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1.
Neurosci Bull ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072450

RESUMO

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aß42, Aß42/Aß40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aß42, Aß42/Aß40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

2.
Cell Commun Signal ; 18(1): 2, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907037

RESUMO

BACKGROUND: Gliomas are the most common and malignant brain tumors. The standard therapy is surgery combined with radiotherapy, chemotherapy, and/or other comprehensive methods. However, the emergence of chemoresistance is the main obstacle in treatment and its mechanism is still unclear. METHODS: We firstly developed a multi-gene signature by integrated analysis of cancer stem cell and drug resistance related genes. The Chinese Glioma Genome Atlas (CGGA, 325 samples) and The Cancer Genome Atlas (TCGA, 699 samples) datasets were then employed to verify the efficacy of the risk signature and investigate its significance in glioma prognosis. GraphPad Prism, SPSS and R language were used for statistical analysis and graphical work. RESULTS: This signature could distinguish the prognosis of patients, and patients with high risk score exhibited short survival time. The Cox regression and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with a well-known chemotherapy impact factor-MGMT promoter methylation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell proliferation, immune response and cell stemness. These mechanisms were confirmed in patient samples. CONCLUSIONS: The signature was an independent and powerful prognostic biomarker in glioma, which would improve risk stratification and provide a more accurate assessment of personalized treatment. Additional file 8 Video abstract.

3.
J Clin Lab Anal ; 34(1): e23030, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31502727

RESUMO

BACKGROUND: Methotrexate (MTX) is the prior drug in ectopic pregnancy (EP). However, approximately 10% of patients suffer from failure by MTX therapy. Reduced folate carrier 1 (RFC1), methylene tetrahydrofolate reductase (MTHFR), and dihydrofolate reductase (DHFR) are involved in the transport and effects of MTX in vivo. In the present study, we aim to investigate the relationship between the genetic polymorphisms of RFC1, MTHFR, and DHFR and the clinical efficacy of MTX in tubal pregnancies. METHODS: 100 patients of EP were enrolled in this study. Polymorphisms of RFC1 G80A, MTHFR C677T, and DHFR A-317G were genotyped. ß-hCG level was detected in day 0, 4, and 7 after MTX injection. Association of MTX efficacy and genetic polymorphisms was analyzed. RESULTS: Methylene tetrahydrofolate reductase C677T was associated with MTX treatment (P = .017). The success rate of first MTX injection was superior in patients with harboring mutation allele of MTHFR gene than that in patients with wild-type gene (P = .001). However, there was no significant association between the polymorphisms of RFC1 G80A, DHFR A-317G, and surgical treatment (P = .709 and .476, respectively). In addition, ß-hCG level decrement was not significantly changed by MTX injection with different polymorphisms of RFC1, MTHFR, and DHFR on either day 4 (P = .214, 0.197 and 0.270, respectively) or day 7 (P = .172, .554, and .726, respectively). CONCLUSION: Our results suggested that the reliable indicator was polymorphism of MTHFR C677T in failure by MTX injection.

4.
Ear Hear ; 41(1): 106-113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884501

RESUMO

OBJECTIVES: Electro-acoustic stimulation (EAS) enhances speech and music perception in cochlear-implant (CI) users who have residual low-frequency acoustic hearing. For CI users who do not have low-frequency acoustic hearing, tactile stimulation may be used in a similar fashion as residual low-frequency acoustic hearing to enhance CI performance. Previous studies showed that electro-tactile stimulation (ETS) enhanced speech recognition in noise and tonal language perception for CI listeners. Here, we examined the effect of ETS on melody recognition in both musician and nonmusician CI users. DESIGN: Nine musician and eight nonmusician CI users were tested in a melody recognition task with or without rhythmic cues in three testing conditions: CI only (E), tactile only (T), and combined CI and tactile stimulation (ETS). RESULTS: Overall, the combined electrical and tactile stimulation enhanced the melody recognition performance in CI users by 9% points. Two additional findings were observed. First, musician CI users outperformed nonmusicians CI users in melody recognition, but the size of the enhancement effect was similar between the two groups. Second, the ETS enhancement was significantly higher with nonrhythmic melodies than rhythmic melodies in both groups. CONCLUSIONS: These findings suggest that, independent of musical experience, the size of the ETS enhancement depends on integration efficiency between tactile and auditory stimulation, and that the mechanism of the ETS enhancement is improved electric pitch perception. The present study supports the hypothesis that tactile stimulation can be used to improve pitch perception in CI users.

5.
Environ Sci Pollut Res Int ; 27(5): 4891-4904, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31845268

RESUMO

Sewage sludge and cabbage (Brassica oleracea) were used to prepare activated carbon by high-temperature inert carbonization with the activator ZnCl2. The physicochemical characteristics of the sludge-based activated carbon (SAC) were analyzed, and the effects on the removal of chemical oxygen demand (COD) from the landfill leachate by the adsorbent dosage, adsorption time, and the solution pH were investigated in different adsorbents. Three-dimensional fluorescence spectroscopy and gas chromatography-mass spectrometry were used to analyze the organic compounds in the leachate before and after adsorption. The results demonstrated that the average iodine content of the SAC was 535.01 mg/g. The average specific surface area was 917.72 m2/g, and the dominant pore size was in the mesoporous range. The optimum parameters for adsorption were a dosage of 3%, adsorption time of 60 min, and pH = 8, and the COD removal rate reached 85.61%. The adsorption of COD on the SAC was best fitted by the Freundlich model. Additionally, the SAC was found to have a high removal efficiency for refractory organic matter and short-chain alkanes, such as humic acid-like substances, in the leachate but was not effective for long-chain alkanes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31832719

RESUMO

RATIONALE: Electrophysiological studies show that systemic nicotine narrows frequency receptive fields and increases gain in neural responses to characteristic frequency stimuli. We postulated that nicotine enhances related auditory processing in humans. OBJECTIVES: The main hypothesis was that nicotine improves auditory performance. A secondary hypothesis was that the degree of nicotine-induced improvement depends on the individual's baseline performance. METHODS: Young (18-27 years old), normal-hearing nonsmokers received nicotine (Nicorette gum, 6mg) or placebo gum in a single-blind, randomized, crossover design. Subjects performed four experiments involving tone-in-noise detection, temporal gap detection, spectral ripple discrimination, and selective auditory attention before and after treatment. The perceptual differences between posttreatment nicotine and placebo conditions were measured and analyzed as a function of the pre-treatment baseline performance. RESULTS: Nicotine significantly improved performance in the more difficult tasks of tone-in-noise detection and selective attention (effect size = - 0.3) but had no effect on relatively easier tasks of temporal gap detection and spectral ripple discrimination. The two tasks showing significant nicotine effects further showed no baseline-dependent improvement. CONCLUSIONS: Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.

7.
Onco Targets Ther ; 12: 10263-10273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819511

RESUMO

Background: Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods: Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results: Siglecs-5, -7, -9, and -16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, -7, and -9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion: Siglec-5, -7, -9, and -16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy.

8.
CNS Neurosci Ther ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880085

RESUMO

AIMS: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated. METHODS: Twenty-four C57BL/6J mice were divided into four groups: a control group; a risperidone-treated group; a lorcaserin-treated group; and a combined risperidone + lorcaserin-treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post-treatment for determination of c-fos activity. In addition, brains of NPY-GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c-fos, as well as NPY and 5-HT2c receptor using immunohistochemistry. RESULTS: There was significantly elevated c-fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone-treated mice. More than 68% c-fos-positive neurons were NPY-expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone-treated group compared with control group. Moreover, we identified that 95% 5-HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5-HT2c receptor agonist. CONCLUSION: Our findings provide critical insight into the mechanisms underlying antipsychotic-induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.

9.
Huan Jing Ke Xue ; 40(10): 4440-4449, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854811

RESUMO

In order to research the impact of continuous extreme rainfall on the water quality of the Dongjiang River, which is a drinking water source, the characteristics of extreme rainfall events in the basin were analyzed for last 38 years. The impacts of these events on water quality are discussed by considering both hydrological data and water quality data. Using SWAT2012 software, a high-precision basin model was established for the flux of major pollutants during extreme rainfall and water quality. The results indicate that there were 173 extreme rainfall events in the Dongjiang River basin over the past 38 years. The annual frequency of extreme rainfall events in high-flow years was higher than in other years. During the year, rainfall was mainly affected by climate, particularly from March to September (80%), with the peak rainfall usually occurring in June. Spatially, the Zengcheng-Bolo-Huizhou-Longmen area had the highest frequency of extreme events. During the study period, rainfall was significantly positively correlated with the concentrations of cyanide, Pb, Fe, Mn, TP, and with turbidity, and the correlation coefficients for the concentrations of TP and turbidity with rainfall were relatively high. Rainfall was significantly negatively correlated with pH, conductivity, the concentration of Zn, as well as some other indicators. These observations show that water quality is affected by rainfall to some extent. Turbidity, TN, ammonia nitrogen, and TP concentrations all showed increasing trends, to different degrees, during rainstorm runoff periods. Turbidity and TP concentrations showed a significant and consistent relationship with flow rate, peaking earlier than the flow rate peak (by approximately 1 d), showing a significant initial flushing effect. The pH curve showed an opposite trend to the flow rate, forming a "V" shape, which may be affected by the rainfall, soil acidity, and confluence conditions in the upstream mountains. Ammonia nitrogen was subject to initial flushing in the early stages of extreme rainfall but was diluted by the clean rainwater; initially, ammonia nitrogen showed high values that declined during the middle and late stages. The variations in pollutant loads were consistent with that of runoff flux, and the peaks in TN, ammonia nitrogen, and TP flux appeared later than the flow peak (by approximately 1 d), thus differing from the pollutant concentration peak. The pollutant load mainly showed a significant increase during storm runoff periods. The proportion of pollutant COD, ammonia nitrogen, and TP transported by 59.48% of the runoff reached 68.42%, 54.68%, and 70.20%, respectively, demonstrating the characteristics of rapid and high-impact pollutant loads. These characteristics have a great influence on the quality of Dongjiang River drinking water and it is suggested that initial rainwater treatment should be strengthened to reduce the negative impact of rainstorm runoff periods on water quality.

10.
Sci Rep ; 9(1): 19283, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848368

RESUMO

Our study aims to estimate the incidence of metachronous second primary lung cancer(SPLC) in initial primary lung cancer(IPLC) survivors and to determine whether radiotherapy affects the risk of metachronous SPLC in the first five years after the diagnosis of lung cancer. Incidence data of IPLC individuals who survived ≥2 years were obtained from SEER-18 database in 2004-2007. Joinpoint regression analysis and competing risk analysis were used to calculate the incidence of metachronous SPLC. Propensity score matching and decision analysis were available to estimate the effect of radiotherapy on metachronous SPLC. 264 of 11657 IPLC survivors with radiotherapy and 1090 of 24499 IPLC survivors without radiotherapy developed metachronous SPLC during 5-year follow-up, respectively. In joinpoint regression analysis, the 5-year incidence of metachronous SPLC in the radiotherapy group was lower than that in the nonradiotherapy group(2385 per 100,000 vs 4748 per 100,000, HR = 0.43,95% CI:0.39-0.47). Competing risk analysis showed that the survivors with radiotherapy were associated with the lower 5 year incidence of metachronous SPLC compared with those without radiotherapy(2.28% vs 4.47%, HR = 0.49,95% CI:0.43-0.57). Through propensity score matching, 4077 pairs of survivors were available to further study that radiotherapy potentially decreased the risk of developing metachronous SPLC with the adjustment of various factors(2.5% vs 3.3%, HR = 0.72, 95% CI:0.55-0.96). Decision analysis suggested that radiotherapy was a negative independent risk factor of metachronous SPLC with clinical net benefit in a range of risk thresholds (2% to 5%). Survivors of IPLC with radiotherapy likely had a low risk of metachronous SPLC during the first five years follow-up, especially non-small cell lung cancer.

11.
Neuromodulation ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710408

RESUMO

OBJECTIVES: Electric stimulation is used to treat a number of neurologic disorders such as epilepsy and depression. However, delivering the required current to far-field neural targets is often ineffective because of current spread through low-impedance pathways. Here, the specific aims are to develop an empirical measure for current passing through the human head and to optimize stimulation strategies for targeting deeper structures, including the auditory nerve, by utilizing the cochlear implant (CI). MATERIALS AND METHODS: Outward input/output (I/O) functions were obtained by CI stimulation and recording scalp potentials in five CI subjects. Conversely, inward I/O functions were obtained by noninvasive transcranial electric stimulation (tES) and recording intracochlear potentials using the onboard recording capability of the CI. RESULTS: I/O measures indicate substantial current spread, with a maximum of 2.2% gain recorded at the inner ear target during tES (mastoid-to-mastoid electrode configuration). Similarly, CI stimulation produced a maximum of 1.1% gain at the scalp electrode nearest the CI return electrode. Gain varied with electrode montage according to a point source model that accounted for distances between the stimulating and recording electrodes. Within the same electrode montages, current gain patterns varied across subjects suggesting the importance of tissue properties, geometry, and electrode positioning. CONCLUSION: These results provide a novel objective measure of electric stimulation in the human head, which can help to optimize stimulation parameters that improve neural excitation of deep structures by reducing the influence of current spread.

13.
Sci Rep ; 9(1): 15247, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649289

RESUMO

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces.

14.
J Alzheimers Dis ; 72(2): 479-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31594220

RESUMO

Abnormal accumulation of amyloid-ß (Aß) in the brain is the most significant pathological hallmark of Alzheimer's disease (AD). We have found that chronic systemic exposure to lipopolysaccharide of Porphyromonas gingivalis (P. gingivalis) induces the accumulation of Aß in the brain of middle-aged mice. On the other hand, recent research has shown that circulating Aß is transferred into the brain; however, the involvement of chronic systemic P. gingivalis infection in the peripheral Aß metabolism is unknown. We hypothesized that chronic P. gingivalis infection expands Aß pools in peripheral inflammatory tissues and thereby contributes to the accumulation of Aß in the brain of patients with periodontitis. We showed that the increased expression of IL-1ß, AßPP770, CatB, Aß1-42, and Aß3-42 was mainly co-localized with macrophages in the liver of P. gingivalis infected mice. Blocking CatB and NF-κB significantly inhibited the P. gingivalis-induced expression of IL-1ß, AßPP770, Aß1-42, and Aß3-42 in RAW264.7 cells. Aß3-42, but not Aß1-42, induced the significant death of macrophages, and the reduction of phagocytic abilities induced by Aß3-42 tended to be higher than that induced by Aß1-42. Additionally, the expression of AßPP770, CatB, Aß1-42, and Aß3-42 was determined in the macrophages of gingival tissues from periodontitis patients. These findings indicate that chronic systemic P. gingivalis infection induces the Aß accumulation in inflammatory monocytes/macrophages via the activation of CatB/NF-κB signaling, thus suggesting monocytes/macrophages serve as a circulating pool of Aß in patients with periodontitis. Taken together, CatB may be a novel therapeutic target for preventing the periodontitis-related AD initiation and pathological progression.

15.
Cancer Epidemiol Biomarkers Prev ; 28(12): 2079-2086, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31533943

RESUMO

BACKGROUND: Gliomas are the most common and malignant intracranial tumors. The standard therapy is surgical resection combined with radiotherapy and chemotherapy. However, the emergence of radioresistance and chemoresistance, which is largely due to DNA damage repair, limits the therapeutic efficacy. Therefore, we identified a high-efficiency DNA damage repair-related risk signature as a predictor for prognosis in lower grade glioma. METHODS: The signature was developed and validated in two independent datasets of the Chinese Glioma Genome Atlas (172 samples) and The Cancer Genome Atlas (451 samples). The time-dependent ROC curve, Cox regression, Nomogram, and Kaplan-Meier analyses were performed to evaluate the prognostic performance of the risk signature. The Metascape and IHC staining were performed to reveal the potential biological mechanism. GraphPad prism, SPSS, and R language were used for statistical analysis and graphical work. RESULTS: This signature could distinguish the prognosis of patients, and patients with high-risk scores exhibited short survival time. The time-dependent ROC curve, Cox regression, and Nomogram model indicated the independent prognostic performance and high prognostic accuracy of the signature for survival. Combined with the IDH mutation status, this risk signature could further subdivide patients with distinct survival. Functional analysis of associated genes revealed signature-related biological process of cell cycle and DNA repair. These mechanisms were confirmed in patient samples. CONCLUSIONS: The DNA damage repair-related signature was an independent and powerful prognostic biomarker in lower grade glioma. IMPACT: The signature may potentially improve risk stratification of patients and provide a more accurate assessment of personalized treatment in clinic.

16.
Philos Trans R Soc Lond B Biol Sci ; 374(1784): 20190197, 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31495315

RESUMO

Tunicates populate a great variety of marine underwater substrates worldwide and represent a significant concern in marine shipping and aquaculture. Adhesives are secreted from the anterior papillae of their swimming larvae, which attach and metamorphose into permanently adhering, filter-feeding adults. We recently described the cellular composition of the sensory adhesive organ of the model tunicate Ciona intestinalis in great detail. Notably, the adhesive secretions of collocytes accumulate at the tip of the organ and contain glycoproteins. Here, we further explore the components of adhesive secretions and have screened for additional specificities that may influence adhesion or cohesion of the Ciona glue, including other carbohydrate moieties, catechols and substrate properties. We found a distinct set of sugar residues in the glue recognized by specific lectins with little overlap to other known marine adhesives. Surprisingly, we also detect catechol residues that likely originate from an adjacent cellular reservoir, the test cells. Furthermore, we provide information on substrate preferences where hydrophobicity outperforms charge in the attachment. Finally, we can influence the settlement process by the addition of hydrophilic heparin. The further analysis of tunicate adhesive strategies should provide a valuable knowledge source in designing physiological adhesives or green antifoulants. This article is part of the theme issue 'Transdisciplinary approaches to the study of adhesion and adhesives in biological systems'.

17.
Neurobiol Dis ; 132: 104567, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31394202

RESUMO

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

18.
Funct Plant Biol ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288904

RESUMO

A field experiment was conducted on Alhagi sparsifolia Shap. with a long-term clipping history (5-8 years) to investigate the adaptation strategy of A. sparsifolia to long-term clipping. The present study found that long-term clipping can reduce self-shading and increase the photosynthesis rate (Pn) in May. During the whole growth season, clipped plants can maintain a high Pn with less variation, which we denote as a 'stable photosynthesis strategy'. Although Pn in unclipped plants was higher than in the long-term clipping treatment in August, clipped plants accumulated more carbohydrates in shoots. The enhanced amount of carbohydrates could be correlated with the greater amount of lignin synthesis in stems. Therefore, long-term clipping induced the transition of A. sparsifolia from herbs to shrubs. After long-term clipping, plants allocated more resources to plant defence against stress, whereas the ratio of resources allocated to leaf growth decreased. Consequently, photosynthesis in long-term clipped plants decreased in August. In PSII, the energy used for both photochemical quenching and non-photochemical quenching decreased in the clipped plants during the early stage of the growth season. In addition, due to the lower stomatal conductance (gs), clipped plants retained more water in their leaves and suffered less water stress. Thus, clipped plants produced less reactive oxygen species (ROS), which in turn, delayed leaf senescence. Plants also exhibited over-compensatory growth after long-term clipping, but this phenomenon was not caused by the increase in specific leaf area (SLA). The stable photosynthesis strategy helped to extend the lifespan of plants in the growth season and improve their adaptation to light, temperature, and water stress.

19.
Oncol Lett ; 18(1): 386-394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289510

RESUMO

Glioblastoma multiforme (GBM) is the most common and malignant type of glioma, with a poor prognosis for patients. The survival time of patients varies greatly due to the complexity of the human genome, which harbors diverse oncogenic drivers. In order to identify the specific driving factors, 325 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database were analyzed in the present study. The level of RELB proto-oncogene, NF-κß subunit (RELB) expression increased with the pathological grade progression of the gliomas, and higher expression levels were present in the mesenchymal subtype and isocitrate dehydrogenase 1 (IDH1) wild-type gliomas. This RELB expression pattern was identified in the CGGA database and observed in three large independent databases. In patients with GBM from the CGGA database, a higher RELB expression level was associated with a shorter survival time, a mesenchymal subtype and IDH1 wild-type gliomas. Kaplan-Meier survival analysis, survival nomograms and Cox analysis demonstrated an independent prognostic value for RELB expression. Moreover, biological function analysis indicated the association of RELB with the 'immune response', 'cell activation' and the 'apoptotic process'. In addition, RELB expression levels exhibited a negative correlation with the levels of microRNA (miR)-139-5p and miR-139-3p. The present study identified the pathological and biological roles of RELB in glioma and revealed its independent prognostic effect. These results suggested that RELB may be used as a prognostic biomarker and potential therapeutic target in glioma.

20.
CNS Neurosci Ther ; 25(9): 965-975, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31180187

RESUMO

BACKGROUND: Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. METHODS: We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. RESULTS: The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. CONCLUSION: In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.

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