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1.
Mediators Inflamm ; 2019: 5271295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582899

RESUMO

Obesity-induced chronic inflammation is known to promote the development of many metabolic diseases, especially insulin resistance, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and atherosclerosis. Pattern recognition receptor-mediated inflammation is an important determinant for the initiation and progression of these metabolic diseases. Here, we review the major features of the current understanding with respect to obesity-related chronic inflammation in metabolic tissues, focus on Toll-like receptors and nucleotide-binding oligomerization domain-like receptors with an emphasis on how these receptors determine metabolic disease progression, and provide a summary on the development and progress of PRR antagonists for therapeutic intervention.

2.
Front Med ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31571160

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

3.
J Org Chem ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599588

RESUMO

The mechanism and origins of stereoselectivity of chiral iron porphyrin-catalyzed asymmetric hydroxylation of ethylbenzene was explored with density functional theory (DFT). The hydrogen atom abstraction is the rate- and stereoselectivity-determining step. In good agreement with experimental results, the formation of (R)-1-phenylethanol product is found to be the most favorable pathway. The transition state of hydrogen atom abstraction which leads to (S)-1-phenylethanol product is unfavorable by 1.7 kcal/mol compared to the corresponding transition state which leads to (R)-1-phenylethanol product. Enantioselectivity arises from attractive π-π stacking interaction between the phenyl group of ethylbenzene substrate and the naphthyl group of the porphyrin ligand.

4.
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.

5.
PLoS One ; 14(9): e0215886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31557166

RESUMO

The progression of cancer through local expansion and metastasis is well recognized, but preventing these characteristic cancer processes is challenging. To this end, a new strategy is required. In this study, we presented a novel dual functional podophyllotoxin derivative, 2-pyridinealdehyde hydrazone dithiocarbamate S-propionate podophyllotoxin ester (PtoxPdp), which inhibited both matrix metalloproteinases and Topoisomerase II. This new podophyllotoxin derivative exhibited significant anti-proliferative, anti-metastatic that correlated with the downregulation of matrix metalloproteinase. In a xenograft animal local expansion model, PtoxPdp was superior to etoposide in tumor repression. A preliminary mechanistic study revealed that PtoxPdp induced apoptosis and autophagy via the PI3K/AKT/mTOR pathway. Furthermore, PtoxPdp could also inhibit epithelial-mesenchymal transition, which was achieved by downregulating both PI3K/AKT/mTOR and NF-κB/Snail pathways. Taken together, our results reveal that PtoxPdp is a promising antitumor drug candidate.

6.
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.

7.
J Agric Food Chem ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31542934

RESUMO

The extensive use of pesticide caused an amount of pressure on the environment and increased the potential human health risk. Glyphosate-based herbicide (GBH) is one of the most widely used pesticides based on a 5-enolpyruvylshikimate-3-phosphate synthase target, which does not exist in vertebrates. Here, we study autophagic effects of the most famous commercial GBH Roundup (RDP) on human A549 cells in vitro. Intracellular biochemical assay indicated opening of mitochondrial permeability transition pore, LC3-II conversion, up-regulation of beclin-1, down-regulation of p62, and the changes in the phosphorylation of AMPK and mTOR induced by RDP in A549 cells. Further experimental results indicated that all the effects induced by RDP were related to its adjuvant polyethoxylated tallow amine, not its herbicidal active ingredient glyphosate isopropylamine salt. All these results showed that RDP has the ability to induce AMPK/mTOR-mediated cell autophagy in human A549 cells. This study would provide a theoretical basis for understanding RDP's autophagic effects on human A549 cells and attract attention on the potential human health risks induced by the adjuvant.

8.
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.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31523936

RESUMO

OBJECTIVE: To analyze the association between neutrophil-to-lymphocyte ratio (NLR) and intravesical prostatic protrusion (IPP) in men with benign prostatic hyperplasia. METHODS: Two hundred and fifty men aged >50 years who presented with lower urinary tract symptoms at our institution between 2014 and 2018 were analyzed. Pearson's method was used for analysis of the correlation between NLR and IPP. Multivariate logistic regression analysis was used to identify predictors of IPP. Further analysis according to total prostate volume (TPV) was performed. RESULTS: The NLR correlated positively with IPP (Pearson's r = 0.459, P < 0.001) and was an independent predictor of IPP ≥10 mm (odds ratio, 2.95; 95% confidence interval, 1.59-5.47; P = 0.0006). Among the 142 men with prostates <40 cm3 , mean NLR was 2.50 ± 0.71 in those with IPP ≥10 mm and 1.71 ± 0.57 in those with IPP < 10 mm (P < 0.001). The NLR differed significantly between those with a prostate <40 cm3 and IPP ≥10 mm and those with a larger prostate and IPP < 10 mm (2.50 ± 0.71 vs 2.07 ± 0.77, respectively; P = 0.020). CONCLUSIONS: NLR can be used as a surrogate marker for presence of IPP. Its clinical value would be especially important in men with a small prostate gland but high IPP. The NLR seemed to be more strongly correlated with IPP than with TPV.

10.
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.

11.
Int J Biol Macromol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31525411

RESUMO

Green lacewing Chrysopa pallens (Rambur) is a general predator of many agricultural pests and plays a pivotal role in reducing crop damage by managing insect pest populations. Odorant binding proteins (OBPs) in insects can sense the semiochemicals in the environment and initiate the delivery of signals to their receptors. However, no Chrysopa pallens OBP (CpalOBP) structure has been reported yet, and their corresponding candidate semiochemicals are still largely unknown. Here, we reported the structure of CpalOBP4 solved with X-ray diffraction and showed its potential ligands. Our results showed that CpalOBP4 has a classical OBP structure with six α-helices and three disulfide bridges, and it can bind with farnesene, 2-tridecanone, cis-3-hexenyl hexanoate, nerolidol and farnesol through a central hydrophobic cavity. Our molecular docking results showed that Met31, Met78, Leu98, Phe141, Leu142 and Pro143 in the hydrophobic cavity were the key residues mediating the interaction of CpalOBP4 with farnesene, 2-tridecanone and cis-3-hexenyl hexanoate, which was further proven by the results that mutations of these residues led to significantly reduced binding affinities of CpalOBP4 for these ligands. Our study provides useful information for the further investigation of the biological function of CpalOBP4 as well as important cues for improving biological control in agriculture.

12.
Cell Res ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520064

RESUMO

Over 150 types of RNA modifications are identified in RNA molecules. Transcriptome profiling is one of the key steps in decoding the epitranscriptomic panorama of these chemical modifications and their potential functions. N7-methylguanosine (m7G) is one of the most abundant modifications present in tRNA, rRNA and mRNA 5'cap, and has critical roles in regulating RNA processing, metabolism and function. Besides its presence at the cap position in mRNAs, m7G is also identified in internal mRNA regions. However, its transcriptome-wide distribution and dynamic regulation within internal mRNA regions remain unknown. Here, we have established m7G individual-nucleotide-resolution cross-linking and immunoprecipitation with sequencing (m7G miCLIP-seq) to specifically detect internal mRNA m7G modification. Using this approach, we revealed that m7G is enriched at the 5'UTR region and AG-rich contexts, a feature that is well-conserved across different human/mouse cell lines and mouse tissues. Strikingly, the internal m7G modification is dynamically regulated under both H2O2 and heat shock treatments, with remarkable accumulations in the CDS and 3'UTR regions, and functions in promoting mRNA translation efficiency. Consistently, a PCNA 3'UTR minigene reporter harboring the native m7G modification site displays both enriched m7G modification and increased mRNA translation upon H2O2 treatment compared to the m7G site-mutated minigene reporter (G to A). Taken together, our findings unravel the dynamic profiles of internal mRNA m7G methylome and highlight m7G as a novel epitranscriptomic marker with regulatory roles in translation.

13.
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.

16.
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.

17.
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.

18.
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.

19.
Mol Cell ; 75(6): 1188-1202.e11, 2019 Sep 19.
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.

20.
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.

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