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1.
Phys Rev Lett ; 127(12): 123902, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34597082

RESUMO

Electromagnetic void space is a medium, while geometrically occupying a finite volume of space, optically equivalent to an infinitesimal point, in which electromagnetic waves do not experience any phase accumulation. Here, we report the first realization of three-dimensional (3D) electromagnetic void space by an all-dielectric photonic crystal possessing vanishing permittivity and permeability simultaneously. The 3D electromagnetic void space offers distinctive functionalities inaccessible to its 2D or acoustic counterparts because of the fundamental changes in topology, which comes from the ascension of dimensionality as well as the transverse nature of electromagnetic waves. In particular, we demonstrate, both theoretically and experimentally, that the transmission through such a 3D void space is unaffected by its inner boundaries, but highly sensitive to the outer boundaries. This enables many applications such as the impurity "antidoping" effect, outer-boundary-controlled switching, and 3D perfect wave steering. Our work paves a road toward 3D exotic optics of an optically infinitesimal point.

2.
Eur J Public Health ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597361

RESUMO

BACKGROUND: This study aimed to investigate associations between health indicators and sleep duration in the general population. METHODS: This cross-sectional data from the National Health and Nutrition Examination Survey. Self-reported sleep duration was classified into short sleep (<7 h/day), regular sleep (7-8 h/day) and long sleep duration (>8 h/day). Health indicators included lifestyle indicators (smoking, alcohol use and physical inactivity), general health indicators (waist circumference and self-reported health condition) and chronic conditions [overweight/obesity, hypertension, diabetes, high cholesterol, chronic low back pain (CLBP) and oral health problems]. A series of multinomial logistic regression analysis were performed, controlling for confounders (age, sex, marital status, ethnic background, education level and poverty-to-income ratio). RESULTS: Data of 12 835 participants were analyzed. The mean (SD) age of participants was 50.0 (±17.4) years, and 50.6% were women. After adjusting for all health indicators, current smoking (OR: 1.37; 95% CI: 1.17-1.61), a poor (OR: 1.52; 95% CI: 1.23-1.88) health condition, CLBP (OR: 1.40; 95% CI: 1.16-1.69) and oral health problems (OR: 1.28; 95% CI: 1.10-1.49) were associated with short sleep duration. No independent association with long sleep duration was observed in this study. CONCLUSIONS: The results confirm that lifestyle indicators (current smoking and physical inactivity), general health indicators (self-reported health condition) and presence of some chronic conditions (CLBP and oral health problems) are associated with short sleep duration. The results did not confirm that any health indicator was associated with long sleep duration.

3.
Int Ophthalmol ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633605

RESUMO

PURPOSE: To reveal the characteristics of vascular changes in retinal arterial occlusion (RAO) using optical coherence tomography angiography (OCTA) and determine the correlated factors with best-corrected visual acuity (BCVA). METHODS: This retrospective study recruited 54 RAO patients and 27 healthy individuals. Ophthalmic examinations including BCVA and OCTA were performed in all the patients and individuals. The OCTA outcomes were analyzed using SPSS software, and the characteristics of vascular changes and BCVA-related factors were summarized. RESULTS: The vessel density in all areas except fovea of both superficial capillary plexus (SCP) and deep capillary plexus (DCP) was significantly reduced in RAO eyes compared with the fellow eyes and normal control eyes (P < 0.05). The vessel density of DCP in all areas except fovea was significantly reduced in the fellow eyes compared with that in the normal control eyes as well (P < 0.05). The retinal thickness in fovea was significantly increased in RAO eyes compared with that in the fellow eyes and normal control eyes (P < 0.05), without any differences in other areas between the RAO eyes and the other two groups (P > 0.05). The retinal thickness in whole area and retinal thickness in fovea were correlated with BCVA, respectively (whole area: r = 0.295, P = 0.030; fovea: r = 0.322, P = 0.018). CONCLUSIONS: OCTA is a fast, noninvasive, and effective examination means for RAO that can display the vascular density and retinal thickness quantitatively and distinctly. RAO patients had reduced vascular density in both eyes and increased foveal retinal thickness in RAO eyes, showing a correlation with BCVA.

4.
J Am Chem Soc ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617436

RESUMO

Production of H2 by methanol reforming is of particular interest due the low cost, ready availability, and high hydrogen content of methanol. However, most current methods either require very high temperatures and pressures or strongly rely on the utilization of large amounts of base. Here we report an efficient, base-free aqueous-phase reforming of methanol homogeneously catalyzed by an acridine-based ruthenium pincer complex, the activity of which was unexpectedly improved by a catalytic amount of a thiol additive. The reactivity of this system is enhanced by nearly 2 orders of magnitude upon addition of the thiol, and it can maintain activity for over 3 weeks, achieving a total H2 turnover number of over 130 000. On the basis of both experimental and computational studies, a mechanism is proposed which involves outer-sphere dehydrogenations promoted by a unique ruthenium complex with thiolate as an assisting ligand. The current system overcomes the need for added base in homogeneous methanol reforming and also highlights the unprecedented acceleration of catalytic activity of metal complexes achieved by the addition of a catalytic amount of thiol.

5.
J Biol Chem ; : 101288, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34634302

RESUMO

The human general transcription factor TFIID is composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). In eukaryotic cells, TFIID is thought to nucleate RNA polymerase II (Pol II) preinitiation complex formation on all protein coding gene promoters and thus, be crucial for Pol II transcription. TFIID is composed of three lobes, named A, B and C. A 5TAF core complex can be assembled in vitro constituting a building block for the further assembly of either lobe A or B in TFIID. Structural studies showed that TAF8 forms a histone fold pair with TAF10 in lobe B and participates in connecting lobe B to lobe C. To better understand the role of TAF8 in TFIID, we have investigated the requirement of the different regions of TAF8 for the in vitro assembly of lobe B and C, and the importance of certain TAF8 regions for mouse embryonic stem cell (ESC) viability. We have identified a region of TAF8 distinct from the histone fold domain important for assembling with the 5TAF core complex in lobe B. We also delineated four more regions of TAF8 each individually required for interacting with TAF2 in lobe C. Moreover, CRISPR/Cas9-mediated gene editing indicated that the 5TAF core-interacting TAF8 domain and the proline-rich domain of TAF8 that interacts with TAF2 are both required for mouse embryonic stem cell survival. Thus, our study defines distinct TAF8 regions involved in connecting TFIID lobe B to lobe C that appear crucial for TFIID function and consequent ESC survival.

6.
Chemosphere ; 287(Pt 2): 132158, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492420

RESUMO

It has been reported that both naturally occurring and artificially created sounds can alter the physiological parameters of various plants. A series of experiments were designed in the present study to estimate the physiological responses and the variation in the Cd decontamination capacity of Festuca arundinacea under sonic wave treatments. Plant seeds were treated by sound waves of frequency 200, 300, 400, 500, and 1000 Hz, and the germinated seedlings were transplanted to Cd-polluted soil. The results showed that all the sonic treatments increased the whole plant dry weight of F. arundinacea compared with that of the control, and the highest value was observed in the 200 Hz treatment. The Cd content in below-ground and aerial tissues of the species increased with increasing frequency till 400 Hz, after which they became constant. A higher proportion of senescent and dead leaf tissues was observed in the high-frequency treatment (1000 Hz), and more Cd was transferred to these failing tissues. Therefore, in the 1000 Hz treatment, a significantly greater amount of Cd could be eliminated by harvesting the senescent and dead leaf tissues of the species compared with that of the other treatments. The concentrations of dissolved organic matter (DOM) and the proportions of hydrophilic fractions which have a strong Cd affinity, in the rhizosphere soil of F. arundinacea increased with the increase in sound frequency. Cd extraction ability of DOM also increased with increasing frequency. This study indicated that a suitable sonic treatment can improve the phytoextraction efficiency of F. arundinacea, and also explained the mechanism from the perspective of the variations in soil DOM.

7.
Aging (Albany NY) ; 13(17): 21587-21598, 2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511432

RESUMO

This study aimed to evaluate the biological role of forkhead box N3 (FOXN3) in human glioma and clarify the possible molecular mechanisms. FOXN3 expression patterns in clinical tissue specimens were characterized via qPCR and Western blotting. Kaplan-Meier survival curve was applied to assess the correlation between FOXN3 expression and overall survival. Effects of FOXN3 over-expression and depletion on glioma cell proliferation, apoptosis, migration and invasion were assessed by CCK8, colony formation assay, flow cytometry, scratch wound healing assay and Transwell invasion assay, respectively. Moreover, the involvement of AKT/murine double minute 2 (MDM2)/p53 pathway was evaluated. Additionally, tumor transplantation model assay was performed to determine the effects of FOXN3 over-expression on glioma cell growth in vivo. Results showed that FOXN3 was significantly down-regulated in glioma tissues compared with normal tissues. Patients with lower FOXN3 expression exhibited a shorter overall survival time. Gain- and loss-of-function analyses demonstrated that FOXN3 over-expression significantly suppressed proliferation, survival and motility of glioma cells, whereas FOXN3 knockdown remarkably promoted glioma cell proliferation, survival and motility. Furthermore, FOXN3 over-expression inhibited the activation of AKT/MDM2/p53 signaling pathway in glioma cells, while FOXN3 depletion facilitated its activation. Additionally, tumor xenograft assays revealed that FOXN3 over-expression retarded glioma cell growth in vivo. Collectively, these findings indicate that FOXN3 inhibits cell growth and invasion through inactivating the AKT/MDM2/p53 signaling pathway and that FOXN3-AKT/MDM2/p53 axis may represent a novel therapeutic target for glioma patients.

8.
Analyst ; 146(20): 6170-6177, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34522939

RESUMO

Triphenyltin chloride (TPhT) is an organotin compound that causes intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT. In this study, a novel SERS substrate was prepared by sputtering an ultra-thin Au layer on a honeycomb-like silver nanoarray fabricated via the nanosphere lithography method. The ultra-thin Au layer was formed by sputtering the intermittent Au nanoparticles on the silver nanoarray, resulting in bimetallic coupling with dramatically increased hotspots and extremely high SERS enhancement with an analytical enhancement factor (AEF) of 6.08 × 109 using Rhodamine 6G (R6G) as the probe molecule. Based on density functional theory (DFT) simulations, the Raman characteristic peaks of TPhT at 999 cm-1 and 655 cm-1 were selected for TPhT detection. The AEF of the SERS substrate HC5-AgAu was calculated to be 3.38 × 106 with the detection concentration of TPhT down to 10-10 M. The as-prepared honeycomb-like silver-gold bimetallic SERS substrate demonstrated great stability and sensitivity for TPhT detection, which might also be applied in monitoring many other environmental pollutants.

9.
Cell Death Dis ; 12(10): 855, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545067

RESUMO

Long non-coding RNAs (lncRNAs) have been found to play critical roles in regulating gene expression, but their function in translational control is poorly understood. We found lnc-OPHN1-5, which lies close to the androgen receptor (AR) gene on chromosome X, increased prostate cancer (PCa) Enzalutamide (Enz) sensitivity via decreasing AR protein expression and associated activity. Mechanism dissection revealed that lnc-OPHN1-5 interacted with AR-mRNA to minimize its interaction with the RNA binding protein (RBP) hnRNPA1. Suppressing lnc-OPHN1-5 expression promoted the interaction between AR-mRNA and hnRNPA1, followed by an increase of ribosome association with AR-mRNA and translation. This effect was reversed by increasing lnc-OPHN1-5 expression. Consistently, the in vivo mice model confirmed that knocking down lnc-OPHN1-5 expression in tumors significantly increased the tumor formation rate and AR protein expression compared with the control group. Furthermore, knocking down hnRNPA1 blocked/reversed shlnc-OPHN1-5-increased AR protein expression and re-sensitized cells to Enz treatment efficacy. Evidence from Enz-resistant cell lines, patient-derived xenograft (PDX) models, clinical samples, and a human PCa study accordantly suggested that patients with low expression of lnc-OPHN1-5 likely have unfavorable prognoses and probably are less sensitive to Enz treatment. In summary, targeting this newly identified lnc-OPHN1-5/AR/hnRNPA1 complex may help develop novel therapies to increase Enz treatment sensitivity for suppressing the PCa at an advanced stage.

10.
Ecotoxicol Environ Saf ; 225: 112744, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481358

RESUMO

Thiamethoxam, an insecticide with high usage and large amounts of environmental residues, has been reported to affect the pupation and survival of honey bee larvae at sublethal concentrations. The molecular mechanisms are not fully understood. In this study, we measured the response of juvenile hormone (JH) to environmental concentrations of thiamethoxam using liquid chromatography-tandem mass spectrometry (LC-MS/MS), monitored the dynamic changes in the transcription of genes encoding major JH metabolic enzymes (CYP15A1, FAMET, JHAMT and JHE) using RT-qPCR, and analysed the transcriptome changes in worker larvae under thiamethoxam stress using RNA-seq. Thiamethoxam significantly increased the levels of JH3 in honey bee larvae, but no significant changes in the transcript levels of the four major metabolic enzymes were observed. Thiamethoxam exposure resulted in 140 differentially expressed genes (DEGs). P450 CYP6AS5 was upregulated, and some ion-related, odourant-related and gustatory receptors for sugar taste genes were altered significantly. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that amino acid metabolism and protein digestion and absorption were influenced by thiamethoxam. These changes may do harm to honey bee caste differentiation, foraging behaviour related to sensory perception and nutrient levels of bee colonies. These results represent the first assessment of the effects of thiamethoxam on JH in honey bee larvae and provides a new perspective and molecular basis for the study of JH regulation and thiamethoxam toxicity to honey bees.


Assuntos
Hormônios Juvenis , Espectrometria de Massas em Tandem , Animais , Abelhas/genética , Cromatografia Líquida , Hormônios Juvenis/toxicidade , Larva/genética , Tiametoxam
11.
Ecotoxicol Environ Saf ; 225: 112731, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488147

RESUMO

Homeostasis disturbance of trace elements has been linked to adverse reproductive consequences, including premature ovarian insufficiency (POI) in women, but limited evidence has been reported so far. This case-control study evaluated the associations between 5 common urinary trace elements [copper (Cu), manganese (Mn), Iron (Fe), Selenium (Se), and zinc (Zn)] and the odds for POI. Urinary concentrations of these 5 metals and serum levels of POI-related reproductive hormones of 169 cases and 209 healthy controls were measured. The urinary levels of Cu and Se in women with POI were significantly higher than those in the controls. The positive associations were observed between Cu levels and the odds of POI [for the medium tertile: odds ratio (OR) = 3.79, 95% CI: 1.98-7.27, p < 0.001; for the highest tertile: OR = 3.85, 95% CI: 2.00-7.41, p < 0.001]. The highest tertile of urinary Se levels was associated with increasing POI risk (for the highest tertile: OR = 2.54, 95% CI: 1.38-4.70, compared with the lowest tertile, p for trend = 0.001). In POI patients, urinary concentrations of Zn and Fe were negatively associated with serum levels of follicle-stimulating hormone (FSH). Our findings suggested that higher exposure levels of Cu and Se might lead to an increased risk of POI.


Assuntos
Insuficiência Ovariana Primária , Oligoelementos , Estudos de Casos e Controles , China , Feminino , Hormônio Foliculoestimulante , Humanos
12.
Ecotoxicol Environ Saf ; 225: 112801, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560614

RESUMO

Soil salinity is a widespread stress in semi-arid forests worldwide, but how to manage nitrogen (N) nutrition to improve plant saline tolerance remains unclear. Here, the cuttings of a widely distributed poplar from central Asia, Populus russikki Jabl., were exposed to either normal or low nitrogen (LN) concentrations for two weeks in semi-controlled greenhouse, and then they were added with moderate salt solution or not for another two weeks to evaluate their physiological, biochemical, metabolites and transcriptomic profile changes. LN-pretreating alleviated the toxicity caused by the subsequent salt stress in the poplar plants, demonstrated by a significant reduction in the influx of Na+ and Cl- and improvement of the K+/Na+ ratio. The other salt-stressed traits were also ameliarated, indicated by the variations of chlorophyll content, PSII photochemical activity and lipid peroxidation. Stress alleviation resulted from two different processes. First, LN pretreatment caused a significant increase of non-structural carbohydrates (NSC), allowed for an increased production of osmolytes and a higher potential fueling ion transport under subsequent salt condition, along with increased transcript levels of the cation/H+ ATPase. Second, LN pretreatment enhanced the transcript levels of stress signaling components and phytohormones pathway as well as antioxidant enzyme activities. The results indicate that early restrictions of N supply could enhance posterior survival under saline stress in poplar plants, which is important for plantation programs and restoration activities in semi-arid areas.


Assuntos
Populus , Carboidratos , Nitrogênio , Populus/genética , Estresse Salino , Tolerância ao Sal
14.
Jpn J Clin Oncol ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580725

RESUMO

BACKGROUND: The pathological classification of well-differentiated pancreatic neuroendocrine tumour (pNET) is based largely upon Ki-67 index. However, current controversies abound about the classification of pNETG1/pNETG2. PATIENTS AND METHODS: Clinicopathological data were retrospectively analysed for 153 pNETG1/pNETG2 patients hospitalized at China-Japan Friendship Hospital. The critical values of pNETG1/pNETG2 were examined by using the area under the receiver operating characteristic curve and survival analysis was used to compare the clinical prognosis of pNETG1/G2. RESULTS: Among them, 52.3% were males. The median age was 49 (18-81) years and the clinical types were pNETG1 (n = 38) and pNETG2 (n = 115). According to the receiver operating characteristic curve, the optimal cut-off value was 5.5% for classifying pNETG1/pNETG2. Significant differences between pNETG1 (n = 101) and pNETG2 (n = 52) existed in overall survival (P = 0.001) and disease-free survival (P = 0.013) when Ki-67 index was 5%. Yet no significant differences existed in overall survival (P = 0.378) or disease-free survival (P = 0.091) between pNETG1 and pNETG2 when Ki-67 index was 3%. Furthermore, multivariate analysis indicated that the revised pathological grade was an independent risk factor for mortality and post-operative recurrence of pNET patients (P = 0.003 and 0.014; hazard ratio (HR) = 4.005 and 2.553). CONCLUSION: Thus, differentiating pNETG1/pNETG2 with Ki-67 index (5%) is proposed as the cut-off value and a new Ki-67 index (5%) is a better predictor of pNET mortality and post-operative recurrence than Ki-67 index (3%).

15.
Ann Diagn Pathol ; 55: 151797, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34509154

RESUMO

BACKGROUND: Glomus tumors are uncommon and mostly benign mesenchymal neoplasms of the perivascular family. To date, only a few cases of glomus tumors occurring in the trachea have been reported. Tracheal glomus tumors simulated low-grade neuroendocrine tumors on clinical and histomorphological examination, so the differential diagnosis between these two entities is very necessary. The latest studies showed that BRAF mutation may be associated with a malignant phenotype of glomus tumors. METHODS: We investigated the clinical, histopathologic, immunohistochemical, and BRAF V600E mutation status of four cases of tracheal glomus tumors. RESULTS: The cases showed a female predilection (male:female, 1:3) with a median age of 35.5. All of the cases had the typical morphological characteristics of glomus tumors, such as uniform round tumor cells with nest-like distribution surrounding thin-walled vessels; two of them met the malignant diagnostic criteria based on the 5th edition of WHO classification, including marked nuclear atypia and any level of mitotic activity. Immunohistochemistry showed diffusely positive for vimentin (4/4), α-SMA (4/4) and collagen IV (4/4), variably reactive for synaptophysin (3/4) and SSTR2 (2/2), and negative for AE1/AE3 (0/4) and chromogranin A (0/4). Three tested cases harbored no BRAF V600E mutation. Three follow-up cases were alive and free of disease with an average follow-up of 89.3 months. CONCLUSIONS: Tracheal glomus tumors are rare mesenchymal tumors that have overlapping morphologic and immunohistochemical features with neuroendocrine neoplasms. Our cases highlight the importance of careful histomorphological examination and comprehensive immunohistochemical study in reaching a correct diagnosis of glomus tumors of the trachea. Other than BRAF mutation, malignant glomus tumors may have a complex mutational profile.

16.
Mol Plant ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509640

RESUMO

Volatile organic compounds play essential roles in plant-environment interactions as well as determining the fragrance of plants. Although gas chromatography-mass spectrometry based untargeted metabolomics is commonly used to assess plant volatiles, it suffers from high spectral convolution, low detection sensitivity, limited annotated metabolites and relatively poor reproducibility. Herein, we report a widely-targeted volatilomics (WTV) method: using "targeted spectra extraction" algorithm to address spectral convolution; constructing a high coverage MS2 spectral tag library to expand volatile annotation; adapting a multiple reaction monitoring mode to improve the sensitivity; and using regression models to adjust for signal drift. The newly developed method was used to profile the volatilome of the rice grain. Compared with the untargeted method, the developed method has higher sensitivity, with for example the signal noise ratio of guaicol being increased from 4.1 to 18.8; high annotation coverage, with the number of annotated volatiles being increased from 43 to 132; better reproducibility, in quality control samples, number of volatiles with relative standard deviation value below 30.0% increased from 14 to 92 after normalization. We also studied the metabolic responses of tomato to environmental stimuli, and profiling the volatilome of different rice accessions. Our work indicates that benzothiazole is a potential airborne signal to prime tomato plants for enhanced defense. This method additionally identified 2-nonanone and 2-heptanone as novel aromatic compounds contributing to rice fragrance. These case studies lead us to believe that this widely-targeted volatilomics method is more efficient than those currently used and will thus considerably promote plant volatilomics studies.

17.
J Clin Pathol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493600

RESUMO

AIM: To elucidate the clinicopathological and immunohistochemical characteristics of micronodular thymomas (MNTs) and micronodular thymic carcinomas (MNCs) with lymphoid stroma. METHODS: We examined four cases of MNTs and three cases of MNCs pathologically and immunohistochemically. RESULTS: There were prominent cystic changes infive of the seven cases. The neoplasms contained epithelial tumour cells arranged in a micronodular growth pattern lined by cystic walls and separated by abundant lymphoid stroma. Only the tumour cell component of MNCs showed signs of malignancy characterised by cytological atypia and increased mitotic activity. Neoplastic MNC epithelial cells showed strong positivity for CD5 and CD117. However, no immature lymphocytes (TdT-positive and CD99-positive) were present in and around the tumour nodules. None of the patients died or suffered from disease due to MNTs or MNCs. CONCLUSION: MNTs and MNCs are rare and less aggressive forms of thymic tumours and can be differentially diagnosed by immunohistochemistry.

18.
Biol Res ; 54(1): 27, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488902

RESUMO

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.


Assuntos
Autofagia , Neoplasias da Próstata , Apoptose , Linhagem Celular Tumoral , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Espécies Reativas de Oxigênio , Triterpenos
19.
Fish Physiol Biochem ; 47(5): 1585-1596, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34414556

RESUMO

Siva1, which induces extensive apoptosis, has been well characterized. To elucidate the molecular function of Siva1 in ricefield eel, molecular characterization and phylogenetic analysis were performed, and the mRNA expression in the ovary at different developmental stages and ovary tissues exposed to H2O2 and Z-VAD-FMK in vitro were also evaluated. The results indicated that ricefield eel Siva1 was highly conserved and contains three conserved motifs, despite 83 amino acid differences upstream of the initiation codon. Phylogenetic analysis demonstrated that ricefield eel Siva1 clusters together with the Siva1 protein of the other fish, with high sequence homology with that of Lates calcarifer. Quantitative real-time polymerase chain reaction analysis showed high siva1 expression levels in the ovary and low expression levels in the liver. The higher mRNA levels of siva1 were detected in the IE and IM, and the lower siva1 mRNA levels were found in the OM, IL, and TE during gonadal development. Additionally, siva1 expression levels in the ovarian tissues were significantly increased at 1 h post incubation (hpi) with H2O2 and then significantly decreased at 2 hpi; however, siva1 expression was upregulated significantly at 4 and 8 hpi, similar to the patterns observed with caspase3, which was used as a molecular marker of apoptosis. Moreover, the siva1 mRNAs were elevated significantly than that in control groups at 1 hpi, but the expression of siva1 was down-regulated dramatically at 2, 4, and 8 hpi, which were similar with that of caspase3 expression profiles after Z-VAD-FMK incubation. What's more, Pearson's correlation coefficients showed strongly positive relationships between siva1 and caspase3. These findings suggest that Siva1 plays an important apoptosis role in gonadal development of ricefield eel.

20.
Oncogene ; 40(40): 5925-5937, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34363021

RESUMO

Low levels of ITLN1 have been correlated with obesity-related colorectal carcinogenesis, however, the specific functions and underlying mechanisms remain unclear. Thus, we sought to explore the inhibitory role of ITLN1 in the tumor-permissive microenvironment that exists during the first occurrence and subsequent development of colorectal carcinoma (CRC). Results indicated that ITLN1 was frequently lost in CRC tissues and ITLN1 to be an independent prognostic predictor of CRC. Orthotopic and subcutaneous tumor xenograft approaches were then used to further confirm the protective role of ITLN1 during tumor progression. Increased ITLN1 expression in CRC cells significantly inhibited local pre-existing vessels sprouting, EPC recruitment and the infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) into tumor tissues without affecting the behavior of CRC cells in vitro. Comparatively, ITLN1-derived MDSCs had a lower suppressive effect on T cell proliferation, NOS2 expression, and ROS production. In addition, ITLN1 overexpression markedly suppressed bone marrow (BM)-derived hematopoietic progenitor cells (HPC) differentiation into MDSCs as well as NOS2 activity on MDSCs. Using H-2b+YFP + chimerism through bone marrow transplantation, increased ITLN1 in HCT116 significantly reduced the BM-derived EPCs and MDSCs in vivo mobilization. Mechanistically, results indicated ITLN1 inhibited tumor-derived IL-17D and CXCL2 (MIP2) through the KEAP1/Nrf2/ROS/IL-17D and p65 NF-ĸB/CXCL2 signaling cascades dependent on PI3K/AKT/GSK3ß. This effect was reversed by the PI3K selective inhibitor LY294002. Collectively, ITLN1 synergistically suppressed IL-17D and CXCL2-mediated tumor vascularization, bone marrow derived EPC recruitment, as well as MDSCs generation and trafficking. Thus, ITLN1 potentially serves as a critical prognostic and therapeutic target for CRC.

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