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1.
Drug Dev Ind Pharm ; : 1-28, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016148

RESUMO

Plasticization, a common method of reducing the polymer melt viscosity in plastics extrusion, was investigated to improve the processability of a pharmaceutical formulation during twin-screw melt granulation. The thermolabile drug gabapentin was used as a model compound given previous work showed the benefit of preparing 80% drug loading gabapentin granules with hydroxypropyl cellulose as thermal binder. The plasticizer triethyl citrate was selected based on physicochemical compatibility with both the thermal binder and gabapentin by assessing polymer melt rheology and drug stability, respectively. Gabapentin was melt granulated at 80% drug loading with pre-plasticized binder using a co-rotating twin-screw extruder. The chemical stability and tabletability of the pre-plasticized granules were assessed to evaluate granule tabletability, drug stability, and process robustness. The granulation of gabapentin was facilitated by pre-plasticization, showing both increased granule growth and the ability to optimize processing conditions by lowering processing temperature. Pre-plasticization of thermal binder was therefore shown to be beneficial during melt granulation as a method of optimizing processing conditions while maintaining granule robustness.

3.
Cell Death Dis ; 11(10): 844, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33041323

RESUMO

Related research has recognized the vital role of methionine cycle metabolism in cancers. However, the role and mechanism of methionine cycle metabolism in hepatocellular carcinoma are still unknown. In this study, we found that [Cu(ttpy-tpp)Br2]Br (Referred to as CTB) could induce hepatocellular carcinoma cells senescence, which is a new copper complex synthesized by our research group. Interestingly, CTB induces senescence by inhibiting the methionine cycle metabolism of HCC cells. Furthermore, the inhibitory effect of CTB on the methionine cycle depends on mitochondrial carrier protein SLC25A26, which was also required for CTB-induced HCC cells senescence. Importantly, we found that CTB-induced upregulation of SLC25A26 could cause abnormal methylation of TERT and inhibited TERT expression, which is considered to be an essential cause of cell senescence. The same results were also obtained in vivo, CTB inhibits the growth of subcutaneously implanted tumors in nude mice and promoted the expression of senescence markers in tumor tissues, and interference with SLC25A26 partially offset the antitumor effect of CTB.

4.
BMJ Open ; 10(10): e037603, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33033019

RESUMO

INTRODUCTION: Recurrent aphthous stomatitis (RAS) is a distressing symptom. There are many ways to treat RAS, such as pudilan anti-inflammatory oral liquid and doxycycline and laser therapy, but these take a long time to produce positive effects and compliance is low. Previous reviews of acupuncture treatment for RAS has been growing, but a systematic review is not available. To assess the efficacy and safety of acupuncture for the management of RAS. METHODS AND ANALYSIS: The following databases will be searched from their inception to 1 February 2020: PubMed, Embase, Cochrane Library, CINAHL, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure and Wanfang. The randomised controlled trials in English or Chinese associated with acupuncture for patients with RAS will be included. Eligible study conference abstracts and reference lists of manuscripts will also be searched. Two reviewers will select the studies, extract data independently. The Cochrane risk of bias tool will be used to assess the risk of bias for the studies. According to heterogeneity testing, data will be synthesised using a random-effects model. A meta-analysis will be performed using Rev Man V.5.3.5 statistical software for each outcome. Subgroup analysis and sensitivity analysis are planned according to clinical evidence. Mean difference or standardised mean difference for continuous data and risk ratio for dichotomous data will be calculated. ETHICS AND DISSEMINATION: No ethical approval is required. This protocol will not involve individual patient information and endangering participant rights. The results will be reported in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/QASUY.

5.
Pharmacol Res ; : 105218, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007418

RESUMO

Endoplasmic reticulum (ER) stress is easily observed in chronic liver disease, which often causes accumulation of unfolded or misfolded proteins in the ER, leading to unfolded protein response (UPR). Regulating protein degradation is an integral part of UPR to relieve ER stress. The major protein degradation system includes the ubiquitin-proteasome system (UPS) and autophagy. All three arms of UPR triggered in response to ER stress can regulate UPS and autophagy. Accumulated misfolded proteins could activate these arms, and then generate various transcription factors to regulate the expression of UPS-related and autophagy-related genes. The protein degradation process regulated by UPR has great significance in many chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), viral hepatitis, liver fibrosis, and hepatocellular carcinoma(HCC). In most instances, the degradation of excessive proteins protects cells with ER stress survival from apoptosis. According to the specific functions of protein degradation in chronic liver disease, choosing to promote or inhibit this process is promising as a potential method for treating chronic liver disease.

6.
Pharmacol Res ; : 105224, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007416

RESUMO

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33017141

RESUMO

Industrial production, environmental monitoring, and clinical medicine put forward urgent demands for high-performance gas sensors. Two-dimensional (2D) materials are regarded as promising gas-sensing materials owing to their large surface-to-volume ratio, high surface activity, and abundant surface-active sites. However, it is still challenging to achieve facilely prepared materials with high sensitivity, fast response, full recovery, and robustness in harsh environments for gas sensing. Here, a combination of experiments and density functional theory (DFT) calculations is performed to explore the application of tellurene in gas sensors. The prepared tellurene nanoflakes via facile liquid-phase exfoliation show an excellent response to NO2 (25 ppb, 201.8% and 150 ppb, 264.3%) and an ultralow theory detection limit (DL) of 0.214 ppb at room temperature, which is excellent compared to that of most reported 2D materials. Furthermore, tellurene sensors present a fast response (25 ppb, 83 s and 100 ppb, 26 s) and recovery (25 ppb, 458 s and 100 ppb, 290 s). The DFT calculations further clarify the reasons for enhanced electrical conductivity after NO2 adsorption because of the interfacial electron transfer from tellurene to NO2, revealing an underlying explanation for tellurene-based gas sensors. These results indicate that tellurene is eminently promising for detecting NO2 with superior sensitivity, favorable selectivity, an ultralow DL, fast response-recovery, and high stability.

8.
Mol Genet Genomics ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025164

RESUMO

Reduced fertility is a common clinical feature of the individuals with Fanconi anemia (FA), a rare autosomal recessive disorder due to deficiency in FA pathway during DNA repair. Our previous study reported that the heterozygous pathogenic variants in FANCA (Fanconi anemia complementation group A) induced premature ovarian insufficiency (POI). However, the genotype-phenotype correlation in POI caused by FANCA variants remains considerably uncertain. Herein, a heterozygous non-frameshift Fanca-mutated mouse strain (Fanca+/hypo) carrying a 9-bp deletion (c.3581del9, p.QEA1194-1196del) was generated. The mutant mice exhibited slightly decreased Fanca protein level in ovaries, suggesting the non-frameshift deletion mutant is hypomorphic. Female fertility test showed decreased number of litters, litter sizes and prolonged litter interval time in the female Fanca+/hypo mice compared to wild-type mice. Follicle counting revealed a consistent decreasing pattern of follicle numbers in Fanca+/hypo females compared to that in wild-type mice with aging. Furthermore, embryonic fibroblasts of Fanca+/hypo mice were hyper-responsive to Mitomycin C in vitro, demonstrating a partial loss of function of this hypomorphic Fanca mutant in DNA repair. Collectively, our experimental observations suggest that the hypomorphic Fanca allele is sufficient to reduce female fertility in mice, providing new insights into the genetic counseling of FANCA variants in subfertile women.

9.
Adv Mater ; : e2002974, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000879

RESUMO

Despite the complexity and structural sophistication that 3D organoid models provide, their lack of vascularization and perfusion limit the capability of these models to recapitulate organ physiology effectively. A microfluidic platform named IFlowPlate is engineered, which can be used to culture up to 128 independently perfused and vascularized colon organoids in vitro. Unlike traditional microfluidic devices, the vascularized organoid-on-chip device with an "open-well" design does not require any external pumping systems and allows tissue extraction for downstream analyses, such as histochemistry or even in vivo transplantation. By optimizing both the extracellular matrix (ECM) and the culture media formulation, patient-derived colon organoids are co-cultured successfully within a self-assembled vascular network, and it is found that the colon organoids grow significantly better in the platform under constant perfusion versus conventional static condition. Furthermore, a colon inflammation model with an innate immune function where circulating monocytes can be recruited from the vasculature, differentiate into macrophage, and infiltrate the colon organoids in response to tumor necrosis factor (TNF)- inflammatory cytokine stimulation is developed using the platform. With the ability to grow vascularized colon organoids under intravascular perfusion, the IFlowPlate platform could unlock new possibilities for screening potential therapeutic targets or modeling relevant diseases.

10.
Phys Chem Chem Phys ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33005909

RESUMO

Toluene's removal mechanism in the atmosphere is mainly attributed to the OH radical, which includes major OH-addition and minor H-abstraction reactions. The cresols and RO2 derived from OH-adducts reacting with O2 have significant impacts on the generation of secondary organic aerosols (SOA) and O3. However, computed branching ratios of various OH-adducts at various theoretical levels are largely inconsistent, mainly because previously reported barrier heights of the OH-addition reaction showed a strong method dependence. In the present study, we demonstrate that this reaction involves a nonnegligible anharmonic effect (during the process of movement of OH to the benzene ring), which has been overlooked by previous studies. The reaction kinetics of toluene + OH was systematically studied by a high-level quantum chemical method (CCSD(T)-F12/cc-pVQZ-F12//B2PLYP-D3/6-311++G(d,p)) combined with RRKM/master equation simulations. The particle-in-a-box approximation was used to treat the anharmonicity in this system. The final total rate coefficient is calculated to be 3.02 × 10-12 cm3 molecule-1 s-1 at 300 K and 1 atm. The main products for toluene + OH are computed as ortho-adducts (69.8%), benzyl radical + H2O (11.9%), ipso-adduct (7.3%), para-adduct (5.1%), and meta-adduct (5.1%). Our results indicate that both high level quantum chemical calculations for the crucial barrier heights and appropriate treatments for the anharmonicity determine the accuracy of the final computed total rate coefficients and branching ratios. Further analysis of the branching ratios of various reaction channels provides insight into the atmosphere-initiated oxidation of toluene.

11.
Cell Stem Cell ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33010822

RESUMO

Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.

12.
Lipids Health Dis ; 19(1): 222, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050938

RESUMO

BACKGROUND: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. METHODS: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. RESULTS: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. CONCLUSIONS: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.

13.
Sci Rep ; 10(1): 17139, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051547

RESUMO

It is of great significance for the efficient utilization of water resources and the construction of the ecological environment in China to fully understand the evolution process of the spatial-temporal pattern of evapotranspiration (ET). With the use of the v2.0 and v2.1 ET data sets combined with the Global Land Data Assimilation System and Noah model, this paper selects pixels as the basic research object to analyse the spatial-temporal variation in ET in China during the 71 years from 1948 to 2018. We first applied the TFPW-MK test to study the annual ET trend in China throughout the 71-year period, including the ET trend of each month from January to December and the annual total ET trend. Moreover, we examined the spatial variation in these trends. In addition, we calculated the variation coefficient of the time series of each pixel's ET throughout the 71-year period and the variation coefficient of the spatial distribution of ET in each year to analyse the spatial-temporal fluctuations in ET in the study area. Finally, the Hurst index was adopted to evaluate the future ET trend. Based on these analyses, we observed the following novel spatial-temporal characteristics of ET: from 1948 to 2018, (1) the ET in most regions covered by 89.5% of all pixels in China exhibits an increasing trend. (2) The ET trend in China varies greatly with the change in months, and many regions show the most or least obvious increasing trend (or decreasing trend) at different times. (3) The area with an increasing trend is the largest in May and the smallest in December, and more than half of the pixels in all months of a year reveal an increasing trend. (4) In the northeast, west and south regions of China, the monthly fluctuation in the ET trend is relatively large, which indicates that the ET trend in these regions is greatly affected by the month. (5) The fluctuation in ET in China is larger in the north than it is in the south and larger in the west than it is in the east. The most stable fluctuation occurs in East China. (6) The ET trend of almost all the pixels in the study area remains consistent from 1948 to 2018, and there are large areas with a notable continuity. This results in the spatial variation in ET in the study area increasing.

14.
Environ Sci Technol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-32966052

RESUMO

A new technique involving large-volume (10 m3) samples of seawater was used to determine the abundance of microplastics (MPs) in the water column in the West Pacific Ocean and the East Indian Ocean. Compared to the conventional sampling methods based on smaller volumes of water, the new data yielded abundance values for the deep-water column that were at least 1-2 orders of magnitude lower. The data suggested that limited bulk volumes currently used for surface sampling are insufficient to obtain accurate estimates of MP abundance in deep water. Size distribution data indicated that the lateral movement of MPs into the water column contributed to their movement from the surface to the bottom. This study provides a reliable dataset for the water column to enable a better understanding of the transport and fate of plastic contamination in the deep-ocean ecosystem.

15.
Life Sci ; 260: 118476, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971102

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and has the third highest mortality rate among all tumors. Previous studies found that phosphatidylinositol glycan anchor biosynthesis class U (PIGU) was highly expressed in hepatocellular carcinoma (HCC), while the function of PIGU in HCC remains unknown. Here, we deeply investigated this issue. The expression levels of PIGU in HCC cells were measured by Western blotting. The functions of PIGU in HCC cells were assessed in vitro, followed by assessing the nuclear factor-kappa B (NF-κB) pathway-related protein levels. The xenograft mouse models were conducted to investigate the effects of PIGU in vivo. Moreover, the effects of PIGU downregulation on natural killer (NK)-92 cell-mediated cell killing were detected. The results showed that PIGU was highly expressed in HCC cells compared with normal liver cells. Functional studies showed that PIGU promoted viability, cell cycle progression, migration, and invasion and suppressed apoptosis in HCC cells. Mechanism studies indicated that PIGU silencing blocked the NF-κB pathway and the blockade of the NF-κB pathway reversed the effects of PIGU overexpression on HCC cell function, including cell viability, migration, invasion, and apoptosis. In vivo studies further verified the effects of PIGU on HCC cell function, and demonstrated that PIGU knockdown suppressed tumorigenesis. Additionally, we proved that PIGU downregulation significantly enhanced the sensitivity of HCC cells to NK-92 cell cytolysis. Collectively, PIGU may promote HCC progression through activating the NF-κB pathway and promoting immune escape, indicating that PIGU may serve as a promising therapeutic target for HCC treatment.

16.
Mater Sci Eng C Mater Biol Appl ; 117: 111345, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919692

RESUMO

Simultaneous measurement of multi-physiological signals can provide effective diagnosis and therapeutic assessment of diseases. This paper reports a carbon nanotube (CNT) - Polydimethylsiloxane (PDMS) - based wearable device with piezo-resistive and voltage-sensing capabilities for simultaneously capturing wrist pulse pressure and cardiac electrical signal. The layout design of sensing elements in the device was guided by analyzing strain distribution and electric field distribution for minimizing the interference between wrist pulse and cardiac electric activity during measurement. Each device was preconditioned under the strain of 20% until the resistance change of the device reached equilibrium. After preconditioning, the relationship between the resistance change and the pressure was calibrated, which determined the device sensitivity to be 0.01 Pa-1 and the linear pressure range of the device to be 0.4 kPa to 14.0 kPa. Mechanisms of CNT-PDMS for sensing strain signal and electrical pulse signal were explored by scanning electron microscopy (SEM) imaging and equivalent circuit modeling. The device was applied to monitor the wrist pulse and ECG signals of volunteers during the recovering process after physical exercises.

17.
J Med Genet ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900840

RESUMO

BACKGROUND: The genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear. METHODS: Two Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid-Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases. RESULTS: We identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13). CONCLUSION: To the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency.

18.
Sci Adv ; 6(35): eaaz4796, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923619

RESUMO

Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.

19.
Neuromodulation ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32964635

RESUMO

OBJECTIVES: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is increasingly used to treat Meige syndrome (MS) and markedly improves symptoms. Stimulation-induced dyskinesia (SID), which adversely affects surgical outcomes and patient satisfaction, may, however, occur in some patients. This study attempts to explore possible causes of SID. MATERIALS AND METHODS: Retrospectively collected clinical data on 32 patients who underwent STN-DBS between October 2016 and April 2019 were analyzed. Clinical outcomes were assessed pre- and post-surgery, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). Patients were divided into a dyskinesia group and a non-dyskinesia group, according to whether or not they experienced persistent SID during follow-up. The coordinates of the active contacts were calculated from post-operative computerized tomography or magnetic resonance imaging, using the inter-commissural line as a reference. At final follow-up, the main stimulatory parameters for further study included pulse width, voltage, and frequency. RESULTS: At final follow-up (mean = 16.3 ± 7.2 months), MS patients had improved BFMDRS total scores compared with pre-surgical scores (mean improvement = 79.0%, p < 0.0001). The mean improvement in BFMDRS total scores in the dyskinesia (n = 10) and non-dyskinesia (n = 22) groups were 81.6 ± 8.8% and 77.9 ± 14.2%, respectively. The mean minimum voltage to induce dyskinesia was 1.7 ± 0.3 V. The programmed parameters of both groups were similar. When compared with the non-dyskinesia group, active stimulatory contact coordinates in the dyskinesia group were inferior (mean left side: z = -2.3 ± 1.7 mm vs. z = -1.2 ± 1.5 mm; p = 0.0282; mean right side: z = -2.7 ± 1.9 mm vs. z = -2.3 ± 1.7 mm; p = 0.0256). The x and y coordinates were similar. CONCLUSION: STN-DBS is an effective intervention for MS, providing marked improvements in clinical symptoms; SID may, however occur in the subsequent programming control process. Comparing patients with/without dyskinesia, the active contacts were located closer to the inferior part of the STN in patients with dyskinesia, which may provide an explanation for the dyskinesia.

20.
Mol Cell Biochem ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965597

RESUMO

Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the key ways to understand and overcome obstacles. Dysregulation of MALAT1 could regulate doxorubicin resistance of hepatocellular carcinoma (HCC), but how MALAT1 involving in managing doxorubicin resistance remains unclear yet. We aimed to elucidate the specific molecular mechanism of MALAT1 with doxorubicin resistance in HCC cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was engaged to detect the expression levels of MALAT1, miR-3129-5p and Nova1 mRNA; MTT, western blot, flow cytometry and luciferase reporter assays were executed to identify the influence of MALAT1 on doxorubicin resistance of HCC cells. Xenograft tumor model was created to confirm the biological function of MALAT1 in doxorubicin resistance of HCC cells in vivo. MALAT1 and Nova1 were upregulated, while miR-3129-5p expression was decreased in doxorubicin-resistant HCC tissues and cells. Knockdown of MALAT1 regulated doxorubicin resistance of HCC cells through inhibiting cell proliferation, migration, invasion and promoting apoptosis, but antisense miR-3129-5p released the functional effect of MALAT1 knockdown. Nova1, as a target gene of miR-3129-5p, reversed the results of miR-3129-5p expression and enhanced doxorubicin resistance of HCC cells. Xenograft tumor model suggested that dysregulation of MALAT1 regulated tumor growth and Nova1 to mediate doxorubicin resistance of HCC cells by as a sponge for miR-3129-5p in vivo. Elevation of LncRNA MALAT1 mediated doxorubicin resistance and the progression of HCC via a MALAT1/miR-3129-5p/Nova1 axis. This study would be expected to enrich the understanding of doxorubicin resistance of HCC and provide new ideas for HCC treatment strategies.

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