to infection, infection site, incisional drainage, incisional swelling, incisional pain, neurological signs, temperature, white blood cell count, and the percentage of neutrophils. Finally, the groups were compared for severity by hospital stay, number of rehospitalizations, number of debridements, duration of antibiotics administration, number of antibiotics administered, and implant removal. Results: Polymicrobial infections comprised 29.9% of SSIs after spinal surgery, and most polymicrobial infections (70.0%) were caused by two species of bacteria only. There was no difference between the groups in terms of clinical manifestations and severity. In total, 96 bacterial strains were isolated from the spinal wounds: 60 strains were gram-positive and 36 were gram-negative pathogenic bacteria. Staphylococcus aureus , Staphylococcus epidermidis , Escherichia coli , and Enterobacter cloacae were cultured in order of the frequency of appearance. Conclusions: Most polymicrobial infections were caused by two bacterial species after spinal surgery. There was no difference in clinical manifestations or severity between polymicrobial and monomicrobial infections.

Evaluation and Comparation of a Novel Surgical Technique and Hemivertebra Resection to the Correction of Congenital Cervical Scoliosis in Lower Cervical and Cervicothoracic Spine

Shuo Cao,Xin Chen,Shengfa Pan,Yinze Diao,Yanbin Zhao,Tian Xia,Weishi Li,Feifei Zhou,Yu Sun 대한척추신경외과학회 2022 Neurospine Vol.19 No.4

Objective: To report concave-side distraction technique to treat congenital cervical scoliosis in lower cervical and cervicothoracic spine. To evaluate and compare clinical and radiographic results of this procedure with classic hemivertebra resection procedure. Methods: This study reviewed 29 patients in last 13 years. These patients were divided into convex-side resection group (group R) and concave-side distraction group (group D). Radiographic assessment was based on parameter changes preoperatively, postoperatively and at last follow-up. Demographic data, surgical data and complications were also evaluated and compared between the 2 groups. Results: In group R, mean age was 8.9 ± 3.3 years and follow-up was 46 ± 18 months. Operation time and blood loss averaged 500 ± 100 minutes, 703 ± 367 mL. In group D, mean age was 9.9 ± 2.8 years and follow-up was 34 ± 14 months. Operation time and blood loss averaged 501 ± 112 minutes, 374 ± 181 mL. Structural Cobb angle was corrected from 29.4° ± 12.5° to 5.3° (2.1°–18.1°) (p = 0.001) and 33.7° ± 14.1° to 12.8° ± 11.4° (p < 0.001) in groups R and D. Compensatory Cobb angle had a spontaneous correction rate of 59.6% (40.0%–80.8%) and 59.7% ± 23.0% in groups R and D. Mandibular incline, clavicle angle and spine coronal balance were significantly improved at last follow-up in both groups. All correction rates were not statistically different between groups. However, group D had significant less blood loss (p < 0.001) and operation time (p = 0.004) per vertebra than group R. Seven patients developed C5 nerve root palsy and recovered by 6 months of follow-up. Conclusion: Both surgical procedures are safe and effective in correcting congenital cervical scoliosis. But concave-side distraction technique has less blood loss and time-consuming during surgery, which provides a better option for the treatment of congenital cervical scoliosis.

The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights

Xiang Qian,Zhao Yongzhao,Lin Jialiang,Jiang Shuai,Li Weishi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and is recognized as a major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, and therapeutic strategies for IDD are currently limited. Oxidative stress plays pivotal roles in the pathogenesis and progression of many age-related diseases in humans, including IDD. Nuclear factor E2-related factor 2 (Nrf2) is a master antioxidant transcription factor that protects cells against oxidative stress damage. Nrf2 is negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) and exerts important effects on IDD progression. Accumulating evidence has revealed that Nrf2 can facilitate the transcription of downstream antioxidant genes in disc cells by binding to antioxidant response elements (AREs) in promoter regions, including heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and NADPH quinone dehydrogenase 1 (NQO1). The Nrf2 antioxidant defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, the inflammatory response of the nucleus pulposus (NP), and calcification of the cartilaginous endplates (EP) in IDD. In this review, we aim to discuss the current knowledge on the roles of Nrf2 in IDD systematically.

Vertebral Artery Variations at the Craniovertebral Junction in “Sandwich” Atlantoaxial Dislocation Patients

Yinglun Tian,Nanfang Xu,Ming Yan,Jinguo Chen,Kan-Lin Hung,Xiangyu Hou,Shenglin Wang,Weishi Li 대한척추신경외과학회 2021 Neurospine Vol.18 No.4

Objective: To summarize the vertebral artery (VA) pattern of 96 “sandwich” atlantoaxial dislocation (AAD) patients and to describe the strategies of reducing the injury of VA during surgery. Methods: From 2009 to 2020, we retrospectively reviewed the 3-dimensional computed tomography angiography data of 96 AAD patients combined with atlas occipitalization and C2–3 fusion, which were diagnosed as “sandwich” AAD and 96 patients as control group patients who were without atlas occipitalization, C2–3 fusion and any other cervical bone deformity at our institution. The variations of each side of VA were described in 3 different parts (C0–1, C1–2, and C2–3) according to the characteristics of the 3-part pathological structures in “sandwich” subgroup. Results: One hundred ninety-two sides of VAs in every group of patients were analyzed and every VA was described separately at 3 different level regions. There were different variations in these 3 different regions: 4 variations in the upper fusion region, 5 variations in the sandwiched region, and 6 variations in the lower fusion region in sandwich AAD patients. And the rate of VA deformity in sandwich AAD patients was much higher and more types of VA variations existed. Conclusion: In “sandwich” AAD patients, deformities of vertebral arteries in craniovertebral junction are more common, and the same VA may have deformities at different levels that severely affect surgical procedures. Therefore, preoperative imaging examination of VA for “sandwich” AAD patients is vital of guiding surgeons to avoid injury of VA during surgery.

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy

Lin Jialiang,Wang Longjie,Wu Yuhao,Xiang Qian,Zhao Yongzhao,Zheng Xuanqi,Jiang Shuai,Sun Zhuoran,Fan Dongwei,Li Weishi 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.