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1.
Dis Colon Rectum ; 62(10): 1158-1166, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31490825

RESUMO

BACKGROUND: Despite the use of neoadjuvant chemoradiation and total mesorectal excision for rectal cancer, lateral pelvic lymph node recurrence is still an important problem. OBJECTIVE: This study aimed to determine the indication for lateral pelvic lymph node dissection in post neoadjuvant chemoradiation rectal cancer. DESIGN: This is a retrospective analysis of a prospectively collected institutional database. SETTINGS: This study was conducted at a tertiary care cancer center from January 2006 through December 2017. PATIENTS: Patients who had rectal cancer with suspected lateral pelvic lymph node metastasis, who underwent total mesorectal excision with lateral pelvic lymph node dissection, were included. MAIN OUTCOME MEASURES: The primary outcome measured was pathologic lateral pelvic lymph node positivity. INTERVENTIONS: The associations between lateral pelvic lymph node size on post-neoadjuvant chemoradiation imaging and pathologic lateral pelvic lymph node positivity and recurrence outcomes were evaluated. RESULTS: A total of 64 patients were analyzed. The mean lateral pelvic lymph node size before and after neoadjuvant chemoradiation was 12.6 ± 9.5 mm and 8.5 ± 5.4 mm. The minimum size of positive lateral pelvic lymph node was 5 mm on post neoadjuvant chemoradiation imaging. Among 13 (20.3%) patients who had a <5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, none were pathologically positive. Among 51 (79.7%) patients who had a ≥5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, 33 patients (64.7%) were pathologically positive. Five-year overall survival and disease-specific survival were higher in the histologic lateral pelvic lymph node negative group than in the lateral pelvic lymph node positive group (overall survival 79.6% vs 61.8%, p = 0.122; disease-specific survival 84.5% vs 66.2%, p= 0.088). After a median 39 months of follow-up, there were no patients in the <5 mm group who died of cancer. There were no lateral compartment recurrences in the entire cohort. LIMITATIONS: Being a single-center retrospective study may limit generalizability. CONCLUSIONS: Post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm was strongly associated with pathologic positivity. No patients with size <5 mm had pathologically positive lymph nodes. Following lateral pelvic lymph node dissection, no patients with a positive lateral pelvic lymph node developed lateral compartment recurrence. Therefore, patients who have rectal cancer with clinical evidence of lateral pelvic lymph node metastasis and post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm should be considered for lateral pelvic lymph node dissection at the time of total mesorectal excision. See Video Abstract at http://links.lww.com/DCR/B3. ¿QUIéN DEBE RECIBIR LINFADENECTOMíA PéLVICA LATERAL DESPUéS DE LA QUIMIORRADIACIóN NEOADYUVANTE?: A pesar del uso de quimiorradiación neoadyuvante y la escisión total de mesorectao para el cáncer de recto, la recurrencia en los ganglios linfáticos pélvicos laterales sigue siendo un problema importante. OBJETIVO: Determinar la indicación para la disección de los ganglios linfáticos pélvicos laterales en el cáncer rectal post quimiorradiación neoadyuvante. DISEÑO:: Análisis retrospectivo de la base de datos institucional prospectivamente recopilada. ESCENARIO: Centro de cáncer de atención terciaria, de enero de 2006 hasta diciembre de 2017. PACIENTES: Pacientes con cáncer de recto con sospecha de metástasis en los ganglios linfáticos pélvicos laterales, que se sometieron a escisión total mesorectal con disección de los ganglios linfáticos pélvicos laterales. PRINCIPALES MEDIDAS DE RESULTADOS: Positividad de ganglios linfáticos pélvicos laterales en histopatología. INTERVENCIONES: Se evaluaron las asociaciones entre el tamaño de los ganglios linfáticos pélvicos laterales en imagenología postquimiorradiación neoadyuvante y la positividad y recurrencia en los ganglios linfáticos pélvicos laterales en histopatología. RESULTADOS: Se analizaron un total de 64 pacientes. La media del tamaño de los ganglios linfáticos pélvicos laterales antes y después de la quimiorradiación neoadyuvante fue de 12.6 ± 9.5 mm y 8.5 ± 5.4 mm, respectivamente. El tamaño mínimo de los ganglios linfáticos pélvicos laterales positivos fue de 5 mm en las imágenes postquimiorradiación neoadyuvante. Entre 13 (20.3%) pacientes que tenían <5 mm de ganglio linfático lateral pélvico después de la quimiorradiación neoadyuvante; ninguno fue positivo en histopatología. Entre 51 (79.7%) pacientes con ganglio linfático pélvico lateral ≥ 5 mm después de la quimiorradiación neoadyuvante; 33 pacientes (64.7%) fueron positivos en histopatología. La supervivencia general a 5 años y la supervivencia específica de la enfermedad fueron mayores en el grupo histológico de ganglio linfático pélvico lateral negativo que en el grupo de ganglio linfático pélvico lateral positivo (Supervivencia general 79.6% vs 61.8%, p = 0.122; Supervivencia específica de la enfermedad 84.5% vs 66.2%, p = 0.088). Después de una mediana de seguimiento de 39 meses, no hubo pacientes en el grupo de <5 mm que hayan fallecido por cáncer. No hubo recurrencias en el compartimento lateral en toda la cohorte. LIMITACIONES: Al ser un estudio retrospectivo en un solo centro puede limitar la generalización. CONCLUSIONES: El tamaño de los ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm se asoció fuertemente con la positividad histopatológica. Ningún paciente con tamaño <5 mm tuvo ganglios linfáticos histopatológicamente positivos. Después de la disección de los ganglios linfáticos pélvicos laterales, ningún paciente con ganglios linfáticos pélvicos laterales positivos desarrolló recurrencia del compartimiento lateral. Por lo tanto, los pacientes con cáncer rectal con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales y tamaño de ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm deben considerarse para disección de los ganglios linfáticos pélvicos laterales en el momento de la escisión total de mesorrecto. Vea el Abstract en video en http://links.lww.com/DCR/B3.

2.
Inorg Chem ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498601

RESUMO

The synthesis and photophysical characterization of a series of tetradentate cyclometalated M(tzpPh-O-CzPy-R) complexes and their analogues are reported, where M is palladium or platinum and a tetradentate cyclometalating ligand contains tzpPh (3-phenyl-[1,2,4]triazolo[4,3-a]pyridine) and CzPy (carbazolylpyridine) moieties linked with an oxygen atom. Variations of the σ-electron-donating group R on the ligand significantly affect the photophysical properties of the complexes. By using the strong electron-withdrawing tzp portion as an acceptor and the carbazole portion as a donor, a series of Pd(II)-based metal-assisted delayed fluorescence (MADF) materials was developed. Electrochemical analysis demonstrates the irreversible reduction process occurs on the tzp ring and the irreversible oxidation process mainly occurs on the metal-phenyl moiety. This is in agreement with the HOMO and LUMO distributions by the DFT calculations, which also shows that the Pt(II) complex has more metal orbital character than those of the Pd(II) complexes. Most of the Pd(II) complexes reported here are highly emissive at 77 K in 2-MeTHF with luminescent lifetimes in the millisecond range (τ = 1.96-2.36 ms) and λmax = 488-499 nm; however, the luminescent lifetimes are shortened to the microsecond range (τ = 26.7-152.9 µs in solution and 57.0-109.9 µs in thin film respectively) at room temperature. The quantum efficiency of the Pd(II) complexes can be increased by more than 8-fold through structure modification with σ-donating groups on the ligand. Especially, the Pd(tzp-3) has a small ΔEST of 0.228 eV and exhibits strong typical MADF in PMMA film. The Pt(II) complex Pt(tzp-2) exhibits high thermal stability (ΔT0.5% = 440 °C) and high quantum efficiency (Φ = 50.1%) in dichloromethane solution with τ of 15.8 µs. The Pt(tzp-2) based bright green OLED achieved a peak EQE of 8.7% and a maximum brightness of 28280 cd/m2 using an unoptimized device structure.

3.
J Mol Cell Biol ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31504667

RESUMO

Most eukaryotic mRNAs are translated in a cap-dependent fashion; however, under stress conditions, the cap-independent translation driven by internal ribosomal entry sites (IRESs) can serve as an alternative mechanism for protein production. Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trans-acting factors. Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood, the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities. A recent screen identified > 1000 putative IRESs from viral and human mRNAs, expanding the scope and mechanism for cap-independent translation. Additionally, a large number of circular RNAs lacking free ends were identified in eukaryotic cells, many of which are found to be translated through IRESs. These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA, implying a hidden proteome produced from cap-independent translation.

4.
J Orthop Surg Res ; 14(1): 310, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514742

RESUMO

BACKGROUND: Quadrilateral plate fractures are a challenging group of acetabular fractures to manage. However, there is little literature that describes the fracture lines of the quadrilateral plate. The aim of this study was to explore the fracture lines of the quadrilateral plate and relevant clinical significance. METHODS: CT data from a series of acetabular fractures were retrospectively analyzed. According to the X-ray, CT, and operative records of the patients, Judet-Letournel classification was carried out for acetabular fractures involving quadrilateral plate. Then, the fracture maps of different types of acetabular fractures in the quadrilateral plate were drawn. To facilitate the characterization of fracture maps, we defined six basic fracture lines. RESULTS: The fracture lines of the three types of acetabular fractures (double-column fracture, T-type fracture, and anterior column with posterior hemitransverse fracture) mainly included upper transverse lines and upper oblique lines. Although the fracture lines of posterior wall fracture and anterior column fracture were mainly upper transverse lines, the fracture lines of the former were in a low position. The fracture lines of transverse fracture and transverse with posterior wall fracture were similar, both of which were mainly upper oblique lines. The fracture lines of posterior column fractures mainly included posterior vertical lines. CONCLUSIONS: The fracture lines of different types of acetabular fractures have certain regularity respectively. Observation of the fracture lines of the quadrilateral plate based on fracture mapping can help orthopedic surgeons to enhance the understanding of the Judet-Letournel classification, which may have some significant guidance on the choice of operation approach and the design of internal fixation devices.

5.
Mol Cell ; 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31399345

RESUMO

The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1's cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.

6.
Asia Pac J Clin Nutr ; 28(3): 457-466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464392

RESUMO

BACKGROUND AND OBJECTIVES: Older adults are at increased risk of micronutrient deficiency, disrupting the balance of oxidation/antioxidation system and leading to serious health burdens. This study aimed to investigate the effect of micronutrient pack on micronutrient status and oxidative/antioxidative biomarkers in institutional older adults. METHODS AND STUDY DESIGN: Subjects aged 65-100 years were randomly assigned to either intervention group or control group (n=49 each), providing a package of micronutrient pack or placebo daily for three months. The concentrations of micronutrients, malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected both at baseline and at the end of the study. RESULTS: The changes in concentrations of serum folate (21.1±1.6 vs 0.6±0.5 nmol/L), vitamin B-1 (3.4±0.4 vs -0.2±0.3 nmol/L), vitamin B-2 (11.5±3.3 vs 2.3±1.4 nmol/L), vitamin B-12 (128.8±34.8 vs 13.3±16.0 pmol/L), 25-hydroxyvitamin D (17.8±1.3 vs -0.8±0.5 ng/mL) and plasma zinc (0.6±1.8 vs -9.6±1.9 µmol/L) over 3-months were significantly increased in the intervention group compared with the control group (all p<0.05). While the prevalence of folate, vitamin B-12 and vitamin D deficiencies were significantly decreased after 3-months intervention (all p<0.05). Moreover, changes in serum MDA level (-1.5±0.2 vs 0.2±0.3 nmol/mL) were remarkably reduced, and the activities of serum GSH-Px (1.3±0.3 vs 0.3±0.2 ng/mL) and plasma SOD (14.3±2.4 vs -2.1±2.4 U/mL) were increased in the intervention group than those of in the control group (all p<0.01). CONCLUSIONS: The micronutrient pack among institutional older adults was well-accepted with good compliance and tolerance. The 3-month intervention may improve micronutrient status and enhance antioxidative capacities.

7.
J Photochem Photobiol B ; 198: 111552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382089

RESUMO

A 58-day cultivation experiment was carried out to investigate the effects of photoperiods on growth, lipid metabolism and oxidative stress of juvenile gibel carp. Juveniles (5.41 ±â€¯0.01 g) were cultured under seven light photoperiods (0 h of light (L):24 h of darkness (D), 4L:20D (12:00-16:00 light), 8L:16D (10:00-18:00 light), 12L:12D (8:00-20:00 light), 16L:8D (6:00-22:00 light), 20L:4D (4:00-24:00 light) and 24L:0D) in an indoor recirculating aquaculture system. The light intensity was 1.02 µmol·m-2·s-1 (at the tank bottom in a 0.5-m water depth). The fish were fed to satiety three times daily (8:30, 14:30 and 18:30). At the end of the experiment, final body weight, specific growth rate, feed efficiency and feed intake were significantly higher in 16L:8D, 20L:4D and 24L:0D groups than those in other groups (P < 0.05). Long-day photoperiods (16L:8D, 20L:4D and 24L:0D) simultaneously promoted lipogenesis, lipolysis and fatty acid oxidation. The increases in lipid retention efficiency, whole body lipid concentration and liver lipid content (P < 0.05) indicated that lipogenesis exceeded fatty acid oxidation. Liver oxidative stress was induced in juvenile gibel carp by short day lengths. The hepatic total antioxidant capacity, superoxide dismutase, glutathione peroxidase and the contents of metabolite glutathione were the highest in the short-day-length groups (0L:24D, 4L:20D and 8L:16D) (P < 0.05). Based on the growth performance and health status in the long-term cultivation experiment, the optimal photoperiods were 16L:8D, 20L:4D and 24L:0D in juvenile gibel carp.

8.
Bosn J Basic Med Sci ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31465717

RESUMO

Aberrant metabolic regulation has been observed in human cancers, but the corresponding regulation in human papillomavirus (HPV) infection-associated cervical cancer is not well understood. Here, we explored potential biomarkers for the early prediction of cervical carcinoma based on the metabolic profile of uterine cervical tissue specimens that were positive for HPV16 infection. Fifty-two fresh cervical tissues were collected from women confirmed to have cervical squamous cell carcinoma (SCC; n = 21) or cervical intraepithelial neoplasia (CIN) stages II-III (n = 20). Eleven healthy women constituted the controls (NCs). Real-time polymerase chain reaction (PCR) was performed to detect HPV infection in the tissues. High-resolution magic angle spinning nuclear magnetic resonance was utilized for the analysis of the metabolic profile in the tissues. The expression of rate-limiting enzymes involved in key metabolic pathways was detected by reverse-transcription quantitative PCR. An independent immunohistochemical analysis was performed using 123 cases of paraffin-embedded cervical specimens. A profile of 17 small molecular metabolites that showed differential expression in HPV16-positive cervical SCC or CIN II-III compared with HPV-negative NCs was identified. According to the profile, the levels of α- and ß-glucose decreased, those of lactate and low-density lipoproteins increased, and the expression of multiple amino acids was altered. Significantly increased transcript and protein levels of glycogen synthase kinase 3 beta (GSK3ß) and glutamate decarboxylase 1 (GAD1) and decreased transcript and protein levels of pyruvate kinase M2 (PKM2) and carnitine palmitoyltransferase 1A (CPT1A) were observed in the patient group (p < 0.05). HPV infection and cervical carcinogenesis drive metabolic modifications that might be associated with the aberrant regulation of enzymes related to metabolic pathways.

10.
Cryobiology ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31449779

RESUMO

Oocyte cryopreservation is an important technology in assisted reproduction and fertility preservation. However, the developmental potential of cryopreserved oocyte remains poor. Osmotic stress injury (OSI) during cryoprotectants (CPAs) loading and unloading steps has critical impact on successful cryopreservation. In order to minimize OSI to oocytes, a microfluidic device was designed and fabricated to achieve continuous CPA concentration change. MII porcine oocytes were loaded and unloaded CPAs with step-wise and microfluidic methods, oocyte volume changes were recorded and compared, loading and unloading duration of microfluidic methods were optimized. The survival and developmental rate of treated oocytes in step-wise and microfluidic linear methods were also evaluated. The results showed that oocyte volume changes with microfluidic method were obviously less than step-wise method, and the survival, cleavage and blastocyst rate of oocytes were 95.3%, 64.4%, and 19.4%, respectively, which were significantly higher than the traditional step-wise method (79.4%, 43.6%, and 9.7%) (p < 0.05). In conclusion, microfluidic device can effectively reduce the osmotic damage to oocytes and improve the survival rate and developmental rate of oocytes, which may provide a new path for oocyte cryopreservation.

11.
Clin Rheumatol ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31428886

RESUMO

INTRODUCTION: Contrast-enhanced ultrasound (CEUS) was recently used to evaluate vascularization within the carotid artery wall, and this process of vascularization was correlated with arteritis activity. We aimed to use CEUS to evaluate disease activity in Takayasu arteritis (TAK) patients. METHOD: We used CEUS to analyze 28 consecutive TAK patients. Disease activity was assessed according to the NIH criteria. We measured CEUS grades and assessed the correlation between contrast features and disease activity. RESULTS: Higher erythrocyte sedimentation rates (ESRs) were found (35 ± 28.7 vs. 13 ± 7.4 mm/h, p < 0.01), and CEUS carotid wall enhancement was more frequently (100% vs. 36.6%, p < 0.01) seen in TAK patients in the active phase than in those in the inactive phase. With increasing CEUS grades, both the artery wall thickness and ESR increased, and patients were more likely to be in the active phase (0 in grade 0, 42.9% in grade 1, and 75% in grade 2). Receiver operating characteristic (ROC) curve analysis showed that CEUS had an area under the ROC curve (AUC) of 0.872 (95% CI 0.785-0.959, p < 0.01), demonstrating good diagnostic accuracy. CONCLUSIONS: Higher CEUS grades reliably identify patients with active TAK. Key Points • No CEUS vascularization is obviously relative with the inactive disease of TAK patients. • Obvious CEUS vascularization is obviously relative with the active disease of TAK patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31382574

RESUMO

OBJECTIVES: The association between peptic ulcer disease (PUD) and osteoporosis remains unclear. We investigated the association between PUD and osteoporosis by classifying individuals based on gender in a prospective study on 10,030 adults in Korea at a 12-year follow-up examination. DESIGN AND SETTING: The baseline survey of the Ansung-Ansan cohort studies was conducted from May 2001 to February 2003, and 10,030 participants (5018 from the Ansung study and 5012 from the Ansan study) completed the examination. PRIMARY OUTCOME MEASURES: The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group. RESULTS: At the 12-year follow-up, osteoporosis had developed in 11.1% (21/189) and 29.9% (56/187) of men and women in the PUD group, respectively. Meanwhile, in the control group, 4.8% (70/1464) and 16.5% (271/1639) of men and women, respectively, were presented with osteoporosis. The incidence rates per 1000 person-years were 20.5% and 68.5% in men and women in the PUD group and 11.2% and 42.3% of men and women in the control group, respectively. The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group (men: hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.02-2.92; women: HR = 1.62, 95% CI = 1.20-2.18). CONCLUSION: The risk of developing osteoporosis was significantly higher in both men and women in the PUD group than in the control group.

14.
Medicine (Baltimore) ; 98(26): e16080, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261519

RESUMO

Osteoporosis is a common problem, especially among postmenopausal women. Postmenopausal women with osteoporosis have major risk factors for osteoporotic fractures. The abuse of epidural steroid injections (ESIs) or the misunderstanding of their proper use could cause osteoporotic fractures. Therefore, we aimed to investigate whether ESIs are associated with osteoporotic fractures in postmenopausal women with low back pain and osteoporosis. Furthermore, we aimed to provide evidence on whether ESIs could be used in postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures.We reviewed the medical records of postmenopausal women with osteoporosis but no fractures. A total of 172 postmenopausal women were divided into 2 groups. Group 1 comprised patients receiving medications and Group 2 comprised patients receiving ESIs. All participants received medications for treating osteoporosis. Each patient's age, bone mineral density, body mass index, medical history, and status with respect to smoking, drinking, physical activity, and exercise were obtained using a questionnaire and medical records.The mean total number of ESIs was 6.2, and the mean cumulative administered dose of glucocorticoids (dexamethasone) was 31 mg. The incidences of fractures in the medication and ESI groups were 22% and 24%, respectively, in the thoracolumbar spine, and 2% and 5%, respectively, in the hip joint.There was no significant difference in the incidences of osteoporotic fractures at the thoraco-lumbar spine and hip joint in postmenopausal women with osteoporosis between those who received ESIs (a mean of 6.2 ESIs, a cumulative dexamethasone dose of 31 mg) and those who did not, with both groups taking anti-osteoporotic medications for low back pain. Our data suggest that ESI treatment using a mean of 6.2 ESIs to deliver a maximum cumulative dexamethasone dose of 31 mg could be safely used in postmenopausal women with osteoporosis, without any significant impact on the their risk for osteoporotic fractures.


Assuntos
Glucocorticoides/administração & dosagem , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Esteroides/administração & dosagem , Idoso , Dexametasona/administração & dosagem , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Injeções Epidurais , Dor Lombar/tratamento farmacológico , Dor Lombar/epidemiologia , Pós-Menopausa , Prevalência , Estudos Retrospectivos , Fraturas da Coluna Vertebral/epidemiologia
15.
J Oral Sci ; 61(3): 431-440, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31327805

RESUMO

Although airborne-particle abrasion, large-grit, acid-etched (SLA) surface technology can promote implant osseointegration; its mechanism remains unclear. By preparing the SLA titanium (Ti) plate (SLA Ti) and Polished Ti plate (Polished Ti), this experiment investigates the expression and distribution of the Yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) in MC3T3-E1 cells. In addition, gene YAP and TAZ silencing on the SLA Ti was conducted to observe changes in the osteoblast differentiation markers, runt-related transcription factor-2 (Runx2) and bone sialoprotein (BSP). The results demonstrated that SLA Ti surface microtopography could induce YAP/TAZ's transfer from the cytoplasm to the nuclei of MC3T3-E1 cells. The expression of YAP/TAZ increased in terms of mRNA and protein. After silencing the YAP/TAZ genes, Runx2 and BSP decreased, suggesting that YAP/TAZ plays an important regulatory role in this process. Meanwhile, the results also showed that SLA microtopography enhanced the expression of integrins α1, α2, and ß1. After silencing the integrin α1, α2, and ß1 genes, YAP and TAZ decreased in terms of mRNA and protein. Therefore, this experiment was the first to confirm that SLA surface microtopography facilitates osteoblast differentiation by regulating YAP/TAZ and confirms that the process can be related to integrins α1, α2, and ß1.

16.
Cell Res ; 29(9): 725-738, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273297

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

17.
Inflammopharmacology ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31352642

RESUMO

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague-Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1ß, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.

18.
BMC Med Genet ; 20(1): 130, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345173

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders. The present study aimed to identify the genetic cause of a Chinese Han family with non-syndromic oculocutaneous albinism (OCA). CASE PRESENTATION: Here, we report an 11-month-old male proband from a Chinese Han non-consanguineous family, who presented with milky skin, yellow white hair, nystagmus, astigmatism, and hypermetropia. We performed the targeted next-generation sequencing (NGS) on the proband and identified two novel compound heterozygous variants (c.1865 T > C (p.Leu622Pro) and exons 17-21 deletion) in OCA2 gene associated with OCA type 2 (OCA2, OMIM 203200). Meanwhile, a previously reported heterozygous mutation (c.4805G > A) in MYO7 gene related with Usher syndrome type 1B was found. The online tools SIFT, PolyPhen-2, and Mutation Taster predicted variant c.1865 T > C was probably damaging. The residue p.Leu622 was in a highly conserved region among species by CLUSTALW. Three-dimensional homology model with I-TASSER indicated that p.Leu622Pro variant disturbed the formation of the α-helix, resulting in a random coil structure. The gross deletion (exons 17-21) in OCA2 gene has was not been reported previously. These two novel variants in OCA2 gene were inherited from each parent respectively, after verification by Sanger sequencing and quantitative PCR (qPCR) in the family. CONCLUSIONS: This study indicates the two novel compound heterozygous mutations in OCA2 gene may be responsible for clinical manifestations of OCA2. It expands the mutation spectrum of OCA2 gene and is helpful to screen for large deletions with targeted NGS protocol in monogenic disease. It also assists the genetic counselling, carrier screening and personalized healthcare of the disease.

19.
Nat Cell Biol ; 21(8): 978-990, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31358969

RESUMO

Although 5-methylcytosine (m5C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the single-nucleotide resolution landscape of messenger RNA m5C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m5C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m5C 'reader' recognizing m5C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m5C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m5C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.

20.
Sci Total Environ ; 688: 867-879, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31255824

RESUMO

Freshwater lakes are threatened by harmful blooms characterized by Cyanobacterial Aggregates (CAs) that are normally aggregated with extracellular polysaccharides released by cyanobacteria to form a phycosphere. It is possible that mutualistic relationships exist between bacteria and cyanobacteria in these CAs wherein bacterial products supplement cyanobacterial growth, and cyanobacterial exudates, in turn, serve as substrates for bacteria, thus augmenting the stability of each constituent. However, little is known about the exact interaction between cyanobacteria and their attached bacteria in CAs. Therefore, in this study, we collected 26 CA samples from Lake Taihu, a large freshwater lake in China from March of 2015 to February of 2016. We then sequenced both the V4 regions of 16S rRNA genes and full metagenomes, resulting in 610 Mb of 16S rRNA gene data and 198.98 Gb of high-quality metagenomic data. We observed that two cyanobacteria genera (Microcystis and Dolichospermum) alternately dominated CAs along the sampling time and specific bacterial genera attached to different cyanobacteria genera dominated CAs. More specifically, Dolichospermum dominates CAs when water temperature is low and total nitrogen is high, while Microcystis dominates CAs when water temperature is high and total nitrogen is low. Moreover, we found specific bacterial genera attached to different cyanobacteria genera dominated CAs. The cyanobacteria-bacteria related pairs Dolichospermum-Burkholderia and Microcystis-Hyphomonas were detected by ecological networks construction. Bacterial communities in CAs were found to be more correlated with the cyanobacterial community (Mantel's r = 0.76, P = 0.001) than with environmental factors (Mantel's r = 0.27, P = 0.017). A potential codependent nitrogen-cycling pathway between cyanobacteria and their attached bacteria was constructed, indicating their functional link. Overall, these results demonstrated that mutualistic relationships do, indeed, exist between cyanobacteria and bacteria in CAs at both taxonomic and gene levels, providing biological clues potentially leading to the control of blooms by interventional strategies to disrupt bacteria-cyanobacteria relationships and co-pathways.

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