Publications by authors named "Fang He"

767 Publications

THADA drives Golgi residency and upregulation of PD-L1 in cancer cells and provides promising target for immunotherapy.

J Immunother Cancer 2021 Aug;9(8)

Zhongshan-Xuhui Hospital, Shanghai Xuhui Central Hospital, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University, Shanghai, China

Background: The abnormal upregulation of programmed death-ligand 1 (PD-L1) in cancer cells inhibits T cell-mediated cytotoxicity, but the molecular mechanisms that drive and maintain PD-L1 expression are still incompletely understood.

Methods: Combined analyses of genomes and proteomics were applied to find potential regulators of PD-L1. In vitro experiments were performed to investigate the regulatory mechanism of PD-L1 by thyroid adenoma associated gene (THADA) using human colorectal cancer (CRC) cells. The prevalence of THADA was analyzed using CRC tissue microarrays by immunohistochemistry. T cell killing assay, programmed cell death 1 binding assay and MC38 transplanted tumor models in C57BL/6 mice were developed to investigate the antitumor effect of THADA.

Results: THADA is critically required for the Golgi residency of PD-L1, and this non-redundant, coat protein complex II (COPII)-associated mechanism maintains PD-L1 expression in tumor cells. THADA mediated the interaction between PD-L1 as a cargo protein with SEC24A, a module on the COPII trafficking vesicle. Silencing THADA caused absence and endoplasmic reticulum (ER) retention of PD-L1 but not major histocompatibility complex-I, inducing PD-L1 clearance through ER-associated degradation. Targeting THADA substantially enhanced T cell-mediated cytotoxicity, and increased CD8+ T cells infiltration in mouse tumor tissues. Analysis on clinical tissue samples supported a potential role of THADA in upregulating PD-L1 expression in cancer.

Conclusions: Our data reveal a crucial cellular process for PD-L1 maturation and maintenance in tumor cells, and highlight THADA as a promising target for overcoming PD-L1-dependent immune evasion.
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http://dx.doi.org/10.1136/jitc-2021-002443DOI Listing
August 2021

Pediatric BMI changes during COVID-19 pandemic: An electronic health record-based retrospective cohort study.

EClinicalMedicine 2021 Aug 16;38:101026. Epub 2021 Jul 16.

Center for Observational Research, Amgen, Inc., 1000 E Oaks Blvd, One Amgen Ctr. Dr. M/S 24-1-C, Thousand Oaks, California 91362, United States.

Background: Beginning March 2020, the COVID-19 pandemic has disrupted different aspects of life. The impact on children's rate of weight gain has not been analysed.

Methods: In this retrospective cohort study, we used United States (US) Electronic Health Record (EHR) data from Optum® to calculate the age- and sex- adjusted change in BMI (∆BMI) in individual 6-to-17-year-old children between two well child checks (WCCs). The mean of individual ∆BMI during 2017-2020 was calculated by month. For September-December WCCs, the mean of individual ∆BMI (overall and by subgroup) was reported for 2020 and 2017-2019, and the impact of 2020 vs 2017-2019 was tested by multivariable linear regression.

Findings: The mean [95% Confidence Interval - CI] ∆BMI in September-December of 2020 was 0·62 [0·59,0·64] kg/m, compared to 0·31 [0·29, 0·32] kg/m in previous years. The increase was most prominent in children with pre-existing obesity (1·16 [1·07,1·24] kg/m in 2020 versus 0·56 [0·52,0·61] kg/m in previous years), Hispanic children (0·93 [0·84,1·02] kg/m in 2020 versus 0·41 [0·36,0·46] kg/m in previous years), and children who lack commercial insurance (0·88 [0·81,0·95] kg/m in 2020 compared to 0·43 [0·39,0·47] kg/m in previous years). ∆BMI accelerated most in ages 8-12 and least in ages 15-17.

Interpretation: Children's rate of unhealthy weight gain increased notably during the COVID-19 pandemic across demographic groups, and most prominently in children already vulnerable to unhealthy weight gain. This data can inform policy decisions critical to child development and health as the pandemic continues to unfold.

Funding: Amgen, Inc.
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http://dx.doi.org/10.1016/j.eclinm.2021.101026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318998PMC
August 2021

Combination of ablative fractional carbon dioxide laser and platelet-rich plasma treatment to improve hypertrophic scars: a retrospective clinical observational study.

Burns Trauma 2021 28;9:tkab016. Epub 2021 Jul 28.

Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University; Burn Institute of PLA; 168 Changhai Road, Yangpu District, Shanghai 200433, China.

Background: Hypertrophic scars are one of the main complications that affect the quality of life of patients after burns. Many methods have been shown to be effective in the treatment of hypertrophic scars, such as ablative fractional CO laser (AFCL) and platelet-rich plasma (PRP). However, there are few studies on the effect of the combined application of these measures. The purpose of this study was to explore the therapeutic effect of AFCL combined with PRP on hypertrophic burn scars.

Methods: A retrospective clinical observation study was conducted on 50 patients with hypertrophic burn scars. The AFCL+PRP group included 31 patients who received AFCL combined with PRP treatment; the AFCL group included 19 patients who received AFCL treatment only. The University of North Carolina 4P Scar Scale (UNC4P) and the Vancouver Scar Scale (VSS) scores that were collected before each treatment were used as indicators of the effectiveness of the previous treatment. The scores recorded at the second, fourth and seventh months were analysed.

Results: The demographic data of the 2 groups were not significantly different. Before treatment, there was no difference in the UNC4P and VSS scores between the 2 groups. There was a significant decline in the UNC4P and VSS total scores over 6 months in both groups ( < 0.05) and scores in the 2 groups were comparable after 3 and 6 months ( < 0.05). UNC4P scores in the AFCL+PRP group decreased from a mean of 8.26 to 2.61 ( < 0.05) with a concomitant drop in VSS scores from a mean of 11.74 to 6.06 ( < 0.01). In the AFCL group UNC4P and VSS scores decreased from 7.68 to 4.63 ( < 0.05) and from 10.89 to 8.16 ( < 0.05), respectively. The sub-items of these 2 assessments were analysed and the results suggest that AFCL combined with PRP can comprehensively improve scarring.

Conclusions: This study shows that PRP is an effective adjunct for AFCL in the treatment of hypertrophic burn scars and that the combination of PRP and AFCL proved to be more useful than AFCL alone. This combination may be a new and effective clinical practice for the treatment of scars. However, larger and higher-level clinical studies are still needed to determine its efficacy and possible mechanisms.
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http://dx.doi.org/10.1093/burnst/tkab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316760PMC
July 2021

The Receptor-Like Kinase Confers Improved Water Use Efficiency and Drought Tolerance to Poplar via Modulating Stomatal Density.

Int J Mol Sci 2021 Jul 6;22(14). Epub 2021 Jul 6.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, College of Biological Sciences and Technology, National Engineering Laboratory of Tree Breeding, Beijing Forestry University, Beijing 100083, China.

Poplar is one of the most important tree species in the north temperate zone, but poplar plantations are quite water intensive. We report here that CaMV 35S promoter-driven overexpression of the gene, which is a member of the LRR-RLKs family from × ( × ), improves water use efficiency and enhances drought tolerance in triploid white poplar. localizes to the plasma membrane. Overexpression plants showed lower stomatal density and larger stomatal size. The abaxial stomatal density was 24-34% lower and the stomatal size was 12-14% larger in overexpression lines. Reduced stomatal density led to a sharp restriction of transpiration, which was about 18-35% lower than the control line, and instantaneous water use efficiency was around 14-63% higher in overexpression lines under different conditions. These phenotypic changes led to increased drought tolerance. overexpression plants not only survived longer after stopping watering but also performed better when supplied with limited water, as they had better physical and photosynthesis conditions, faster growth rate, and higher biomass accumulation. Taken together, our data suggest that can alter the development pattern of stomata to reduce stomatal density, which then restricts water consumption, conferring enhanced drought tolerance to poplar. This makes trees promising candidates for establishing more water use efficient plantations.
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http://dx.doi.org/10.3390/ijms22147245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303786PMC
July 2021

A review on interplay between small RNAs and oxidative stress in cancer progression.

Mol Cell Biochem 2021 Jul 22. Epub 2021 Jul 22.

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, 603 103, India.

Oxidative stress has been known to be the underlying cause in many instances of cancer development. The new aspect of cancer genesis that has caught the attention of many researchers worldwide is its connection to non-coding RNAs (ncRNAs). ncRNAs may not be protein coding, but in light of the more recent discovery of their wide range of functions, the term 'dark matter of the genome' has been rendered inapplicable. There is an extensive mention of colon cancer as an example, where some of these ncRNAs and their manipulations have seen significant progress. As of now, the focus is on discovering a non-invasive, cost-effective method for diagnosis that is easier to monitor and can be conducted before visible symptoms indicate cancer in a patient, by which time it may already be too late. The concept of liquid biopsies has revolutionized recent diagnostic measures. It has been possible to detect circulating parts of the cancer genome or other biomarkers in the patients' bodily fluids, resulting in the effective management of the disease. This has led these ncRNAs to be considered effective therapeutic targets and extrinsic modifications in several tumor types, proven to be effective as therapy. However, there is a vast scope for further understanding and pertinent application of our acquired knowledge and expanding it in enhancing the utilization of ncRNAs for a better prognosis, quicker diagnosis, and improved management of cancer. This review explores the prognosis of cancer and related mutations by scrutinizing small ncRNAs in the disease.
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http://dx.doi.org/10.1007/s11010-021-04228-9DOI Listing
July 2021

Preparation of Poly(Ionic Liquid) Microbeads via Cooling-Assisted Phase Separation Method.

Macromol Rapid Commun 2021 Jul 19:e2100275. Epub 2021 Jul 19.

Research and Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen, Guangdong, 518057, China.

We report a simple and large-scale non-chemical preparation of uniform poly(ionic liquid) (PIL) microbeads via a cooling-assisted phase separation method (CAPS). For this method, PIL bulk was dissolved to form a saturated solution in a mixed solvent composed of good solvent and non-solvent at a relatively high temperature. Then, the uniform PIL microbeads were prepared by cooling the solution to room temperature or a lower temperature in the absence of stabilizer. The size of microbeads can be controlled by adjusting the preparation parameters, including PIL concentration, cooling rate, and agitation state. The scale of preparation can be up to 10 g, and the yield of PIL microbeads was more than 70% or 88% when the solution was cooled to room temperature or 0 °C, respectively. The formation mechanism of PIL microbeads was discussed by tracing the nucleation and growth process by the transmittance of light of the solution during cooling. The application of this method to other polymer microbeads preparation was finally discussed by choosing different good solvent and non-solvent. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/marc.202100275DOI Listing
July 2021

[Recurrence factors for myelin oligodendrocyte glycoprotein antibody disease in children and the effect of recurrence prevention regimens].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Jul;23(7):724-729

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha 410007, China.

Objective: To study the clinical features and recurrence factors of myelin oligodendrocyte glycoprotein (MOG) antibody disease in children and the effect of recurrence prevention regimens.

Methods: A retrospective analysis was performed on the medical data of 41 children with MOG antibody disease who were hospitalized in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from December 2014 to September 2020. According to the presence or absence of recurrence, they were divided into a monophasic course group (=19) and a recurrence group (=22). According to whether preventive treatment for recurrence was given, the children with recurrence were further divided into a preventive treatment group and a non-preventive treatment group. The clinical features were analyzed for all groups, and the annualized relapse rate (ARR) was compared before and after treatment with prevention regimens.

Results: For these 41 children, acute disseminated encephalomyelitis was the most common initial manifestation and was observed in 23 children (56%). Of the 41 children, 22 (54%) experienced recurrence, with 57 recurrence events in total, among which optic neuritis was the most common event (17/57, 30%). The proportion of children in the recurrence group who were treated with corticosteroids for less than 3 months in the acute phase was higher than that in the monophasic course group (64% 32%; < 0.05). There was no significant difference in the ARR between the preventive treatment and non-preventive treatment groups ( > 0.05). The assessment of preventive treatment regimens for 32 cases showed that the children treated with rituximab or azathioprine had a significant reduction in the ARR during treatment ( < 0.05).

Conclusions: More than half of the children with MOG antibody disease may experience recurrence. Most children with recurrence are treated with corticosteroids for less than 3 months in the acute phase. Rituximab and azathioprine may reduce the risk of recurrence.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292654PMC
July 2021

Relevance of Physical Activities, Sedentary Behaviors, and Genetic Predisposition in Body Fatness: Population-Based Study on Chinese Adults.

Obes Facts 2021 9;14(4):346-356. Epub 2021 Jul 9.

West China School of Public Health, Sichuan University, Chengdu, China.

Introduction: Little attention has been paid to the interacting effect of specific intensities of physical activities (PAs) and sedentary lifestyle, like television watching, and genetic predisposition on body composition indices among Chinese adults. Herein, we aimed to examine whether specific types of PAs and sedentary behaviors (SBs) were associated with body composition indices among Chinese adults and to further explore whether these associations interacted with the genetic predisposition to high BMI.

Methods: Cross-sectional data regarding PAs and time spent on SBs and dietary intake of 3,976 Chinese adults (54.9% women) aged 25-65 years in Southwest China were obtained via questionnaires in 2013-2015. Weight, height, and waist circumference (WC) were measured, and BMI, percentage of body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) of the participants were calculated. Genetic risk score (GRS) was calculated on 9 established BMI-associated SNPs among Chinese adults.

Results: When the participants were stratified by GRS for BMI, significant associations were only found for adults with high GRS for BMI: moderate-to-vigorous physical activity (MVPA) was negatively associated with WC and %BF and positively related to FFMI. The adjusted positive relationship of time spent watching television with BMI, WC, %BF, and FMI were also just found between adults with high weighted GRS for high BMI: for every 1 h increment in television watching, the BMI, WC, %BF, and FMI of the participants increased by 0.2 kg/m2, 0.9 cm, 0.3%, and 0.1 kg/m2, respectively (p < 0.02).

Conclusion: MVPA may be a protective factor against obesity, and prolonged television watching may accentuate adiposity. These putative effects may be more pronounced among individuals with a high genetic risk of a high BMI.
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http://dx.doi.org/10.1159/000515380DOI Listing
July 2021

Familial SYN1 variants related neurodevelopmental disorders in Asian pediatric patients.

BMC Med Genomics 2021 Jul 9;14(1):182. Epub 2021 Jul 9.

Department of Pediatrics, Xiangya Hospital, Central South University, No. 86, Xiangya Road, Kaifu District, Changsha, 410008, China.

Background: SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years.

Methods: In the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder.

Results: Two maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients' clinical manifestations vary in genders and individuals, even in the same pedigree.

Conclusion: We firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.
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http://dx.doi.org/10.1186/s12920-021-01028-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272254PMC
July 2021

Antiparasitic mebendazole (MBZ) effectively overcomes cisplatin resistance in human ovarian cancer cells by inhibiting multiple cancer-associated signaling pathways.

Aging (Albany NY) 2021 07 7;13(13):17407-17427. Epub 2021 Jul 7.

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

Ovarian cancer is the third most common cancer and the second most common cause of gynecologic cancer death in women. Its routine clinical management includes surgical resection and systemic therapy with chemotherapeutics. While the first-line systemic therapy requires the combined use of platinum-based agents and paclitaxel, many ovarian cancer patients have recurrence and eventually succumb to chemoresistance. Thus, it is imperative to develop new strategies to overcome recurrence and chemoresistance of ovarian cancer. Repurposing previously-approved drugs is a cost-effective strategy for cancer drug discovery. The antiparasitic drug mebendazole (MBZ) is one of the most promising drugs with repurposing potential. Here, we investigate whether MBZ can overcome cisplatin resistance and sensitize chemoresistant ovarian cancer cells to cisplatin. We first established and characterized two stable and robust cisplatin-resistant (CR) human ovarian cancer lines and demonstrated that MBZ markedly inhibited cell proliferation, suppressed cell wounding healing/migration, and induced apoptosis in both parental and CR cells at low micromole range. Mechanistically, MBZ was revealed to inhibit multiple cancer-related signal pathways including ELK/SRF, NFKB, MYC/MAX, and E2F/DP1 in cisplatin-resistant ovarian cancer cells. We further showed that MBZ synergized with cisplatin to suppress cell proliferation, induce cell apoptosis, and blunt tumor growth in xenograft tumor model of human cisplatin-resistant ovarian cancer cells. Collectively, our findings suggest that MBZ may be repurposed as a synergistic sensitizer of cisplatin in treating chemoresistant human ovarian cancer, which warrants further clinical studies.
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http://dx.doi.org/10.18632/aging.203232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312413PMC
July 2021

Comorbidities of scars in China: a national study based on hospitalized cases.

Burns Trauma 2021 10;9:tkab012. Epub 2021 Jun 10.

Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, P.R.China.

Background: Scar comorbidities seriously affect the physical and mental health of patients, but few studies have reported the exact epidemiological characteristics of scar comorbidities in China. This study aimed to investigate the prevalence of scar comorbidities in China.

Methods: The data of 177,586 scar cases between 2013 and 2018 were obtained from the Hospital Quality Monitoring System based on the 10th edition of the International Classification of Diseases coding system. The total distribution of scar comorbidities and their relationship with age, aetiology and body regions were analysed.

Results: Six comorbidities (contracture, malformation, ocular complications, adhesion, infection and others) were the main focus. In general, male patients outnumbered females and urban areas outnumbered rural areas. The proportion of contractures was the highest at 59,028 (33.24%). Students, workers and farmers made up the majority of the occupation. Han Chinese accounted for the majority of the ethnic. The highest proportion of scar contracture occurred at 1-1.9 years of age (58.97%), after which a significant downward trend was observed. However, starting from 50 years of age, ocular complications increased gradually and significantly, eventually reaching a peak of 34.49% in those aged >80 years. Scar contracture was the most common comorbidity according to aetiology, and the highest proportion was observed in patients who were scalded (29.33%). Contractures were also the most frequent comorbidity in hands (10.30%), lower limbs (6.97%), feet (6.80%) and upper limbs (6.02%). The mean and median hospitalization durations were 12.85 and 8 days, respectively.

Conclusions: Contractures were the most common comorbidities, and different comorbidities tended to occur at different ages and with different causative factors.
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http://dx.doi.org/10.1093/burnst/tkab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240520PMC
June 2021

Balancing Strength and Ductility in Al Matrix Composites Reinforced by Few-Layered MoS through In-Situ Formation of Interfacial AlMo.

Materials (Basel) 2021 Jun 25;14(13). Epub 2021 Jun 25.

School of Materials Science and Engineering and Tianjin Key Laboratory of Composites and Functional Materials, Tianjin University, Tianjin 300350, China.

In this work, few-layered MoS (FLM) nanosheet-reinforced Al matrix composites are developed through powder metallurgy and hot extrusion. The microstructure, mechanical properties, and strengthening mechanisms have been systematically investigated. It is found that AlMo and AlS can be formed in-situ during the sintering process, resulting in the improvement of interfacial bonding between FLM and Al matrix. With 1.5 wt.% of FLM addition, an improved tensile strength of 234 MPa with a high elongation of 17% can be obtained. Moreover, the strengthening mechanisms are also demonstrated to be grain refinement, dislocation strengthening, and load transfer, and the calculation indicates that load transfer is the main contribution factor. This work will inspire more new designs of metal matrix composites with balanced strength and ductility.
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http://dx.doi.org/10.3390/ma14133561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269559PMC
June 2021

Development and validation of a predictive model for severe postpartum hemorrhage in women undergoing vaginal delivery: A retrospective cohort study.

Int J Gynaecol Obstet 2021 Jun 24. Epub 2021 Jun 24.

Department of Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, China.

Objective: To develop a predictive tool to accurately screen women at high risk of severe postpartum hemorrhage (SPPH) undergoing vaginal delivery.

Methods: We analyzed 28 150 mothers who underwent vaginal delivery after 28 weeks of pregnancy in the Third Affiliated Hospital of Guangzhou Medical University from January 2015 to August 2019. Two-thirds of the cohort were randomly allocated to a training set (n = 18 766) and the rest to a validation set (n = 9384). In the training set, we built a radiomic nomogram based on multivariate logistic analysis, and calibration and C-index were evaluated. The performance of the validated nomogram was then tested in the validation cohort.

Results: Independent risk factors for SPPH in women undergoing vaginal delivery were previous cesarean section, history of PPH, in vitro fertilization, anemia, intrauterine death, prolonged labor, low-lying placenta, placental abruption, placenta accreta spectrum, and macrosomia. Good calibration was observed for the probability of SPPH in the validation cohort, and the C-index of the nomogram for the prediction of SPPH was 0.861 (95% confidence interval 0.820-0.902).

Conclusion: This model would be a useful tool to accurately screen for women at high-risk of SPPH undergoing vaginal delivery. It would be expected to be an effective tool to guide clinical practice and further reduce maternal mortality.
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http://dx.doi.org/10.1002/ijgo.13797DOI Listing
June 2021

Establishment and Validation of the Detection of TERT Promoter Mutations by Human Gliomas U251 Cell Lines.

Biomed Res Int 2021 1;2021:3271395. Epub 2021 Jun 1.

The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, Yuzhong District, Chongqing 400016, China.

Gliomas are the most common type of primary brain tumor, yet the prognosis for glioma patients remains poor. Mutations in the promoter region of the telomerase reverse transcriptase gene (TERTp) are associated with diagnosis and poor prognosis in gliomas. Here, we developed a precise and rapid Sanger sequencing assay to screen or TERTp mutations. We established the Sanger sequencing approach for the detection of TERTp mutations based on human glioma cell lines U251 and assessed the analytical validation by determining the accuracy, sensitivity, precision, and specificity. In our study, we verified the accuracy of Sanger sequencing by the real-time polymerase chain reaction method. Our data showed that TERTp mutations were detected at an analytical sensitivity of 10% per mutant. The precision and specificity validation also showed the desired results. In total, 147 glioma patients were investigated for TERTp mutations, and of each patient, clinical data and molecular characteristics were analyzed. We found that anaplastic oligodendroglioma had the highest frequency of TERTp mutations (66.7%). No differences in TERTp mutation frequency were observed between frozen tissue specimens and formalin-fixed and paraffin-embedded tissue. TERTp mutations were associated with older patients (≥45 years), whereas isocitrate dehydrogenase (IDH) mutations were inclined to a younger age (<45 years), frontal location, and pathologic stage II-III patients. IDH mutations were significantly associated with O6-methylguanine-DNA methyltransferase (MGMT) methylation ( = 0.003) and lower Ki-67 protein expression ( = 0.011). Moreover, MGMT methylation was enriched in IDH-mutant/TERTp-mutant gliomas, and Ki-67 protein expression was the highest in the IDH-wild type/TERTp-mutant group. Taken together, the findings of this study indicate the establishment of a rapid, precise, and practical Sanger sequencing technique for TERTp mutations in gliomas that may show promising results in clinical applications.
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http://dx.doi.org/10.1155/2021/3271395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187059PMC
June 2021

Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision.

Jpn J Clin Oncol 2021 Jun 21. Epub 2021 Jun 21.

Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.

Background: The efficacy of the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer in elderly patients has not been established.

Methods: A total of 3096 locally advanced rectal cancer patients who received neoadjuvant chemotherapy, along with neoadjuvant chemoradiotherapy and total mesorectal excision, with or without adjuvant chemotherapy, between January 2010 and December 2018, were studied retrospectively. Patients were divided into elderly (>75 years) and younger (≤75 years) groups, and propensity score matching was used to balance a potentially confounding clinical bias. Overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and local recurrence-free survival rates for the two groups were compared. Hazard ratios (HR) with 95% confidence intervals (CI) for different clinicopathological variables were calculated to determine predictors of 3-year overall survival.

Results: Mean follow-up was 39.0 (range, 5-140) months. The overall 3-year overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates were 86.1, 87.6, 80.0, 82.4 and 95.4%, respectively. Only 3-year overall survival rates differed significantly between the elderly (77.2%) and younger (88.9%) groups (P = 0.01). Cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates did not differ significantly between the two groups. Significant negative independent prognostic factors for 3-year overall survival were age >75 years (HR = 2.016, 95% CI 1.157-23.511, P = 0.01) and high pathologic TNM stage (yp stage III, P < 0.001).

Conclusion: For elderly locally advanced rectal cancer patients who have good health and performance status, the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision can result in disease-related survival rates and oncological outcomes similar to those experienced by younger patients. The decision to use this treatment approach in elderly patients should not be based solely on chronological age.
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http://dx.doi.org/10.1093/jjco/hyab095DOI Listing
June 2021

A functional autophagy pathway is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs).

Am J Transl Res 2021 15;13(5):4233-4250. Epub 2021 May 15.

Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University Qingdao 266061, China.

Mesenchymal stem cells (MSCs) are capable of differentiating into bone, cartilage and adipose tissues. We identified BMP9 as the most potent osteoinductive BMP although detailed mechanism underlying BMP9-regulated osteogenesis of MSCs is indeterminate. Emerging evidence indicates that autophagy plays a critical role in regulating bone homeostasis. We investigated the possible role of autophagy in osteogenic differentiation induced by BMP9. We showed that BMP9 upregulated the expression of multiple autophagy-related genes in MSCs. Autophagy inhibitor chloroquine (CQ) inhibited the osteogenic activity induced by BMP9 in MSCs. While overexpression of ATG5 or ATG7 did not enhance osteogenic activity induced by BMP9, silencing expression in MSCs effectively diminished BMP9 osteogenic signaling activity and blocked the expression of the osteogenic regulator Runx2 and the late marker osteopontin induced by BMP9. Stem cell implantation study revealed that silencing in MSCs profoundly inhibited ectopic bone regeneration and bone matrix mineralization induced by BMP9. Collectively, our results strongly suggest a functional autophagy pathway may play an essential role in regulating osteogenic differentiation induced by BMP9 in MSCs. Thus, restoration of dysregulated autophagic activity in MSCs may be exploited to treat fracture healing, bone defects or osteoporosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205769PMC
May 2021

RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion.

Front Oncol 2021 31;11:665273. Epub 2021 May 31.

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Activity of transcription factors is normally regulated through interaction with other transcription factors, chromatin remodeling proteins and transcriptional co-activators. In distinction to these well-established transcriptional controls of gene expression, we have uncovered a unique activation model of transcription factors between tyrosine kinase ABL and RUNX2, an osteoblastic master transcription factor, for cancer invasion. We show that ABL directly binds to, phosphorylates, and activates RUNX2 through its SH2 domain in a kinase activity-dependent manner and that the complex formation of these proteins is required for expression of its target gene MMP13. Additionally, we show that the RUNX2 transcriptional activity is dependent on the number of its tyrosine residues that are phosphorylated by ABL. In addition to regulation of RUNX2 activity, we show that ABL transcriptionally enhances RUNX2 expression through activation of the bone morphogenetic protein (BMP)-SMAD pathway. Lastly, we show that ABL expression in highly metastatic breast cancer MDA-MB231 cells is associated with their invasive capacity and that ABL-mediated invasion is abolished by depletion of endogenous RUNX2 or MMP13. Our genetic and biochemical evidence obtained in this study contributes to a mechanistic insight linking ABL-mediated phosphorylation and activation of RUNX2 to induction of MMP13, which underlies a fundamental invasive capacity in cancer and is different from the previously described model of transcriptional activation.
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http://dx.doi.org/10.3389/fonc.2021.665273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201617PMC
May 2021

Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights.

Front Immunol 2021 31;12:683879. Epub 2021 May 31.

Guangdong Laboratory of Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, Institute of Subtropical Animal Nutrition and Feed, College of Animal Science, South China Agricultural University, Guangzhou, China.

Diseases caused by pathogenic bacteria in animals (e.g., bacterial pneumonia, meningitis and sepsis) and plants (e.g., bacterial wilt, angular spot and canker) lead to high prevalence and mortality, and decomposition of plant leaves, respectively. Melatonin, an endogenous molecule, is highly pleiotropic, and accumulating evidence supports the notion that melatonin's actions in bacterial infection deserve particular attention. Here, we summarize the antibacterial effects of melatonin , in animals as well as plants, and discuss the potential mechanisms. Melatonin exerts antibacterial activities not only on classic gram-negative and -positive bacteria, but also on members of other bacterial groups, such as . Protective actions against bacterial infections can occur at different levels. Direct actions of melatonin may occur only at very high concentrations, which is at the borderline of practical applicability. However, various indirect functions comprise activation of hosts' defense mechanisms or, in sepsis, attenuation of bacterially induced inflammation. In plants, its antibacterial functions involve the mitogen-activated protein kinase (MAPK) pathway; in animals, protection by melatonin against bacterially induced damage is associated with inhibition or activation of various signaling pathways, including key regulators such as NF-κB, STAT-1, Nrf2, NLRP3 inflammasome, MAPK and TLR-2/4. Moreover, melatonin can reduce formation of reactive oxygen and nitrogen species (ROS, RNS), promote detoxification and protect mitochondrial damage. Altogether, we propose that melatonin could be an effective approach against various pathogenic bacterial infections.
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http://dx.doi.org/10.3389/fimmu.2021.683879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201398PMC
May 2021

Effect of Soil Properties and Aging Time on Oral and Inhalation Bioaccessibility of Copper Oxide Nanoparticles in Soils.

Bull Environ Contam Toxicol 2021 Jun 16. Epub 2021 Jun 16.

School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, China.

In this study, soils spiked with copper oxide nanoparticles (CuO NPs) or Cu(NO) and aged as long as 90 days were utilized to investigate effect of soil properties and aging on oral and inhalation bioaccessibility of CuO NPs. Results showed that oral bioaccessibility of CuO NPs in gastric phase (GP) ranged from 70% to 84%, it significantly decreased to 50%-70% in intestinal phase (IP). The inhalation bioaccessibility of CuO NPs in artificial lysosomal fluid (ALF) ranged from 66% to 85%, and much higher than that in Gamble's solution (GS, 3.3%-23%). By comparing CuO NPs to Cu(NO) bioaccessibility, insignificant difference was found. The aging time (D15 and D90) had limited effect on their oral and inhalation bioaccessibility. CEC and free Al were positively and clay content was negatively correlated with CuO NPs inhalation bioaccessibility, while Cu(NO) inhalation bioaccessibility decreased with increasing soil clay content and pH. Our findings provide an essential basis to evaluate the human health risks of CuO NPs.
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http://dx.doi.org/10.1007/s00128-021-03287-4DOI Listing
June 2021

A self-assembling nanoparticle: Implications for the development of thermostable vaccine candidates.

Int J Biol Macromol 2021 Jul 5;183:2162-2173. Epub 2021 Jun 5.

Institute of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Hangzhou 310058, China. Electronic address:

Effective controls on viral infections rely on the continuous development in vaccine technology. Nanoparticle (NP) antigens are highly immunogenic based on their unique physicochemical properties, making them molecular scaffolds to present soluble vaccine antigens. Here, viral targets (113-354 aas) were genetically fused to N terminal of mi3, a protein that self-assembles into nanoparticles composed of 60 subunits. With transmission electron microscopy, it was confirmed that target-mi3 fusion proteins which have insertions of up to 354 aas in N terminal form intact NPs. Moreover, viral targets are surface-displayed on NPs as indicated in dynamic light scattering. NPs exhibit perfect stability after long-term storage at room temperature. Moreover, SP-E2-mi3 NPs enhance antigen uptake and maturation in dendritic cells (DCs) via up-regulating marker molecules and immunostimulatory cytokines. Importantly, in a mouse model, SP-E2-mi3 nanovaccines against Classical swine fever virus (CSFV) remarkably improved CSFV-specific neutralizing antibodies (NAbs) and cellular immunity related cytokines (IFN-γ and IL-4) as compared to monomeric E2. Specially, improved NAb response with more than tenfold increase in NAb titer against both CSFV Shimen and HZ-08 strains indicated better cross-protection against different genotypes. Collectively, this structure-based, self-assembling NP provides an attractive platform to improve the potency of subunit vaccine for emerging pathogens.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.024DOI Listing
July 2021

Survivin promotes rheumatoid arthritis fibroblast-like synoviocyte cell proliferation, and the expression of angiogenesis-related proteins by activating the NOTCH pathway.

Int J Rheum Dis 2021 Jul 7;24(7):922-929. Epub 2021 Jun 7.

Medical School, Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, China.

Background: Survivin have been shown to play a crucial role in rheumatoid arthritis (RA); however, the regulatory mechanism of survivin in RA has not been fully elucidated. This study aims to investigate the effect of survivin on the proliferation and apoptosis of human RA fibroblast-like synoviocyte (RA-HFLS) cells in RA and its underlying mechanism through the NOTCH pathway.

Methods: The RA synovial tissues of 65 RA patients with partial resection of synovium of knee joint by arthroscopy were collected. The expression of survivin in synovial tissue was detected by immunohistochemistry, and the correlation of survivin expression and clinical-pathological parameters of patients was analyzed. In vitro, the proliferation of HFLS and RA-HFLS were detected by MTT; the apoptosis of HFLS and RA-HFLS were detected by flow cytometry; the expression of survivin proteins, key protein factors (Notch1, Jagged1, Hes1) in the Notch pathway, and angiogenesis-related proteins (vascular endothelial growth factor receptor 1 [VEGFR1], Ang1, Ang2) were determined by western blot.

Results: We found that survivin was highly expressed in RA synovial tissues and RA-HFLS cells, and was positively correlated with erythrocyte sedimentation rate, cyclic citrullinated peptide, C-reactive protein, Disease Activity Score of 28 joints and other pathological indexes. Knockdown survivin induces RA-HFLS cell apoptosis, suppresses proliferation and the expression of VEGFR1, Ang1, Ang2. In addition, blocking Notch pathway using FLI-06 significantly down-regulated survivin expression. When survivin is up-regulated, it promotes RA-HFLS cell proliferation, the expression of VEGFR1, Ang1, Ang2 and suppresses apoptosis by activating the NOTCH.

Conclusion: This study confirmed that survivin promotes RA-HFLS cell proliferation, the expression of angiogenesis-related proteins and suppresses apoptosis by activating the NOTCH pathway.
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http://dx.doi.org/10.1111/1756-185X.14150DOI Listing
July 2021

Near-infrared light-controllable MXene hydrogel for tunable on-demand release of therapeutic proteins.

Acta Biomater 2021 08 31;130:138-148. Epub 2021 May 31.

State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha 410082 P.R. China. Electronic address:

Precise delivery of therapeutic protein drugs that specifically modulate desired cellular responses is critical in clinical practice. However, the spatiotemporal regulation of protein drugs release to manipulate the target cell population in vivo remains a huge challenge. Herein, we have rationally developed an injectable and Near-infrared (NIR) light-responsive MXene-hydrogel composed of TiC, agarose, and protein that enables flexibly and precisely control the release profile of protein drugs to modulate cellular behaviors with high spatiotemporal precision remotely. As a proof-of-concept study, we preloaded hepatic growth factor (HGF) into the [email protected] ([email protected]/HGF) to activate the c-Met-mediated signaling by NIR light. We demonstrated NIR light-instructed cell diffusion, migration, and proliferation at the user-defined localization, further promoting angiogenesis and wound healing in vivo. Our approach's versatility was validated by preloading tumor necrotic factor-α (TNF-α) into the composite hydrogel ([email protected]/TNF-α) to promote the pro-apoptotic signaling pathway, achieving the NIR light-induced programmed cell deaths (PCD) of tumor spheroids. Taking advantage of the deep-tissue penetrative NIR light, we could eradicate the deep-seated tumors in a xenograft model exogenously. Therefore, the proposed MXene-hydrogel provides the impetus for developing therapeutic synthetic materials for light-controlled drug release under thick tissue, which will find promising applications in regenerative medicine and tumor therapy. STATEMENT OF SIGNIFICANCE: Current stimuli-responsive hydrogels for therapeutic proteins delivery mainly depend on self-degradation, passive diffusion, or the responsiveness to cues relevant to diseases. However, it remains challenging to spatiotemporally deliver protein-based drugs to manipulate the target cell population in vivo in an "on-demand" manner. Therefore, we have rationally constructed an injectable and Near-infrared (NIR) light-responsive composite hydrogel by embedding TiC MXene and protein drugs within an agarose hydrogel to enable the remote control of protein drugs delivery with high spatiotemporal precision. The NIR light-controlled release of the growth factor or cytokine has been carried out to regulate receptor-mediated cellular behaviors under deep tissue for skin wound healing or cancer therapy. This system will provide the potential for precision medicine through the development of intelligent drug delivery systems.
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http://dx.doi.org/10.1016/j.actbio.2021.05.027DOI Listing
August 2021

High-resolution genome-wide association study and genomic prediction for disease resistance and cold tolerance in wheat.

Theor Appl Genet 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Crop Biology, College of Agronomy, Shandong Agricultural University, Tai'an 271018, China.

Key Message: High-resolution genome-wide association study (GWAS) facilitated QTL fine mapping and candidate gene identification, and the GWAS based genomic prediction models were highly predictive and valuable in wheat genomic breeding. Wheat is a major staple food crop and provides more than one-fifth of the daily calories and dietary proteins for humans. Genome-wide association study (GWAS) and genomic selection (GS) for wheat stress resistance and tolerance related traits are critical to understanding their genetic architecture for improvement of breeding selection efficiency. However, the insufficient marker density in previous studies limited the utility of GWAS and GS in wheat genomic breeding. Here, we conducted a high-resolution GWAS for wheat leaf rust (LR), yellow rust (YR), powdery mildew (PM), and cold tolerance (CT) by genotyping a panel of 768 wheat cultivars using genotyping-by-sequencing. Among 153 quantitative trait loci (QTLs) identified, 81 QTLs were delimited to ≤ 1.0 Mb intervals with three validated using bi-parental populations. Furthermore, 837 stress resistance-related genes were identified in the QTL regions with 12 showing induced expression by YR and PM pathogens. Genomic prediction using 2608, 4064, 3907, and 2136 pre-selected SNPs based on GWAS and genotypic correlations between the SNPs showed high prediction accuracies of 0.76, 0.73, and 0.78 for resistance to LR, YR, and PM, respectively, and 0.83 for resistance to cold damage. Our study laid a solid foundation for large-scale QTL fine mapping, candidate gene validation and GS in wheat.
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http://dx.doi.org/10.1007/s00122-021-03863-6DOI Listing
June 2021

Red blood cell distribution width and serum CA-125 level as prognostic markers in acute exacerbation of chronic obstructive pulmonary disease.

J Int Med Res 2021 May;49(5):3000605211020229

Respiratory Department, Beijing Chaoyang District Shuangqiao Hospital, Beijing, China.

Objective: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a primary cause of hospitalization and death in COPD. Serum CA-125 and red blood cell distribution width (RDW) are related to AECOPD. We investigated correlations between serum markers and AECOPD.

Methods: In total, 132 patients with AECOPD were included from January 2017 to December 2019. Participants were followed for 1 year. Patients were assigned to the poor prognosis (n = 40) or good prognosis (n = 92) group. We collected serum samples and general clinical information and conducted routine blood tests. We used logistic regression, receiver operating characteristic (ROC), and area under the ROC curve (AUC) analyses to assess differences between groups.

Results: We found significant differences between groups (odds ratio, 95% confidence interval) for age (1.046, 1.005-1.09), RDW (2.012, 1.339-3.023), and cancer antigen 125 (CA-125; 1.022, 1.006-1.039); these remained risk factors for AECOPD prognosis in multivariate analyses. RDW and CA-125 in combination was significant in ROC curve analysis. The AUC of RDW, CA-125, and these combined were 0.691, 0.779, and 0.772, respectively. Patients with RDW >12.75% and CA-125 >15.65 U/mL were predicted to have poor prognosis.

Conclusions: We found that RDW and CA-125 are potential prognostic indicators for AECOPD.
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http://dx.doi.org/10.1177/03000605211020229DOI Listing
May 2021

An Aptamer-Based Antagonist against the Receptor for Advanced Glycation End-Products (RAGE) Blocks Development of Colorectal Cancer.

Mediators Inflamm 2021 5;2021:9958051. Epub 2021 May 5.

College of Biology, Hunan University, Changsha, China.

Tumor angiogenesis plays a crucial role in colorectal cancer development. Dysregulation of the receptor for the advanced glycation end-products (RAGE) transmembrane signaling mediates inflammation, resulting in various cancers. However, the mechanism of the RAGE signaling pathway in modulating development of colorectal cancer has not been explored. In this study, an aptamer-based RAGE antagonist (Apt-RAGE) was used to inhibit interaction between RAGE and S100B, thus blocking downstream NFB-mediated signal transduction. results showed that Apt-RAGE effectively inhibited S100B-dependent and S100B-independent RAGE/NFB activation in colorectal HCT116 cancer cells, thus decreasing proliferation and migration of cells. Notably, expression and secretion of VEGF-A were inhibited, implying that Apt-RAGE can be used as an antiangiogenesis agent in tumor therapy. Moreover, Apt-RAGE inhibited tumor growth and microvasculature formation in colorectal tumor-bearing mice. Inhibition of angiogenesis by Apt-RAGE was positively correlated with suppression of the RAGE/NFB/VEGF-A signaling. The findings of this study show that Apt-RAGE antagonist is a potential therapeutic agent for treatment of colorectal cancer.
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http://dx.doi.org/10.1155/2021/9958051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116144PMC
May 2021

Treatment for the Benign Childhood Epilepsy With Centrotemporal Spikes: A Monocentric Study.

Front Neurol 2021 6;12:670958. Epub 2021 May 6.

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China.

To date, there is no specific treatment guideline for the benign childhood epilepsy with centrotemporal spikes (BECTS). Several countries recommend levetiracetam, carbamazepine, sodium valproate, oxcarbazepine, and lamotrigine as first-line drugs. Nevertheless, some of these drugs are associated with cognitive decline. Available studies that investigated the efficacy of levetiracetam and sodium valproate on BECTS involved small sample sizes. This study aimed to evaluate the efficacy of levetiracetam and sodium valproate on cognition, and to investigate the prognostic factors for BECTS as whole. Clinical data and treatment status of all patients with BECTS at Xiangya Hospital, Central South University followed from 2008 to 2013 were analyzed retrospectively. Since electrical status epilepticus in sleep (ESES) has been confirmed to play a role in cognitive deterioration, in order to evaluate the response to drugs and their cognitive effects, we created two groups of patients according to the levels of spike wave index (SWI): group 1; 0-50% SWI and group 2; >50% SWI at the last follow up. A total of 195 cases were enrolled: 49.7% received monotherapies, 24.1% duotherapies and 27.2% polytherapies. Medications included; levetiracetam plus other drug (s) (75.9%), levetiracetam alone (32.8%), sodium valproate plus other drug (s) (31.3%), and sodium valproate alone (5.1%). After 2 years of treatment and follow up, 71% of the cases had a good seizure outcome, 15.9% had an improvement of SWI, and 91.7% had a normal DQ/IQ. Sodium valproate combined with levetiracetam, and sodium valproate alone correlated with good improvement of SWI, whereas, focal spikes were linked with poor improvement. For both groups (group 1 and group 2): monotherapy, levetiracetam alone, and a normal DQ/IQ at seizure onset correlated with good cognitive outcomes, in contrast, polytherapy, sodium valproate plus other drug (s), levetiracetam plus sodium valproate, an initial SWI of ≥85%, and multifocal spikes were linked to cognitive deterioration. Monotherapy, particularly levetiracetam seems to be a good first-line therapy which can help in normalizing the electroencephalograph and preventing cognitive decline. Polytherapy, mostly the administration of sodium valproate seems to relate with poor cognition, therefore, it is recommended to avoid it.
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http://dx.doi.org/10.3389/fneur.2021.670958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134665PMC
May 2021

An insight into the genome of a Listeria monocytogenes strain isolated from a bloodstream infection and phylogenetic analysis.

J Clin Lab Anal 2021 Jul 16;35(7):e23824. Epub 2021 May 16.

Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.

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http://dx.doi.org/10.1002/jcla.23824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274992PMC
July 2021

Development of a simplified and inexpensive RNA depletion method for plasmid DNA purification using size selection magnetic beads (SSMBs).

Genes Dis 2021 May 20;8(3):298-306. Epub 2020 May 20.

Ministry of Education Key Laboratory of Diagnostic Medicine, School of Laboratory and Diagnostic Medicine, Chongqing Medical University, Chongqing, 400016, PR China.

Plasmid DNA (pDNA) isolation from bacterial cells is one of the most common and critical steps in molecular cloning and biomedical research. Almost all pDNA purification involves disruption of bacteria, removal of membrane lipids, proteins and genomic DNA, purification of pDNA from bulk lysate, and concentration of pDNA for downstream applications. While many liquid-phase and solid-phase pDNA purification methods are used, the final pDNA preparations are usually contaminated with varied degrees of host RNA, which cannot be completely digested by RNase A. To develop a simple, cost-effective, and yet effective method for RNA depletion, we investigated whether commercially available size selection magnetic beads (SSMBs), such as Mag-Bind® TotalPure NGS Kit (or Mag-Bind), can completely deplete bacterial RNA in pDNA preparations. In this proof-of-principle study, we demonstrated that, compared with RNase A digestion and two commercial plasmid affinity purification kits, the SSMB method was highly efficient in depleting contaminating RNA from pDNA minipreps. Gene transfection and bacterial colony formation assays revealed that pDNA purified from SSMB method had superior quality and integrity to pDNA samples cleaned up by RNase A digestion and/or commercial plasmid purification kits. We further demonstrated that the SSMB method completely depleted contaminating RNA in large-scale pDNA samples. Furthermore, the Mag-bind-based SSMB method costs only 5-10% of most commercial plasmid purification kits on a per sample basis. Thus, the reported SSMB method can be a valuable and inexpensive tool for the removal of bacterial RNA for routine pDNA preparations.
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http://dx.doi.org/10.1016/j.gendis.2020.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093646PMC
May 2021

Combining Serum DNA Methylation Biomarkers and Protein Tumor Markers Improved Clinical Sensitivity for Early Detection of Colorectal Cancer.

Int J Genomics 2021 21;2021:6613987. Epub 2021 Apr 21.

Department of Clinical Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, Jiangsu 210014, China.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide and in China. Early CRC screening is the best approach to reduce its incidence and mortality rates. The ColoDefense test, a multiplex qPCR assay simultaneously detecting both methylated and genes, has demonstrated improved clinical performance on either methylation biomarker alone for CRC screening with both blood and stool samples.

Method: Leftover blood chemistry test samples from 125 CRC, 35 advanced adenoma, and 35 small polyp patients and 92 healthy control subjects were examined by the ColoDefense test. Among these samples, the levels of three circulating tumor markers, CEA, AFP, and CA19-9, were also measured for 106 CRC, 28 advanced adenoma, and 20 small polyp patients and all control subjects.

Results: Due to the smaller volume and extended storage in nonfrozen state, the ColoDefense test with these samples exhibited reduced performance for all stages of CRC and advanced adenomas. The performance of CEA, AFP, and CA19-9 and their various combinations was also evaluated for CRC screening to identify the tumor marker combinations with the best performance. When combined with the ColoDefense test, the identified combinations did improve the clinical performance.

Conclusion: These results suggested a rational path towards developing a CRC screening method that takes advantage of leftover blood chemistry test samples. The successful development of such a method will undoubtedly help promote early CRC screening by increasing its accessibility for the general public.
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http://dx.doi.org/10.1155/2021/6613987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084680PMC
April 2021

External application of N alleviates toxicity of Cd on poplars via starch and sucrose metabolism.

Tree Physiol 2021 May 7. Epub 2021 May 7.

College of Landscape Architecture, Sichuan Agricultural University, Chengdu 611130, China.

Phytoremediation technology can help achieve moderate cost and considerable effect, with respect to the remediation of heavy metal pollution in soil and water. Many previous studies have suggested the role of N in the alleviation of effects of heavy metal on plants. Herein, we sought to determine the molecular mechanisms by which additional N supplementation mitigates Cd toxicity in poplars using a combination of physiological, transcriptomic, and phosphoproteomic analyses. The application of N can alleviate the toxicity of Cd to Populus by reducing chlorophyll degradation, maintaining the stability of ions inside and outside the cell membrane, and increasing the soluble sugar content. Plant samples from the control (CK), Cd stress, and Cd_N treatments were used for an integrated analysis of the transcriptome, as well as for phosphoproteomics analysis. Moreover, 1,314 differentially expressed genes (DEGs) and 119 differentially expressed kinase genes were discovered. Application of additional N under Cd stress promoted the phosphorylation process. Furthermore, 51 significantly enriched phosphorylated protein sites and 23 differentially expressed kinases were identified using phosphoproteomic and proteomic analyses. Importantly, transcriptomic and phosphoproteomic analyses jointly determined that the application of N could activate corresponding gene expression [UDP-glucose-dehydrogenase (UGD), GAUT, PME, pectin lyase, UDP-glucose-pyrophosphorylase 2 (UGP2), sucrose phosphate synthase (SPS), SUS, and SPP2] and protein phosphorylation (UGP2 and SPS) in the sugar and starch synthesis pathways, which promoted the synthesis of sucrose and soluble sugar and subsequently alleviated the damage caused by Cd.
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http://dx.doi.org/10.1093/treephys/tpab065DOI Listing
May 2021
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