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1.
Sci Rep ; 9(1): 12128, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431657

RESUMO

Presbycusis or age-related hearing loss (ARHL) is the most common sensory deficit in the human population. A substantial component of the etiology stems from pathological changes in sensory and non-sensory cells in the cochlea. Using a non-obese diabetic (NOD) mouse model, we have characterized changes in both hair cells and spiral ganglion neurons that may be relevant for early signs of age-related hearing loss (ARHL). We demonstrate that hair cell loss is preceded by, or in parallel with altered primary auditory neuron functions, and latent neurite retraction at the hair cell-auditory neuron synapse. The results were observed first in afferent inner hair cell synapse of type I neurites, followed by type II neuronal cell-body degeneration. Reduced membrane excitability and loss of postsynaptic densities were some of the inaugural events before any outward manifestation of hair bundle disarray and hair cell loss. We have identified profound alterations in type I neuronal membrane properties, including a reduction in membrane input resistance, prolonged action potential latency, and a decrease in membrane excitability. The resting membrane potential of aging type I neurons in the NOD, ARHL model, was significantly hyperpolarized, and analyses of the underlying membrane conductance showed a significant increase in K+ currents. We propose that attempts to alleviate some forms of ARHL should include early targeted primary latent neural degeneration for effective positive outcomes.

2.
Kidney Blood Press Res ; 44(4): 743-753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31401635

RESUMO

BACKGROUND: Primary hyperoxaluria type 3 (PH3) is a rare autosomal recessive disorder that affects glyoxylate metabolism. PH3 is caused by defects in 4-hydroxy-2-oxoglutarate aldolase, which is encoded by the HOGA1 gene. However, only 3 cases of PH3 have been described in Asians until today. This study aimed to determine the clinical and mutation spectra of patients from mainland China with PH3. METHODS: We applied targeted next-generation sequencing to four non-consanguineous, unrelated Chinese families with PH3 to identify the genes hosting disease-causing mutations. This approach was confirmed by Sanger sequencing. RESULTS: Five patients (2 boys and 3 girls) from four unrelated Chinese families were admitted because of kidney stones. Five HOGA1 gene sequence mutations were detected, including two novel mutations, c.811C>T (p.R271C) and c.812G>A (p.R271H). These compound heterozygous mutations were detected in a female PH3 patient (patient 4). Other patients included 2 boys who had heterozygous c.834_834+1GG>TT and c.834G>A (p.A278A) mutations (patients 1 and 2), a girl with homozygous c.834G>A (p.A278A) mutation (patient 3), and a girl with heterozygous c.834_834+1GG>TT and c.346C>T (p.Q116X) mutations (patient 5). The mutations in the c.834_834+1 region, including c.834G>A, c.834+1G>T, and c.834_834+1GG>TT, account for 5/8 of alleles in our study and 3/4 of alleles reported among Chinese patients. All patients in this study received hyperhydration and urine alkalinization treatment. CONCLUSION: Five PH3 cases were reported. Potential mutation hot spot region (c.834_834+1) in the Chinese population and two novel mutations were found.

3.
Int. braz. j. urol ; 45(3): 549-559, May-June 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1012314

RESUMO

ABSTRACT Objective: To study the expression patterns of long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) and the changes in cell proliferation, apoptosis, migration and invasion induced by silencing CCAT1 in bladder cancer cells. Materials and Methods: The expression levels of CCAT1 were determined using realtime quantitative polymerase chain reaction in cancerous tissues and paired normal tissues from 34 patients with bladder cancer. The relationship between clinical characteristics and CCAT1 expression was analyzed. And then we conducted cell experiments. Bladder urothelial carcinoma cell lines T24 and 5637 cells were transfected with CCAT1 small interfering RNA (siRNA) or scramble siRNA. Cell proliferation and apoptosis changes were determined using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometry assay. Migration and invasion changes were measured using a wound healing assay and a trans-well assay. microRNAs (miRNAs) were predicted by Starbase 2.0, and their differential expression levels were studied. Results: CCAT1 was significantly upregulated in bladder cancer (P < 0.05). CCAT1 upregulation was positively related to tumor stage (P = 0.004), tumor grade (P = 0.001) and tumor size (P = 0.042). Cell proliferation, migration and invasion were promoted by abnormally expressed CCAT1. miRNAs miR-181b-5p, miR-152-3p, miR-24-3p, miR-148a-3p and miR-490-3p were potentially related to the aforementioned functions of CCAT1. Conclusion: CCAT1 plays an oncogenic role in urothelial carcinoma of the bladder. In addition, CCAT1 may be a potential therapeutic target in this cancer.

4.
BMC Med Genet ; 20(1): 85, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109299

RESUMO

BACKGROUND: Glycogen storage disease type I (GSD I), also known as von Gierk disease, is a metabolic disorder leading to the excessive accumulation of glycogen and fat in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay and growth retardation, which can be indicated by height, weight, blood glucose and blood lipids. CASE PRESENTATION: Here we present a 16-year-old male patient with GSD Ia complicated with hepatic adenoma and combined with hepatitis B. As a chronic hepatitis B patient, the patient was admitted to hospital in order to further clarify the nature of hepatic space occupancy because of suspicion of hepatocellular carcinoma. However, the imaging studies did not support hepatocellular carcinoma certainly. And by tracing his clinical history, we suggested that he might suffer from GSD I. Finally the diagnosis was confirmed by MRI (Gd-EOB-DTPA), liver biopsy and whole exome sequencing (WES). The WES discovered a homozygous point mutation at the exon 5 of G6PC gene at 17th chromosome, c.G648 T (p.L216 L, NM_000151, rs80356484). This pathogenic mutation causes CTG changing to CTT at protein 216. Though both codons encode leucine, this silent mutation creates a new splicing site 91 bp downstream of the authentic splice site. According to previous research, this mutation is a disease causal variant for GSD Ia, and has a high frequency among GSD patients in China and Japan. This patient was finally diagnosed as GSD Ia complicated with hepatic adenoma and combined with chronic hepatitis B, and received corn starch therapy immediately after GSD was suspected. After receiving corn starch therapy, the height and weight of the patient were increased, and the secondary sexual characteristics were developed, including beard, pubic hair and seminal emission. Unexpectedly, the liver adenomas were still increasing, and we did not find any cause to explain this phenomenon. CONCLUSION: This patient was diagnosed as GSD Ia combined with chronic hepatitis B, who responded to corn starch intervention. For childhood patients with hypoglycaemia, hyperlipidemia, puberty delay and growth retardation, GSD should be considered. Gene sequencing is valuable for the quick identification of GSD subtypes.

5.
Funct Plant Biol ; 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064640

RESUMO

Most studies on salt tolerance in plants have been conducted using glycophytes like Arabidopsis thaliana (L.) Heynh., with limited resistance to salinity. The xerohalophyte Zygophyllum xanthoxylum (Bunge) Engl. is a salt-accumulating desert plant that efficiently transports Na+ into vacuoles to manage salt and exhibits increased growth under salinity conditions, suggesting a unique transcriptional response compared with glycophytes. We used transcriptome profiling by RNA-seq to compare gene expression in roots of Z. xanthoxylum and A. thaliana under 50 mM NaCl treatments. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis suggested that 50 mM NaCl was perceived as a stimulus for Z. xanthoxylum whereas a stress for A. thaliana. Exposure to 50 mM NaCl caused metabolic shifts towards gluconeogenesis to stimulate growth of Z. xanthoxylum, but triggered defensive systems in A. thaliana. Compared with A. thaliana, a vast array of ion transporter genes was induced in Z. xanthoxylum, revealing an active strategy to uptake Na+ and nutrients from the environment. An ascorbate-glutathione scavenging system for reactive oxygen species was also crucial in Z. xanthoxylum, based on high expression of key enzyme genes. Finally, key regulatory genes for the biosynthesis pathways of abscisic acid and gibberellin showed distinct expression patterns between the two species and auxin response genes were more active in Z. xanthoxylum compared with A. thaliana. Our results provide an important framework for understanding unique patterns of gene expression conferring salt resistance in Z. xanthoxylum.

6.
Int Braz J Urol ; 45(3): 549-559, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038865

RESUMO

OBJECTIVE: To study the expression patterns of long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) and the changes in cell proliferation, apoptosis, migration and invasion induced by silencing CCAT1 in bladder cancer cells. MATERIALS AND METHODS: The expression levels of CCAT1 were determined using realtime quantitative polymerase chain reaction in cancerous tissues and paired normal tissues from 34 patients with bladder cancer. The relationship between clinical characteristics and CCAT1 expression was analyzed. And then we conducted cell experiments. Bladder urothelial carcinoma cell lines T24 and 5637 cells were transfected with CCAT1 small interfering RNA (siRNA) or scramble siRNA. Cell proliferation and apoptosis changes were determined using a Cell Counting Kit-8 (CCK-8) assay and a fl ow cytometry assay. Migration and invasion changes were measured using a wound healing assay and a trans-well assay. microRNAs (miRNAs) were predicted by Starbase 2.0, and their differential expression levels were studied. RESULTS: CCAT1 was signifi cantly upregulated in bladder cancer (P < 0.05). CCAT1 upregulation was positively related to tumor stage (P = 0.004), tumor grade (P = 0.001) and tumor size (P = 0.042). Cell proliferation, migration and invasion were promoted by abnormally expressed CCAT1. miRNAs miR-181b-5p, miR-152-3p, miR-24-3p, miR-148a-3p and miR-490-3p were potentially related to the aforementioned functions of CCAT1. CONCLUSION: CCAT1 plays an oncogenic role in urothelial carcinoma of the bladder. In addition, CCAT1 may be a potential therapeutic target in this cancer.


Assuntos
RNA Longo não Codificante/análise , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Citometria de Fluxo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , Sincalida/análise , Fatores de Tempo , Regulação para Cima , Cicatrização/genética
7.
Phys Med Biol ; 64(10): 105024, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30939459

RESUMO

A novel beam filter consisting of multiple aperture devices (MADs) has been developed for dynamic fluence field modulation (FFM) in CT. Each MAD achieves spatial modulation of x-ray through fine-scale, highly attenuating tungsten bars of varying widths and spacings. Moiré patterns produced by relative motions between two MADs provide versatile classes of modulation profiles. The dual-MAD filter can be designed to achieve specific classes of target profiles. The designed filter was manufactured through a laser-sintering process and integrated to an experimental imaging system that enables linear actuation of the MADs. Dynamic FFM was achieved through a combination of beam shape modulation (by relative MAD motion) and amplitude modulation (by view-dependent mAs). To correct for gains associated with the MADs, we developed an algorithm to account for possible focal spot changes during/between scans and spectral effects introduced by the MADs. We performed FFM designs for phantoms following two imaging objectives: (1) to achieve minimum mean variance in filtered backprojection (FBP) reconstruction, and (2) to flatten the fluence behind the phantom. Comparisons with conventional FFM strategies involving a static bowtie and pulse width modulation were performed. The dual-MAD filter produced modulation profiles closely matched with the design target, providing varying beam widths not achievable by the static bowtie. The entire range of modulation profiles was achieved by 0.373 mm of MAD displacement. The correction algorithm effectively alleviated ring artifacts as a result of MADs while preserving phantom details such as wires and tissue boundaries. Dynamic FFM enabled by the MADs were effective in achieving the imaging objectives and demonstrated superior FFM capabilities compared to the static bowtie. In an ellipse phantom, the FFM of objective 1 achieved the lowest mean variance in all cases investigated. The FFM of objective 2 produce nearly isotropic local noise power spectrum and homogeneous noise magnitude. The dual-MAD filter provides an effective tool for fluence control in CT to overcome limitations of conventional static bowties and to further enable patient-specific FFM studies for a wide range of dose and image quality objectives.

8.
Parasit Vectors ; 12(1): 96, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30867025

RESUMO

BACKGROUND: Three main enzymes including cathepsin B, cathepsin D and acid phosphatase are involved in vitellin degradation, which is a major biochemical event of the embryonic development and can provide nutrients and metabolites for tick embryos. In the present study, the mRNA expression profiles and enzymatic activity of cathepsin B, cathepsin D and acid phosphatase were investigated during embryonic development in the tick Haemaphysalis longicornis. RESULTS: The results revealed that all three enzymes were expressed throughout embryonic development. Both cathepsin B and acid phosphatase transcripts were accumulated during the first four days. Cathepsin B reached its highest expression on day 5, whereas the peak expression of acid phosphatase and cathepsin D occurred on day 11. The highest activity of cathepsin B was observed on the first day of egg development, whereas cathepsin D reached its highest activity on day 13. Acid phosphatase activity increased gradually during the first five days and then remained stable until the end of egg development. CONCLUSIONS: Three enzymes were expressed and activated in eggs, and also presented different dynamic changes with the development of embryos. The profiles of both mRNA expression and enzymatic activity of these enzymes indicate that they are controlled orderly and play multiple roles during embryonic development in ticks.


Assuntos
Fosfatase Ácida/genética , Catepsina B/genética , Catepsina D/genética , Regulação da Expressão Gênica no Desenvolvimento , Ixodidae/enzimologia , Fosfatase Ácida/metabolismo , Animais , Catepsina B/metabolismo , Catepsina D/metabolismo , Feminino , Ixodidae/embriologia , Ixodidae/genética
9.
Biomed Pharmacother ; 110: 717-726, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30553198

RESUMO

BACKGROUND AND PURPOSE: The aim of this study was to investigate the interactions between mGluR5 and NMDAR during the development of tolerance to the analgesic effect of chronic morphine following disruption of the link between mGluR5 and NMDAR. METHODS: For these experiments, mGluR5 knockout (KO) mice, Shank3 ΔC mutant mice and their littermate controls were used. Repeated morphine treatment through intrathecal injections (i.t. 10 µg/10 µl twice daily for 5 days) was used to induce antinociceptive tolerance and thermal hyperalgesia, which was determined by tail-flick latency and calculated as a percentage of the maximum possible effect (%MPE). Expression of NMDAR subunits (NR1, NR2A and NR2B) and phosphorylation of NR2B in cortex were evaluated by Western blot. RESULTS: Chronic morphine treatment increased the total expression of mGluR5 and NR2A but not NR1 and NR2B in the cortex and enhanced the phosphorylation of NR2B in wild-type mice after tolerance developed. mGluR5 KOs had attenuated morphine-induced tolerance and thermal hyperalgesia and reduced chronic morphine-induced phosphorylation of NR2B but not total NR2A expression. Shank3 ΔC mice were used to imitate the loss of the physiological connection between mGluR5 and NMDAR, and the mice showed a similar analgesic effect to morphine as their littermate controls, and there were no differential effects on NMDAR subunits compared with controls during the development of morphine-induced tolerance. CONCLUSIONS: It may be mGluR5-mediated PKC signalling that plays the most significant role in the mechanisms underlying morphine-induced antinociceptive tolerance rather than the physiological connection between mGluR5 and NMDAR.


Assuntos
Analgésicos Opioides/uso terapêutico , Tolerância a Medicamentos/fisiologia , Morfina/uso terapêutico , Medição da Dor/efeitos dos fármacos , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Analgésicos Opioides/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfina/farmacologia , Medição da Dor/métodos , Subunidades Proteicas/metabolismo , Receptor de Glutamato Metabotrópico 5/deficiência
10.
BMC Genomics ; 19(1): 866, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30509164

RESUMO

BACKGROUND: The goat is an important farm animal. Reproduction is an important process of goat farming. The ovary is the most important reproductive organ for goats. In recent years, an increasing number of long non-coding RNAs (lncRNAs) have been implicated in the regulation of mammal reproduction. However, there are few studies on the function of lncRNAs in reproduction, particularly lncRNAs in the ovary. RESULTS: The sequencing of goat ovaries generated 1,122,014,112 clean reads, and 4926 lncRNAs and 1454 TUCPs (transcripts of uncertain coding potential) were identified for further analysis by using the coding potential analysis software, CNCI, CPC and Pfam-sca. There were 115 /22 differential lncRNAs /TUCPs transcripts between the ovaries of the luteal phase and the follicular phase. We predicted the related genes of lncRNA /TUCP based on co-expression and co-localization methods. In total, 2584 /904 genes were predicted by co-expression, and 326/73 genes were predicted by co-localization. The functions of these genes were further analyzed with GO and KEGG analysis. The results showed that lncRNAs /TUCPs, which are highly expressed in goat ovaries in the luteal phase, are mainly associated with the synthesis of progesterone, and we filtered the lncRNAs /TUCPs, such as XR_001918177.1 and TUCP_001362, which may regulate the synthesis of progesterone; lncRNAs /TUCPs, which are highly expressed in goat ovaries in the follicular phase, are mainly associated with oogenesis and the maturation of oocytes, and we filtered the lncRNAs /TUCPs that may regulate the oogenesis and maturation of oocyte, such as XR_001917388.1 and TUCP_000849. CONCLUSION: The present study provided the genome expression profile of lncRNAs /TUCPs in goat ovaries at different estrus periods and filtered the potential lncRNAs /TUCPs associated with goat reproduction. These results are helpful to further study the molecular mechanisms of goat reproduction.

11.
J Am Soc Hypertens ; 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30509779

RESUMO

The present study intended to evaluate the variation of the hypertensive prevalence detected on a single-day blood pressure (BP) value against that on an average of 3-day BP values. This study included 1185 residents (age 21-94, 62.6 ± 14.0 years, 491 males) for BP measurements over three separate visits within a 7-day period. The newly diagnosed hypertension on the first day BP value was recorded as hypertension by epidemiological method, whereas that on the average of 3-day BP values as hypertension by clinical method. True positive rate (TPR) was the ratio of the newly diagnosed hypertensives by clinical method to those by epidemiological method. The overestimation ratio was calculated based on the following formula: (epidemiological prevalence-clinical prevalence)/epidemiological prevalence. Our results showed that of the 367 newly diagnosed hypertensives by epidemiological method, 308 were confirmed by clinical method, and with a TPR of 83.9%. The epidemiological prevalence of hypertension was higher than the clinical prevalence (41.1% vs. 36.1%) with an overestimation ratio of 12.2%. In addition, the participants aged <65 years had a lower TPR (77.9% vs. 87.8%, P = .012) against the participants aged ≥65 years. Furthermore, participants with systolic BP values of <160 mm Hg (78.2% vs. 100%, P < .001) or diastolic BP values of <100 mm Hg also had a lower TPR (70.1% vs. 100%, P = .006) compared with those having a systolic BP of 140-159 mm Hg or diastolic BP 90-99 mm Hg. It is concluded that in this population, the hypertension prevalence by epidemiological method is overestimated by 12.2% against clinical hypertension prevalence.

12.
Exp Appl Acarol ; 76(4): 513-522, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30413990

RESUMO

The tick Dermacentor everestianus mainly distributed in Tibet, China and Nepal, and can transmit some pathogens causing great damages in Qinghai-Tibet Plateau. This study investigated the life cycle and development characteristics of D. everestianus under field conditions. The average duration of the whole life cycle of D. everestianus was 124.4 days, with the host available in the field plot. Under natural conditions, the mean feeding, preoviposition and oviposition period of female ticks were 6.1, 17.9 and 21.2 days, respectively. The incubation time of eggs was the longest phase in the life cycle of the ticks (26 days on average). Moreover, the weight of engorged females was highly positively correlated with the number of the eggs that were laid (r = 0.81, P < 0.05). The reproductive efficiency index and reproductive fitness index in females were 7.3 and 5.9, respectively. The above findings suggest that the tick D. everestianus have evolved well adaptability to the highland areas.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30447942

RESUMO

Apocynum venetum is an eco-economic plant species with high adaptability to saline and arid environments. Our previous work has found that A. venetum could absorb large amount of Na+ and maintain high K+ level under saline conditions. To investigate whether K+ and Na+ could simultaneously enhance drought resistance in A. venetum, seedlings were exposed to osmotic stress (-0.2 MPa) in the presence or absence of additional 25 mM NaCl under low (0.01 mM) and normal (2.5 mM) K+ supplying conditions, respectively. The results showed that A. venetum should be considered as a typical K+-efficient species since its growth was unimpaired and possessed a strong K+ uptake and prominent K+ utilization efficiency under K+ deficiency condition. Leaf K+ concentration remained stable or was even significantly increased under osmotic stress in the presence or absence of NaCl, compared with that under control condition, regardless of whether the K+ supply was sufficient or not, and the contribution of K+ to leaf osmotic potential consistently exceeded 37%, indicating K+ is the uppermost contributor to osmotic adjustment of A. venetum. Under osmotic stress, the addition of 25 mM NaCl significantly increase Na+ accumulation in leaves and the contribution of Na+ to osmotic adjustment, thus improving the relative water content, concomitantly, promoting the photosynthetic activity resulting in an enhancement of overall plant growth. These findings suggested that, K+ and Na+ simultaneously play crucial roles in the osmotic adjustment and the maintenance of water status and photosynthetic activity, which is beneficial for A. venetum to cope with drought stress.

14.
Mol Cancer ; 17(1): 143, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285771

RESUMO

BACKGROUND: Extracellular communication within the tumor microenvironment plays a critical role in tumor progression. Although exosomes can package into long non-coding RNAs (lncRNAs) to mediate extracellular communication, the role of exosomal lncRNA PTENP1 in bladder cancer (BC) remains unclear. METHOD: We detected PTENP1 expression between patients with BC and healthy controls; the expression occurred in tissues and exosomes from plasma. We assessed the diagnostic accuracy by the receiver operating characteristic curve (ROC) and the area under curve (AUC). Cell phenotypes and animal experiments were performed to determine the effect of exosomal PTENP1. RESULTS: PTENP1 was significantly reduced in BC tissues and in exosomes from plasma of patients with BC (P < 0.05). We found that PTENP1 was mainly wrapped by exosomes. Exosomal PTENP1 could distinguish patients with BC from healthy controls (AUC = 0.743; 95% confidence interval (CI) = 0.645-0.840). Normal cells secreted exosomal PTENP1 and transmitted it to BC cells, thus inhibiting the biological malignant behavior of BC cells by increasing cell apoptosis and reducing the ability to invade and migrate (P < 0.05). Exosomal PTENP1 could suppress tumor growth in vivo. Furthermore, exosomal PTENP1 mediated the expression of PTEN by competitively binding to microRNA-17. CONCLUSION: Exosomal PTENP1 is a promising novel biomarker that can be used for the clinical detection of BC. Exosomes derived from normal cells transfer PTENP1 to BC cells, which reduce the progression of BC both in vitro and in vivo and suggest that exosomal PTENP1 participates in normal-cell-to-bladder-cell communication during the carcinogenesis of BC.

15.
Chem Biol Interact ; 297: 50-56, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30365942

RESUMO

Neuroblastoma (NB) is a type of solid extracranial tumor that usually occurs in babies and children. Chemotherapy is a common method for NB treatment, however, the drug resistance exerts during the chemotherapy of NB. Galectin-1 is a member of galectin family and plays a potent role in the development of chemotherapy and radiotherapy resistance. However, the effect of galectin-1 on cisplatin resistance in NB remains unknown. The present study aimed to investigate the role of galectin-1 in cisplatin resisitance and the potential mechanism. Human neuroblastoma SH-SY5Y and SK-N-SH cells were treated with cisplatin and/or galectin-1/siRNA targeting galectin-1 (si-Gal-1). The cell viability was measured by MTT assay. The IC50 values for cisplatin of neuroblastoma cells were calculated. The expression levels of autophagy markers including microtubule-associated protein light chain 3 (LC3B), Beclin-1, and p62 were detected by western blot. We found that cisplatin inhibited cell viability of SH-SY5Y and SK-N-SH in a dose-dependent manner. Cisplatin induced the ratio of LC3B-II/LC3B-I and Beclin-1 expression, and inhibited the p62 expression. Knockdown of galectin-1 decreased the IC50 for cisplatin of SH-SY5Y and SK-N-SH cells and inhibited cisplatin-induced autophagy. Moreover, inhibition of autophagy suppressed galectin-1-induced increase in IC50 for cisplatin. In conclusion, galectin-1 knockdown enhanced cisplatin sensitivity of neuroblastoma cells by inhibiting autophagy. The findings might provid a novel therapeutic target to overcome cisplatin resistance in chemotherapy of NB.

16.
Int J Nanomedicine ; 13: 6073-6078, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323594

RESUMO

Purpose: The delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration with potential for clinical applications. Gene transfection is more difficult, however, for hiPSCs and hiPSC-CMs than for somatic cells. Despite improvements in transfection and transduction, the efficiency, cytotoxicity, safety, and cost of these methods remain unsatisfactory. The objective of this study is to examine gene transfection in hiPSCs and hiPSC-CMs using magnetic nanoparticles (NPs). Methods: Magnetic NPs are unique transfection reagents that form complexes with nucleic acids by ionic interaction. The particles, loaded with nucleic acids, can be guided by a magnetic field to allow their concentration onto the surface of the cell membrane. Subsequent uptake of the loaded particles by the cells allows for high efficiency transfection of the cells with nucleic acids. We developed a new method using magnetic NPs to transfect hiPSCs and hiPSC-CMs. HiPSCs and hiPSC-CMs were cultured and analyzed using confocal microscopy, flow cytometry, and patch clamp recordings to quantify the transfection efficiency and cellular function. Results: We compared the transfection efficiency of hiPSCs with that of human embryonic kidney (HEK 293) cells. We observed that the average efficiency in hiPSCs was 43%±2% compared to 62%±4% in HEK 293 cells. Further analysis of the transfected hiPSCs showed that the differentiation of hiPSCs to hiPSC-CMs was not altered by NPs. Finally, robust transfection of hiPSC-CMs with an efficiency of 18%±2% was obtained. Conclusion: The difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers a novel approach for transfection of hiPSCs and hiPSC-CMs without the need for viral vector generation.


Assuntos
Células-Tronco Pluripotentes Induzidas/metabolismo , Nanopartículas de Magnetita/química , Transfecção/métodos , Diferenciação Celular , Células HEK293 , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Lipídeos/química , Nanopartículas de Magnetita/ultraestrutura , Miócitos Cardíacos/citologia
17.
BMC Genomics ; 19(1): 734, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305014

RESUMO

BACKGROUND: Nuclear reprogramming reinstates totipotency or pluripotency in somatic cells by changing their gene transcription profile. This technology is widely used in medicine, animal husbandry and other industries. However, certain deficiencies severely restrict the applications of this technology. RESULTS: Using single-embryo RNA-seq, our study provides complete transcriptome blueprints of embryos generated by cumulus cell (CC) donor nuclear transfer (NT), embryos generated by mouse embryonic fibroblast (MEF) donor NT and in vivo embryos at each stage (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst). According to the results from further analyses, NT embryos exhibit RNA processing and translation initiation defects during the zygotic genome activation (ZGA) period, and protein kinase activity and protein phosphorylation are defective during blastocyst formation. Two thousand three constant genes are not able to be reprogrammed in CCs and MEFs. Among these constant genes, 136 genes are continuously mis-transcribed throughout all developmental stages. These 136 differential genes may be reprogramming barrier genes (RBGs) and more studies are needed to identify. CONCLUSIONS: These embryonic transcriptome blueprints provide new data for further mechanistic studies of somatic nuclear reprogramming. These findings may improve the efficiency of somatic cell nuclear transfer.

18.
Med Phys ; 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30372536

RESUMO

PURPOSE: Model-based iterative reconstruction (MBIR) algorithms such as penalized-likelihood (PL) methods exhibit data-dependent and shift-variant properties. Image quality predictors have been derived to prospectively estimate local noise and spatial resolution, facilitating both system hardware design and tuning of reconstruction methods. However, current MBIR image quality predictors rely on idealized system models, ignoring physical blurring effects and noise correlations found in real systems. In this work, we develop and validate a new set of predictors using a physical system model specific to flat-panel cone-beam CT (FP-CBCT). METHODS: Physical models appropriate for integration with MBIR analysis are developed and parameterized to represent nonidealities in FP projection data including focal spot blur, scintillator blur, detector aperture effect, and noise correlations. Flat-panel-specific predictors for local spatial resolution and local noise properties in PL reconstructions are developed based on these realistic physical models. Estimation accuracy of conventional (idealized) and FP-specific predictors is investigated and validated against experimental CBCT measurements using specialized phantoms. RESULTS: Validation studies show that flat-panel-specific predictors can accurately estimate the local spatial resolution and noise properties, while conventional predictors show significant deviations in the magnitude and scale of the spatial resolution and local noise. The proposed predictors show accurate estimations over a range of imaging conditions including varying x-ray technique and regularization strength. The conventional spatial resolution prediction is sharper than ground truth. Using conventional spatial resolution predictor, the full width at half maximum (FWHM) of local point spread function (PSF) is underestimated by 0.2 mm. This mismatch is mostly eliminated in FP-specific prediction. The general shape and amplitude of local noise power spectrum (NPS) FP-specific predictions are consistent with measurement, while the conventional predictions underestimated the noise level by 70%. CONCLUSION: The proposed image quality predictors permit accurate estimation of local spatial resolution and noise properties for PL reconstruction, accounting for dependencies on the system geometry, x-ray technique, and patient-specific anatomy in real FP-CBCT. Such tools enable prospective analysis of image quality for a range of goals including novel system and acquisition design, adaptive and task-driven imaging, and tuning of MBIR for robust and reliable behavior.

19.
Biomed Pharmacother ; 106: 1661-1667, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30119242

RESUMO

Nowadays, neonatal sepsis has gradually become a global problem for its high incidence and increasing mortality. Previous studies have reported that miR-15a and miR-16 are two important modulators in neonatal sepsis. However, the upstream molecular mechanism of miR-15a/16 cluster is still mysterious. This study aims to explore a lncRNA can bind with miR-15a/16 in neonatal sepsis. Microarray analysis helped us found top ten lncRNAs which were downregulated in neonatal sepsis serum. Among these ten lncRNAs, SNHG16 was uncovered to significantly downregulated both miR-15a and miR-16. According to the result of subcellular fractionation assay, SNHG16 was mainly located in the cytoplasm of RAW264.7 cell, indicating the potential ceRNA role of SNHG16. Mechanism investigations revealed that SNHG16 could act as a ceRNA to upregulate TLR4 which is the target mRNA of miR-15a/16 cluster. At last, rescue assays demonstrated that SNHG16 reversed the effects of miR-15a/16 on LPS-induced inflammatory pathway. In summary, SNHG16 can act as a ceRNA to modulate miR-15a/16 cluster, thereby affecting LSP-induced inflammatory pathway which was downregulated by miR-15a/16 cluster.

20.
J Plant Physiol ; 229: 89-99, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30055520

RESUMO

The well-known neurotransmitter 5-hydroxytryptamine (serotonin) not only regulates sleep and mood in humans and animals but may also play important roles in modulating growth, development, and defense responses, such as seed germination, flowering, and abiotic stress tolerance, in plants. Serotonin inhibits primary root (PR) growth; however, the physiological and molecular mechanisms underlying serotonin-mediated PR growth inhibition remain largely unclear. Here, we investigate the effects of serotonin on root growth and development in Arabidopsis. Serotonin inhibits PR elongation by affecting both the meristem and elongation zones. In the meristem zone, serotonin represses both meristem cell division potential and stem cell niche activity. Serotonin induces H2O2 overaccumulation in the elongation zone and reduces O2- accumulation in the meristem zone by a UPB1 pathway, thereby disrupting reactive oxygen species (ROS) equilibrium in root tips, thus resulting in PR growth inhibition. Serotonin also regulates auxin distribution in root tips by decreasing auxin-related gene expression and repressing auxin transport through modulation of AUX1 and PIN2 abundances in root tips. Taken together, our data indicate that high concentrations of serotonin result in stress responses in plants by inhibiting PR elongation through the regulation of H2O2 and O2- distribution in PR tips and through an auxin pathway via the repression of auxin biosynthesis and transport.


Assuntos
Ácidos Indolacéticos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serotonina/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Meristema/efeitos dos fármacos , Meristema/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo
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