Publications by authors named "Wei-Ping Li"

180 Publications

Phragmunis a suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Neurochem Int 2021 Jul 9;147:105051. Epub 2021 May 9.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen, 518035, China. Electronic address:

Glioblastoma (GBM) is a highly aggressive brain tumor. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Studies investigating the mechanism revealed that PGA diminished the binding efficiency of ETS family of transcription factor (ELK1) and Serum response factor (SRF), and suppressed ELK1-SRF complex-dependent transcription, which decreased the transcriptional levels of downstream genes Early growth response protein 1 (EGR1)-Polycomb ring finger (BMI1), thus inducing the imbalanced regulation between Myeloid cell leukaemia-1 (MCL1) and F-Box and WD repeat domain containing 7 (FBXW7). Finally, orthotopic xenograft models were established to confirm the anti-glioma effect of PGA on tumour growth. We showed, for the first time, that the cytotoxic effects of PGA occurred by inducing MCL1 inhibition and FBXW7 activation by blocking ELK1-SRF complex-dependent transcription. The blockage of ELK1-mediated transcription resulted in the suppression of EGR1-BMI1, which led to the upregulation of FBXW7 expression and downregulation of MCL1. These findings suggested that PGA could be a therapeutic drug candidate for the treatment of recurrent GBM by targeting the ELK1-SRF complex.
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http://dx.doi.org/10.1016/j.neuint.2021.105051DOI Listing
July 2021

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report.

World J Clin Cases 2021 Apr;9(12):2899-2907

Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Background: QT interval prolongation can induce torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Recently, an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset. Moreover, recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome (LQTS) and TdP development.

Case Summary: A 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks. The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein. Once after a high fever, the patient suddenly lost consciousness, and electrocardiogram (ECG) showed transient TdP onset after frequent premature ventricular contraction. The patient recovered sinus rhythm and consciousness spontaneously, and post-TdP ECG revealed a prolonged QTc interval of 560 ms. The patient's clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still's disease (AOSD). There was no evidence of cardiac involvement. After the AOSD diagnosis, discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval. The genetic analysis identified that the patient and her father had heterozygous mutations in (c.1370C>T) and (c.7725A>C). During the 2-year follow-up period, the patient had no recurrence of any arrhythmia and maintained normal QTc interval.

Conclusion: This case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset. Genetic analysis should be considered to identify individuals at high risk of developing TdP.
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http://dx.doi.org/10.12998/wjcc.v9.i12.2899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058677PMC
April 2021

Moschamindole induces glioma cell apoptosis by blocking Mia40-dependent mitochondrial intermembrane space assembly and oxidative respiration.

Phytother Res 2021 Jun 15;35(6):3390-3405. Epub 2021 Apr 15.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Glioblastoma multiforme (GBM) is the most frequent, lethal, and aggressive tumor of the central nervous system in adults. In this study, we found for the first time that moschamindole (MCD), a rare phenolic amide with 8/6/6/5/5 rings, is a major bioactive constituent derived from Phragmites communis Trin (Poaceae) that exhibits a potential cytotoxic effect on both TMZ-resistant GBM cell lines and xenograft models. MCD-induced intrinsic apoptosis signals and mitochondrial dysfunction were confirmed by cell cycle arrest, caspase-3/7 activation, and membrane potential depolarization. Furthermore, investigations exploring the mechanism showed that MCD specifically inhibits Mia40-mediated oxidative folding of mitochondrial intermembrane space (IMS) proteins via PCR assay and immunoblot analysis. MCD relies on its positive charge to associate with mitochondrial oxidative respiration, thus blocking energy metabolism and inducing apoptosis. Overexpression and upregulation of Mia40 were proven to reverse MCD-induced apoptosis and were correlated with the chemoresistance of GBM in vitro and in vivo, respectively. Taken together, our study demonstrates that Mia40 is a potential target of the chemoresistance of glioblastoma and suggests that MCD might be a potential agent for the individualized treatment of chemoresistant GBM based on mitochondrial metabolic characteristics and Mia40 expression.
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http://dx.doi.org/10.1002/ptr.7061DOI Listing
June 2021

[Distribution Characteristics of Microplastics in Ice Sheets and Its Response to Salinity and Chlorophyll a in the Lake Wuliangsuhai].

Huan Jing Ke Xue 2021 Feb;42(2):673-680

Inner Mongolia Water Saving Agricultural Engineering Research Center, Inner Mongolia Normal University, Hohhot 010022, China.

There are sparse reports on the distribution of microplastics in the ice sheets of freshwater lakes. In this study, the abundance, color, shape, and species of microplastics in the ice sheet of Lake Wuliangsuhai were characterized using field sampling and microscope observations. Fourier-transform infrared spectroscopy (FTIR) and correlation analysis were used to examine the distribution of microplastics contained in the lake and its relationships with salinity and chlorophyll a. The results show that the average abundance of microplastics in the Lake Wuliangsuhai ice sheet is 56.75-141 n·L, which is approximately 10-100 times higher than in the surface water of the Lake Wuliangsuhai. Fibers were the most common type of microplastics followed by fragments. Overall abundance showed a decreasing trend in the downstream horizontal direction and was positively correlated with salinity in the vertical direction. The abundance of microplastic in the surface ice and bottom ice was greater than in the middle of the ice and near bottom of the ice. There was no correlation between the abundance of microplastic and the concentration of chlorophyll a. In addition, due to the capturing effect of the ice, microplastic particles are temporarily stored in the ice sheet in winter, which are released into water in spring. This study provides baseline information to inform microplastic pollution control measures in Lake Wuliangsuhai.
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http://dx.doi.org/10.13227/j.hjkx.202007042DOI Listing
February 2021

[Contents determination of eight phenolic compounds in Perilla frutescens leaves of different cultivation years and harvesting periods].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):567-574

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College Beijing 100193, China.

A method was established for content determination of two kinds of phenolic acids, including rosmarinic acid)(RA) and caffeic acid(CA), and six kinds of flavonoids including scutellarein-7-O-diglucuronide(SDG), luteolin-7-O-diglucuronide(LDG), apigenin-7-O-diglucuronide(ADG), scutellarin-7-O-glucuronide(SG), luteolin-7-O-glucuronide(LG), and apigenin-7-O-glucuronide(AG) in Perilla frutescens leaves. The content of eight chemical components was measured based on ten P. frutescens germplasms of different chemotypes of volatile oil, different cultivated years, and different harvesting periods. The results showed that there was a great difference between the two kinds of constituents of different germplasms. The total content of the two phenolic acids was 2.24-34.44 mg·g~(-1), and the total content of the six flavonoids was 11.55-34.71 mg·g~(-1). Then according to content from most to least, the order of each component was RA(2.13-33.97 mg·g~(-1)), LDG(1.31-14.80 mg·g~(-1)), SG(1.97-8.45 mg·g~(-1)), ADG(2.68-7.60 mg·g~(-1)), SDG(1.16-5.87 mg·g~(-1)), LG(0.78-1.91 mg·g~(-1)), AG(0.56-1.00 mg·g~(-1)), and CA(0.11-0.68 mg·g~(-1)). The chemical contents of the 5 PA-type germplasms in 2017 were mostly higher than those in 2018 showing a large variation with the cultivation years. These contents of two kinds of phenolic acids of 9 germplasms fluctuated with the harvesting time. The content decreased before early flower spike(the 3~(rd) to 18~(th) in August) at first and began to increase in flowering and fruiting period(the 18~(th) in August to 2~(nd) in September). However, these contents had slowly decreasing trend after 2~(nd) in September till 17~(th) in the same month. Interestingly, the content raised again in the maturity of fruits. The variation tendency of contents in six kinds of flavonoids components was inconsistent in different germplasms with the variation of harvesting time. The content of flavonoids in part of germplasms was negatively correlated with the fluctuation of phenolic acids. There was no correlation between phenolic acids and chemical type of the volatile oil. This paper may provide a reference for the high-quality germplasm of P. frutescens cultivation.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201114.101DOI Listing
February 2021

H-Plasty Repair Technique Improved Tibiofemoral Contact Mechanics After Repair for Adjacent Radial Tears of Posterior Lateral Meniscus Root: A Biomechanical Study.

Arthroscopy 2021 Feb 20. Epub 2021 Feb 20.

Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P. R. China.

Purpose: To compare the time-zero tibiofemoral contact mechanics among the 4 different suturing repairs: transtibial pullout suture repair, suture anchor repair, side-to-side repair, and H-plasty repair.

Methods: Twenty-four human cadaveric knees were included. Each lateral meniscus condition (intact, radial tear, and repair) was tested under a 1000-N axial compressive load at 0°, 30°, 60°, and 90° of flexion. Four different repair techniques, transtibial pullout, suture anchor, side-to-side, and H-plasty repair technique, were tested. Tibiofemoral mean and peak contact pressure and contact area in the lateral and medial compartments were measured by Tekscan sensors.

Results: Radial tears adjacent to the posterior lateral meniscus root produced significantly decreased contact area and increased mean and peak contact pressures in the lateral compartment across all angles (P < .05). All repair groups could improve the contact mechanics relative to the torn condition (P < .05), but only H-plasty repair showed no significant difference in the mean and peak contact pressure and contact area compared with that of the intact state at all flexion angles (P > .05).

Conclusions: The results showed that the tibiofemoral contact mechanics after adjacent radial tears of the posterior lateral meniscal root were improved to the intact level by H-plasty repair at time-zero. The additional vertical mattress sutures act as "stabilizers" to provide a more stable environment in distributing vertical tibiofemoral pressure. The other 3 repair techniques also significantly improved lateral tibiofemoral contact mechanics relative to the corresponding tear conditions.

Clinical Relevance: The results of this study suggest that H-plasty repair can restore the biomechanical properties to the intact state. Since it was a time-zero cadaveric study, the results should be carefully used in clinical practices.
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http://dx.doi.org/10.1016/j.arthro.2021.02.017DOI Listing
February 2021

Using extended complexity theory to test SMEs' adoption of Blockchain-based loan system.

PLoS One 2021 5;16(2):e0245964. Epub 2021 Feb 5.

Railway Police College, Zhengzhou, China.

Blockchain-based loan system can be summed up as: information exchange between various government departments; information exchange between enterprises and various financial institutions; detection of the actual use of loans in the form of encrypted currency. This technology is supposed to reduce a lot of financing costs for SMEs on average. Therefore, this research extends complexity theory to discover the factors that affect the use of Blockchain loan systems by SMEs. Complexity, perceived risk, perceived fairness and reward sensitivity prove to have significant effects on usage intention. Complexity proves to have moderating effects on other relationships. This research may contribute to the system performance improvement and provide opportunities for SMEs to share information with financial institutions or individuals around the world, thereby providing investors with equal opportunities for competition.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245964PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864469PMC
February 2021

Cassane diterpenoid derivative induces apoptosis in IDH1 mutant glioma cells through the inhibition of glutaminase in vitro and in vivo.

Phytomedicine 2021 Feb 11;82:153434. Epub 2020 Dec 11.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China. Electronic address:

Background: Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system in adults. The discovery of novel anti-GBM agents based on the isocitrate dehydrogenase (IDH) mutant phenotypes and classifications have attracted comprehensive attention.

Purpose: Diterpenoids are a class of naturally occurring 20-carbon isoprenoid compounds, and have previously been shown to possess high cytotoxicity for a variety of human tumours in many scientific reports. In the present study, 31 cassane diterpenoids of four types, namely, butanolide lactone cassane diterpenoids (I) (1-10), tricyclic cassane diterpenoids (II) (11-15), polyoxybutanolide lactone cassane diterpenoids (III) (16-23), and fused furan ring cassane diterpenoids (IV) (24-31), were tested for their anti-glioblastoma activity and mechanism underlying based on IDH1 mutant phenotypes of primary GBM cell cultures and human oligodendroglioma (HOG) cell lines.

Results: We confirmed that tricyclic-type (II) and compound 13 (Caesalpin A, CSA) showed the best anti-neoplastic potencies in IDH1 mutant glioma cells compared with the other types and compounds. Furthermore, the structure-relationship analysis indicated that the carbonyl group at C-12 and an α, β-unsaturated ketone unit fundamentally contributed to enhancing the anti-glioma activity. Studies investigating the mechanism demonstrated that CSA induced oxidative stress via causing glutathione reduction and NOS activation by negatively regulating glutaminase (GLS), which proved to be highly dependent on IDH mutant type glioblastoma. Finally, GLS overexpression reversed the CSA-induced anti-glioma effects in vitro and in vivo, which indicated that the reduction of GLS contributed to the CSA-induced proliferation inhibition and apoptosis in HOG-IDH1-mu cells.

Conclusion: Therefore, the present results demonstrated that compared with other diterpenoids, tricyclic-type diterpenoids could be a targeted drug candidate for the treatment of secondary IDH1 mutant type glioblastoma through negatively regulating GLS.
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http://dx.doi.org/10.1016/j.phymed.2020.153434DOI Listing
February 2021

Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation.

Cancer Cell Int 2021 Jan 6;21(1):24. Epub 2021 Jan 6.

Department of Neurosurgery, Shenzhen Second People's Hospital/the First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518035, China.

Background: Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110β (PI3Kβ) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kβ.

Methods: To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient's specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kβ inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated.

Results: MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients' specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kβ and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin.

Conclusion: Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kβ and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.
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http://dx.doi.org/10.1186/s12935-020-01728-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789614PMC
January 2021

Tibiofemoral Contact Mechanics After Horizontal or Ripstop Suture in Inside-Out and Transtibial Repair for Meniscus Radial Tears in a Porcine Model.

Arthroscopy 2021 03 20;37(3):932-940.e2. Epub 2020 Nov 20.

Department of Orthopedics, Sun Yat sen Memorial Hospital, Sun Yat sen University, Guangzhou, P. R. China. Electronic address:

Purpose: To compare tibiofemoral contact mechanics after horizontal or ripstop (horizontal plus vertical) sutures in inside-out and transtibial repair for meniscal radial tears with 10 porcine knees in each group.

Methods: Ten matched pairs of porcine knees were tested under a 1500-N axial compressive load at 0°, 30°, 60°, and 90° of knee flexion. Each knee underwent 4 testing conditions consecutively: (1) intact, (2) medial meniscal radial tear, (3) horizontal suture repair configuration, and (4) ripstop suture repair configuration. Tekscan sensors measured tibiofemoral contact pressure and contact area in the medial and lateral compartments.

Results: All repair groups improved their contact mechanics when compared with the tear state among all flexion angles analyzed (all P < .05). Furthermore, ripstop sutures with both inside-out and transtibial repairs restored intact knee contact area and pressures (peak and mean) in the medial compartment at all flexion angles, whereas the horizontal sutures alone failed to do so for contact pressures at 60° and 90° and for contact surface areas at all flexion angles. However, the aforementioned parameters were not significantly different between inside-out sutures and transtibial sutures, regardless of horizontal or ripstop configuration (P > .05).

Conclusions: Radial tears of the meniscus in a porcine model significantly decreased medial contact area and increased mean and peak contact pressure. Both inside-out and transtibial ripstop repairs for radial tears aid in restoring intact tibiofemoral contact mechanics at all assessed knee flexion angles.

Clinical Relevance: Our results suggest that both inside-out and transtibial ripstop repairs for radial tears can restore tibiofemoral contact mechanics to the intact state. Since the study were performed in an open fashion porcine model, the results should be carefully used in clinical practices, and the efficacy of the techniques through arthroscopic method should be further explored.
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http://dx.doi.org/10.1016/j.arthro.2020.10.031DOI Listing
March 2021

[Thrombolytic effects of recombinant staphylokinase on coronary thrombosis in miniature pigs].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Jul;36(4):369-374

Yueyang Vocational and Technical College, Yueyang 414000.

Objective: To evaluate the thrombolytic effects of recombinant staphylokinase and compare it with those of recombinant streptokinase.

Methods: Thirty Chinese experimental miniature pigs were divided into five groups, namely, solvent control group, positive drug control group and three recombinant staphylokinase groups, six in each group. The thrombus of coronary artery was formed by surgical thoracotomy and direct current stimulation in anesthetized animals. Intravenous administration was started after the thrombus of coronary artery was formed for 30 minutes, and the method of first injection and then constant speed infusion by peristaltic pump was used. The solvent control group was injected intravenously with solvent, the positive drug control group was given recombinant streptokinase 4 mg·kg intravenously, and the three recombinant staphylokinase groups were given recombinant staphylokinase at the doses of 4, 2 and 1 mg.kg intravenously. The volume of intravenous injection was 5 ml, which was completed within 1 min, the speed of infusion was 0.5 ml·min, which was completed within 60 min, and the animals were sacrificed 120 minutes later. Before and 30, 60 and 120 min after administration, the venous blood samples were collected. At the end of the experiment, the coronary artery segments of the thrombosis site were taken, and the euglobulin dissolution time (ELT), blood fibrinogen content (FBG), fibrinogen degradation product (FDP) and wound bleeding volume were measured respectively. The coronary thrombolysis rate, myocardial ischemia degree and ischemia range were measured.

Results: Compared with the solvent control group, ELT in the experimental group was significantly shortened (<0.05 or <0.01), FBG degradation in a few experimental animals was more than 20%, FDP was significantly increased (<0.05 or <0.01), and there was no significant effect on blood pressure and heart rate of small pigs. Compared with the control group, the maximum thrombus area was decreased by 34.3% and 15.4% (<0.05) in the high and middle dose groups of the experimental group. Compared with the same dose of recombinant streptokinase, recombinant staphylokinase had stronger thrombolytic effect (<0.05 or <0.01) on the coronary thrombus caused by electrical stimulation, less bleeding side effects and the same effect on the degree and range of myocardial infarction as recombinant streptokinase.

Conclusion: Compared with recombinant streptokinase, recombinant staphylokinase has faster thrombolysis speed, higher fibrin specificity and less bleeding side effects. In general, 2 mg.kg recombinant staphylokinase has better efficacy and safety.
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http://dx.doi.org/10.12047/j.cjap.5994.2020.079DOI Listing
July 2020

[Occurrence Characteristics and Quality Estimation of Microplastics in Drainage Ditches in Hetao Irrigation District of Inner Mongolia].

Huan Jing Ke Xue 2020 Oct;41(10):4590-4598

Inner Mongolia Irrigation and Drainage Development Center, Hohhot 010020, China.

Microplastic pollution due to land runoff has gained increasing attention as it is closely associated with human beings. In this study, we analyzed the occurrence characteristics of microplastics in drainage channel and main drainage channel in Hetao irrigation district of Inner Mongolia and estimated its quality. Through field sampling, the density separation of suspension method and microscope observation, Fourier infrared spectrum measurement, and proportional flow method, the abundance distribution, shape, color, particle size, and chemical composition of microplastics in the water body and sediment of the drainage channel and main drainage channel in the Hetao irrigation district were identified. The mass of microplastics transported in the main drainage channel was also estimated. The results showed that the value range of microplastic abundance in the water body of the drainage channel and the main drainage channel in Hetao irrigation district was 2880-11200 n ·m, and the value range of microplastic abundance in the sediment was 100-292 n ·kg. Fiber was the most common microplastic form, occupying 34.98%-70.39% and 42.24%-58.56% in the water and sediment, respectively. The color of microplastics was mainly transparent, which occupied 46.43%-61.51% and 40.41%-57.44% in the water and sediment, respectively. The largest particle size of microplastics was<0.5 mm, accounting for 46.43%-61.51% and 43.27%-54.79% in the water and sediment microplastics, respectively. It was concluded that polyethylene was the most common type (43%), followed by polystyrene (34%) and polypropylene (16%) using Fourier infrared spectroscopy. It was estimated that the main drainage channel in the Hetao irrigation district could transport 116.06 kg of microplastics into Lake Ulansuhai every day, and a serious microplastic pollution effect was generated due to the accumulation of microplastics in Lake Wulangsuhai. This study can provide reference for the pollution of microplastics in Hetao irrigation district of Inner Mongolia.
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http://dx.doi.org/10.13227/j.hjkx.202003259DOI Listing
October 2020

The role of adjuvant chemotherapy in stage I-III male breast cancer: a SEER-based analysis.

Ther Adv Med Oncol 2020 20;12:1758835920958358. Epub 2020 Sep 20.

Department of Breast Cancer, Cancer Centre, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, No.123 Huifu West, Yuexiu District, Guangzhou510080, China.

Background And Aims: Male breast cancer is an uncommon disease. The benefit of adjuvant chemotherapy in the treatment of male breast cancer patients has not been determined. The aim of this study was to explore the value of adjuvant chemotherapy in men with stage I-III breast cancer, and we hypothesized that some male patients may safely skip adjuvant chemotherapy.

Methods: Male breast cancer patients between 2010 and 2015 from the Surveillance Epidemiology and End Results database were included. Univariate and multivariate Cox analyses were used to analyse the factors associated with survival. The propensity score matching method was adopted to balance baseline characteristics. Kaplan-Meier curves were used to evaluate the impacts of adjuvant chemotherapy on survival. The primary endpoint was survival.

Results: We enrolled 514 patients for this study, including 257 patients treated with chemotherapy and 257 patients without. There was a significant difference in overall survival (OS) but not in breast cancer-specific survival (BCSS) between the two groups ( < 0.001 for OS and  = 0.128 for BCSS, respectively). Compared with the non-chemotherapy group, the chemotherapy group had a higher 4-year OS rate (97.5% 95.2%,  < 0.001), while 4-year BCSS was similar (98% 98.8%,  = 0.128). The chemotherapy group had longer OS than the non-chemotherapy group among HR+, HER2-, tumour size >2 cm, lymph node-positive male breast cancer patients ( < 0.05). Regardless of tumour size, there were no differences in OS or BCSS between the chemotherapy and non-chemotherapy cohorts for lymph node-negative patients (OS:  > 0.05, BCSS:  > 0.05). Adjuvant chemotherapy showed no significant effects on both OS and BCSS in patients with stage I (OS:  = 0.100, BCSS:  = 0.858) and stage IIA breast cancer (OS:  > 0.05, BCSS:  > 0.05).

Conclusion: For stage I and stage IIA patients, adjuvant chemotherapy could not improve OS and BCSS. Therefore, adjuvant chemotherapy might be skipped for stage I and stage IIA male breast cancer patients.
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http://dx.doi.org/10.1177/1758835920958358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509722PMC
September 2020

A novel surgical technique for arthroscopic repair of type II posterior lateral meniscal root tear.

Knee 2020 Oct 30;27(5):1560-1566. Epub 2020 Aug 30.

Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China. Electronic address:

Background: Several suture repair techniques have been reported for radial tear close to the posterior lateral meniscal root (type II PLMRT). However, no study has evaluated the clinical results after repair using the FasT-Fix system. This paper describes a novel H-plasty surgical repair technique and reports its clinical results.

Methods: From January 2015 to January 2017, 47 patients underwent repair of type II PLMRT with concomitant anterior cruciate ligament reconstruction and were included in this study. Assessments performed preoperatively and at final follow-up included the Lysholm score, subjective International Knee Documentation Committee (IKDC) score, and knee stability assessments (pivot-shift test, Lachman test, KNEELAX arthrometer side-to-side difference). Magnetic resonance imaging was used to compare the lateral meniscal extrusion pre- versus postoperatively. Second-look arthroscopy was performed to evaluate the meniscal healing in 38 cases.

Results: Forty-seven patients were followed up for an average of 30.7 months (range 18-46 months). No patients experienced meniscal mechanical symptoms. At final follow-up, there were significant improvements in the Lysholm score, IKDC score, knee stability assessments, and lateral meniscal extrusion compared with the preoperative values. In the 38 of 47 patients that underwent second-look arthroscopy after an average of 17.5 months (range 14-19 months), all repairs (100%) were completely healed.

Conclusions: The novel H-plasty repair using the FasT-Fix system was an effective surgical treatment for type II PLMRT. Considering the satisfactory clinical results and the convenience of the surgery, H-plasty repair is recommended to be used preferentially.
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http://dx.doi.org/10.1016/j.knee.2020.07.100DOI Listing
October 2020

Adjuvant chemotherapy could benefit early-stage ER/PR positive mucinous breast cancer: A SEER-based analysis.

Breast 2020 Dec 9;54:79-87. Epub 2020 Sep 9.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Purpose: The aim of this study was to explore the value of adjuvant chemotherapy in patients with early-stage ER/PR-positive mucinous carcinoma.

Methods: We identified early-stage ER/PR-positive mucinous carcinoma patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity-score matching (PSM) analysis to eliminate selection bias and differences in baseline characteristics. Univariate and multivariate analyses were performed to identify significant prognostic factors. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS), which were evaluated with the Kaplan-Meier method.

Results: After propensity score matching, 805 pairs were selected. Patients with early-stage ER/PR-positive mucinous adenocarcinoma in the chemotherapy group had a better OS, but not BCSS, than those in the nonchemotherapy group after PSM (OS: p < 0.001; BCSS: p = 0.285). After stratifying by tumor size and lymph node status, adjuvant chemotherapy could significantly improve the OS of early-stage ER/PR-positive patients with tumors larger than 3 cm (p = 0.004) if they had negative lymph nodes (LNs). For patients positive LNs, the OS was significantly different between the chemotherapy group and the non-chemotherapy group when the tumors were larger than 1 cm (T = 1-2.9 cm, p = 0.006; T>3 cm, p = 0.049, respectively).

Conclusion: Adjuvant chemotherapy maybe improves prognosis in patients with negative LNs and tumors larger than 3 cm, or patients with LNs metastasis and tumors larger than 1 cm. We suggest considering clinical characteristics meanwhile when deciding chemotherapy or not. Randomized controlled trials (RCT) are expected to confirm our results in the future.
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http://dx.doi.org/10.1016/j.breast.2020.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502365PMC
December 2020

All-Inside Arthroscopic Modified Broström Technique to Repair Anterior Talofibular Ligament Provides a Similar Outcome Compared With Open Broström-Gould Procedure.

Arthroscopy 2021 01 7;37(1):268-279. Epub 2020 Sep 7.

Department of Orthopedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangdong, People's Republic of China. Electronic address:

Purpose: To introduce an all-inside modified Broström technique to suture the anterior talofibular ligament (ATFL) and inferior extensor retinaculum (IER) under arthroscopy and to compare its outcomes with those of the conventional open procedure.

Methods: All patients who underwent arthroscopic or open repair of the ATFL between June 2014 and December 2017 were included in this study. Visual analog scale (VAS), Karlsson and Peterson (K-P), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot, and Tegner activity scores, as well as manual anterior drawer test (ADT), were used to evaluate the patients preoperatively and ≥2 years after surgery. The Sefton grading system was used to assess the level of satisfaction after surgery. Detailed surgical data and intraoperative findings were documented at the time of surgery.

Results: A total of 67 patients, 31 in the arthroscopic group and 36 in the open group, were included in this study (43 men and 24 women, mean body mass index 24.00, range 19.53 to 30.03). The surgical duration in the arthroscopic group (median, 34 minutes; range, 25 to 74) was significantly shorter than that in the open group (mean, 43.08 ± 8.11 minutes; 95% confidence interval [CI] 40.34 to 45.83) (P = .007). At the last follow-up, the subjective functional scores and ADT results improved significantly in both cohorts (P < .001). However, no significant difference was found in the VAS score (1.74 ± 1.24, 95% CI 1.29 to 2.2, in the open group versus 1.58 ± 1.2, 95% CI 1.18 to 1.99, in the arthroscopic group; P = .581), AOFAS score (91.71 ± 5.46, 95% CI 89.71 to 93.71, versus 90.67 ± 5.59, 95% CI 88.78 to 92.56; P = .444), K-P score (87.52 ± 7.59, 95% CI 84.73 to 90.3, versus 88.75 ± 5.56, 95% CI 86.87 to 90.63; P = .446), and ADT evaluation (normal: 96.77% versus 94.44%, P = .557) between the arthroscopic and open groups, respectively. In addition, 28 cases (90.32%) in the arthroscopic group and 32 (88.89%) in the open group achieved satisfactory results based on the Sefton grading system (P = .736). Seventeen patients (47.2%) in the open group and 18 patients (58.1%) in the arthroscopic group underwent Tegner evaluation after surgery, which showed no significant difference (5, interquartile range [IQR] 1 in the open group versus 5, IQR 3 in the arthroscopic group; P = .883). Complications were reported in 4 (11.1%) and 2 (6.5%) patients who underwent open and arthroscopic surgeries, respectively (P = .813).

Conclusions: Both open and arthroscopic modified Broström surgeries generated favorable outcomes, with a significant improvement compared with the preoperative condition. Compared with the open Broström-Gould procedure, the all-inside arthroscopic modified Broström technique produced equivalent functional and clinical results at a minimum of 2 years after the operation, with a shorter surgical duration. Arthroscopic repair might be a safe and viable alternative to open surgery for lateral ankle stabilization.

Level Of Evidence: III.
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http://dx.doi.org/10.1016/j.arthro.2020.08.030DOI Listing
January 2021

Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis.

Cell Death Dis 2020 07 6;11(7):503. Epub 2020 Jul 6.

Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.

Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 μM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.
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http://dx.doi.org/10.1038/s41419-020-2710-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338517PMC
July 2020

[Planting density of Perilla frutescens PA-type].

Zhongguo Zhong Yao Za Zhi 2020 Apr;45(7):1627-1632

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100193, China.

Two medicinal PA type Perilla germplasms were planted at five planting densities(D1,2 500 plants/Mu;D2,5 500 plants/Mu;D3,8 500 plants/Mu;D4,11 500 plants/Mu;D5,14 500 plants/Mu;1 Mu≈667 m~2). A total of 17 traits, including leaf shape, plant type, yield, volatile oil content and composition, were recorded and studied. With the planting density increased, the leaves appeared narrow, plants small, the deciduous leaves increased, and the leaf yield per plant was low, but the leaf yield per Mu increases significantly with the planting density, and was basically stable after reaching D4. The extraction rate of volatile oil from leaves at planting density D2-D5 was about 0.1% higher than that of D1, and there was no significant difference in the relative content of perillaldehyde, among 5 density. In order to achieve high leaf yield, it is recommended to plant at a density of D4, 11 500 plants/Mu(plant spacing is 15 cm, and row spacing is 40 cm); while comprehensive leaf yield and leaf morphology are recommended to be planted at a density of D2, 5 500 plants/Mu(plant spacing is 30 cm, and row spacing is 40 cm). At the same time, dense planting resistance of two germplasms were different. Number of secondary branches, first section with leaves and plant types were most important feature for the evaluation of the density tolerance of PA-type Perilla. This study provided a reference for the suitable density of PA-type Perilla, and laid a foundation for further study of the tolerance characteristics of different Perilla.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200205.103DOI Listing
April 2020

Risk of breast cancer-related death in women with a prior cancer.

Aging (Albany NY) 2020 04 6;12(7):5894-5906. Epub 2020 Apr 6.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P.R. China.

The overall risk of developing a second primary cancer is increasing. The purpose of this study was to analyze the survival of patients with breast cancer diagnosed after a prior cancer and identify risk factors of breast cancer death in this population. Using the SEER database, we identified 1,310 woman diagnosed with breast cancer between 2010 and 2015 after a prior cancer as the primary cohort. Clinicopathological characteristics were compared using the Student -test and chi-square test. Fine and Gray's regression was used to evaluate the effect of treatments on breast cancer death. After propensity score matching (PSM), 9,845 pairs of patients with breast cancer as the prior or second cancer diagnosed between 2010 and 2011 were included as a second cohort. PSM-adjusted Kaplan-Meier and Cox hazards models were used to evaluate the impact of prior cancer on survival. The results showed that survivors of gynecologic cancers (e.g., ovarian cancer) had a higher risk of developing breast cancer than survivors of gastrointestinal and urinary tract cancers. More patients died of breast cancer than of prior urinary cancer (53.3% vs. 40%, P < 0.05) and melanoma (66.7% vs. 33.3%, P < 0.05). The ratio of breast cancer deaths to prior cancer deaths was significantly higher in patients with diagnoses interval ≥ 3 years than in those with the interval < 3 years (2.67 vs. 0.69, P < 0.001). Breast cancer-specific survival and overall survival rates were significantly lower in women with breast cancer as the second primary cancer than in those with breast cancer as the prior cancer, especially among hormone receptor-positive women. However, breast cancer treatment decreased the risk of breast cancer -specific death (hazard ratio = 0.695, 95% confidence interval: 0.586-0.725, P < 0.001). Breast cancer patients with prior cancers must be carefully considered for clinical trials.
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http://dx.doi.org/10.18632/aging.102984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185107PMC
April 2020

Depletion of Microglia Attenuates Dendritic Spine Loss and Neuronal Apoptosis in the Acute Stage of Moderate Traumatic Brain Injury in Mice.

J Neurotrauma 2020 01 18;37(1):43-54. Epub 2019 Sep 18.

Brain Center, Shenzhen Key Laboratory of Neurosurgery, The First Affiliated Hospital of Shenzhen University, Second People's Hospital, Shenzhen, Guangdong, China.

Microglia are the primary immune cells in the central nervous system and undergo significant morphological and transcriptional changes after traumatic brain injury (TBI). However, their exact contribution to the pathogenesis of TBI is still debated and remains to be elucidated. In the present study, thy-1 GFP mice received a colony-stimulating factor 1 receptor inhibitor (PLX3397) for 21 consecutive days, then were subjected to moderate fluid percussion injury (FPI). Brain samples were collected at 1 day and 3 days after FPI for flow cytometry analysis, immunofluorescence, dendrite spine quantification, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and Western blot. We found that PLX3397 treatment significantly attenuated the percentages of resident microglia and infiltrated immune cells. Depletion of microglia promoted neurite outgrowth, preserved dendritic spines and reduced total brain cell and neuronal apoptosis after FPI, which was accompanied by decreased the protein levels of endoplasmic reticulum stress marker proteins, C/EBP-homologous protein and inositol-requiring kinase 1α. Taken together, these findings suggest that microglial depletion may exert beneficial effects in the acute stage of FPI.
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http://dx.doi.org/10.1089/neu.2019.6460DOI Listing
January 2020

Effect of astragalosides on long non-coding RNA expression profiles in rats with adjuvant-induced arthritis.

Int J Mol Med 2019 Oct 22;44(4):1344-1356. Epub 2019 Jul 22.

Department of Pharmacology, College of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, which occurs in ~1.0% of the general population. Increasing studies have suggested that long non‑coding RNAs (lncRNAs) may serve important roles in various biological processes and may be associated with the pathogenesis of different types of disease, including RA. Astragalosides (AST) has been used as a traditional Chinese medicine for the treatment of RA. However, the mechanism underlying its therapeutic effect has remained unclear to date. Thus, there is an urgent need to elucidate the possible mechanism of AST in the treatment of RA from the perspective of lncRNAs. In the present study, the lncRNAs and mRNAs of a vehicle group, animal model group and AST treatment (control) group were determined by Arraystar Rat lncRNA/mRNA microarray. The differentially expressed genes with a fold change >1.5 and P<0.05 were selected and analyzed. Gene Ontology (GO) and pathway analysis was performed using the Database for Annotation, Visualization and Integration Discovery, and the coding‑non‑coding gene co‑expression network was drawn based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. Based on node degree and the correlation between bioinformatics analysis and RA, the critical differentially expressed lncRNAs were selected, analyzed and verified by reverse transcription‑quantitative PCR (RT‑qPCR) analysis. The results showed that, following AST treatment, up to 75 lncRNAs and 247 mRNAs were found to be differentially expressed among the three groups. GO and pathway analysis manifested that 135 GO terms and 17 pathways were enriched by differentially expressed genes. Four lncRNAs (MRAK012530, MRAK132628, MRAK003448 and XR_006457) were selected as the critical lncRNAs and their trend in expression showed consistency between the RT‑qPCR and microarray data. In conclusion, AST had a regulatory effect on differentially expressed lncRNAs during the development of RA, and four lncRNAs could be selected as critical therapeutic targets of AST.
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http://dx.doi.org/10.3892/ijmm.2019.4281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713426PMC
October 2019

Enhanced weathering as a trigger for the rise of atmospheric O level from the late Ediacaran to the early Cambrian.

Sci Rep 2019 07 23;9(1):10630. Epub 2019 Jul 23.

CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, 230026, China.

A shift toward a higher oxygen level in both ocean and atmosphere systems during the late Ediacaran to the early Cambrian has been suggested from multiple indirect proxies. However, the mechanism and magnitude of this oxidation remain unclear. To solve this issue, we measured carbon isotopes in both carbonate and organic matter as well as their trace element compositions for an Ediacaran-Cambrian sequence in the Lower Yangtze basin, South China. The δC and δC excursions of this sequence are coupled and can be compared with contemporaneous global carbon isotope curves. A 2‰ rise in ΔC occurred from the late Ediacaran to the early Cambrian, suggesting a substantial increase in atmospheric oxygen level from 16% to 30% of the present atmospheric level (PAL). Furthermore, the distribution pattern of rare earth elements and the concentrations of water-insoluble elements in the carbonates indicate a sudden enhancement in chemical weathering of the continental crust during the early Cambrian, which may be a trigger for the rise of atmospheric O level. Both the supply of a large amount of nutrients due to the enhanced continental weathering and the contemporary increase of atmospheric oxygen concentrations may have promoted the appearance of large metazoans in the early Cambrian.
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http://dx.doi.org/10.1038/s41598-019-47142-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650434PMC
July 2019

Tumor location of the central and nipple portion is associated with impaired survival for women with breast cancer.

Cancer Manag Res 2019 9;11:2915-2925. Epub 2019 Apr 9.

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P. R. China,

Background: Tumor location in the breast varies, with the highest frequency in the upper outer quadrant and lowest frequency in the lower inner quadrant. Nevertheless, tumors in the central and nipple portion (TCNP) are poorly studied types of breast cancer; therefore, we aimed to clarify the clinicopathological characteristics and prognostic features of TCNP.

Methods: Using the Surveillance, Epidemiology, and End Results database, we identifed 105,037 patients diagnosed with tumor in the breast peripheral quadrant (TBPQ) (n=97,046) or TCNP (n=7,991). The chi-squared test was used to compare categorical variables across TCNP and TBPQ. Cox proportional hazard models with hazard ratios were applied to estimate the factors associated with prognosis.

Results: The median follow-up was over 43 months. Compared with TBPQ, TCNP patients were signifcantly older (age ≥66 years: 40.4% vs 34.1%, P<0.001), with larger tumor sizes (>20 mm size: 46.9% vs 37.3%, P<0.001), higher proportions of TNM stage II-III (18.6% vs 9.9%, P<0.001), and more mastectomies (58.1% vs 37.8%, P<0.001). The breast cancer-specifc survival (BCSS)/overall survival (OS) rate was signifcantly worse for TCNP than for TBPQ. Multivariate Cox analysis showed a higher hazard ratios for TCNP over TBPQ (BCSS: hazard ratios =1.160, P=0.005, 95% CI: 1.046-1.287; OS: hazard ratios =1.301, P<0.001, 95% CI: 1.211-1.398). A subgroup analysis revealed inferior outcomes for TCNP in TNM stage II-III and breast subtype subgroup. Multivariate logistic regression indicated that TCNP was an independent contributing factor to LN metastasis.

Conclusions: TCNP was associated with older age, larger tumor size, higher TNM stage, and lymph node metastasis. Compared with TBPQ, TCNP had adverse impacts on BCSS and OS.
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http://dx.doi.org/10.2147/CMAR.S186205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461001PMC
April 2019

Furanodienone overcomes temozolomide resistance in glioblastoma through the downregulation of CSPG4-Akt-ERK signalling by inhibiting EGR1-dependent transcription.

Phytother Res 2019 Jun 21;33(6):1736-1747. Epub 2019 Apr 21.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen, 518035, China.

Glioblastoma multiforme (GBM) is a highly aggressive type of brain tumour. Patients with GBM respond poorly to chemotherapy and have poor survival outcomes. Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), has been shown to contribute to critical processes, such as cell survival, proliferation, and chemotherapy resistance, during glioma progression. In this study, we found that furanodienone (FUR), a diene-type sesquiterpene isolated from the rhizomes of Rhizoma curcumae, exhibited a potential cytotoxic effect on temozolomide (TMZ)-resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways. Studies investigating the mechanism demonstrated that FUR suppressed CSPG4-Akt-ERK signalling, inflammatory responses, and cytokine levels but activated caspase-dependent pathways and mitochondrial dysfunction. Furthermore, an immunofluorescence assay and a dual-luciferase reporter assay revealed that inhibition of EGR1-mediated transcription might have contributed to the FUR-dependent blockade of CSPG4 signalling and glioma cell survival. These results established a link between FUR-induced CSPG4 inhibition and the suppression of EGR1-dependent transcription. Attenuation of ERK1/2 and cytokine signalling might have generated the EGR1-dependent negative feedback loop of the CSPG4 pathway during FUR-induced apoptosis. These findings suggested that FUR could be a therapeutic candidate for the treatment of malignant glioma via targeting CSPG4 signalling.
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http://dx.doi.org/10.1002/ptr.6363DOI Listing
June 2019

[Study on morphological classification and chemical-type of Perilla frutescens cultivated germplasm].

Zhongguo Zhong Yao Za Zhi 2019 Feb;44(3):454-459

Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College Beijing 100193, China.

Fifty cultivated Perilla seeds were collected all over the country and planted in Beijing experiment field for morphology and chemical-type researches. Twenty morphological characteristics were selected and observed, and the essential oil from leaves was extracted by steam distillation and analyzed by GC-MS to confirm chemical-types. There were significant diversities in plant height, leaf color and morphology, and fruit color and weight. Clustering analysis was carried out based on these morphological characteristics. Six types were divided with their chemical-type designated. Type Ⅰ: Six germplasms, attributed to P. frutescens var. crispa, with dwarf plants, thin creased purple leaf, named Crispa, their chemical types were diversified, including EK, PAPK, PA and PK. Type Ⅱ: Six germplasms, attributed to P. frutescens var. crispa, plants were taller than type I and with thin and creased green leaf, named Big Crispa, all PK type. Type Ⅲ: Seventeen germplasms, attributed to P. frutescens var. frutescens with leaf color upside green and underside purple, tall plant and wide distribution all over the China, named Ordinary Frutescens, all PK. Type Ⅳ: Four germplasms, attributed to P. frutescens var. acuta with tall plant and small seed, named Acuta, all PK. Type Ⅴ: Seven germplasms, attributed to P. frutescens var. frutescens with green leaves, tall plants and long clusters, named Long-spike Frutescens, all PK. Type Ⅵ: Ten germplasms, attributed to P. frutescens var. frutescens with big, thick and creased leaf, named Thick-leaf Frutescens, including PK, PP, PL and PA. The morphological classification of this paper would lay the foundation for the taxonomic naming and following evaluation of the Perilla germplasm resources.This study also showed that there was no correspondence but a certain correlation between volatile oil chemical-types and subspecies classification and morphological characteristics of Perilla.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20180820.010DOI Listing
February 2019

Impaired decidualization caused by downregulation of circadian clock gene BMAL1 contributes to human recurrent miscarriage†.

Biol Reprod 2019 07;101(1):138-147

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Recurrent miscarriage (RM) is characterized by two or more consecutive losses of a clinically established intrauterine pregnancy at early gestation. To date, the etiology of RM remains poorly understood. Impaired decidualization is thought to predispose women to subsequent pregnancy failure. The transcriptional factor brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1) controls circadian rhythms and regulates a very large diversity of physiological processes. BMAL1 is essential for fertility. Here, we investigated the expression and function of BMAL1 in human decidualization and its relation with RM. A total of 39 decidua samples were collected. We also examined human endometrial stromal cells (HESCs) and primary endometrial stromal cells (ESCs), and primary decidual stromal cells (DSCs) isolated from decidua of first-trimester pregnancies. Compared to normal pregnant women, the expression of BMAL1 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, the transcription of BMAL1 in both HESCs and primary ESCs was increased. This is in line with the relatively higher expression of BMAL1 in DSCs than in ESCs. Silencing of BMAL1 resulted in impaired decidualization. Moreover, levels of tissue inhibitors of metalloproteinases (TIMPs) increased significantly upon decidualization. Further experiments demonstrated that BMAL1 silencing curtails the ability of DSCs to restrict excessive trophoblast invasion via downregulation of TIMP3. Our study demonstrates a functional role for BMAL1 during decidualization: the downregulation of BMAL1 in RM leads to impaired decidualization and aberrant trophoblast invasion by regulating TIMP3 and consequently predisposing individuals for RM.
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http://dx.doi.org/10.1093/biolre/ioz063DOI Listing
July 2019

Effect of danefukang on symptoms and biomarkers in women with endometriosis.

Taiwan J Obstet Gynecol 2019 Mar;58(2):218-222

Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Gynecologic Oncology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

Objective: The purpose of this study was to observe the efficacy of Danefukang (DEFK) soft extract for the treatment of symptoms associated with endometriosis, and its effect on quality of life, the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores, and on levels of carbohydrate antigen (CA)-125, tumor necrosis factor (TNF)-α, and interleukin (IL)-6.

Materials And Methods: A total of 174 patients with endometriosis treated from January 2010 to December 2013 were randomly divided into a control group treated with mifepristone (n = 87) or DEFK (n = 87). Both groups were treated for 3 months. Symptoms, quality of life, SAS, SD scores, and levels of CA-125, TNF-α, and IL-6 were evaluated before and after treatment.

Results: The effectiveness rate was 93.10% in the DEFK group and 81.61% in the mifepristone control group (χ = 4.215, P < 0.05). Treatment with DEFK resulted in a greater improvement in quality of life, SDS, and SAS scores compared with mifepristone (all, P < 0.05). DEFK treatment also resulted in a greater decrease of CA-125, TNF-α, and IL-6 levels compared with mifepristone (all, P < 0.05).

Conclusion: Based on the current results - improved symptoms, attenuated depression and anxiety, and reduced the levels of pro-inflammatory cytokines and CA-125 -treatment with DEFK is a meaningful option for patients with endometriosis. DEFK fills an unmet need in the pharmacologic treatment of endometriosis.
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http://dx.doi.org/10.1016/j.tjog.2019.01.009DOI Listing
March 2019

Santacruzamate A Ameliorates AD-Like Pathology by Enhancing ER Stress Tolerance Through Regulating the Functions of KDELR and Mia40-ALR and .

Front Cell Neurosci 2019 4;13:61. Epub 2019 Mar 4.

Shenzhen Key Laboratory of Neurosurgery, Brain Center, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital, Shenzhen, China.

Aggregated amyloid-β protein (Aβ) and Aβ-induced neuronal apoptosis have been implicated as critical factors in the pathophysiology of Alzheimer's disease (AD). Certain preclinical results have indicated that the increased accumulation of protein aggregates in AD-affected neurons activates the unfolded protein response (UPR), a pathological phenomenon, which predominantly mediates the aberrant endoplasmic reticulum (ER) stress and apoptotic cascades in neuronal cells. In the present study, we confirmed that Santacruzamate A (STA, a natural product isolated from a Panamanian marine cyanobacterium) attenuates Aβ protein fragment 25-35 (Aβ)-induced toxicity in PC12 cells and rescues cognitive deficits in APPswe/PS1dE9 mice by enhancing ER stress tolerance. We first demonstrated the anti-apoptotic effects of STA by evaluating caspase-3 activity, annexin V/propidium iodide (PI) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Behavioral testing of STA-treated APPswe/PS1dE9 mice showed that the pronounced memory impairments were ameliorated and that the consolidated memories were stably maintained over a 2-week period. The mechanistic studies provided evidence that STA inhibited Aβ-induced UPR and ER stress by regulating the ER retention signal (KDEL) receptor, which reinforced the retention of resident chaperones in the ER lumen. Furthermore, STA regulated the expression of the mitochondrial intermembrane space assembly protein 40 (Mia40) and augmenter of liver regeneration (ALR), which ultimately attenuated the mitochondrial fission and apoptosis pathways. Together, our present findings suggest that the KDEL receptor and Mia40-ALR play a role in mitigating Aβ-induced neurotoxicity, which might in turn positively regulate learning and memory. These observations support that STA may be a promising agent for reversing the progression of AD.
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http://dx.doi.org/10.3389/fncel.2019.00061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409322PMC
March 2019

Mild hypothermia reduces endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after severe traumatic brain injury.

Brain Behav 2019 04 4;9(4):e01248. Epub 2019 Mar 4.

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: Mild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress-induced apoptosis after severe TBI is still unknown.

Methods: In the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze.

Results: Our results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p-eIF2α/eIF2α, ATF4, CHOP and IRE-1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI.

Conclusions: Our findings illustrated that mild hypothermia could reduce ER stress-induced apoptosis and improve neuronal functions after severe traumatic brain injury.
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http://dx.doi.org/10.1002/brb3.1248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456779PMC
April 2019

Local Administration of Magnesium Promotes Meniscal Healing Through Homing of Endogenous Stem Cells: A Proof-of-Concept Study.

Am J Sports Med 2019 03 20;47(4):954-967. Epub 2019 Feb 20.

Department of Orthopaedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Although many strategies have been developed to modify the biological and biomechanical environment of the meniscal suture repair to improve the chances of healing, the failure rates remain high. Thus, new methods to promote meniscal regeneration and repair are needed.

Hypothesis: Administration of magnesium (via a repair using magnesium stitches) might enhance recruitment and adherence of endogenous stem cells to the site of the lesion, thereby promoting in situ meniscal regeneration and chondroprotective functions.

Study Design: Controlled laboratory study.

Methods: Synovial fluid-derived mesenchymal stem cells (SMSCs) were identified and isolated from the knees of rabbits with a meniscal injury of 4 weeks' duration. An in vitro analysis of adherence and chemotaxis of SMSCs was performed. For the in vivo assay, rabbits (n = 120) with meniscal lesions were divided into 3 groups: repair with high-purity magnesium stitches (Mg group), repair with absorbable sutures (Control group), and no repair (Blank group). Healing of the regenerated tissue and degeneration of the articular cartilage were evaluated by gross and histological analysis at postoperative weeks 1, 3, 6, and 12. The mechanical properties of the repaired meniscus were also analyzed (tensile testing).

Results: In vitro, magnesium promoted the adhesion and migration of SMSCs, which were identified and increased in the knee joints with meniscal lesions. Moreover, fibrochondrogenesis of SMSCs was stimulated by magnesium. Compared with the other groups, the Mg group had enhanced tissue regeneration, lower cartilage degeneration, and retained mechanical strength at 12 weeks after meniscal repair.

Conclusion/clinical Relevance: Magnesium could be used for in situ meniscal repair due to the potential capacity of magnesium to recruit endogenous stem cells and promote synthesis of fibrocartilaginous matrix.
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http://dx.doi.org/10.1177/0363546518820076DOI Listing
March 2019