Publications by authors named "Jing Ruan"

79 Publications

A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.

Adv Sci (Weinh) 2021 Sep 31;8(18):e2004721. Epub 2021 Jul 31.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, P. R. China.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli-responsive drug delivery antibacterial hydrogel ([email protected]@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel-sol transformation to release the gene-targeted drug DC_AC50 on demand in response to low-density near-infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of [email protected]@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene-targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the [email protected]@DC_AC50+NIR group and normal group. This NIR light-triggered gene-targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202004721DOI Listing
September 2021

Deubiquitinating enzymes (DUBs): decipher underlying basis of neurodegenerative diseases.

Mol Psychiatry 2021 Jul 20. Epub 2021 Jul 20.

Department of Neurological Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Neurodegenerative diseases (NDs) are characterized by the aggregation of neurotoxic proteins in the central nervous system. Aberrant protein accumulation in NDs is largely caused by the dysfunction of the two principal protein catabolism pathways, the ubiquitin-proteasome system (UPS), and the autophagy-lysosomal pathway (ALP). The two protein quality control pathways are bridged by ubiquitination, a post-translational modification that can induce protein degradation via both the UPS and the ALP. Perturbed ubiquitination leads to the formation of toxic aggregates and inclusion bodies that are deleterious to neurons. Ubiquitination is promoted by a cascade of ubiquitinating enzymes and counter-regulated by deubiquitinating enzymes (DUBs). As fine-tuning regulators of ubiquitination and protein degradation, DUBs modulate the stability of ND-associated pathogenic proteins including amyloid β protein, Tau, and α-synuclein. Besides, DUBs also influence ND-associated mitophagy, protein secretion, and neuroinflammation. Given the various and critical functions of DUBs in NDs, DUBs may become potential therapeutic targets for NDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-021-01233-8DOI Listing
July 2021

Research Progress on Phytopathogenic Fungi and Their Role as Biocontrol Agents.

Front Microbiol 2021 28;12:670135. Epub 2021 May 28.

College of Plant Protection, Gansu Agricultural University, Lanzhou, China.

Phytopathogenic fungi decrease crop yield and quality and cause huge losses in agricultural production. To prevent the occurrence of crop diseases and insect pests, farmers have to use many synthetic chemical pesticides. The extensive use of these pesticides has resulted in a series of environmental and ecological problems, such as the increase in resistant weed populations, soil compaction, and water pollution, which seriously affect the sustainable development of agriculture. This review discusses the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds. Finally, further studies on plant-pathogenic fungal resources with better biocontrol effects can help find new beneficial microbial resources that can control diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.670135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192705PMC
May 2021

Author Correction: Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria.

Blood Cancer J 2021 May 6;11(5):85. Epub 2021 May 6.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-021-00476-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102493PMC
May 2021

Dose-Dependent Carbon-Dot-Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism.

Adv Sci (Weinh) 2021 04 25;8(8):2002404. Epub 2021 Feb 25.

Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai JiaoTong University School of Medicine Shanghai 200011 China.

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose-dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL, Cdot-induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25-100 µg mL activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS-producing nanoparticles in tumor imaging and therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202002404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061404PMC
April 2021

Extracellular vesicles in neuroinflammation: Pathogenesis, diagnosis, and therapy.

Mol Ther 2021 06 23;29(6):1946-1957. Epub 2021 Apr 23.

School of Pharmaceutical Sciences, Wenzhou Medical University, 325035 Wenzhou, China; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany. Electronic address:

Extracellular vesicles (EVs) are bilayer membrane vesicles and act as key messengers in intercellular communication. EVs can be secreted by both neurons and glial cells in the central nervous system (CNS). Under physiological conditions, EVs contribute to CNS homeostasis by facilitating omnidirectional communication among CNS cell populations. In response to CNS injury, EVs mediate neuroinflammatory responses and regulate tissue damage and repair, thereby influencing the pathogenesis, development, and/or recovery of neuroinflammatory diseases, including CNS autoimmune diseases, neurodegenerative diseases, stroke, CNS traumatic injury, and CNS infectious diseases. The unique ability of EVs to pass through the blood-brain barrier further confers them an important role in the bidirectional communication between the CNS and periphery, and application of EVs enables the diagnosis, prognosis, and therapy of neuroinflammatory diseases in a minimally invasive manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymthe.2021.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178458PMC
June 2021

Promoting reactive oxygen species generation: a key strategy in nanosensitizer-mediated radiotherapy.

Nanomedicine (Lond) 2021 04 15;16(9):759-778. Epub 2021 Apr 15.

Department of Ophthalmology, Ninth People's Hospital of Shanghai, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

The radiotherapy enhancement effect of numerous nanosensitizers is based on the excessive production of reactive oxygen species (ROS), and only a few systematic reviews have focused on the key strategy in nanosensitizer-mediated radiotherapy. To clarify the mechanism underlying this effect, it is necessary to understand the role of ROS in radiosensitization before clinical application. Thus, the source of ROS and their principle of tumor inhibition are first introduced. Then, nanomaterial-mediated ROS generation in radiotherapy is reviewed. The double-edged sword effect of ROS and the potential dangers they may pose to cancer patients are subsequently addressed. Finally, future perspectives regarding ROS-regulated nanosensitizer applications and development are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/nnm-2020-0448DOI Listing
April 2021

Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria.

Blood Cancer J 2021 Mar 16;11(3):58. Epub 2021 Mar 16.

Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-021-00451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966366PMC
March 2021

Histone lactylation drives oncogenesis by facilitating mA reader protein YTHDF2 expression in ocular melanoma.

Genome Biol 2021 03 16;22(1):85. Epub 2021 Mar 16.

Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.

Background: Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.

Results: Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.

Conclusion: We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02308-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962360PMC
March 2021

Effective treatment of aplastic anemia secondary to chemoradiotherapy using cyclosporine A.

Authors:
Jing Ruan Bing Han

Chin Med J (Engl) 2021 Jan 19. Epub 2021 Jan 19.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CM9.0000000000001365DOI Listing
January 2021

Acquired pure red cell aplasia and T cell large granular lymphocytic leukaemia in patients with autoimmune polyglandular syndrome type 1.

BMC Med Genomics 2021 01 19;14(1):22. Epub 2021 Jan 19.

Hematology Department, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.

Background: Pure red cell aplasia (PRCA) and large granular lymphocytic leukaemia (LGLL) are very rare complications of autoimmune polyendocrine syndrome type 1 (APS1). Here, we report a case of APS1 with PRCA and LGLL. Previous cases were reviewed, and possible mechanisms are discussed.

Case Presentation: A 31-year-old female presented with anaemia and was diagnosed with PRCA in our centre. She also had hypoparathyroidism for 24 years, premature ovarian failure for 10 years, osteoporosis for 5 years, recurrent pneumonia with bronchiectasis for 4 years and chronic diarrhoea for 1 year. Boosted whole-exome analysis showed AIRE heterozygous mutations, confirming the diagnosis as APS1. LGLL was diagnosed during follow-up. The PRCA responded well to glucocorticoid. treatment CONCLUSION: AIRE is causally related to the development of LGLL and consequent PRCA, which may be due to some immunological mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-020-00866-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814426PMC
January 2021

Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study.

Drug Des Devel Ther 2020 30;14:5711-5719. Epub 2020 Dec 30.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People's Republic of China.

Background: For symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) may be an option if these patients do not respond or become tolerant to cyclosporine A (CsA).

Methods: We enrolled 101 NSAA patients who were refractory or intolerant to CsA with no chance of HSCT or ATG treatment and treated these patients with tacrolimus for at least 6 months, with follow-up for at least one year.

Results: The overall response rate (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%), and the median time to optimal response was 6 (3~10) months. Thirty-two (31.7%) cases had elevated creatinine levels. Eight (7.9%) cases had elevations in AST/ALT. A total of 25.6% (10/39) of patients relapsed at the end of follow-up. Age (=0.0005), FK concentration (4.0~12 ng/mL, =0.0005) and intolerance to CsA (=0.012) were the independent risk factors for ORR. Treg cell levels pre-FK treatment were much lower than those of healthy controls (3.7±0.6% vs 6.8±0.7%, =0.0004) but increased significantly after FK treatment (3.7±0.6% vs 7.1±0.8%, =0.0039).

Conclusion: Our data suggest that tacrolimus is a salvage treatment for patients with NSAA that is refractory or intolerant to CsA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S275975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779311PMC
September 2021

Correlation of the Plasma Concentration of Eltrombopag With Efficacy in the Treatment of Refractory Aplastic Anemia: A Single-Centre Study in China.

Front Pharmacol 2020 16;11:582625. Epub 2020 Nov 16.

Department of Hematology, Peking Union Medical Colleague Hospital, Chinese Academy of Medical Science, Beijing, China.

Eltrombopag (ELT) can be effective in the treatment of relapse/refractory aplastic anemia (AA) patients. Responses and adverse drug reactions (ADRs) differed greatly among individuals treated at the same dosage of ELT. Patients diagnosed with nonsevere aplastic anemia (NSAA) between January 2018 and January 2019 in Peking Union Medical Colleague Hospital who were refractory to immunosuppressive therapy were treated with ELT and followed up for at least 6 months. Plasma concentrations of ELT were detected by high-performance liquid chromatography-mass spectrometry after at least two months of ELT treatment and treatment at the same dosage for at least 2 weeks. The dose-concentration, concentration-response and concentration-ADR relationships were evaluated. Among the 72 patients treated with ELT during the study period, 44 patients with complete data were enrolled. Six (13.6%) were males, and 38 were females (86.4%), with a median age of 54 years [interquartile range (IQR): 38.5-63]. At the time the ELT plasma concentration was detected, the median dosage of ELT was 75 (IQR 50-100) mg/d, the median time of total ELT exposure was 3 (IQR 2.0-6.0) months, and 37 (70.5%) patients had responded to ELT. The median concentration of ELT was 10.4 μg/ml (IQR 3.7-24.4 μg/ml). The concentration of ELT was positively correlated with the daily dose of ELT ( = 0.68, < 0.001). Multivariate logistic regression analysis showed that the risk of inefficacy of ELT at a concentration between 11.2 and 15.2 μg/ml was 0.028-fold (95% CI: 0.001-0.864; = 0.041) of that at a concentration between 3.2 and 7.2 μg/ml. The cutoff value for the concentration of ELT showing efficacy was 12.50 μg/ml according to the receiver operation characteristic curve. A higher risk of ADR was related to a longer total exposure to ELT ( = 0.012). Although the correlation was not significant, the odds ratio increased with the ELT concentration, suggesting that it was possible that an elevated risk of ADR was correlated with the ELT blood concentration. ELT is effective for the treatment of NSAA and has acceptable side effects. The plasma concentration of ELT was correlated with the dose and the effects of ELT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.582625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751734PMC
November 2020

Hierarchical Clustering of Cutaneous Melanoma Based on Immunogenomic Profiling.

Front Oncol 2020 30;10:580029. Epub 2020 Nov 30.

Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Cutaneous melanoma is an aggressive malignancy with high heterogeneity. Several studies have been performed to identify cutaneous melanoma subtypes based on genomic profiling. However, few classifications based on assessments of immune-associated genes have limited clinical implications for cutaneous melanoma. Using 470 cutaneous melanoma samples from The Cancer Genome Atlas (TCGA), we calculated the enrichment levels of 29 immune-associated gene sets in each sample and hierarchically clustered them into Immunity High (Immunity_H, n=323, 68.7%), Immunity Medium (Immunity_M, n=135, 28.7%), and Immunity Low (Immunity_L, n=12, 2.6%) based on the ssGSEA score. The ESTIMATE algorithm was used to calculate stromal scores (range: -1,800.51-1,901.99), immune scores (range: -1,476.28-3,780.33), estimate scores (range: -2,618.28-5,098.14) and tumor purity (range: 0.216-0.976) and they were significantly correlated with immune subtypes (Kruskal-Wallis test, < 0.001). The Immunity_H group tended to have higher expression levels of HLA and immune checkpoint genes (Kruskal-Wallis test, < 0.05). The Immunity_H group had the highest level of naïve B cells, resting dendritic cells, M1 macrophages, resting NK cells, plasma cells, CD4 memory activated T cells, CD8 T cells, follicular helper T cells and regulatory T cells, and the Immunity_L group had better overall survival. The GO terms identified in the Immunity_H group were mainly immune related. In conclusion, immune signature-associated cutaneous melanoma subtypes play a role in cutaneous melanoma prognosis stratification. The construction of immune signature-associated cutaneous melanoma subtypes predicted possible patient outcomes and provided possible immunotherapy candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.580029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735560PMC
November 2020

Tacrolimus is effective in relapsed/refractory autoimmune cytopenias: results of a single-center retrospective study.

Hematology 2020 Dec;25(1):478-483

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, People's Republic of China.

Background: The standard therapies for autoimmune cytopenias, including idiopathic thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and Evans syndrome (ES), are corticosteroids and intravenous immunoglobulin G. However, the recurrence rate is high.

Method: Data from 80 patients with ITP, AIHA and ES who were refractory to corticosteroids/relapsed and were treated with tacrolimus from January 2018 to January 2019 in Peking Union Medical Colleague Hospital were reviewed retrospectively.

Results: There were 24 males and 56 females, with a median age of 43 (14-81) years, including 66 with ITP, 11 with AIHA and 3 with ES. The median disease duration before tacrolimus was 16 (2-432) months. The complete response (CR) rates were 30.3%, 63.6% and 0%; the overall response (OR) rates were 63.6%, 72.7% and 66.7% for ITP, AIHA and ES, respectively; and the median time to response was 3 (2-10) months. In a median of 18 (10-24) months of follow-up time, 21.4% of ITP patients relapsed at a median time of 7 months. No relapse was found for patients with AIHA and ES. Side effects occurred in 16.3% of patients, including elevated creatinine (= 3, 3.8%), gastrointestinal reactions (= 3, 3.8%), and pulmonary infection (= 2, 2.5%), and resulted in 3 patients stopping tacrolimus. The OR rate was found to be related with age ( = 0.01) but not with sex ( = 0.62), the duration of disease ( = 0.66), tacrolimus concentration ( = 0.99) or disease type ( = 0.84).

Conclusion: Tacrolimus can achieve a durable response with mild side effects in patients with steroid-refractory/relapsed autoimmune cytopenias. Patients with younger age had a better response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/16078454.2020.1852763DOI Listing
December 2020

Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene-a case report.

BMC Med Genet 2020 11 10;21(1):221. Epub 2020 Nov 10.

Department of Hematology, Peking Union Medical College, Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Background: Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies.

Case Presentation: A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed.

Conclusions: A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12881-020-01158-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654184PMC
November 2020

Correction to: Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China.

Ann Hematol 2021 Jan;100(1):307

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04301-1DOI Listing
January 2021

Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways.

Reprod Biol Endocrinol 2020 Oct 12;18(1):100. Epub 2020 Oct 12.

Department of Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 201204, China.

Background: Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis.

Methods: JEG-3 cells were cocultured with HO and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting.

Results: CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the HO-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with HO. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the HO-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis.

Conclusions: These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-020-00658-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549196PMC
October 2020

Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China.

Ann Hematol 2020 Dec 17;99(12):2755-2761. Epub 2020 Sep 17.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

Eltrombopag has shown a promising effect on patients with refractory/relapsed aplastic anemia (AA). However, data in Asian patients are limited due to the short launching time. Data from relapsed/refractory AA patients treated with eltrombopag in Peking Union Medical College Hospital from December 2017 to May 2019 were analyzed retrospectively. Totally 41 patients including 37 non-severe AA and 4 severe AA were analyzed with a median age of 47 (13~81) years old. The dosage of eltrombopag varies from 25 mg every other day (qod) to 100 mg every day (qd) (median 75 mg qd) with the duration of 13 (3~23) months. The overall response rates were 51.2%, 58.5%, and 55.2% at 3-month, 6-month, and 1-year follow-up. Seventy-five percent of patients achieved the best response below the dosage of 75 mg qd at 3 (1-6) months. Two patients stopped eltrombopag after achieving complete remission and remained stable. Two patients relapsed and evolved to myelodysplastic syndrome. Adverse events included gastrointestinal discomfort, hepatic toxicity, and skin reactions, which were mild and controllable. Eltrombopag is effective for Chinese relapsed/refractory AA patients with a relatively lower dose and acceptable side effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04266-1DOI Listing
December 2020

FDG PET/CT Findings in Biliary Papillomatosis.

Clin Nucl Med 2020 Oct;45(10):798-799

From the Departments of Hepatobiliary Surgery.

Biliary papillomatosis is a rare disease with high malignant potential. A 64-year-old woman underwent FDG PET/CT, which showed an intense FDG uptake in the location of an aggregated biliary papillomatosis with high-grade intraepithelial neoplasia/carcinoma in situ but did not show FDG uptake in the sporadic, small biliary papilloma. FDG PET/CT may be an effective method to identify the components of the malignant transformation of biliary papillomatosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/RLU.0000000000003243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469870PMC
October 2020

LINC00319 promotes osteosarcoma progression by regulating the miR-455-3p/NFIB axis.

J Gene Med 2020 11 28;22(11):e3248. Epub 2020 Jul 28.

Department of Psychology, Huangshi Psychiatric Hospital, Huangshi, Hubei, China.

Background: Numerous studies have shown that aberrant expression of long non-coding RNAs (lncRNAs) is associated with the development and metastasis of osteosarcoma (OS). However, the role and function of LINC00319 with respect to regulating OS progression is unknown. The present study aimed to reveal the function and related mechanism of LINC00319 in OS.

Methods: The expression of LINC00319, miR-455-3p and nuclear factor IB (NFIB) in OS cells and tissues was determined using a reverse transcriptase-polymerase chain reaction (PCR). The sublocalization of LINC00319 was predicted by the lncATLAS database (http://lncatlas.crg.eu) and RNA fluorescence in situ hybridization (FISH) was further performed to detect the subcellular localization of LINC00319. LINC00319, miR-455-3p and NFIB target sites were predicted by StarBase (http://starbase.sysu.edu.cn/index.php) and validated using a dual luciferase reporter gene assay. We subsequently performed LINC00319 gain- and loss-of-function studies to define the role of LINC00319 in OS cell migration.

Results: PCR results showed that lncRNA LINC00319 exhibited high expression in tumor cells and tissue. Moreover, LINC00319 was positioned in the cytoplasm, which was identified by FISH. Knockdown of lncRNA LINC00319/NFIB or overexpression of miR-455-3p blocked the migration of OS cells. In addition, the inhibitory effect of migration with the knockdown of lncRNA LINC00319 was partially blocked by administration of miR-455-3p inhibitor.

Conclusions: lncRNA LINC00319 may promote OS progression by regulating the miR-455-3p/NFIB axis, which probably serves as an innovative potential indicator of prognosis and a target of therapy for OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgm.3248DOI Listing
November 2020

Predicting worse survival for newly diagnosed T cell lymphoma based on the decreased baseline CD16-/CD16 + monocyte ratio.

Sci Rep 2020 05 8;10(1):7757. Epub 2020 May 8.

Department of Hematology, Peking Union Medical College Hospital, Beijing, 100730, China.

T cell non-Hodgkin lymphoma (T-NHL) is highly invasive and heterogeneous without accurate prognosis prediction. We proposed peripheral CD16-/CD16 + monocytes the additional indicators for T-NHL prognosis. We prospectively recruited 31 T-NHL patients without previous treatment. The CD16-/CD16 + monocyte ratio before chemotherapy was calculated and regular follow up was performed to calculate prognostic prediction value. Tumor associated macrophages (TAM) in tumor tissue were counted and transcriptome sequencing of CD16- and CD16 + monocytes was applied to explore potential mechanisms. We found that T-NHL patients had higher ratio of total monocytes especially the CD16 + monocytes along with a decreased ratio of CD16-/CD16 + monocytes, compared to the health control. The 1-year overall survival rate was 0.492 and 0.755 for CD16- monocyte/CD16 + monocyte ratio of <11 and ≥11(p < 0.05), respectively. The peripheral CD16-/CD16 + monocyte ratio was significantly relevant with the pathological CD68/CD206 macrophage ratio. The differently expressed genes in CD16- and CD16 + monocytes from T-NHL patients were mainly involved in signaling molecules related to tumor microenvironment. Pro-tumor genes were identified in monocyte subsets especially in CD16 + monocytes. In conclusion, the ratio of peripheral CD16-/CD16 + monocyte helps to stratify the prognosis of T-NHL. The relatively increased CD16 + monocytes may contribute to the pro-tumor microenvironment of T-NHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-64579-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211003PMC
May 2020

Deubiquitinating enzymes (DUBs): DoUBle-edged swords in CNS autoimmunity.

J Neuroinflammation 2020 Apr 6;17(1):102. Epub 2020 Apr 6.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Chashan High Education Park, Wenzhou, 325035, China.

Multiple sclerosis (MS) is the most common autoimmune disease of the CNS. The etiology of MS is still unclear but it is widely recognized that both genetic and environmental factors contribute to its pathogenesis. Immune signaling and responses are critically regulated by ubiquitination, a posttranslational modification that is promoted by ubiquitinating enzymes and inhibited by deubiquitinating enzymes (DUBs). Genome-wide association studies (GWASs) identified that polymorphisms in or in the vicinity of two human DUB genes TNFAIP3 and USP18 were associated with MS susceptibility. Studies with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided biological rationale for the correlation between these DUBs and MS. Additional studies have shown that other DUBs are also involved in EAE by controlling distinct cell populations. Therefore, DUBs are emerging as crucial regulators of MS/EAE and might become potential therapeutic targets for the clinical treatment of MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-020-01783-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132956PMC
April 2020

Experimental Study and Failure Criterion Analysis on Combined Compression-Shear Performance of Self-Compacting Concrete.

Materials (Basel) 2020 Feb 5;13(3). Epub 2020 Feb 5.

Jiangsu Provincial Transportation Construction Bureau, Nanjing 210004, China.

To investigate the combined compression-shear performance of self-compacting concrete (SCC), eight groups of concrete specimens under different axial compression ratios were designed, and the composite performance under different axial stresses was carried out by hydraulic servo machine. The uniaxial and tensile splitting strength of SCC were also included in the study. The failure modes of SCC were presented, discussed, and compared with normal concrete (NC). The characteristic points of stress-strain curves of SCC specimens from the experiments were extracted and analyzed under different axial compression stress. Based on the experimental results, the shear strength of compression-shear load was divided into cohesive stress and residual friction stress. The variation of residual stress and cohesive stress under the combined compression-shear stress was analyzed, and the relationship was obtained by numerical regression. Research results indicated that the residual stress increases linearly with the compression stress while the cohesive stress increased at first and then decreased. The research found that the friction coefficient of SCC was much smaller than NC due to the lack of interlocking effect. Utilizing the compression-shear strength of SCC, the material failure criteria of SCC were proposed from the view of shear failure strength and octahedral stress space, which could fit the experimental results confidently following the mathematical regression analysis. The comparison with data from other literature shows favorable consistence with the obtained criteria. The results of the study could be beneficial complement in engineering practices where SCC was applicable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma13030713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040608PMC
February 2020

Long Non-coding RNA LINC-PINT Suppresses Cell Proliferation and Migration of Melanoma via Recruiting EZH2.

Front Cell Dev Biol 2019 20;7:350. Epub 2019 Dec 20.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Long non-coding RNAs (lncRNAs) have been identified as crucial regulators in many human cancers. Many lncRNAs show aberrant expression in cancer, and some of them play critical roles in tumor proliferation, invasion, and metastasis. However, the regulatory functions of lncRNAs in melanoma progression remain to be elucidated. We utilized the Real-time PCR methodology to determine the expression of LINC-PINT in melanoma cell lines. To evaluate the effect of LINC-PINT on tumorigenesis of melanoma, we used Cell Counting Kit-8 (CCK8) and colony formation assay. Flow cytometry assay was used to detect the function of LINC-PINT on cell cycle status. PINT-interacting proteins were identified by chromatin isolation using RNA purification (ChIRP). Microarray assay and bioinformatics analysis were used to find the potential target genes of LINC-PINT and the status of LINC-PINT target gene candidate was verified using chromatin immunoprecipitation assay (ChIP). LINC-PINT plays a role in suppressing the tumorigenicity of melanoma, which was further determined by xenograft model assay. LINC-PINT was significantly downregulated in melanoma tissues and cell lines. The overexpression of LINC-PINT in tumor cells resulted in significant tumor growth reduction and migration inhibition in A375, Mum2B and CRMM1 cells. Results based on the xenograft model were further consistent with the findings that LINC-PINT impeded growth and metastasis of melanoma cells. Microarray assay and bioinformatics analysis indicated that CDK1, CCNA2, AURKA, and PCNA were potential targets of LINC-PINT. In conclusion, LINC-PINT inhibits the tumorigenicity of melanoma through recruiting EZH2 to the promoter of its target genes, leading to H3K27 trimethylation and epigenetic silencing of target genes. LINC-PINT may serve as a novel diagnostic and therapeutic target for melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2019.00350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934058PMC
December 2019

Insights into the epigenetic effects of nanomaterials on cells.

Biomater Sci 2020 Feb 6;8(3):763-775. Epub 2019 Dec 6.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, China. and Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, China.

With the development of nanotechnology, nanomaterials are increasingly being applied in health fields, such as biomedicine, pharmaceuticals, and cosmetics. Concerns have therefore been raised over their toxicity and numerous studies have been carried out to assess their safety. Most studies on the toxicity and therapeutic mechanisms of nanomaterials have revealed the effects of nanomaterials on cells at the transcriptome and proteome levels. However, epigenetic modifications, for example DNA methylation, histone modification, and noncoding RNA expression induced by nanomaterials, which play an important role in the regulation of gene expression, have not received sufficient attention. In this review, we therefore state the importance of studying epigenetic effects induced by nanomaterials; then we review the progress of nanomaterial epigenetic research in the assessment of toxicity, therapeutic, and other mechanisms. We also clarify the possible study directions for future nanomaterial epigenetic research. Finally, we discuss the future development and challenges of nanomaterial epigenetics that must still be addressed. We hope to understand the potential toxicity of nanomaterials and clearly understand the therapeutic mechanism through a thorough investigation of nanomaterial epigenetics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9bm01526dDOI Listing
February 2020

Multiple Stereoelectroencephalography-Guided Radiofrequency Thermocoagulations for Polymicrogyria With Startle Seizures: A Case Report.

Front Neurol 2019 18;10:1095. Epub 2019 Oct 18.

Tsinghua University Yuquan Hospital, Beijing, China.

The best results of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) were observed in epilepsies with more limited lesions, but this procedure is rarely used in a wide range of brain malformation. We report a rare case of polymicrogyria (PMG) combined with drug-resistant startle seizures. Presurgical monitoring was performed using SEEG owing to the large lesion and complexity of PMG. According to the intracranial electrode results, the seizure onset was extensive, with the onset starting earlier in the cingulate sulcus and insular pole than in other sites of the other electrodes. Multi-point and multi-step SEEG-guided RF-TC was used for diffuse lesion and functional protection. RF-TC was first applied to the cingulate sulcus and insular pole, and our patient was rendered free from startle seizures after 2 weeks. Two weeks of observation helped us to observe the efficacy of RF-TC and the changes of SEEG, so as to make the next TC scheme. The patient still had spontaneous seizures after the first treatment. RF-TC was then applied to other sites involved earlier. Finally, the patient reached Engel class IIa for a follow-up period of 1 year. There were no additional startle seizures, and important functional areas were protected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.01095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813566PMC
October 2019

Heavy-Ion Carbon Radiation Regulates Long Non-Coding RNAs in Cervical Cancer HeLa Cells.

J Cancer 2019 28;10(21):5022-5030. Epub 2019 Aug 28.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People's Republic of China.

Improving the effects of radiotherapy, such as heavy ion radiation, is currently a research priority for oncotherapy. Long non-coding RNAs (lncRNAs) are a subtype of noncoding RNAs involved in the therapeutic response to tumor radiotherapy. However, little is known about the variations in lncRNAs that occur after heavy ion radiation therapy. In this study, we established two kinds of Agilent Human lncRNA arrays and examined the effects of heavy ion radiation and X-ray irradiation on HeLa cells. We compared the differences in lncRNA expression (>=2-fold changes) between cells treated with the two types of radiation and control cells and identified 504 lncRNAs and 285 mRNAs that were differentially expressed. Among these lncRNAs, TCONS-00009910 was the most highly up-regulated lncRNA, while NONHSAT060631 was the most down-regulated lncRNA in both groups. To validate these sequencing data, RT-PCR was performed, and similar findings were obtained. GO and KEGG pathway analyses were employed to probe the potential functions of the affected lncRNAs. Numerous lncRNAs were changed after radiation exposure, showing that they may have important functions in the response to tumour radiotherapy. The present findings may help to elucidate the mechanism by which lncRNAs affect the clinical responses of cancer to radiation and may provide potential diagnostic and therapeutic targets for cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.30846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775614PMC
August 2019

Bioinspired nanocomposites film with highly-aligned silicon carbide nanowires and polyvinyl alcohol for mechanical and thermal anisotropy.

Nanotechnology 2019 Jul 22;30(27):275602. Epub 2019 Mar 22.

State Key Laboratory of High Performance Ceramics & Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China. Structural Ceramics and Composites Engineering Research Center, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100039, People's Republic of China.

This work reports a bioinspired anisotropic nanocomposite by polar solution assisted mechanical stretching method, consisting of polyvinyl alcohol (PVA) and silicon carbide nanowires (SiCNWs) with aligned morphology in one direction. Inspired by the structural mimicry of myofibers, in which the uniaxial mechanical property of materials can be improved evidently, highly-aligned SiCNWs and PVA chains that interact using intermolecular force can be obtained. Hysteresis is observed and reversible deformation occurs while tensile-relaxation cycles are applied to the 100% stretched SiCNWs/PVA nanocomposites. The nanocomposites exhibit excellent properties and the tensile strength of 100% stretched SiCNWs/PVA nanocomposites is 188.30 ± 4.2 MPa and elastic modulus is 6.95 GPa, which are increased by 421.90% and 581.37% compared with pure PVA. Finite element simulation of fracture mechanism shows good agreement with the experimental results. An improvement of thermal conductivity is also achieved in well-aligned SiCNWs/PVA. The work imitates the structure of mammal muscle and also has great potential for the macroscopic application of one-dimensional nanomaterials as super flexible heat dissipation materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/ab127fDOI Listing
July 2019

An Automatic Channel Selection Approach for ICA-Based Motor Imagery Brain Computer Interface.

J Med Syst 2018 Nov 6;42(12):253. Epub 2018 Nov 6.

The Key Laboratory of Intelligent Computing and Signal Processing, Ministry of Education, Anhui University, Hefei, China.

Independent component analysis (ICA) is a potential spatial filtering method for the implementation of motor imagery brain-computer interface (MIBCI). However, ICA-based MIBCI (ICA-MIBCI) is sensitive to electroencephalogram (EEG) channels and the quality of the training data, which are two crucial factors affecting the stability and classification performance of ICA-MIBCI. To address these problems, this paper is mainly focused on the investigation of EEG channel optimization. As a reference, we constructed a single-trial-based ICA-MIBCI system with commonly used channels and common spatial pattern-based MIBCI (CSP-MIBCI). To minimize the impact of artifacts on EEG channel optimization, a data-quality evaluation method, named "self-testing" in this paper, was used in a single-trial-based ICA-MIBCI system to evaluate the quality of single trials in each dataset; the resulting self-testing accuracies were used for the selection of high-quality trials. Given several candidate channel configurations, ICA filters were calculated using selected high-quality trials and applied to the corresponding ICA-MIBCI implementation. Optimal channels for each dataset were assessed and selected according to the self-testing results related to various candidate configurations. Forty-eight MI datasets of six subjects were employed in this study to validate the proposed methods. Experimental results revealed that the average classification accuracy of the optimal channels yielded a relative increment of 2.8% and 8.5% during self-testing, 14.4% and 9.5% during session-to-session transfer, and 36.2% and 26.7% during subject-to-subject transfer compared to CSP-MIBCI and ICA-MIBCI with fixed the channel configuration. This work indicates that the proposed methods can efficiently improve the practical feasibility of ICA-MIBCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10916-018-1106-3DOI Listing
November 2018
-->