Publications by authors named "Xin Tang"

525 Publications

Carbohydrate analysis of Mortierella alpina by colorimetry and HPLC-ELSD to reveal accumulation differences of sugar and lipid.

Biotechnol Lett 2021 Apr 17. Epub 2021 Apr 17.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, People's Republic of China.

Objectives: To establish reliable methods for the extraction and quantification of the total carbohydrate and intracellular saccharides from Mortierella alpina and study the changes between carbohydrate and lipid in fermentation process.

Results: The extraction of mycelia with HCl following a photometric phenol-sulphuric acid reaction was identified as an optimal method for total carbohydrate analysis in Mortierella alpina, which the extraction efficiency performed 1.1-3.6 fold than other five methods. The total carbohydrate content increased from initial 19.26 to 25.86% during early fermentation process and declined gradually thereafter, while the fatty acid was increasing from 8.47 to 31.03%. For separation and qualitative estimation of intracellular saccharides, the acetonitrile/water freeze-thaw method for extraction and Sugar-Pak I column for separation proved to be possible. With the glucose rapidly decreasing at the beginning of growth, the trehalose accumulated rapidly from 1.63 to 5.04% and then decreased slightly but maintain above 4% of dry biomass.

Conclusions: This work established comprehensive carbohydrate extraction and analysis methods of Mortierella alpina and identified the main saccharide in fermentation process which indicated that the accumulation of fatty acids was related to the change of intracellular carbohydrate content.
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http://dx.doi.org/10.1007/s10529-021-03120-2DOI Listing
April 2021

Homeodomain proteins POU-M2, antennapedia and abdominal-B are involved in regulation of the segment-specific expression of the clip-domain serine protease gene CLIP13 in the silkworm, Bombyx mori.

Insect Sci 2021 Apr 16. Epub 2021 Apr 16.

State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, 400716, China.

Clip-domain serine proteases (CLIPs) play important roles in insect innate immunity and development. Our previous studies indicated that CLIP13, an epidermis-specific gene, was involved in cuticle remodeling during molting and metamorphosis in the silkworm, Bombyx mori. However, the transcriptional regulatory mechanism and regulatory pathways of CLIP13 remained unclear. In the present study, we investigated CLIP13 expression and the regulation pathway controlled by 20-hydroxyecdysone (20E) in the silkworm. At the transcriptional level, expression of CLIP13 exhibited pronounced spatial and temporal specificity in different regions of the epidermis; homeodomain transcription factors POU-M2, antennapedia (Antp), and abdominal-B (Abd-B) showed similar expression change trends as CLIP13 in the head capsule, thorax, and abdomen, respectively. Furthermore, results of cell transfection assays, electrophoretic mobility shift assays, and chromatin immunoprecipitation demonstrated that POU-M2, Antp, and Abd-B were involved in the transcriptional regulation of CLIP13 by directly binding to their cis-response elements in CLIP13 promoter. RNA interference-mediated silencing of POU-M2, Antp, and Abd-B led to a decrease of CLIP13 expression in the head capsule, the epidermis of the 1st to 3rd thoracic segments and the 7th to 10th abdominal segments, respectively. Consistent with CLIP13, 20E treatment significantly upregulated expression of POU-M2, Antp, and Abd-B in the silkworm epidermis. Taken together, these data suggest that 20E positively regulates transcription of CLIP13 via homeodomain proteins POU-M2, Antp, and Abd-B in different regions of the silkworm epidermis during metamorphosis, thus affecting the molting process. Our findings provide new insight into the functions of homeodomain transcription factors in insect molting.
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http://dx.doi.org/10.1111/1744-7917.12916DOI Listing
April 2021

Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications.

J Cell Mol Med 2021 Apr 3. Epub 2021 Apr 3.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta-related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p-FoxO3a) in placental tissue from healthy pregnant women and pre-eclampsia patients were first compared. Then, HTR-8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit-8, wound-healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT-PCR and ChIP-qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p-FoxO3a was increased in pre-eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule-1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.
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http://dx.doi.org/10.1111/jcmm.16499DOI Listing
April 2021

Molecular Evolution of Infectious Pancreatic Necrosis Virus in China.

Viruses 2021 Mar 16;13(3). Epub 2021 Mar 16.

Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Department of Aquatic Animal Diseases and Control, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China.

Passive virus surveillance was performed in twenty-nine salmon and trout farms from seven provinces and districts in China during the period 2017-2020. A total of 25 infectious pancreatic necrosis virus (IPNV) isolates were obtained, mainly from rainbow trout (). The molecular evolution of these Chinese IPNV isolates and the previously reported Chinese IPNV strains ChRtm213 and WZ2016 was analyzed, based on their VP2 gene coding region sequences (CDS). All 27 Chinese IPNV isolates clustered within genogroups I and V, with 24 of the IPNV isolates belonging to genogroup I (including ChRtm213 and WZ2016), and only three isolates clustering in genogroup V. The Chinese genogroup I IPNV isolates lacked diversity, composing six haplotypes with 41 polymorphic sites, and the identity of nucleotide and amino acid sequences among the entire VP2 gene CDS from these isolates was 97.44%-100% and 98.19%-100%, respectively. Divergence time analyses revealed that the Chinese genogroup I IPNV isolates likely diverged from Japanese IPNV isolates in 1985 (95% highest posterior density (HPD), 1965-1997), and diverged again in 2006 (95% HPD, 1996-2013) in China. Each of the three Chinese genogroup V IPNV isolates has a unique VP2 gene CDS, with a total of 21 polymorphic sites; the identity of nucleotide and amino acid sequences among all VP2 gene CDS from these isolates was 98.5%-99.5% and 98.6%-99.0%, respectively. The data demonstrate that genogroups I and V are more likely the currently prevalent Chinese IPNV genotypes.
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http://dx.doi.org/10.3390/v13030488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998647PMC
March 2021

Pulmonary Artery Size Measurements: A Comparison Study Between Electrocardiogram-Gated and Nonelectrocardiogram-Gated Computed Tomography.

J Comput Assist Tomogr 2021 Mar 12. Epub 2021 Mar 12.

From the Department of Radiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Department of Radiology, The First Affiliated Hospital of Nanjing Medical University Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.

Objectives: The aim of this study was to determine the difference and correlation in pulmonary artery (PA) size when measured from the electrocardiogram (ECG)-gated computed tomography (CT) and non-ECG-gated CT.

Methods: In the retrospective study, 279 patients who underwent both ECG-gated CT and non-ECG-gated CT were enrolled. Maximum and minimum diameters of main pulmonary artery (MPA), right pulmonary artery (RPA), and ascending aorta (AAO) were measured, whereas mean diameters of MPA and RPA were obtained. The same PA size parameters were also measured on non-ECG-gated CT.

Results: There was a significant difference in maximum and minimum PA diameters between ECG-gated CT and non-ECG-gated CT, whereas mean PA diameters showed no statistically difference. The PA parameters showed a strong positive correlation between these 2 examinations.

Conclusions: The PA size was different between ECG-gated CT and non-ECG-gated CT, whereas the PA size parameters on non-ECG-gated CT could be used to predict those with ECG-gated CT, which allow for confident prediction of pulmonary hypertension and guide further surgical intervention.
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http://dx.doi.org/10.1097/RCT.0000000000001144DOI Listing
March 2021

Management strategies of pediatric ipsilateral olecranon with associated radial neck fractures based on multicenter experience.

J Orthop Surg Res 2021 Mar 30;16(1):232. Epub 2021 Mar 30.

Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: The ipsilateral olecranon with associated radial neck fractures does not include in the Bado classification of Monteggia fractures and equivalent lesions. The primary aims of this retrospective multicenter study were to characterize this type of injury and, noting its unique properties, evaluate the results of the treatment, determine the prognostic factors that influence the radiological and clinical outcome, and also give treatment strategies.

Methods: Between July 2011 and July 2016, forearm fracture patient charts were retrospectively reviewed from seven pediatric trauma centers. Patients diagnosed with ipsilateral olecranon with associated radial neck fractures and followed up for at least 24 months were included. Fracture characteristics, treatment, outcome, and complications were assessed. The clinical outcome of treatments was evaluated by the Mayo Elbow Performance Score (MEPS) and the Flynn criteria. Fisher's exact test and ANOVA test were used; significance was defined as P < 0.05.

Results: One hundred thirty-seven consecutive patients (54 girls and 83 boys) from 8292 forearm fractures patients, the mean age of 7.5 years (1.5 to 14.8), with fractures of the ipsilateral olecranon with associated radial neck fractures were identified. One hundred twenty-five patients had radiologic and clinical follow-up. According to a simplified classification system with "operate" and "don't operate" groups, including five subtypes proposed in this study, ipsilateral olecranon with associated radial neck fractures subtypes could be classified with significantly different characteristics and outcome in treatment and complications.

Conclusions: Fractures of the ipsilateral olecranon associated with the radial neck are not so rare as previously reported. Complications and poor outcomes were easy to encounter without knowing this type of fracture. Appropriate treatment strategies could be made according to a simple classification system based on the treatment result of follow-up.

Level Of Evidence: Retrospective comparative study; Level III.
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http://dx.doi.org/10.1186/s13018-021-02373-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008540PMC
March 2021

[Application of omics technology in oleaginous microorganisms].

Sheng Wu Gong Cheng Xue Bao 2021 Mar;37(3):846-859

School of Food Science and Technology, Jiangnan University, Wuxi 214122, Jiangsu, China.

Microbial oils are potential resources of fuels and food oils in the future. In recent years, with the rapid development of systems biology technology, understanding the physiological metabolism and lipid accumulation characteristics of oleaginous microorganisms from a global perspective has become a research focus. As an important tool for systems biology research, omics technology has been widely used to reveal the mechanism of high-efficiency production of oils by oleaginous microorganisms. This provides a basis for rational genetic modification and fermentation process control of oleaginous microorganisms. In this article, we summarize the application of omics technology in oleaginous microorganisms, introduced the commonly used sample pre-processing and data analysis methods for omics analysis of oleaginous microorganisms, reviewe the researches for revealing the mechanism of efficient lipid production by oleaginous microorganisms based on omics technologies including genomics, transcriptomics, proteomics (modification) and metabolomics (lipidomics), as well as mathematical models based on omics data. The future development and application of omics technology for microbial oil production are also proposed.
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http://dx.doi.org/10.13345/j.cjb.200642DOI Listing
March 2021

The role of GABAergic signalling in neurodevelopmental disorders.

Nat Rev Neurosci 2021 Mar 26. Epub 2021 Mar 26.

Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.

GABAergic inhibition shapes the connectivity, activity and plasticity of the brain. A series of exciting new discoveries provides compelling evidence that disruptions in a number of key facets of GABAergic inhibition have critical roles in the aetiology of neurodevelopmental disorders (NDDs). These facets include the generation, migration and survival of GABAergic neurons, the formation of GABAergic synapses and circuit connectivity, and the dynamic regulation of the efficacy of GABAergic signalling through neuronal chloride transporters. In this Review, we discuss recent work that elucidates the functions and dysfunctions of GABAergic signalling in health and disease, that uncovers the contribution of GABAergic neural circuit dysfunction to NDD aetiology and that leverages such mechanistic insights to advance precision medicine for the treatment of NDDs.
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http://dx.doi.org/10.1038/s41583-021-00443-xDOI Listing
March 2021

Administration of B7-H3 targeted chimeric antigen receptor-T cells induce regression of glioblastoma.

Signal Transduct Target Ther 2021 Mar 26;6(1):125. Epub 2021 Mar 26.

Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, China.

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http://dx.doi.org/10.1038/s41392-021-00505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994554PMC
March 2021

Distinguishing cardiac myxomas from cardiac thrombi by a radiomics signature based on cardiovascular contrast-enhanced computed tomography images.

BMC Cardiovasc Disord 2021 Mar 25;21(1):152. Epub 2021 Mar 25.

Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, 610041, Sichuan, China.

Background: Cardiac myxomas (CMs) and thrombi are associated with high morbidity and mortality. These two conditions need totally different treatments. However, they are difficult to distinguish using naked eye. In clinical, misdiagnoses occur now and then. This study aimed to compare the characteristics of CMs and cardiac thrombi and investigate the value of a radiomics signature in distinguishing CMs from cardiac thrombi, based on cardiovascular contrast-enhanced computed tomography (CECT) images.

Methods: A total of 109 patients who had CMs (n = 59) and cardiac thrombi (n = 50) were enrolled in this retrospective study from 2009 to 2019. First, the lesion characteristics of cardiovascular CECT images were documented and compared by two radiologists. Then all patients were randomly allotted to either a primary group or a validation group according to a 7:3 ratio. Univariate analysis and the least absolute shrinkage and selection operator were used to select robust features. The best radiomics signature was constructed and validated using multivariate logistic regression. An independent clinical model was created for comparison.

Results: The best radiomics signature was developed using eight selected radiomics. The classification accuracies of the radiomics signature were 90.8% and 90.9%, and the area under the receiver operating characteristic curves were 0.969 and 0.926 in the training and testing cohorts, respectively. Cardiovascular CECT images showed that the two diseases had significant differences in location, surface, Hydrothorax, pericardial effusion and heart enlargement. The naked eye findings were used to create the clinical model. All metrics of the radiomics signature were higher than those of clinical model.

Conclusions: Compared with clinical model, the radiomics signature based on cardiovascular CECT performed better in differentiating CMs and thrombi, suggesting that it could help improving the diagnostic efficiency.
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http://dx.doi.org/10.1186/s12872-021-01961-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993472PMC
March 2021

The Prognostic Value of Radiomics Features Extracted From Computed Tomography in Patients With Localized Clear Cell Renal Cell Carcinoma After Nephrectomy.

Front Oncol 2021 5;11:591502. Epub 2021 Mar 5.

Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

Background And Purpose: Radiomics is an emerging field of quantitative imaging. The prognostic value of radiomics analysis in patients with localized clear cell renal cell carcinoma (ccRCC) after nephrectomy remains unknown.

Methods: Computed tomography images of 167 eligible cases were obtained from the Cancer Imaging Archive database. Radiomics features were extracted from the region of interest contoured manually for each patient. Hierarchical clustering was performed to divide patients into distinct groups. Prognostic assessments were performed by Kaplan-Meier curves, COX regression, and least absolute shrinkage and selection operator COX regression. Besides, transcriptome mRNA data were also included in the prognostic analyses. Endpoints were overall survival (OS) and disease-free survival (DFS). Concordance index (C-index), decision curve analysis and calibration curves with 1,000 bootstrapping replications were used for model's validation.

Results: Hierarchical clustering groups from nephrographic features and mRNA can divide patients into different prognostic groups while clustering groups from corticomedullary or unenhanced phase couldn't distinguish patients' prognosis. In multivariate analyses, 11 OS-predicting and eight DFS-predicting features were identified in nephrographic phase. Similarly, seven OS-predictors and seven DFS-predictors were confirmed in mRNA data. In contrast, limited prognostic features were found in corticomedullary (two OS-predictor and two DFS-predictors) and unenhanced phase (one OS-predictors and two DFS-predictors). Prognostic models combining both nephrographic features and mRNA showed improved C-index than any model alone (C-index: 0.927 and 0.879 for OS- and DFS-predicting, respectively). In addition, decision curves and calibration curves also revealed the great performance of the novel models.

Conclusion: We firstly investigated the prognostic significance of preoperative radiomics signatures in ccRCC patients. Radiomics features obtained from nephrographic phase had stronger predictive ability than features from corticomedullary or unenhanced phase. Multi-omics models combining radiomics and transcriptome data could further increase the predictive accuracy.
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http://dx.doi.org/10.3389/fonc.2021.591502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973240PMC
March 2021

AhR/miR-23a-3p/PKCα axis contributes to memory deficits in ovariectomized and normal aging female mice.

Mol Ther Nucleic Acids 2021 Jun 18;24:79-91. Epub 2021 Feb 18.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, Heilongjiang Province 150086, China.

The mechanism of estrogen deficiency-induced cognitive impairment is still not fully elucidated. In this study, we assessed the effect of microRNA (miRNA) on the memory of long-term estrogen-deficient mice after ovariectomy (OVX) and normal aging. We observed that 5-month OVX and 22-month-old normal aging female mice showed significantly impaired spatial and object recognition memory, declined hippocampal long-term potentiation (LTP), and decreased hippocampal protein kinase C α (PKCα) protein. Quantitative real-time PCR analysis showed upregulated miRNA-23a-3p (miR-23a-3p) in the hippocampus of 5-month OVX and 22-month-old female mice. , overexpression of miR-23a-3p downregulated PKCα by binding the 3¢ UTRs of mRNAs, which was prevented by its antisense oligonucleotide AMO-23a. , adeno-associated virus-mediated overexpression of miR-23a-3p (AAV-pre-miR-23a-3p) suppressed hippocampal PKCα and impaired the memory of mice. Chromatin immunoprecipitation analysis showed that aryl hydrocarbon receptor (AhR) binds the promoter region of miR-23a-3p. The AhR-dependent downregulation of PKCα could be prevented by AMO-23a as well. Furthermore, knockdown of miR-23a-3p using AAV-AMO-23a rescued the cognitive and electrophysiological impairments of OVX and normal aging female mice. We conclude that long-term estrogen deficiency impairs cognition and hippocampal LTP by activating the AhR/miR-23a-3p/PKCα axis. The knockdown of miR-23a-3p may be a potentially valuable therapeutic strategy for estrogen deficiency-induced memory deficits.
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http://dx.doi.org/10.1016/j.omtn.2021.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940705PMC
June 2021

Operative choice for displaced proximal humeral fractures in adolescents with open visible physis: A comparative study of external fixator vs. Kirschner wire.

Injury 2021 Mar 9. Epub 2021 Mar 9.

Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Background: For adolescents with severely displaced proximal humeral fracture (PHF), surgery is a good choice yielding excellent outcomes, and Kirchner wire (KW) is a cost-effective choice for fixation. Purpose of this study is to compare the clinical outcomes of external fixator (EF) and KW for the treatment of PHF in adolescents.

Methods: Patients of PHF operated at our institute, from January 2008 to January 2016, were reviewed retrospectively. Demographic data, including sex, age at the time of surgery, operated side, and hardware choice, were collected from the hospital database. Preoperative radiographs were reviewed and classified according to Neer-Horwitz classification. Shoulder function was evaluated at the last follow-up using the American Shoulder and Elbow Surgeons (ASES) score. Complications, including infection, malunion, nonunion, stiffness of the shoulder joint, and failure of fixation were also recorded.

Results: Thirty-five patients, including 23 males and 12 females, were included in the EF group, whereas 40 patients, including 25 males and 15 females, were included in the KW group (P = 0.867). The average age of patients in the EF group was 13.3 ± 1.7 years, and that of KW was 13.6 ± 1.8 years (P = 0.409). Patients in both groups were followed-up for at least 12 months. The operative time in the EF group (42.4 ± 11.2 min) was significantly shorter than those in the KW group (54 ± 13.6 min) (P < 0.001). The frequency of fluoroscopy in the EF group (12 ± 2.4 times) was significantly less than those in the KW group (17 ± 2.8 times (P < 0.001). The rate of open reduction was significantly higher in KW (35%) group than those in the EF group (0%) (P < 0.001). There was no case of nonunion and malunion in both groups.

Conclusion: External fixator is superior to Kirschner wire in the treatment of proximal humeral fractures in adolescents with shorter operative time and lower rate of open reduction with comparable clinical outcomes.
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http://dx.doi.org/10.1016/j.injury.2021.03.015DOI Listing
March 2021

Plasma Resolvin D2 to Leukotriene B Ratio Is Reduced in Diabetic Patients with Ischemic Stroke and Related to Prognosis.

Biomed Res Int 2021 26;2021:6657646. Epub 2021 Feb 26.

Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Diabetes mellitus (DM) aggravates symptoms and prognosis of acute ischemic stroke (AIS), and inflammation plays an important role therein. Resolvin D2 (RvD2) is one of the specialized pro-resolving mediators (SPMs), while leukotriene B (LTB) is a classic proinflammatory mediator. The ratio of RvD2 to LTB is an index of pro-resolving/proinflammatory balance. We aim to explore the role of RvD2/LTB ratio in ischemic stroke complicated with DM.

Methods: The plasma levels of RvD2 and LTB were analyzed by enzyme immunoassay in stroke patients with DM (DM + AIS group) or without DM (nonDM+AIS group). Patients were followed up at 90 days after stroke onset, and modified Rankin Score (mRS) was assessed. The association of RvD2/LTB ratio with stroke severity and prognosis was also analyzed.

Results: The plasma levels of RvD2 were positively correlated to LTB. The RvD2/LTB ratio in DM + AIS group was lower than that in the nonDM+AIS group. No correlation was found between the RvD2/LTB ratio and infarct size or NIHSS score. The RvD2/LTB ratio at baseline was significantly lower in the poor prognosis group (mRS ≥ 3) than that in the good prognosis group (mRS ≤ 2).

Conclusions: Our study indicated that the balance between pro-resolving and proinflammatory mediators was impaired by diabetes in ischemic stroke. The RvD2/LTB ratio may serve as a biomarker of prognosis for ischemic stroke.
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http://dx.doi.org/10.1155/2021/6657646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935571PMC
February 2021

Two-stage strategy for neglected Monteggia fracture in children: A retrospective study of 51 patients.

Medicine (Baltimore) 2021 Mar;100(10):e25129

Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Abstract: A neglected Monteggia fracture is defined as the fracture of the proximal ulna associated with radial head dislocation (RHD) without undergoing any treatment for 4 weeks or more after injury. One-stage operation of ulnar corrective osteotomy and open reduction of RHD might result in many complications. Therefore, a two-stage strategy, including ulnar osteotomy (UO) with or without annular ligament reconstruction (ALR), was adopted at our institute since 2010.We performed a retrospective review of 51 patients with neglected Monteggia fracture between January 2010 and January 2018. Patients with bilateral problems or concomitant injuries in the ipsilateral extremity were excluded. Radiological and clinical data were collected from Hospital Database and clinical visits. All patients were divided into 2 groups based on the status of the ALR: the UO alone (UO) group and the ALR group.There were 15 patients in the UO group and 36 patients in the ALR group. The age in the UO group (6.1 ± 2.3, year) was significantly younger than the ALR group (9.8 ± 2.8, year) (P < .001). Concerning the duration from initial injury to surgery, there was a significant difference between the UO group (8.6 ± 3.2 months) and the ALR group (23.3 ± 12.6 months, P < .001). Concerning the preoperative elbow function, there was no significant difference between the UO group (67.6 ± 5.0) and the ALR group (66.6 ± 4.4) according to the Mayo elbow performance score (MEPS) (P = .51). Concerning the postoperative parameters, including postoperative ROM of the joint, removal of external fixator (6.7 ± 0.8, 6.9 ± 0.9 weeks) (P = .55), lengthening (8.9 ± 2.5, 10.3 ± 2.5 mm) (P = .10) and MEPS (92.7 ± 2.1, 91.6 ± 2.1) (P = .08), there was no significant difference between the UO group and ALR group.Two-stage strategy is a reasonable choice for selected patients with long-lasting RHD with ulnar deformity.
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http://dx.doi.org/10.1097/MD.0000000000025129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969315PMC
March 2021

TAK1 Phosphorylates RASSF9 and Inhibits Esophageal Squamous Tumor Cell Proliferation by Targeting the RAS/MEK/ERK Axis.

Adv Sci (Weinh) 2021 Mar 6;8(5):2001575. Epub 2021 Jan 6.

Department of Cardiothoracic Surgery Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases Nantong Clinical Medical Research Center of Cardiothoracic Disease Institution of Translational Medicine in Cardiothoracic Diseases Affiliated Hospital of Nantong University 20 Xisi Road Nantong 226001 China.

TGF--activated kinase 1 (TAK1), a serine/threonine kinase, is a key intermediate in several signaling pathways. However, its role in tumorigenesis is still not understood well. In this study, it is found that TAK1 expression decreases in esophageal tumor tissues and cell lines. In vitro experiments demonstrate that proliferation of esophageal tumor cells is enhanced by knockdown of TAK1 expression and attenuated by elevated expression of TAK1. Using a subcutaneous tumor model, these observations are confirmed in vivo. Based on the results from co-immunoprecipitation coupled with mass spectrometry, Ras association domain family 9 (RASSF9) is identified as a downstream target of TAK1. TAK1 phosphorylates RASSF9 at S284, which leads to reduced RAS dimerization, thereby blocking RAF/MEK/ERK signal transduction. Clinical survey reveals that TAK1 expression is inversely correlated with survival in esophageal cancer patients. Taken together, the data reveal that TAK1-mediated phosphorylation of RASSF9 at Ser284 negatively regulates esophageal tumor cell proliferation via inhibition of the RAS/MEK/ERK axis.
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http://dx.doi.org/10.1002/advs.202001575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927628PMC
March 2021

Quercetin induces pro-apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro.

Thorac Cancer 2021 Mar 11. Epub 2021 Mar 11.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, Tianjin, China.

Background: Quercetin, a natural flavonoid compound, is a potent cancer therapeutic agent widely found in fruit and vegetables. It has been reported to induce growth inhibition and apoptosis in both A549 and H1299 human lung cancer cells. However, the effect of quercetin-induced autophagy on apoptosis and the possible autophagy mechanism in A549 and H1299 cells have not yet been critically examined.

Methods: A549 and H1299 cells were treated with different concentrations of quercetin for 24 hours. Cell growth was measured by cell counting kit-8 (CCK-8) assay, whereas apoptosis was assessed by western blotting analysis of apoptotic proteins. The levels of proteins and genes involved in autophagy were determined by western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Autophagosomes were also observed by transmission electron microscopy (TEM) and LC3 immunofluorescence.

Results: Quercetin inhibited cell viability and induced mitochondria-dependent apoptosis in both A549 and H1299 cells in a dose-dependent. Moreover, quercetin also promoted the expression of LC3-II and beclin 1 and suppressed the expression of p62. The mRNA levels of LC3-II, beclin 1, Atg5, Atg7, and Atg12 were upregulated by quercetin treatment. Autophagy inhibition with 3-methyladenine could effectively inhibit quercetin-induced apoptosis. In addition, quercetin dose-dependently elevated the levels of SIRT1 protein and the pAMPK-AMPK ratio. Quercetin-induced autophagy was attenuated by SIRT1 inhibitor EX527 and SirT1 knockdown by small interfering RNA (siRNA).

Conclusions: Quercetin-induced autophagy contributes to apoptosis in A549 and H1299 lung cancer cells, which involved the SIRT1/AMPK signaling pathway.
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http://dx.doi.org/10.1111/1759-7714.13925DOI Listing
March 2021

Assessing Engagement in Chinese Upper Secondary School Students Using the Chinese Version of the Schoolwork Engagement Inventory: Energy, Dedication, and Absorption (CEDA).

Front Psychol 2021 18;12:638189. Epub 2021 Feb 18.

Department of Psychology, Bielefeld University, Bielefeld, Germany.

The schoolwork engagement inventory: Energy, Dedication, and Absorption (EDA) is a measure of students' engagement in schoolwork and has been demonstrated valid in Western student populations. In this study, we adapted this inventory to and tested its psychometric appropriates in Chinese upper secondary school students (CEDA). Participants were 1,527 general high school students and 850 vocational high school students. The mean age of the total sample was 16.21 years (54.4% females, age span: 15-19 years). The results of confirmatory factor analyses (CFA) showed that a modified one-factor model fitted the data best. The results of the multigroup CFA showed that the factor structure was metrically invariant across school tracks (i.e., general or vocational high school) and scalarly invariant across gender and school types (i.e., ordinary or key school). Moreover, schoolwork engagement was negatively related to emotional exhaustion and positively related to self-efficacy, perseverance of effort, teacher-student relationships, and life satisfaction. Overall, the CEDA can be regarded as a valid measure for the assessment of student engagement in the Chinese upper secondary school context.
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http://dx.doi.org/10.3389/fpsyg.2021.638189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930215PMC
February 2021

Effects of diuretics on intradialytic hypotension in maintenance dialysis patients: a systematic review and meta-analysis.

Int Urol Nephrol 2021 Mar 6. Epub 2021 Mar 6.

Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan, China.

Purpose: Intradialytic hypotension (IDH) is a serious complication in dialysis patients. Diuretics might reduce the incidence of IDH by decreasing ultrafiltration. However, the effect of diuretics on IDH in maintenance dialysis patients is still unclear.

Methods: We searched Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure and clinical trials registries from 1945 to May 2019. Randomized controlled trials (RCTs) or observational studies about IDH in maintenance dialysis with diuretics were included.

Results: Seven studies including 28,226 patients were included, of which 4 were RCTs involving mineralocorticoid receptor antagonists (MRAs) and 3 were observational studies involving loop diuretics. There was a trend that a lower incidence rate of IDH in maintenance dialysis patients who used loop diuretics than control, although the result was not statistically significant (OR 0.65, 95% CI 0.34-1.22, P = 0.18). Similarly, lower incidence rate of all-cause mortality (OR 0.92, 95% CI 0.87-0.99; P = 0.02) and cardiovascular (CV) mortality (OR 0.86, 95% CI 0.75-0.99, P = 0.03) in dialysis patients who used loop diuretics than control. On the contrary, there were no significant difference in the incidence of IDH (OR 1.35, 95% CI 0.78-2.34, P = 0.29) and all-cause mortality (OR 0.73, 95% CI 0.26-2.01; P = 0.54) and CV mortality (OR 0.57, 95% CI 0.14-2.25; P = 0.42) in maintenance dialysis patients who used MRAs compared with control.

Conclusion: Loop diuretics, but not MRAs, might have a potential benefit to reduce the incidence rate of IDH, all-cause mortality and CV mortality. More high-quality studies are needed to strengthen the arguments.
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http://dx.doi.org/10.1007/s11255-021-02805-xDOI Listing
March 2021

[Modified single-needle arthroscopic repair technique for the treatment of longitudinal meniscal tear].

Zhongguo Gu Shang 2021 Feb;34(2):114-20

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Objective: To compare therapeutic efficacy of modified single-needle arthroscopic repair technique and Fast-Fix technique in repairing longitudinal meniscus injuries.

Methods: From July 2016 to July 2017, patients with longitudinal meniscus injuries who underwent meniscal repair surgery were retrospectively analyzed. Ninety-one patients treated with modified single-needle technique and 77 patients were treated with Fast-Fix technique, the average age were (26.7±7.6) and (27.9±6.1) years old respectively, the average lengths of follow-up were (32.5±9.2) and (33.2±11.9) months, respectively. Operation cost, suture time, intraoperative failure rate and postoperative failure rate were used as clinical outcomes, MRI of knee joint was used as main diagnosis and evaluation basis; 2000 IKDC subjective score, Lysholm score and Tegner activity scale were compared between two groups preoperatively, 12 months after operation and at the latest follow-up. Intraoperative and postopertaive complications were observed.

Results: Compared with Fast-Fix group, patients in modified single-needle technique group had lower operation costs [(645.7±133.1 vs.(12 184.8±4 709.8), <0.01)], and average time per suture was shorter[(4.5±2.1) vs.(5.9±2.7), <0.001)];and there were no significant difference in intraoperative failure rate and postoperative failure rate between two groups. There were no statistical differences in subjective function score, Lysholm score, Tegner activity knee joint at 12 months after opertaion and the latest follow-up (>0.05);These scores between two groups at the latest followup were significantly improved compared with those of before operation(<0.000 1).

Conclusion: Modified single-needle arthrscopicrepair technique could achieve the similar therapeutic efficacy as Fast-Fix technique, and it has advantageds of simple opertion and more economical. This study recommends clinical application of modified single-needle arthrscopic repair technique in treating meniscus injuries.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2021.02.004DOI Listing
February 2021

Heat shock protein-90alpha (Hsp90α) stabilizes hypoxia-inducible factor-1α (HIF-1α) in support of spermatogenesis and tumorigenesis.

Cancer Gene Ther 2021 Mar 4. Epub 2021 Mar 4.

Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Center, Los Angeles, CA, USA.

Hypoxia-inducible factor-1 (HIF-1), a master transcriptional factor for protecting cells from hypoxia, plays a critical role in spermatogenesis and tumorigenesis. For the past two decades, numerous small molecule inhibitors that block mRNA synthesis, protein translation, or DNA binding of HIF-1α have entered clinical trials. To date, few have advanced to FDA approval for clinical applications due to limited efficacy at their toxicity-tolerable dosages. New windows for developing effective and safe therapeutics require better understanding of the specific mechanism of action. The finding that a chaperone-defective mutant heat shock protein-90-alpha (Hsp90α) blocks spermatogenesis, a known hypoxia-driven process in mouse testis prompted us to focus on the role of Hsp90α in HIF-1α. Here we demonstrate that Hsp90α gene knockout causes a dramatic reduction of the high steady-state level of HIF-1α in the testis, blocking sperm production and causing infertility of the mice. In HIF-1α-dependent tumor cells, we found that Hsp90α forms protein complexes with hypoxia-elevated HIF-1α and Hsp90α knockout prevents hypoxia-induced HIF-1α accumulation. In contrast, downregulation of Hsp90β had little effect on hypoxia-induced accumulation of HIF-1α. Instead, Hsp90β protects signaling molecules responsible for cellular homeostasis from assault by 17-AAG (17-N-allylamino-17-demethoxygeldanamycin), a general ATPase inhibitor of both Hsp90α and Hsp90β. Since targeting Hsp90β gene is lethal in both cultured cells and in mice, our new finding explains the toxicity of the previous inhibitor trials and identifies the specific binding of Hsp90α to HIF-1α as a new therapeutic window for developing safer and more effective treatment of male infertility and cancer.
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http://dx.doi.org/10.1038/s41417-021-00316-6DOI Listing
March 2021

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy.

Thorac Cancer 2021 Apr 3;12(8):1219-1230. Epub 2021 Mar 3.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non-small-cell lung cancer (NSCLC) remains unclear.

Methods: Cell counting kit-8 (CCK-8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.

Results: Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin-1 (Fer-1) or knockdown of iron-responsive element-binding protein 2 (IREB2) notably weakened curcumin-induced anti-tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin-induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.

Conclusion: Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046146PMC
April 2021

Novel Use of Pennig External Fixation for the Treatment of Pediatric Syndactyly.

Tech Hand Up Extrem Surg 2021 Mar 1. Epub 2021 Mar 1.

Departments of Orthopedics Geriatrics, Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Syndactyly is one of the most common congenital limb malformations, second only to polydactyly. Syndactyly is treated with surgical intervention. During separation, free skin grafting or skin flap transplantation is required to allow for adequate skin closure. We introduce a novel application method of the Pennig external fixation device for the management of pediatric syndactyly without skin grafting. The Pennig minifixator was used in syndactyly to expand the web space soft tissue in order to allow a Z-plasty to be performed in a second operation. All patients had developed sufficient skin tissue from the external fixation. No infection, cutaneous necrosis or nonunion was noted in any of the patients. All patients had a satisfactory outcome in terms of final appearance and digit function. On the basis of the principle of strain-stress, use of the Penning external minifixator allows development of sufficient tissue in the web space for a second phase of reconstruction in syndactyly. The need for skin grafting and risk of blood vessel damage were avoided in this study, and, the incidence of skin necrosis and scar formation was reduced. Both the patients' families and our research members expressed high satisfaction with the postoperative function and appearance. Overall, application of the Pennig external fixation frame in our novel method is effective for the management of syndactyly and should be studied further. Level of Evidence: Level IV, case series.
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http://dx.doi.org/10.1097/BTH.0000000000000342DOI Listing
March 2021

[Effectiveness of modified patellar tendon reconstruction using hamstring autograft in the treatment of chronic patellar tendon ruptures and defects].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Feb;35(2):160-165

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To investigate the effectiveness of modified patellar tendon reconstruction using hamstring autograft in the treatment of chronic patellar tendon rupture and defects.

Methods: The clinical data of 11 patients with chronic patellar tendon rupture and defects admitted between January 2015 and August 2018 were retrospectively analyzed. The patient were treated with inverted U-shaped reconstruction technique using hamstring autografts, in which 2 bone tunnels were created at the level of 1/2 and lower 3/4 of the patella, and 1 bone tunnel was created beneath the tibial tuberosity. There were 8 males and 3 females with an average age of 30.1 years (range, 10-61 years). The average interval from the primary injury to the operation was 9.5 months (range, 2-36 months). According to Yousef classification, there were 7 cases of type A2, 3 cases of type B2, and 1 case of type C2. The length of the patella tendon defect was measured when the patella was reducted intraoperatively with an average of 4.5 cm (range, 2.7-7.1 cm). Subjective function scores [including International Knee Documentation Committee (IKDC) subjective score, Tegner activity level, and Lysholm score] were evaluated before operation and at last follow-up. The loss of knee extension, Caton index, and thigh circumference difference at 15 cm above the patella between bilateral limbs were also measured.

Results: All patients were followed up 24-66 months (mean, 34.2 months). All incisions were primary healing, and there were no complications such as wound infection, venous thrombosis of the lower extremities, stiffness of the knee joint, graft failure, neurovascular injury, . No second revision surgery was performed during the follow-up. At last follow-up, the subjective function scores (IKDC subjective score, Tegner activity level, Lysholm score), loss of knee extension, thigh circumference difference, and Caton index were significantly improved when compared with those before operation ( <0.05). Two patients still had patella alta, with Caton indexes of 1.29 and 1.32, respectively.

Conclusion: In the treatment of chronic patellar tendon ruptures and defects, the modified patellar tendon reconstruction using hamstring autograft can significantly improve the postoperative knee function, restore the normal range of knee extension, enhance the extensor and correct the patella alta.
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http://dx.doi.org/10.7507/1002-1892.202010032DOI Listing
February 2021

MicroRNA-182 promotes epithelial-mesenchymal transition by targeting FOXN3 in gallbladder cancer.

Oncol Lett 2021 Mar 12;21(3):200. Epub 2021 Jan 12.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.

Increasing evidence has suggested an association between the expression profiles of microRNAs (miRs) and gallbladder cancer (GBC). Recently, miR-182 has been demonstrated to exert tumor-promoting effects. However, the biological activity and molecular mechanisms of miR-182 in GBC remain unclear. The results of the present study demonstrated that miR-182 expression was significantly upregulated in GBC tissues and cell lines (GBC-SD and SGC-996). In addition, miR-182-knockdown attenuated epithelial-mesenchymal transition (EMT) in GBC cells, as indicated by decreased cell migratory and invasive abilities, decreased vimentin expression, and increased E-cadherin expression. The activities of β-catenin and its downstream factors, Cyclin D1 and c-Myc, were also demonstrated to decrease following miR-182-knockdown. Forkhead box N3 (FOXN3) was identified as the direct target of miR-182. Overexpression of FOXN3 ameliorated EMT and the β-catenin pathway. Taken together, the results of the present study suggested that miR-182 promotes EMT in GBC cells by targeting FOXN3, which suppresses the Wnt/β-catenin pathway.
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http://dx.doi.org/10.3892/ol.2021.12461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816289PMC
March 2021

Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma.

Cancer Immunol Immunother 2021 Feb 4. Epub 2021 Feb 4.

Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, Sichuan Province, People's Republic of China.

Background: T cell with chimeric antigen receptors (CAR-T) has presented remarkable efficacy for blood cancer as an emerging immunotherapy. However, for solid tumors, the therapeutic efficacy is much impaired due to the lack of infiltration and persistence of CAR-T in tumor tissue. Thus, we constructed an interleukin-7-loaded oncolytic adenovirus and combined the use of oncolytic virus and CAR-T to improve the therapeutic outcome.

Methods: We constructed an interleukin-7-loaded oncolytic adenovirus (oAD-IL7) and a B7H3-targeted CAR-T and explored the efficacy of the single use of oAD-IL7, B7H3-CAR-T, or the combined therapy for glioblastoma in vitro and in vivo. The improved CAR-T anti-tumor efficacy was evaluated according to the proliferation, survival, persistence, exhaustion of T cells, and tumor regression.

Results: Constructed oAD-IL7 and B7H3-CAR-T presented moderate cytotoxicity during in vitro study, but failed to induce a thorough and persistent anti-tumor therapeutic efficacy in vivo. The combination of oAD-IL7 and B7H3-CAR-T in vitro resulted in enhanced T cell proliferation and reduced T cell apoptosis. The joint efficacy was further confirmed using tumor-bearing xenograft mice. During in vivo study, the mice treated with both oAD-IL7 and B7H3-CAR-T showed prolonged survival and reduced tumor burden. According to the ex vivo study, oAD-IL7 improved the proliferation and persistence of tumor-infiltrating B7H3-CAR-T, but failed to reverse the exhaustion.

Conclusions: Our results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma.
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http://dx.doi.org/10.1007/s00262-021-02856-0DOI Listing
February 2021

Reciprocal Antagonism between MicroRNA-138 and SIRT1 and Its Implications for the Angiogenesis of Endothelial Cells.

J Vasc Res 2021 Feb 3:1-16. Epub 2021 Feb 3.

Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China,

MicroRNAs and sirtuins are important epigenetic regulators of gene expression and both contribute significantly to postnatal vascular development. However, the crosstalk between miRNAs and sirtuins in the modulation of angiogenesis has rarely been discussed. Here, we investigated the interactions between miR-138 and sirtuins in the process of angiogenesis. We found that overexpression of miR-138 markedly suppressed the proliferation, migration, and tube-forming capacities of the endothelial cells. And, miR-138 inhibitor-treated endothelial cells showed a reversed phenotype. Furthermore, miR-138 plays a negative role in vascular development in vivo. Western blot and qPCR assays demonstrated that SIRT1 was silenced by miR-138, and a luciferase reporter assay showed that miR-138 bound to the 3'-UTR of SIRT1. The re-expression of SIRT1 alleviated miR-138-mediated suppression of angiogenesis. Furthermore, silencing SIRT1 could boost the level of miR-138. And, upon miR-138 inhibitor treatment, SIRT1 silencing no longer reduced the angiogenic ability of endothelial cells significantly. These results demonstrated that the circuitry involving miR-138 and SIRT1 may participate in vascular homeostasis and also offered the possibility of identifying a new approach in the treatment of angiogenic diseases.
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http://dx.doi.org/10.1159/000511786DOI Listing
February 2021

A natural antisense transcript acts as a negative regulator for the maize drought stress response gene ZmNAC48.

J Exp Bot 2021 Mar;72(7):2790-2806

State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China, Sichuan Agricultural University, Wenjiang 611130, Sichuan, China.

Although plant-specific NAC transcription factors play crucial roles in response to abiotic stress, few reports describe the regulation of NAC genes in maize (Zea mays) by the cis-natural antisense transcripts (cis-NATs). In this study, 521 NAC genes from Gramineae were classified, of which 51 NAC genes contained cis-NATs. ZmNAC48 and cis-NATZmNAC48 co-localized to the same cell nucleus, and both transcripts responded to drought stress. Arabidopsis plants overexpressing ZmNAC48 had improved drought tolerance, lower rate of water loss, enhanced stomatal closure, and higher rates of survival. Transient expression in both maize protoplasts and tobacco leaves indicated that cis-NATZmNAC48 reduced ZmNAC48 expression. Western blotting and ribosome profiling analyses confirmed that cis-NATZmNAC48 lacked protein coding potential. Furthermore, the cis-NAT-derived small-interfering RNAs (nat-siRNAs) generated from the overlapping regions of ZmNAC48 and cis-NATZmNAC48 were detected in maize and transgenic Arabidopsis. Cis-NATZmNAC48 overexpressing maize showed higher water loss rate, increased stomatal opening, and had more dead leaves. Expression of ZmNAC48 and nat-siRNA was decreased in these plants. Taken together, our study indicates that both ZmNAC48 and cis-NATZmNAC48 are involved in plant drought stress responses, and that the double-stranded RNA-dependent mechanism is involved in the interaction between cis-NATZmNAC48 and ZmNAC48. Additionally, cis-NATZmNAC48 may negatively regulate ZmNAC48 to affect stomatal closure of maize.
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http://dx.doi.org/10.1093/jxb/erab023DOI Listing
March 2021

Histone methyltransferase WHSC1 inhibits colorectal cancer cell apoptosis via targeting anti-apoptotic BCL2.

Cell Death Discov 2021 Jan 19;7(1):19. Epub 2021 Jan 19.

Departments of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

WHSC1 is a histone methyltransferase that facilitates histone H3 lysine 36 dimethylation (H3K36me2), which is a permissive mark associated with active transcription. In this study, we revealed how WHSC1 regulates tumorigenesis and chemosensitivity of colorectal cancer (CRC). Our data showed that WHSC1 as well as H3K36me2 were highly expressed in clinical CRC samples, and high WHSC1 expression is associated with poorer prognosis in OS patients. WHSC1 reduction promoted colon cancer cell apoptosis both in vivo and in vitro. We found that B cell lymphoma-2 (BCL2) expression, an anti-apoptotic protein, is markedly decreased in after WHSC1 depletion. Mechanistic characterization indicated that WHSC1 directly binds to the promoter region of BCL2 gene and regulate its H3K36 dimethylation level. What's more, our study indicated that WHSC1 depletion promotes chemosensitivity in CRC cells. Together, our results suggested that WHSC1 and H3K36me2 modification might be optimal therapeutic targets to disrupt CRC progression and WHSC1-targeted therapy might potentially overcome the resistance of chemotherapeutic agents.
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http://dx.doi.org/10.1038/s41420-021-00402-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815777PMC
January 2021

Minimally invasive approach with external fixator for intra-articular calcaneal fractures in children.

Medicine (Baltimore) 2021 Jan;100(1):e22393

Department of Orthopaedic Surgery.

Abstract: Calcaneal fractures are rare in pediatric population, with more displaced intra-articular fractures encountered due to the increasing number of high-energy trauma. Operative interventions are gaining popularity because of the unsatisfactory outcomes of traditional conservative methods. This study investigated the clinical outcomes of a minimally invasive technique using the sinus tarsi approach and external fixator in the treatment of intra-articular calcaneal fractures in pediatric patients.Patients who underwent open reduction between January 2010 and January 2018 at our institute were included in this study and reviewed retrospectively. Radiological and clinical parameters were all recorded and analyzed.Overall, 29 patients were included in the study, including 23 boys and 6 girls (10.2 ± 2.2 years old). The average follow-up was 29.5 months postoperatively (range, 26-72 months). Bohler angle was 15.2 ± 3.3° preoperatively, and 34.0 ± 3.8° postoperatively (P < .001); Gissane angle was 101.8 ± 6.2 degrees preoperatively, and 129.7 ± 6.2° postoperatively (P < .001). The average length of incision was 3.4 ± 0.7 cm. At the last follow-up, all patients showed satisfactory clinical outcomes and the score was 90.0 ± 2.3 according to American Orthopedic Foot and Ankle Society Scale.Minimally invasive approach with external fixator is an effective method for treating displaced intra-articular calcaneal fractures in pediatric patients, with a lower incidence of wound-related complications and good cosmetic outcomes.
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http://dx.doi.org/10.1097/MD.0000000000022393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793431PMC
January 2021