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1.
Phys Rev Lett ; 132(17): 171001, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38728703

ABSTRACT

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

2.
Radiother Oncol ; 191: 110077, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176656

ABSTRACT

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.


Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Brachytherapy/adverse effects , Prostatic Neoplasms/radiotherapy , Retrospective Studies , Prostate-Specific Antigen , CD8-Positive T-Lymphocytes , Radiotherapy Dosage
3.
Phys Rev Lett ; 129(22): 221301, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36493436

ABSTRACT

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.


Subject(s)
Electricity , Electrons
4.
Phys Rev Lett ; 129(22): 221802, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36493447

ABSTRACT

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.


Subject(s)
Cell Nucleus , Photons
5.
Zhonghua Yi Xue Za Zhi ; 102(43): 3463-3468, 2022 Nov 22.
Article in Chinese | MEDLINE | ID: mdl-36396363

ABSTRACT

Objective: To explore the feasibility and accuracy of 0-1 h high sensitivity cardiac troponin I (hs-cTnI) concentration and its changes in judging non-ST segment elevation myocardial infarction (NSTEMI), and to investigate the feasibility of a simplified process. Methods: Patients with acute chest pain and suspected NSTEMI who were admitted to the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were selected. Hs-cTnI test was carried out for the selected patients at the time of visit (0 h) and 1 h after visit. According to the 0-1 h hs-cTnI diagnostic process and threshold standard recommended by European Society of Cardiology (ESC) guidelines in 2015, the laboratory adjudication was determined. Cardiologists who did not participate in the project design and did not know the results of hs-cTnI test performed the clinical judgment according to the routine diagnosis and treatment process of emergency department. Taking clinical judgment as the gold standard, the diagnostic efficacy of 0-1 h hs-cTnI concentration and its change recommended by the guidelines for judging NSTEMI in Chinese population was analyzed. The guide process was simplified. Under the condition of not considering the time of chest pain, the guideline threshold was used for test and judgement, and the diagnostic efficacy of the simplified process was evaluated. Results: A total of 1 534 patients were enrolled in the study, aged (62±12) years and 952 (62.1%) patients were male. Among them, 402 patients (26.2%) were clinically diagnosed as NSTEMI and 1 132 patients (73.8%) were diagnosed as non-NSTEMI. According to the diagnosis and determination process recommended by the guidelines, NSTEMI was excluded in 672 patients (42.8%), and 464 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical determination reached 92.4% (1 050/1 136), the sensitivity of excluding diagnosis was 99.5% (95%CI: 98.0%-99.9%), the negative predictive value was 99.7% (95%CI: 98.8%-99.9%), and the negative likelihood ratio was 0.008 (95%CI: 0.002-0.335). The diagnostic specificity was 92.6% (95%CI: 90.9%-94.0%), the positive predictive value was 81.9% (95%CI: 78.0%-85.2%), and the positive likelihood ratio was 12.739 (95%CI: 10.356-15.670). According to the simplified process, NSTEMI was excluded in 675 patients (44.0%), and 463 patients (30.2%) were diagnosed as NSTEMI. The consistency rate with clinical judgment was 92.4% (1 051/1 138), the sensitivity of exclusion diagnosis was 99.3% (95%CI: 97.6%-99.8%), the negative predictive value was 99.6% (95%CI: 98.6%-99.9%), and the negative likelihood ratio was 0.012 (95%CI: 0.004-0.389). The diagnostic specificity was 92.6% (95%CI: 90.9%-94.0%), the positive predictive value was 81.9% (95%CI: 78.0%-85.2%), and the positive likelihood ratio was 12.705 (95%CI: 10.328-15.630). There was no significant difference in diagnostic efficacy between the simplified process and the recommended process (all P>0.05). Conclusion: The diagnostic process for judging NSTEMI according to the 0-1 h hs-cTnI concentration and its change criteria recommended by the 2015 ESC guidelines is applicable in the Chinese population and remains highly accurate in judging NSTEMI without considering the duration of chest pain at the time of presentation.


Subject(s)
Myocardial Infarction , Troponin I , Female , Humans , Male , Chest Pain , Emergency Service, Hospital , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Predictive Value of Tests , Middle Aged , Aged
6.
Radiother Oncol ; 155: 80-85, 2021 02.
Article in English | MEDLINE | ID: mdl-33172830

ABSTRACT

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.


Subject(s)
Brachytherapy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Retrospective Studies
7.
Zhonghua Yi Xue Za Zhi ; 100(26): 2049-2053, 2020 Jul 14.
Article in Chinese | MEDLINE | ID: mdl-32654452

ABSTRACT

Objective: To investigate the effect of blocking penile blood drainage at the root of the rat penis on cell retention, penile erectile function, and histopathological changes when erectile dysfunction (ED) is treated by intracavernous injection (ICI) of stem cells. Methods: Thirty male SD rats were randomly divided into sham operation group (n=6), ED model group (n=6), treatment group A (blockade group, n=9) and treatment group B (non-blockade group, n=9). Twenty-four hours after the model was established, group A and group B were treated by ICI of 1 × 10(6) adipose-derived stem cells (ADSCs). Before ICI, the penile blood drainage in group A was temporarily blocked with a rubber tourniquet at the root of the penis which was removed 5 minutes after the injection. The dynamic changes of the local fluorescent signal of the penis and the expression of the fluorescent signal in the lung were detected after ICI. The maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) was measured to evaluatethe erectile function, and histopathological changes of the penis were observed after 28 days. Results: At different time points (0, 10 and 60 min), the intensity of the bioluminescent signal (×10(6)·p·s(-1)·sr·cm(-2)) in group A had a similar trend when compared with that in group B, and the differences were not statistically significant (8.76±1.17 vs 8.16±1.12, 6.45±1.47 vs 6.72±0.69, 3.77±0.30 vs 3.36±1.06, all P>0.05). A large number of ADSCs could be found in the lungs in both treatment groups after 60 min of ICI. There was no statistically significant difference in erectile function (0.44±0.11 vs 0.43±0.07) and histopathological change (0.08±0.02 vs 0.08±0.03) regardless of the occlusion of blood drainage at the root of the penis (all P>0.05). Conclusion: Temporarily blocking of penile blood drainage has no obvious advantage in improving cell retention and efficacy when ADSCs are used to treat ED of rat models.


Subject(s)
Erectile Dysfunction , Adipose Tissue , Animals , Disease Models, Animal , Drainage , Humans , Male , Penile Erection , Penis , Rats , Rats, Sprague-Dawley
8.
Eur Rev Med Pharmacol Sci ; 24(6): 2928-2937, 2020 03.
Article in English | MEDLINE | ID: mdl-32271410

ABSTRACT

OBJECTIVE: Several long noncoding RNAs (lncRNAs) display functional effects in the tumorigenesis and progression of cervical cancer (CC). We aimed to investigate the roles of lncRNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (ROR1­AS1) in the development of CC patients. PATIENTS AND METHODS: Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was performed for the determination of ROR1­AS1 levels in both CC tissues and cell lines. The clinical value of ROR1­AS1 expression in CC patients was statistically analyzed. After transfection with si-ROR1­AS1 in SiHa and HeLa cells, cellular growth and apoptosis were examined by Cell Counting Kit (CCK-8) assay, cell colony formation, and flow cytometry. Then, wound-healing assays and transwell assays were performed to evaluate cell migration and invasion, respectively. The related proteins of epithelial-mesenchymal transition (EMT) markers and Wnt/ß-catenin signaling pathway was assessed using Western blot assays. RESULTS: We found that that the expressions of ROR1­AS1 were distinctly increased in CC tissues and cell lines. Clinical study revealed that high ROR1­AS1 expression was associated with distant metastasis, FIGO stage, and shorter five-year survival. Functional assays by performing in vitro assays revealed that inhibition of ROR1­AS1 distinctly suppressed CC cell proliferation, colony formation, migration and invasion, and promoted apoptosis. Based on results of Western blot, we showed that the downregulation of ROR1­AS1 inhibited the levels of N-cadherin and vimentin. In addition, the distinctly decreased levels of c-myc, ß-catenin, and cyclin D1 were observed in CC cells transfected with si-ROR1­AS1. CONCLUSIONS: Our results suggest that ROR1­AS1 is likely to serve as an efficient therapeutic approach in respect of CC treatment. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma.


Subject(s)
Epithelial-Mesenchymal Transition , RNA, Long Noncoding/metabolism , Receptor Tyrosine Kinase-like Orphan Receptors/metabolism , Uterine Cervical Neoplasms , beta Catenin/metabolism , Apoptosis , Cell Proliferation , Female , Humans , Middle Aged , RNA, Long Noncoding/genetics , Receptor Tyrosine Kinase-like Orphan Receptors/genetics , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/metabolism , Wnt Signaling Pathway
9.
Phys Rev Lett ; 124(11): 111301, 2020 Mar 20.
Article in English | MEDLINE | ID: mdl-32242731

ABSTRACT

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

10.
Zhonghua Yi Xue Za Zhi ; 100(7): 538-540, 2020 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-32164107

ABSTRACT

Objective: To investigate the effectiveness and safety of CT-guided intrapulmonary injection of indocyanine green (ICG) for preoperative localization of small pulmonary nodules and ground glass opacities. Methods: From October 2018 to July 2019, a total of 34 consecutive patients (39 nodules) who were suspected to be lung cancer and underwent thoracoscopic surgery were enrolled. The size of the nodules was 0.3-2.0 (0.9±0.3) cm, including 6 solid nodules, 9 impure ground glass nodules and 24 pure ground glass nodules. Before operation, ICG was injected into the lung under the guidance of CT for localization. The patient's nodules location, operation and pathology were recorded. The main outcome measures were localization success rate and complication rate. Results: Seven patients (20.6%) had mild complications including six pneumothorax and one intrapulmonary hemorrhage,but all these patients need no special treatment. There was no ICG related side effection all patients. ICG fluorescence can be observed in all localized nodules during surgery. In two patients, the fluorescence was diffused in the thoracic cavity, but the lesion can still be found at the brightest spot of fluorescence. Thirty-eight (97.4%) lesions were successfully found under fluorescence guidance, only one nodule was not found because of its small size (0.3 cm). The shortest fluorescence retention time was more than 5 hours. Conclusion: CT-guided intrapulmonary injection of ICG for localization of pulmonary nodules and ground glass opacities is safe and effective.


Subject(s)
Multiple Pulmonary Nodules , Humans , Indocyanine Green , Lung Neoplasms , Solitary Pulmonary Nodule , Thoracic Surgery, Video-Assisted , Tomography, X-Ray Computed
11.
Phys Rev Lett ; 123(22): 221301, 2019 Nov 29.
Article in English | MEDLINE | ID: mdl-31868422

ABSTRACT

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

12.
Phys Rev Lett ; 123(16): 161301, 2019 Oct 18.
Article in English | MEDLINE | ID: mdl-31702340

ABSTRACT

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.

14.
J Transl Med ; 17(1): 173, 2019 05 23.
Article in English | MEDLINE | ID: mdl-31122242

ABSTRACT

BACKGROUND: Prostate cancer is an extremely heterogeneous disease. Despite being clinically similar, some tumours are more likely to recur after surgery compared to others. Distinguishing those that need adjuvant or salvage radiotherapy will improve patient outcomes. The goal of this study was to identify circulating microRNA that could independently predict prostate cancer patient risk stratification after radical prostatectomy. METHODS: Seventy-eight prostate cancer patients were recruited at the Odette Cancer Centre in Sunnybrook Health Sciences Centre. All patients had previously undergone radical prostatectomy. Blood samples were collected simultaneously for PSA testing and miRNA analysis using NanoString nCounter technology. Of the 78 samples, 75 had acceptable miRNA quantity and quality. Patients were stratified into high- and low-risk categories based on Gleason score, pathological T stage, surgical margin status, and diagnostic PSA: patients with Gleason ≥ 8; pT3a and positive margin; pT3b and any margin; or diagnostic PSA > 20 µg/mL were classified as high-risk (n = 44) and all other patients were classified as low-risk (n = 31). RESULTS: Using our patient dataset, we identified a four-miRNA signature (miR-17, miR-20a, miR-20b, miR-106a) that can distinguish high- and low-risk patients, in addition to their pathological tumour stage. High expression of these miRNAs is associated with shorter time to biochemical recurrence in the TCGA dataset. These miRNAs confer an aggressive phenotype upon overexpression in vitro. CONCLUSIONS: This proof-of-principle report highlights the potential of circulating miRNAs to independently predict risk stratification of prostate cancer patients after radical prostatectomy.


Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Aged , Cell Line, Tumor , Circulating MicroRNA/genetics , Humans , Male , Middle Aged , Prostatic Neoplasms/genetics
15.
Phys Rev Lett ; 120(24): 241301, 2018 Jun 15.
Article in English | MEDLINE | ID: mdl-29956956

ABSTRACT

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.

16.
Curr Oncol ; 25(2): 170-175, 2018 04.
Article in English | MEDLINE | ID: mdl-29719433

ABSTRACT

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.


Subject(s)
Biomedical Research/organization & administration , Early Detection of Cancer/methods , Prostatic Neoplasms/diagnosis , Ambulatory Care Facilities/organization & administration , Biological Specimen Banks/organization & administration , Genetic Predisposition to Disease , Humans , Kallikreins/blood , Male , Observational Studies as Topic , Ontario , Program Evaluation , Prostate-Specific Antigen/blood , Prostatic Neoplasms/etiology , Prostatic Neoplasms/genetics , Risk Factors
17.
Appl Radiat Isot ; 127: 130-136, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28586704

ABSTRACT

The characteristics of the surface inactive layer of a 1-kg-mass p-type point-contact germanium detector were studied. The thickness of the inactive layer and its uniformity on the top and lateral surfaces were measured. A charge collection efficiency function was developed according to the Monte Carlo simulation to describe the charge collection capacity along the depth within this inactive layer. In the energy range below 18keV, the surface, bulk, and total spectra of 57Co, 133Ba, 137Cs, and 60Co from simulations based on the charge collection efficiency function were well consistent with those from experiments.

18.
Hum Exp Toxicol ; 36(8): 802-812, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27596071

ABSTRACT

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- ß1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- ß1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- ß1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- ß1 activation.


Subject(s)
Gene Expression Regulation/drug effects , Metal Nanoparticles/toxicity , Nickel/toxicity , Pulmonary Fibrosis/chemically induced , Transforming Growth Factor beta1/metabolism , Animals , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Transforming Growth Factor beta1/genetics
19.
Eur Rev Med Pharmacol Sci ; 20(11): 2201-8, 2016 06.
Article in English | MEDLINE | ID: mdl-27338043

ABSTRACT

OBJECTIVE: MiR-18a is a miRNA that is aberrantly overexpressed in triple-negative breast cancer (TNBC). However, its biophysical function in TNBC is still not clear. In this study, we investigated the association among miR-18a dysregulation, Dicer dysregulation and paclitaxel (PTX) resistance in TNBC cells. PATIENTS AND METHODS: 20 TNBC patients who received neoadjuvant chemotherapy before surgery were recruited. MiR-18a expression was quantified using QRT-PCR. The effects of miR-18a overexpression or knockdown on cell viability and apoptosis of PTX sensitive MDA-MB-231 cells and PTX resistant MDA-MB-231 cells after PTX treatment were studied. The influence of miR-18a overexpression on Dicer expression was measured by qRT-PCR and Western blot analysis. RESULTS: Tissues from patients with stable disease (SD, n = 5) and progressive disease (PD, n = 2) to paclitaxel (PTX) containing neoadjuvant chemotherapy had significantly higher miR-18a expression than that from patients with partial response (PR, n = 13). MDA-MB-231/PTX cells had higher miR-18a expression than MDA-MB-231 cells. MiR-18a overexpression directly led to Dicer repression at mRNA and protein level. MiR-18a overexpression significantly increased PTX IC50 and reduced PTX induced cell apoptosis, while miR-18a suppression substantially decreased PTX IC50 and increased PTX induced cell apoptosis. CONCLUSIONS: This study found that miR-18a is an important miRNA that suppresses Dicer expression and increases PTX resistance in TNBC cells.


Subject(s)
MicroRNAs/metabolism , Paclitaxel/pharmacology , Triple Negative Breast Neoplasms/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , Up-Regulation/drug effects
20.
BMC Genomics ; 17: 142, 2016 Feb 27.
Article in English | MEDLINE | ID: mdl-26920613

ABSTRACT

BACKGROUND: Zinc finger proteins (ZFPs) play an important role in regulating plant responses to abiotic stress. However, little is known about the function of LSD1-like-type ZFP in saline-alkaline (SA) stress resistance of rice. In this study, OsLOL5 (GenBank No. AJ620677), containing two LSD1-like-type C2C2 domains, was isolated and analyzed its protection roles in transgenic plants and yeast. OsLOL5 was located in the nucleus as evidenced by the bombardment of onion epidermal cells. RESULTS: OsLOL5 expression significantly increased in rice leaves and roots under 150 mmol L-1 NaCl, 30 mM NaHCO3, and 10 mmol L-1 H2O2 treatment, respectively. Overexpression of OsLOL5 in yeast resulted in SA tolerance at significant level. Transgenic Arabidopsis plants overexpressing OsLOL5 grew well in the presence of both NaCl and NaHCO3 treatments, whereas wild-type plants exhibited chlorosis, stunted growth phenotype, and even death. SA stress caused significant changes in the malondialdehyde (MDA) contents in non-transgenic plants compared with those in transgenic lines. Transgenic rice overexpressing OsLOL5 exhibited stronger resistance than NT under NaHCO3 treatment, as demonstrated by its greater shoot length, and fresh weight. The genes associated with oxidative stress, such as OsAPX2, OsCAT, OsCu/Zn-SOD, and OsRGRC2, were significantly upregulated in OsLOL5-overexpressing rice. The results suggested that OsLOL5 improved SA tolerance in plants, and regulated oxidative and salinity stress retardation via the active oxygen detoxification pathway. CONCLUSIONS: The yeast INVScI bacterium grew significantly better than the control strain under NaCl, NaHCO3, and H2O2 treatments. These findings illustrated that OsLOL5 overexpression enhanced yeast resistance for SA stress through active oxygen species. The present study showed that the OsLOL5 genes involved in the ROS signaling pathways may combine with the model plant Arabidopsis and rice in LDS1-type ZFP by ROS signaling pathways that regulate cell necrosis. We speculated that the OsLOL5 active oxygen scavenging system may have coordinating roles. The present study further revealed that OsLOL5 ZFP could regulate oxidative stress function, but could also provide a basis for salt-resistant rice strains.


Subject(s)
Arabidopsis/physiology , Oryza/genetics , Plant Proteins/genetics , Saccharomyces cerevisiae/physiology , Salt Tolerance/genetics , Arabidopsis/genetics , Cloning, Molecular , Malondialdehyde/metabolism , Oryza/physiology , Oxidative Stress , Plants, Genetically Modified/genetics , Plants, Genetically Modified/physiology , Reactive Oxygen Species/metabolism , Saccharomyces cerevisiae/genetics , Signal Transduction , Stress, Physiological , Zinc Fingers
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