Publications by authors named "Jing Ni"

202 Publications

Adverse Events as a Potential Clinical Marker of Antitumor Efficacy in Ovarian Cancer Patients Treated With Poly ADP-Ribose Polymerase Inhibitor.

Front Oncol 2021 6;11:724620. Epub 2021 Sep 6.

Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, China.

Background: PARP inhibitor (PARPi) is an important progress in ovarian cancer treatment. The available evidence suggests that BRCA mutation and homologous recombination deficiency (HRD) are effective biological markers for PARPi. Here we investigated the relationship between adverse events (AEs) and efficacy of PARPi in ovarian cancer patients.

Methods: Seventy-eight patients with ovarian cancer patients underwent Olaparib and Niraparib from July 2018 to July 2020 were analyzed. AEs were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Chi-square test or fisher exact tests was performed to observe the association between categorical variables. Logistic regression analysis was conducted to investigate the independent variables for disease control response (DCR). Progression-free survival (PFS) was compared between AEs variables by log-rank test.

Results: Patients with AEs in the first one week had a higher DCR compared with those after one week (86.11% 60.98%, p=0.013). Patients with serious AEs (SAEs) had a significantly higher DCR (81.40% 60.60%, p=0.045). There were associations between anemia and DCR in both occurrence (79.63% 56.52%, p=0.037) and grade (100% 73.17%, p=0.048). The median PFS of patients with hematological toxicity was longer than that of patients with no-hematological toxicity (30 20 weeks, p=0.047). Patients with hematological toxicity within four weeks had prolonged median PFS than those with hematological toxicity after four weeks (40 22 weeks, p=0.003).

Conclusions: The early presence of AEs and SAEs in hematological toxicity of PARPi were related to the antitumor efficacy, which might be a valid and easily measurable clinical marker in ovarian cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.724620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450569PMC
September 2021

Kawasaki Disease- Management Strategies Given Symptoms Overlap to COVID-19: A Review.

JNMA J Nepal Med Assoc 2021 Apr 30;59(236):417-424. Epub 2021 Apr 30.

Children's Hospital of Shaanxi Provincial People's Hospital, 3rd Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an Shanxi, 710001, China.

Kawasaki disease is an acute, self-limiting vasculitis in children. Early treatment is necessary to prevent cardiovascular complications. The acute phase of Kawasaki disease may present with hemodynamic instability. An association between viral respiratory infections and Kawasaki disease has been reported. Studies have shown that Kawasaki and Kawasaki-like disease may be associated with and have symptoms overlapping COVID-19. Children with COVID-19 may present as Kawasaki-like disease with pediatric inflammatory multisystem syndrome, or macrophage activation syndrome. Clinicians need to be aware of the early diagnosis and management of Kawasaki disease to prevent the development of coronary artery aneurysms. The symptoms overlap of multisystem inflammatory disease seen in COVID-19 adds to the difficulties in timely diagnosis and treatment. Children with Kawasaki disease require regular follow-up plans for coronary artery aneurysms. This adds to the difficulties during the changed environment of COVID-19 for control and prevention. Missed diagnosis and early treatment of Kawasaki disease with immunoglobulin and aspirin results in the development of coronary artery aneurysm in up to 25% of cases, with grave consequences. Here, we briefly review the management of typical and atypical Kawasaki disease which has symptoms overlapping with the multisystem inflammatory disease as seen in COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.31729/jnma.5698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369595PMC
April 2021

Comprehensive metabolite profile of multi-bioactive extract from tree peony (Paeonia ostii and Paeonia rockii) fruits based on MS/MS molecular networking.

Food Res Int 2021 10 14;148:110609. Epub 2021 Jul 14.

National Engineering Technology Research Center for Oil Peony, College of Landscape Architecture and Arts, Northwest A&F University, Yangling 712100, China. Electronic address:

Tree peony seed, traditionally used for edible oil production, is rich in α-linolenic acid. However, little attention is given to the fruit by-products during seed oil production. The present work aimed to comprehensively investigate the phytochemical constituents and multiple biological activities of different parts of tree peony fruits harvested from Paeonia ostii and Paeonia rockii. 130 metabolites were rapidly identified through UPLC-Triple-TOF-MS on the basis of MS/MS molecular networking. Metabolite quantification was performed through the targeted approach of HPLC-ESI-QQQ-MS. Eight chemical markers were screened via principal component analysis (PCA) for distinguishing species and tissues. Interestingly, two dominant compounds, paeoniflorin and trans-resveratrol, are specially localized in seed kernel and seed coat, respectively. Unexpectedly, the extracts of fruit pod and seed coat showed significantly stronger antioxidant, antibacterial, and anti-neuroinflammatory activities than seed kernel from both P. ostii and P. rockii. Our work demonstrated that tree peony fruit is promising natural source of bioactive components and provided its potential utilization in food and pharmaceutical industries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodres.2021.110609DOI Listing
October 2021

extract protects human neuroblastoma SH-SY5Y cells against oxidative glutamate toxicity by activating redoxosome-p66Shc.

Exp Ther Med 2021 Sep 5;22(3):951. Epub 2021 Jul 5.

Sydney Pharmacy School, The University of Sydney, Sydney, New South Wales 2006, Australia.

extract (GBE), a traditional Chinese herbal medicine component, is widely used to alleviate symptoms of neurodegenerative diseases. It has been confirmed that GBE exerts its pharmacological effect mainly due to its antioxidant activity; however, the molecular mechanism responsible for this effect remains unclear. The aim of the present study was to investigate the detailed mechanism of GBE, the main component of dropping medicine, against oxidative glutamate toxicity in human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were untreated or pretreated with GBE followed by glutamate stimulation. Cell viability was assessed using an MTT assay. In addition, oxidative stress indexes, including intracellular ROS generation and NADPH oxidase and caspase activity, were also measured. The protein expression of key signaling factors involved in the redoxosome-p66Shc pathway was evaluated to elucidate the neuroprotective effect of GBE. The results showed that GBE treatment significantly attenuated the glutamate-induced cytotoxicity in SH-SY5Y cells by suppressing oxidative stress. A mechanical study revealed that redoxosome-p66Shc activation was associated with glutamate-induced cytotoxicity, which caused mitochondrial dysfunction and cell death. Interestingly, GBE treatment attenuated the activation of redoxosome-p66Shc in a dose-dependent manner, which suggested that the protective effect of GBE on SH-SY5Y cells against oxidative glutamate toxicity may be mediated by the modulation of redoxosome-p66Shc signaling. The current findings contribute to a better understanding of the therapeutic effect of GBE and indicate that redoxosome-p66Shc signaling might be a novel therapeutic target in the prevention and/or treatment of neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290427PMC
September 2021

Finite Element Analysis of Cushioned Diabetic Footwear Using Ethylene Vinyl Acetate Polymer.

Polymers (Basel) 2021 Jul 9;13(14). Epub 2021 Jul 9.

School of Mechanical Engineering, Hangzhou Dianzi University, Hangzhou 310018, China.

With the development of societies, diabetic foot ulcers have become one of the most common diseases requiring lower extremity amputation. The early treatment and prevention of diabetic foot ulcers can considerably reduce the possibility of amputation. Using footwear to redistribute and relieve plantar pressure is one of the important measures for the treatment and prevention of diabetic foot ulcers. Thus, the evaluation and prediction of the distribution of plantar pressure play an important role in designing footwears. Herein, the finite element method was used to study plantar pressure under two kinds of foot models, namely, the skeletal structure foot model and the whole foot model, to explore the influence of human bones on the pressure of the soles of the feet and obtain accurate foot pressure. Simulation results showed that under the two models, the plantar pressure and the pressure from the footwear with ethylene vinyl acetate were all reduced. The total deformation demonstrated a slight increase. These stresses are very useful as they enable the design of suitable orthotic footwear that reduces the amount of stress in individuals with diabetic foot ulcers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym13142261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309306PMC
July 2021

Genomic Sequence Analysis of Nucleopolyhedrovirus Isolated from Yunnan Sericulture Region, China.

Indian J Microbiol 2021 Sep 26;61(3):383-390. Epub 2021 May 26.

Sericulture and Apiculture Research Institute, Yunnan Academy of Agricultural Science, Mengzi, Yunnan China.

The blood pathogens of grasserie caused by nucleopolyhedrovirus BmNPV have a serious impact on the sericulture industry. To understand the genetic status of BmNPV endemic strains in the Yunnan sericulture region, the structure and complete genome sequence of BmNPV isolated from Baoshan city of Yunnan Province were described and compared to known strains. The BmNPV-Baoshan isolate was a nucleopolyhedrovirus parasitized in silkworm larvae. Its genome has 128, 452 bp with a G + C content of 40.4%. Phylogenetic analysis clustered the virus with China BmNPV isolates; BmNPV-Baoshan was closely related to BomaNPV-S1 (both strains originated from the same ancestor). BmNPV-Baoshan strain has gene deletion, missing 4 repeat units of 30-bp palindrome structure compared to BmNPV-T3 strain. The aim of this study was to elucidate the evolution of the virus further and provide insights for the protection of virus-induced hematologic sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12088-021-00947-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263839PMC
September 2021

Evaluation of life expectancy loss associated with submicron and fine particulate matter (PM and PM) air pollution in Nanjing, China.

Environ Sci Pollut Res Int 2021 Jul 15. Epub 2021 Jul 15.

Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.

Particulate matters with an aerodynamic diameter ≤1 μm (PM) significantly increased mortality risk, and the effect of PM was even greater than that of PM (aerodynamic diameter ≤2.5 μm). But the quantitative impact of PM on life expectancy was unknown. We aim to examine the extent to which that people's life expectancy was shortened by PM and PM. We obtained daily data on deaths, PM and PM records, and weather variables during 2016-2017 in Nanjing, China. Years of life lost (YLLs) were calculated by matching each decedent's age and sex to the Chinese life table. The fitted nonlinear dose-response associations of YLLs with PM and PM were estimated by utilizing a generalized additive model with a Gaussian link that controlled for confounding factors including meteorological variables, day of week, and long-term trend and seasonality. The effect estimates were presented as the YLLs when PM and PM concentrations fell in different ranges. Life expectancy losses attributable to PM and PM were calculated. Stratified analyses were also performed by age, sex, and death causes. Significant PM-YLL associations were observed, with greater increases in YLLs associated with PM (68.9 thousand). PM was estimated to reduce life expectancy, which was greater than PM (PM: 1.67 years; PM: 1.55 years). For PM, greater years of loss in PM-related life expectancy were found in the female group, ≥65 years group, and cardiovascular disease group. Exposure to PM had a greater impact on life expectancy loss than did PM. Constant efforts are urgently needed to control PM air pollution to improve people's longevity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-15244-zDOI Listing
July 2021

Hyaluronic acid physiological saline for enlarging deficient gingival papillae: a randomized controlled clinical trial and an study.

Ann Transl Med 2021 May;9(9):759

2nd Dental Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai, China.

Background: loss of the interdental papillae leads to the formation of a black triangle, which compromises smile esthetics and contributes to food impaction and plaque accumulation. The aim of this study was to evaluate the efficacy of the injection of hyaluronic acid (HA) and compare it to that of physiological saline solution in the restoration of deficient gingival papillae and .

Methods: Twenty-four patients with 68 deficient gingival papillae were recruited for this clinical trial with a split-mouth design. The deficient gingival papillae on one side of the anterior maxilla were injected with HA, and those on the other side were injected with physiological saline solution. The heights of the gingival papillae and the areas of the black triangles were measured from clinical photographs obtained before and 6 and 12 months after treatment. Additionally, the proliferation and migration of gingival fibroblasts were evaluated after HA and physiological saline treatment by an study.

Results: the results revealed that the injection of HA yielded 0.198 and 0.28 mm gingival papilla increasement at 6 and 12 months, respectively, relative to the baseline (P<0.05). However, deficient gingival papillae also grew by 0.278 mm at 12 months in the group that received physiological saline solution (P<0.05). The injection of HA significantly improved deficient gingival papillae 6 months earlier than the injection of physiological saline solution. HA also significantly accelerated the proliferation and migration of gingival fibroblasts .

Conclusions: The present study confirms that the injection of HA could increase the height of gingival papillae for improving gingival papilla defects. However, the effect is not superior to that of physiological saline solution. This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-ONC-17011781) (28/06/2017). http://www.chictr.org.cn/showproj.aspx?proj=19931.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-7599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246166PMC
May 2021

A Missense Variant Associated with Autosomal Dominant Midfrequency Hearing Loss Alters Subnuclear Localization and Transcriptional Capabilities.

Biomed Res Int 2021 21;2021:5574136. Epub 2021 Jun 21.

Department of Otolaryngology, School of Clinical Medicine, Xi'an Medical University, Xin Wang Road No. 1, Xi'an 710041, China.

Background: The pathogenic variant, POU class 4 transcription factor 3 (), is reported to cause autosomal dominant nonsyndromic hearing loss (ADNSHL). Previously, we have examined a four-generation midfrequency sensorineural hearing loss (MFSNHL) family (no. 6126) and established c.602T>C (p.Leu201Pro) as a potential disease-causing variant.

Objectives: We explored the structural and functional alterations that the c.602T>C (p.Leu201Pro) variant enforces on the POU4F3 protein.

Methods: We utilized wild-type (WT) and mutant (MUT) c.602T>C plasmid incorporation into HeLa cells to assess functional changes, by immunofluorescence and luciferase assays. To predict protein structural alterations in the MUT versus WT POU4F3, we also generated 3D structures to compare both types of POU4F3 proteins.

Results: The WT POU4F3 is ubiquitously present in the nucleus, whereas the MUT form of POU4F3 exhibits a more restricted nuclear presence. This finding is different from other publications, which report a cytoplasmic localization of the MUT POU4F3. We also demonstrated that, as opposed to WT POU4F3, the MUT POU4F3 had 40% reduced luciferase activity.

Conclusions: The reduced nuclear presence, combined with reduced transcriptional activity, suggests that the c.602T>C variant alters cellular activity and may contribute to the pathogenicity of -related hearing loss. It, also, provides more evidence of the pathophysiological characteristics of MFSNHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5574136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238589PMC
September 2021

Case Report: Extragonadal Yolk Sac Tumors Originating From the Endometrium and the Broad Ligament: A Case Series and Literature Review.

Front Oncol 2021 11;11:672434. Epub 2021 Jun 11.

Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Yolk sac tumors (YSTs) of the endometrium and the broad ligament are very rare, with only 29 cases and one case of each other reported before in the English literature. Due to lack of standard guidelines, the treatment strategies of these diseases are controversial. Here, we share two cases of YSTs originating from the endometrium and the broad ligament respectively and review related literature. A 35-year-old woman was diagnosed with endometrial YST in our center and underwent surgery followed by chemotherapy with BEP (bleomycin, cisplatin and etoposide) regimen for six courses. After follow-up for 21 months, there is still no evidence of relapse. Another 36-year-old woman was admitted to our department with YST of the broad ligament. She was treated with surgery followed by chemotherapy with BEP regimen and was lost to follow-up after completing therapy. The case of endometrial YST we shared was similar to cases reported before, while the case with YST of the broad ligament we shared was the second case reported worldwide. Both of these two cases were treated with surgery combined with chemotherapy with BEP regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.672434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240588PMC
June 2021

One-year outcome of single-stent crossover versus accurate ostial stenting for isolated left anterior descending ostial stenosis.

Coron Artery Dis 2021 May 18. Epub 2021 May 18.

Department of Cardiology, Rui Jin Hospital Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Background: The optimal strategy of percutaneous coronary intervention (PCI) for isolated left anterior descending (LAD) ostial lesions remains debatable. This study aimed to compare clinical outcomes of patients with isolated LAD ostial stenosis treated by single-stent crossover versus accurate ostial stenting.

Methods: A total of 216 eligible consecutive patients with isolated de novo LAD ostial stenosis were enrolled, and were stratified according to the stenting techniques. Clinical follow-up was performed by review of medical charts or telephone contact with the patients, and repeat angiography was made at 9-12 months after the procedure. Major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, non-fatal stroke and target vessel revascularization (TVR) were recorded.

Results: Single-stent crossover and accurate ostial stenting were applied to 78 (36%) and 138 (64%) patients, respectively. During a mean of 13 ± 4.1 months of follow-up, the rate of composite MACE (19.6 vs. 8.9%; P = 0.040) was higher in LAD ostial stenosis patients treated with accurate ostial stenting than those treated with single-stent crossover technique, mainly driven by more frequent TVR (17.4 vs. 7.7%; P = 0.048). PCI strategy was an independent predictor of MACE (hazard ratio 2.561; 95% CI, 1.041-6.299; P = 0.021) in the multivariable Cox regression analysis.

Conclusions: Our retrospective study suggests that the single-stent crossover technique is associated with a better 1-year clinical outcome compared with accurate ostial stenting in patients with isolated LAD ostial stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000001071DOI Listing
May 2021

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China.

J Ovarian Res 2021 May 17;14(1):68. Epub 2021 May 17.

Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42# Baiziting street, Nanjing, Jiangsu, 210009, People's Republic of China.

Background: Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China.

Methods: Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity.

Results: Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060-0.759) and disease control rate (DCR) of 50% (95%CI = 0.140-0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event.

Conclusion: It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-021-00803-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127179PMC
May 2021

Stimulation of astrocytic sigma-1 receptor is sufficient to ameliorate inflammation- induced depression.

Behav Brain Res 2021 07 4;410:113344. Epub 2021 May 4.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Jiangsu, China. Electronic address:

Astrocytes play important roles in the development of depression. As a promising target for antidepressant development, sigma-1 receptor (Sig-1R) is reported to promote activation of astrocyte in chronic stress-induced depression in our previous study. However, astrocytes are hyper-activated in inflammation-induced depression, raising concerns of whether stimulation of astrocytic Sig-1R would exert antidepressant-like effect in inflammation-induced depression. Here we reported that specific stimulation of astrocytic Sig-1R using adeno-associated virus (AAV) significantly attenuated lipopolysaccharide (LPS)- induced depressive-like behavior in the forced swim test (FST), tail suspension test (TST), sucrose preference test, and improved the memory function in novel object recognition test. Besides, specific stimulation of astrocytic Sig-1R decreased the activation of astrocyte and microglia, as well as increased brain-derived neurotrophic factor (BDNF) in LPS-induced depression. In primary cultured astrocytes, overexpression of Sig-1R also reduced the expression of IL-1β, TNF-α, iNOS during inflammation-treated astrocyte. Taken together, the results suggest that specific stimulation of astrocytic Sig-1R ameliorates inflammation-induced depressive-like behavior, providing the evidence that astrocytic Sig-1R could represent a reliable therapeutic target for depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2021.113344DOI Listing
July 2021

Long non-coding RNA CRNDE suppressing cell proliferation is regulated by DNA methylation in chronic lymphocytic leukemia.

Leuk Res 2021 06 29;105:106564. Epub 2021 Mar 29.

Department of Hematology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China. Electronic address:

Long non-coding RNA CRNDE and DNA methylation play a vital role in the occurrence and development of chronic lymphocytic leukemia (CLL). This study attempted to investigate the biological role of CRNDE methylation in CLL. The expression and methylation levels of CRNDE in CLL cell lines (MEC-1 and HG3) before or after methylation inhibitor (5-Aza-2'-deoxycytidine, 5-Aza-CdR) treatment was detected by quantitative real-time PCR or methylation-Specific PCR. The relationship among CRNDE, miR-28 and NDRG2 was verified by luciferase reporter assay. The effect of CRNDE overexpression and 5-Aza-CdR treatment on cell proliferation and apoptosis of MEC-1 and HG3 cells were assessed by CCK8 and flow cytomery. Compared with normal B lymphocytes, CRNDE was down-regulated and the methylation level of CRNDE was increased in MEC-1 and HG3 cells. Then, 5-Aza-CdR treatment caused an increase of CRNDE expression in MEC-1 and HG3 cells by demethylation. The overexpression or demethylation of CRNDE inhibited cell proliferation and promoted apoptosis in MEC-1 and HG3 cells by up-regulating CRNDE expression. Moreover, CRNDE functioned as a competing endogenous RNA to repress miR-28, which controlled its down-stream target NDRG2. CRNDE overexpression inhibited cell proliferation and promoted apoptosis via miR-28/NDRG2 axis in CLL. In conclusion, our data elaborated that CRNDE expression was regulated by DNA methylation, and the protective effect of CRNDE on CLL was attributed to the inhibition of proliferation in CLL via miR-28/NDRG2 axis. Thus, this work highlights a novel competing endogenous RNA circuitry involving key regulators of CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2021.106564DOI Listing
June 2021

On-site CO bio-sequestration in anaerobic digestion: Current status and prospects.

Bioresour Technol 2021 Jul 23;332:125037. Epub 2021 Mar 23.

School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai 200093, China.

The advantages of anaerobic digestion (AD) technology in organic solid waste treatment for bioenergy recovery are evidenced in worldwide. Recently, more attention has been paid to on-site biogas research, as well as biogenic CO sequestration from AD plant, to promote "carbon neutral". Single-phase and two-phase AD system can be incorporated with various CO bioconversion technologies through H mediated CO bioconversion (in-situ and ex-situ biogas upgrading), or other emerging strategies for CO fixation without exogenous H injection; these include in-situ direct interspecies electron transfer reinforcement, electromethanogenesis, and off-gas reutilization. The existing and potential scenarios for on-site CO bio-sequestration within the AD framework are reviewed from the perspectives of metabolic pathways, functional microorganisms, the limitations on reaction kinetics. This review concluded that on-site CO bio-sequestration is a promising solution to reduce greenhouse gas emissions and increase renewable energy recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2021.125037DOI Listing
July 2021

Transjugular intrahepatic portosystemic shunt in patients treated with a balloon tamponade for variceal hemorrhage without response to high doses of vasoactive drugs: A real-world multicenter retrospective study.

J Dig Dis 2021 May 16;22(5):236-245. Epub 2021 Apr 16.

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.

Objective: To evaluate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) and non-TIPS therapy (endoscopy and/or nonselective beta-blockers [NSBB]) in patients with cirrhosis and active variceal hemorrhage who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis.

Methods: Medical records of cirrhotic patients who did not respond to high-dose vasoactive drugs and required balloon tamponade for hemostasis at five university hospitals in China between January 2011 and December 2018 were reviewed. Treatment outcomes were compared between the TIPS and the non-TIPS groups.

Results: Treatment failure of variceal hemorrhage within 5 days was reported in six patients of the non-TIPS group (N = 70) and none of the TIPS group (N = 66) (P = .028). The TIPS group had a higher 1-year variceal rebleeding-free rate compared with the non-TIPS group (95.5% vs 60.0%, P < .001). One patient treated with TIPS and nine with non-TIPS therapy experienced rebleeding within 5 days and 6 weeks after the intervention (P = .009). The cumulative 1-year survival rate was higher in the TIPS group than in the non-TIPS group (93.9% vs 78.6%, P = .01). The TIPS group had a higher incidence of hepatic encephalopathy within one year compared with the non-TIPS group (18.2% vs 4.3%, P = .026).

Conclusion: For patients with cirrhosis and active variceal bleeding who do not respond to high-dose vasoactive agents and require a balloon tamponade for hemostasis, TIPS may be an appropriate treatment choice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1751-2980.12978DOI Listing
May 2021

Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action.

Pharmacol Res 2021 04 5;166:105481. Epub 2021 Feb 5.

First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China. Electronic address:

Cardiovascular disease (CVD) remains the major cause of death worldwide, accounting for almost 31% of the global mortality annually. Several preclinical studies have indicated that ginseng and the major bioactive ingredient (ginsenosides) can modulate several CVDs through diverse mechanisms. However, there is paucity in the translation of such experiments into clinical arena for cardiovascular ailments due to lack of conclusive specific pathways through which these activities are initiated and lack of larger, long-term well-structured clinical trials. Therefore, this review elaborates on current pharmacological effects of ginseng and ginsenosides in the cardiovascular system and provides some insights into the safety, toxicity, and synergistic effects in human trials. The review concludes that before ginseng, ginsenosides and their preparations could be utilized in the clinical treatment of CVDs, there should be more preclinical studies in larger animals (like the guinea pig, rabbit, dog, and monkey) to find the specific dosages, address the toxicity, safety and synergistic effects with other conventional drugs. This could lead to the initiation of large-scale, long-term well-structured randomized, and placebo-controlled clinical trials to test whether treatment is effective for a longer period and test the efficacy against other conventional therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105481DOI Listing
April 2021

The role of the PIK3CA gene in the development and aging of the brain.

Sci Rep 2021 01 11;11(1):291. Epub 2021 Jan 11.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.

The CLOVES syndrome is an overgrowth disease arising from mosaic activating somatic mutations in the PIK3CA gene. These mutations occur during fetal development producing malformation and overgrowth of a variety of tissues. It has recently been shown that treatment with low doses of a selective inhibitor of Class I PI3K catalytic subunit p110α, the protein product of the PIK3CA gene, can yield dramatic therapeutic benefits for patients with CLOVES and PROS (a spectrum of PIK3CA-related overgrowth syndromes). To assess the long-term effects of moderate loses of p110α activity, we followed development and growth of mice with heterozygous loss of p110α (Pik3ca) over their entire lifetimes, paying particular attention to effects on the brain. While homozygous deletion of the Pik3ca gene is known to result in early embryonic lethality, these Pik3ca mice displayed a longer lifespan compared to their wild-type littermates. These mice appeared normal, exhibited no obvious behavioral abnormalities, and no body weight changes. However, their brains showed a significant reduction in size and weight. Notably, mice featuring deletion of one allele of Pik3ca only in the brain also showed gradually reduced brain size and weight. Mechanistically, either deletion of p110α or pharmacological inhibition of p110α activity reduced neurosphere size, but not numbers, in vitro, suggesting that p110α activity is critical for neuronal stem cells. The phenotypes observed in our two genetically engineered mouse models suggest that the sustained pharmacological inhibition of the PIK3CA activity in human patients might have both beneficial and harmful effects, and future treatments may need to be deployed in a way to avoid or minimize adverse effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-79416-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801510PMC
January 2021

Salidroside protects against cardiomyocyte apoptosis and ventricular remodeling by AKT/HO-1 signaling pathways in a diabetic cardiomyopathy mouse model.

Phytomedicine 2021 Feb 4;82:153406. Epub 2020 Nov 4.

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Background: Diabetic cardiomyopathy is characterized by both systolic and diastolic dysfunction due to decreased contractility, as well as reduced compliance of the myocardium. Oxidative stress plays a significant role in diabetes mellitus and its cardiovascular complications. Salidroside, a glucoside of the phenylpropanoid tyrosol, reportedly increases the levels of the antioxidative enzymes, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 (HO-1) to counteract oxidative stress; however, the underlying mechanisms are poorly understood.

Purpose: Here we investigate the potential cardio-protective effects of salidroside and its mechanism in a diabetic animal model.

Methods: Male db/m, db/db, and age-matched wild-type mice were treated with salidroside at low dose (0.025 mg/kg) or high dose (0.05 mg/kg) by gavage every day for 12 weeks. Cardiac function and structure were assessed by echocardiography and histopathological examination. H9C2 cardiomyocytes were exposed in vitro to advanced glycosylation end products (400 μg/ml) and treated with salidroside (0.1, 1, or 10 μM). The expression of signaling-related genes were explored by western blotting and real-time PCR.

Results: Salidroside treatment significantly improved diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis in vivo. Mechanistically, salidroside markedly up-regulates HO-1 expression by activation of the AKT signaling pathway.

Conclusion: Salidroside protects against cardiomyocyte apoptosis and ventricular remodeling in diabetic mice. This cardio-protective effect of salidroside is dependent on AKT signaling activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2020.153406DOI Listing
February 2021

Correspondence on ' in individuals at risk for rheumatoid arthritis'.

Authors:
Tianyue Sun Jing Ni

Ann Rheum Dis 2020 Dec 3. Epub 2020 Dec 3.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-219347DOI Listing
December 2020

Pathogenic Heteroplasmic Somatic Mitochondrial DNA Mutation Confers Platinum-Resistance and Recurrence of High-Grade Serous Ovarian Cancer.

Cancer Manag Res 2020 2;12:11085-11093. Epub 2020 Nov 2.

Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People's Republic of China.

Purpose: Platinum resistance is a primary barrier to improving the survival rate of ovarian cancer. The relationship between mtDNA somatic mutations and response to platinum-based chemotherapy in ovarian cancer has not been well clarified.

Patients And Methods: Here, we employed the next-generation sequencing (NGS) platform to identify mtDNA mutations of the unrelated high-grade serous ovarian cancer (HGSOC) patients.

Results: We identified 569 germline variants and 28 mtDNA somatic mutations, and found the platinum-sensitive relapsed HGSOC patients had more synonymous mutations while the platinum-resistant relapsed HGSOC patients had more missense mutations in the mtDNA somatic mutations. Meanwhile, we found that the HGSOC patients who harbored heteroplasmic pathogenic mtDNA somatic mutations had significantly higher prevalence of both platinum-resistance and relapse than those without (80.0% versus 16.7%, p=0.035). Additionally, we observed that the tumor tissues had significantly higher lactate-to-pyruvate (L/P) ratio than the paired nontumor tissues (p<0.001), and L/P ratio of tumors with any heteroplasmic pathogenic mtDNA mutations was significantly higher than that of the tumors free of pathogenic mtDNA mutations (p=0.025).

Conclusion: Our findings indicate that these heteroplasmic pathogenic mtDNA somatic mutations may cause decreased respiratory chain activity and lead to the metabolism remodeling that seem to be beneficial for progression of both platinum-based chemotherapy resistance and relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S277724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646460PMC
November 2020

Bioactive components, antioxidant and antimicrobial activities of Paeonia rockii fruit during development.

Food Chem 2021 May 22;343:128444. Epub 2020 Oct 22.

College of Landscape Architecture and Arts, Northwest A&F University, Yangling 712100, China; National Engineering Technology Research Center for Oil Peony, Yangling 712100, China. Electronic address:

In last ten years, much attention focused on tree peony fruit (TPF) for edible oil production despite other potential utilization. The present study identified and quantified 29 bioactive components by liquid chromatography-electrospray ionization-triple quadrupole-mass spectrometry (LC-ESI-QqQ-MS) targeted approach during the development of TPF. Trans-resveratrol, benzoic acid, luteolin, and methyl gallate were selected as predominant chemical markers between seeds and pods through principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). Extremely high levels of paeoniflorin (1893 mg/100 g) and trans-resveratrol (1793 mg/100 g) were observed at stage 2 (S2) and S6 in seeds, respectively. Antioxidant activities determined by ABTS, DPPH, and FRAP assays showed significant correlations with total phenolic content (TPC) and total flavonoid content (TFC). The strongest antibacterial effects of pod and seed against Staphylococcus aureus and Proteus vulgaris occurred at initial stages and maturation stages. TPF could be a potential source of bioactive compounds with functional properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2020.128444DOI Listing
May 2021

Anlotinib as Exploratory Therapy for Platinum-Resistant Ovarian Cancer: A Retrospective Study on Efficacy and Safety.

Onco Targets Ther 2020 5;13:9857-9863. Epub 2020 Oct 5.

Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, People's Republic of China.

Purpose: Survival of platinum-resistant ovarian cancer (PROC) patients is significantly shortened to around 12 months. Anlotinib is a new multi-target tyrosine kinase inhibitor. The goal of this study is to evaluate the efficacy and safety of anlotinib in PROC patients.

Patients And Methods: PROC patients treated with anlotinib in Jiangsu Cancer Hospital between June 2018 to September 2019 were recruited. Most patients received an initial bolus of 12mg orally once daily on days 1-14 of a 21-day cycle (except one received a dose of 10mg and another one received a dose of 8mg orally once a day). The adverse events (AEs) and efficacy were analyzed by CTCAE 4.0 and RECIST 1.1.

Results: Of all 15 enrolled patients, 12 patients received anlotinib as multi-line therapy and 3 patients received it as maintenance therapy. In the multi-line therapy group, eight patients received anlotinib monotherapy and four patients received anlotinib combined with chemotherapy. Ultimately, evaluation showed that one patient achieved partial response (PR), five patients achieved stable disease (SD) and one patient had progressive disease (PD) with monotherapy, yielding objective response rate (ORR) of 14.3% (95% CI=0.01-0.58) and disease control rate (DCR) of 85.7% (95% CI=0.42-0.99). One patient achieved PR, two patients achieved SD with combination therapy, yielding ORR of 33.3% (95% CI=0.02-0.87) and DCR of 100% (95% CI=0.31-1.00). Three patients with maintenance therapy were followed up for 5, 8, and 11 months, respectively. The most grade 1-2 AEs were hand-foot syndrome, nausea, and hypertension. Serious AEs (SAEs) (Grade 3-4) were observed in one patient with oral ulcer and another patient with hand-foot syndrome that were managed by dose reduction.

Conclusion: Anlotinib was of promising efficacy and well tolerated in PROC patients. This is the first retrospective study about exploratory therapy for ovarian cancer patients with anlotinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S268613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547134PMC
October 2020

The fabrication of LiNbO memristors for electronic synapses using oxygen annealing.

Nanotechnology 2021 Jan;32(2):025706

School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Cheng Du, People's Republic of China.

Based on the LiNbO (LN) single crystal thin film prepared using Ar etching, an LN thin film memristor was fabricated by oxygen annealing. Atomic force microscope, scanning electron microscope and electron paramagnetic resonance test results show that the method uniformly reduces the amount of oxygen vacancies on the surface of the material. The current-voltage scanning (I-V scanning), retention and endurance test results show that this method effectively reduces the possibility of breakdown and increases the retention and endurance performance of the device. By adjusting the parameters of the electric pulse, the annealed sample successfully emulated spike-rate dependent plasticity, pulse-paired facilitation, post-tetanic potentiation, Ebbinghaus forgetting curve and the spike-time dependent plasticity. These results indicate that the device prepared herein could be used as an electronic synapse in the field of brain-like neuromorphic computing systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/abb1ebDOI Listing
January 2021

Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study.

Lancet Oncol 2020 10;21(10):1378-1386

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk.

Methods: In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10 p=5 × 10 p=5 × 10 p=5 × 10, and p=5 × 10) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2-4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor.

Findings: The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10) showed the strongest association with gastric cancer risk (p=7·56 × 10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (p<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22-1·94], p=2·67 × 10) and a high genetic risk (2·08 [1·61-2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (p<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46-2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29-0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62-1·56).

Interpretation: Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer.

Funding: National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(20)30460-5DOI Listing
October 2020

Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas.

Cell Rep 2020 09;32(13):108196

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

Loss of PTEN, the negative regulator of PI3K activity, is frequent in glioblastomas (GBMs). However, the role of the two major PI3K isoforms, p110α and p110β, in PTEN-deficient gliomagenesis remains unknown. We show that PTEN-deficient GBM largely depends on p110α for proliferation and p110β for migration. Genetic ablation of either isoform delays tumor progression in mice, but only ablating both isoforms completely blocks GBM driven by the concurrent ablation of Pten and p53. BKM120 (buparlisib) treatment only modestly prolongs survival in mice bearing intracranial Pten/p53 null tumors due to partial pathway inhibition. BKM120 extends the survival of mice bearing intracranial tumors in which p110β, but not p110α, has been genetically ablated in the Pten/p53 null glioma, indicating that BKM120 fails to inhibit p110β effectively. Our study suggests that the failure of PI3K inhibitors in GBM may be due to insufficient inhibition of p110β and indicates a need to develop brain-penetrant p110α/β inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.108196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571617PMC
September 2020

Identification of new susceptibility loci associated with rheumatoid arthritis.

Ann Rheum Dis 2020 12 31;79(12):1565-1571. Epub 2020 Aug 31.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China

Objectives: The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA).

Methods: We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function.

Results: We identified five new susceptibility loci (, , , and ; p <5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets.

Conclusion: This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-217351DOI Listing
December 2020

Expression pattern of mA regulators is significantly correlated with malignancy and antitumor immune response of breast cancer.

Cancer Gene Ther 2021 04 6;28(3-4):188-196. Epub 2020 Aug 6.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, China.

More than 24 regulators have been revealed to dynamically participant in N6-methyladenosine (mA) RNA methylation, and play critical roles in tumorigenesis and development of cancers. However, their functional roles have not been comprehensively clarified in breast cancer. Here we systematically analyzed the RNA sequencing data of 24 main mA RNA methylation regulators in 775 breast cancer patients from The Cancer Genome Atlas dataset. Consensus clustering of the 24 mA regulators was carried out and identified two patient subgroups, RNA methylation 1/2 (RM1/2). RM1 demonstrated generally lower RNA methylation modification than that of RM2, and had significantly shorter overall survival. The hallmarks of PI3K/AKT signaling in cancer, KRAS signaling and angiogenesis were significantly enriched in RM1. Moreover, the association between mA regulators and antitumor immune response was also investigated in this study and revealed that RM2 was associated with significantly higher expressions of HLA-A, higher numbers of tumor-infiltrating CD8 T cells, helper T cells and activated NK cells, but lower expressions of PD-L1, PD-L2, TIM3, and CCR4 than RM1. In conclusion, the expression pattern of mA regulators was significantly correlated with the malignancy, prognosis and antitumor immune response in breast cancer, which might serve as potential targets and biomarkers for immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41417-020-00208-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057950PMC
April 2021

Integration of GWAS and eQTL Analysis to Identify Risk Loci and Susceptibility Genes for Gastric Cancer.

Front Genet 2020 10;11:679. Epub 2020 Jul 10.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Genome-wide association studies (GWAS) have identified several susceptibility loci for gastric cancer (GC), but the majority of identified single-nucleotide polymorphisms (SNPs) fall within the non-coding region and are likely to exert their biological function by modulating gene expression. To systematically estimate expression-associated SNPs (eSNPs) that confer genetic predisposition to GC, we evaluated the associations of 314,203 stomach tissue-specific eSNPs with GC risk in three GWAS datasets (2,631 cases and 4,373 controls). Subsequently, we conducted a gene-based analysis to calculate the cumulative effect of eSNPs through sequence kernel association combined test and Sherlock integrative analysis. At the SNP-level, we identified two novel variants (rs836545 at 7p22.1 and rs1892252 at 6p22.2) associated with GC risk. The risk allele carriers of rs836545-T and rs1892252-G exhibited higher expression levels of ( = 3.70 × 10) and ( = 3.20 × 10), respectively. Gene-based analyses identified and as novel susceptibility genes for GC. and were significantly overexpressed in GC tissues than in their adjacent tissues ( = 5.59 × 10 and = 3.90 × 10, respectively), and high expression level of these two genes was associated with an unfavorable prognosis of GC patients ( = 1.30 × 10 and = 7.60 × 10, respectively). Co-expression genes with these two novel genes in normal stomach tissues were significantly enriched in several cancer-related pathways, including P53, MAPK and TGF-beta pathways. In summary, our findings confirm the importance of eSNPs in dissecting the genetic basis of GC, and the identified eSNPs and relevant genes will provide new insight into the genetic and biological basis for the mechanism of GC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.00679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366424PMC
July 2020
-->