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1.
J Proteomics ; 230: 103999, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33017647

RESUMO

To reveal calcium-mediated germination in soybean, a gel-free/label-free proteomics was performed in radicle of seed imbibed with CaCl2. Morphological analysis presented promoting and suppressing performance of seed growth under 5 and 50 mM CaCl2, respectively. A total of 106 and 581 proteins were identified in response to 5 and 50 mM CaCl2, respectively. Among 33 proteins, which were simultaneously affected by 5 and 50 mM CaCl2 imbibition, proteins related to protein metabolism, cell, development, and stress showed reversed abundance in response to CaCl2 on dose-dependent manner. Notably, protein abundance of late embryogenesis abundant (LEA) 4-5, LEA4, and dehydrin decreased and increased by 5 and 50 mM CaCl2, respectively, consistent with the transcript level. Moreover, inhibited biosynthesis of gibberellic acid repressed growth of 5 mM CaCl2-imbibed soybean, while inhibition of abscisic acid biosynthesis released the suppressing effects of 50 mM CaCl2. Taken together, these results suggest that decreased or increased protein abundance of LEA4-5, LEA4, and dehydrin might determine promoting or suppressing effects of low or high level of calcium on soybean through enhancing seed sensitivity to gibberellic acid or abscisic acid during radicle protrusion. SIGNIFICANCE: Calcium serves as a versatile signal in plant growth; however, calcium-mediated germination on dose-dependent manner remains elusive. In this study, dual effects of calcium on radicle protrusion in soybean were investigated using proteomic approach. Radicle growth of germinating seed was improved by 5 mM CaCl2; however, it was retarded by 50 mM CaCl2. Late embryogenesis abundant (LEA) 4-5, LEA4, and dehydrin displayed converse profiles in response to low and high concentrations of CaCl2 at both protein abundance and gene expression level. Inhibited biosynthesis of gibberellic acid (GA) significantly impeded radicle protrusion in presence of low concentration of CaCl2, while inhibiting of abscisic acid (ABA) biosynthesis released suppression induced by high concentration of CaCl2. These findings suggest that LEA proteins are associated with calcium-mediated radicle protrusion on dose-dependent manner, and seed sensitivity to GA and ABA might determine promoting and suppressing effects of calcium on radicle protrusion in soybean.

2.
Neural Regen Res ; 16(2): 333-337, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32859793

RESUMO

The arcuate fasciculus is a critical component of the neural substrate of human language function. Surgical resection of glioma adjacent to the arcuate fasciculus likely damages this region. In this study, we evaluated the outcome of surgical resection of glioma adjacent to the arcuate fasciculus under the guidance of magnetic resonance imaging and diffusion tensor imaging, and we aimed to identify the risk factors for postoperative linguistic deficit. In total, 54 patients with primary glioma adjacent to the arcuate fasciculus were included in this observational study. These patients comprised 38 men and 16 women (aged 43 ± 11 years). All patients underwent surgical resenction of glioma under the guidance of magnetic resonance imaging and diffusion tensor imaging. Intraoperative images were updated when necessary for further resection. The gross total resection rate of the 54 patients increased from 38.9% to 70.4% by intraoperative magnetic resonance imaging. Preoperative language function and glioma-to-arcuate fasciculus distance were associated with poor language outcome. Multivariable logistic regression analyses showed that glioma-to-arcuate fasciculus distance was the major independent risk factor for poor outcome. The cutoff point of glioma-to-arcuate fasciculus distance for poor outcome was 3.2 mm. These findings suggest that intraoperative magnetic resonance imaging combined with diffusion tensor imaging of the arcuate fasciculus can help optimize tumor resection and result in the least damage to the arcuate fasciculus. Notably, glioma-to-arcuate fasciculus distance is a key independent risk factor for poor postoperative language outcome. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, China (approval No. S2014-096-01) on October 11, 2014.

3.
Food Chem ; 338: 127980, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32927201

RESUMO

Quercetin has various biological activities, but its poor water solubility and stability limit its applications. In this study, ß-cyclodextrin was used as the host and quercetin was encapsulated in its cavity to prepare an inclusion compound. Then, a nanofilm was formed using electrospinning. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric differential scanning calorimetry (TG-DSC) were used to characterize the properties of the inclusion compound nanofilms. SEM images showed that the nanofilm prepared by optimizing the electrospinning process parameters had a good nanofiber structure. XRD, FTIR and TG/DSC characterization of the nanofilm showed that quercetin was encapsulated in the cavity of ß-cyclodextrin and was present in the nanofilm. The quercetin was slowly released from the nanofilm and still had good bacteriostatic effects on Staphylococcus aureus and Escherichia coli, indicating that the process of embedding and electrospinning did not affect the antibacterial activity of quercetin.

4.
J Ethnopharmacol ; 264: 113379, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32916235

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Thalictrum minus L., which is widespread across Eurasia, is utilized as a folk medicine for treating dysentery, bedsore, fungal infection and lung inflammation in China, Mongolia and Iran. AIM OF THE STUDY: A Mongolian folk medicinal plant named Thalictrum minus L. (TML) has been extensively used for the treatment of lung inflammation, bacterial and fungal infection and tuberculosis. Our present study aims to investigate the effectiveness of TML against particulate matter (PM)-induced acute lung injury (ALI) and the potential underlying mechanisms. MATERIALS AND METHODS: Initially, HPLC-Q-TOF was applied for the qualitative analysis and HPLC was used for quantitative analysis of main components in TML. Then, the mice model of ALI was induced by PM via intratracheally instilled with 50 mg/kg body weight of Standard Reference Material1648a (SRM1648a), and TML (10, 20, 40 mg/kg) were administered orally 1 h prior to PM. The efficacy and molecular mechanisms in the presence or absence of TML were elucidated. RESULTS: Eleven main ingredients were detected in TML and the contents of homoorientin and berberine were quantified. Additionally, the results demonstrated that TML profoundly inhibited weight loss in mice and ameliorated lung pathological injury induced by PM. Furthermore, we also found that TML significantly decreased the lung wet to dry weight (W/D) ratios, reduced total protein in bronchoalveolar lavage fluid (BALF), and effectively attenuated PM-induced increased leukocyte and macrophages in BALF. Meanwhile, TML could pronouncedly inhibited myeloperoxidase (MPO) activity in lung tissues, decreased the PM-induced inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), reduced nitric oxide (NO) and increased superoxide dismutase (SOD) in BALF. In addition, TML markedly facilitated the expression of p-AMPK-Nrf2 and suppressed the expression of KEAP, prohibited the activation of the MAPKs-NLRP3/caspase-1 and cyclooxygenase-2 (COX2), and inhibited apoptotic pathways. CONCLUSION: These findings indicated that TML attenuated PM-induced ALI through suppressing the release of inflammatory cytokines and alleviating oxidative damage correlated with the AMPK-Nrf2/KEAP signaling pathways, MAPKs-NLRP3/caspase-1 signaling pathways, as well as apoptotic pathways.

5.
J Ethnopharmacol ; 264: 113381, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32946961

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury. AIM OF THE STUDY: To investigate their systemic and individual mechanism of each compound in combination GRS. MATERIALS AND METHODS: The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury. RESULTS: Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2. CONCLUSIONS: Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.

6.
Sci Total Environ ; 750: 141404, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33182165

RESUMO

The toxic effect of high-dose of short-chain chlorinated paraffins (SCCPs) has been extensively studied, however the possible health risks induced by SCCPs at low-dose remain largely unknown. In this study, a comprehensive toxicology analysis of SCCPs was conducted with the exposure levels from the environmental dose to the Lowest Observed Adverse Effect Level (LOAEL) of 100 mg/kg/day. General toxicology analysis revealed inconspicuous toxicity of the environmental dose of SCCPs, high dose SCCP exposure inhibited the growth rate and increased the liver weight of rat. Metabolomics analysis indicated that SCCP-induced toxicity was triggered at environmentally relevant doses. First, inhibition of energy metabolism was observed with the decrease in blood glucose and the dysfunction of TCA cycle, which may have contributed to lower body weight gain in rats exposed to a high dose of SCCPs. Second, the increase of free fatty acids indicated the acceleration of lipid metabolism to compensate for the energy deficiency caused by hypoglycemia. Lipid oxidative metabolism inevitably leads to oxidative stress and stimulates the up-regulation of antioxidant metabolites such as GSH and GSSH. The up-regulation of polyunsaturated fatty acids (PUFAs) and phospholipids composed of arachidonic acid indicates the occurrence of inflammation. Dysfunction of lipid metabolism can be an indicator of SCCP-induced liver injury.


Assuntos
Hidrocarbonetos Clorados , Parafina , Animais , China , Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/toxicidade , Metabolismo dos Lipídeos , Masculino , Metabolômica , Parafina/análise , Parafina/toxicidade , Ratos , Ratos Sprague-Dawley
7.
Sci Total Environ ; 753: 142019, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33207464

RESUMO

Fire is an intrinsic feature of terrestrial ecosystems as well as a key Earth system process that significantly influences ecosystem patterns, the carbon cycle, and climate. Although local and regional paleofires across China have been investigated, the history of these phenomena at the national scale as well as possible drivers remain unknown. This study investigated spatiotemporal patterns in fire activity across China based on 107 individual site charcoal records. The aim of this work was to discuss the possible impact of climate and human activities on fire in China. Results showed that fire activities across China declined gradually overall between the early Holocene (12 ka BP) and the middle Holocene (7.3 ka BP) but then sharply increased in occurrence after 7.3 ka BP. Data showed that although regional fire activities did not vary synchronously, more events tended to occur in the late Holocene and there were relative less in the early-to-middle Holocene. These changes in Holocene fire activity closely mirrored millennial scale moisture variations across China. Intensified human activities over the last 3 ka might also be responsible for a sharp increase in fire activity. Variable trends in fire activities within regions might also be attributed to large-scale climatic controls modulated by local factors, which determined burn likelihood. This study enhances our insights into the fire history of China and may help to provide improved future projections for such phenomena given current climate change.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33147694

RESUMO

Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1-5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio: 9.91; 95% confidence interval: 4.11-23.88). The chances of failure were inversely related to the HR increase percentage (p for trend <0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.

9.
BMC Microbiol ; 20(1): 341, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176689

RESUMO

BACKGROUND: Vibrio scophthalmi is an opportunistic bacterial pathogen, which is widely distributed in the marine environment. Earlier studies have suggested that it is a normal microorganism in the turbot gut. However, recent studies have confirmed that this bacterial strain can cause diseases in many different marine animals. Therefore, it is necessary to investigate its whole genome for better understanding its physiological and pathogenic mechanisms. RESULTS: In the present study, we obtained a pathogenic strain of V. scophthalmi from diseased half-smooth tongue sole (Cynoglossus semilaevis) and sequenced its whole genome. Its genome contained two circular chromosomes and two plasmids with a total size of 3,541,838 bp, which harbored 3185 coding genes. Among these genes, 2648, 2298, and 1915 genes could be found through annotation information in COG, Blast2GO, and KEGG databases, respectively. Moreover, 10 genomic islands were predicted to exist in the chromosome I through IslandViewer online system. Comparison analysis in VFDB and PHI databases showed that this strain had 334 potential virulence-related genes and 518 pathogen-host interaction-related genes. Although it contained genes related to four secretion systems of T1SS, T2SS, T4SS, and T6SS, there was only one complete T2SS secretion system. Based on CARD database blast results, 180 drug resistance genes belonging to 27 antibiotic resistance categories were found in the whole genome of such strain. However, there were many differences between the phenotype and genotype of drug resistance. CONCLUSIONS: Based on the whole genome analysis, the pathogenic V. scophthalmi strain contained many types of genes related to pathogenicity and drug resistance. Moreover, it showed inconsistency between phenotype and genotype on drug resistance. These results suggested that the physiological mechanism seemed to be complex.

10.
Brain ; 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33188687

RESUMO

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

11.
Int J Nanomedicine ; 15: 8623-8639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177822

RESUMO

Background: To improve responses to tumor microenvironments for achieving a better therapeutic outcome in combination cancer therapy, poly(ε-caprolactone)-SS-poly(methacrylic acid) diblock copolymer (PCL-SS-PMAA) with a disulfide linkage between the hydrophobic and hydrophilic junctions was synthesized. Materials and Methods: Repeating units of PCL and PMAA in PCL-SS-PMAA were controlled and formulated into polymersomes (PSPps). Truncated octahedral Fe3O4 nanoparticles (IONPs) were synthesized and encapsulated to produce IONPs-PSPps NPs and doxorubicin (DOX) was further loaded to produce IONPs-PSPps@DOX NPs for theranostic applications. Results: IONPs-PSPps NPs remained a superparamagnetic property with a saturation magnetization value of 85 emu⋅gFe3O4 -1 and a relaxivity value of 180 mM-1⋅s-1. Upon exposure to an alternating magnetic field (AMF), IONPs-PSPps NPs increased temperature from 25°C to 54°C within 15 min. Among test groups, the cell apoptosis was greatest in the group exposed to IONPs-PSPps@DOX NPs with AMF and magnet assistance. In vivo T2-weighted magnetic resonance images of A549 tumor-bearing mice also showed highest contrast and greatest tumor suppression in the tumor with AMF and magnet assistance. Conclusion: IONPs-PSPps@DOX NPs are a potential theranostic agent having multifaceted applications involving magnetic targeting, MRI diagnosis, hyperthermia and chemotherapy.

12.
AAPS PharmSciTech ; 21(8): 317, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175339

RESUMO

Polymer additives have been widely reported to affect the crystallization of amorphous drugs, while the underlying mechanism is poorly understood. The present study aims to investigate the relationship between the crystal growth and the molecular mobility of amorphous nifedipine (NIF) in the presence and absence of low-concentration poly(ethylene oxide) (PEO). The addition of 3% w/w PEO yields approximately a 5-fold increase in the crystal growth rate of NIF in the glassy matrix and a 10-fold increase in the supercooled liquid. Broadband dielectric spectroscopy is performed to investigate the molecular mobility of amorphous pure NIF system and NIF doped with low-concentration PEO. With 3% w/w PEO, the structural relaxation time τα of amorphous NIF significantly decreases, indicating an increase in the global molecular mobility. However, the increase of the molecular mobility is insufficient to explain the 5- to 10-fold increase of the crystal growth rate at the same τα scale. Moreover, we compare the accelerating effect of PEO in NIF-PEO systems to other PEO-doped systems. The accelerating effect of low-concentration PEO on the crystal growth of amorphous drugs is found to be independent of the Flory-Huggins interaction, Tg of the drug, or the increase of the global molecular mobility. These findings suggest that an in-depth understanding regarding the effects of polymer additives on the crystallization of drugs should consider the localized mobility of the host molecules near the crystal-liquid interface.

13.
Nature ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177715

RESUMO

Despite its success in achieving the long-term survival of 10-30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune 'checkpoint' therapy3-5 (so called because its aim is to block proteins that inhibit checkpoint signalling pathways in T cells, thereby freeing those immune cells to target cancer cells). Here we show that inhibiting PCSK9-a key protein in the regulation of cholesterol metabolism6-8-can boost the response of tumours to immune checkpoint therapy, through a mechanism that is independent of PCSK9's cholesterol-regulating functions. Deleting the PCSK9 gene in mouse cancer cells substantially attenuates or prevents their growth in mice in a manner that depends on cytotoxic T cells. It also enhances the efficacy of immune therapy that is targeted at the checkpoint protein PD1. Furthermore, clinically approved PCSK9-neutralizing antibodies synergize with anti-PD1 therapy in suppressing tumour growth in mouse models of cancer. Inhibiting PCSK9-either through genetic deletion or using PCSK9 antibodies-increases the expression of major histocompatibility protein class I (MHC I) proteins on the tumour cell surface, promoting robust intratumoral infiltration of cytotoxic T cells. Mechanistically, we find that PCSK9 can disrupt the recycling of MHC I to the cell surface by associating with it physically and promoting its relocation and degradation in the lysosome. Together, these results suggest that inhibiting PCSK9 is a promising way to enhance immune checkpoint therapy for cancer.

14.
Int J Exp Pathol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146930

RESUMO

Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment.

15.
Biomed Res Int ; 2020: 5178397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33145351

RESUMO

The mammalian orosomucoid-like gene family (ORMDL), containing ORMDL1, ORMDL2, and ORMDL3, is the important regulator of sphingolipid metabolism, which is relevant to cell growth, proliferation, migration, and invasion. Since the role of ORMDL1 in cancers remained unclear, the main purpose of our study was to explore the expression patterns and prognostic values of ORMDL1 in different tumors, especially in cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B cell lymphoma (DLBCL), acute myeloid leukemia (LAML), and thymoma (THYM). Bioinformatics tools including GEPIA, CCLE, LinkedOmics, cBioPortal, and TIMER databases were used. As a result, the expression levels of ORMDL1 in tumor tissues and normal tissues varied in different cancers, especially significantly upregulated in CHOL, DLBCL, LAML, and THYM. Moreover, ORMDL1 mRNA was also highly expressed in cell lines of DLBCL and LAML. Further studies showed that ORMDL1 overexpression was associated with poor prognosis in DLBCL, but not significant in CHOL, LAML, and THYM. Consistently, there were genetic alterations of ORMDL1 in DLBCL, and patients with genetic alterations indicated worse survival. Coexpressed genes and related biological events with ORMDL1 in DLBCL were found via LinkedOmics, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between ORMDL1 and cancer immune cells was investigated, and ORMDL1 expression was positively correlated with infiltrating levels of B cells. In conclusion, ORMDL1 is suggested to be a tumorigenic factor and considered as the potential therapeutic target and prognostic biomarker in DLBCL.

16.
J Cell Mol Med ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135290

RESUMO

Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up-regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up-regulate the expression of CDK16 by sponging miR-584-5p. The expression of miR-584-5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR-584-5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR-584-5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR-584-5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment.

17.
Colloids Surf B Biointerfaces ; : 111443, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33203600

RESUMO

Combining dual drugs in one vehicle to cancer cells offers spatiotemporal localization of drug at the site of action, leading to synergistic therapeutic effects and reduced side effects. To improve pH/redox responsiveness to the tumor microenvironments for cancer therapy, a pH/redox-responsive micelle based on poly(ε-caprolactone)-SS-poly(methacrylic acid) (PCL-SS-PMAA) diblock copolymer was fabricated for dual drug delivery. The PCL-SS-PMAA was formulated into a core-shell micelle (PSPm) in an aqueous solution. The critical micelle concentration (CMC) values of PSPm were 7.94 × 10-3 mg mL-1 at pH 5.0 and 1.00 × 10-2 mg mL-1 at pH 7.4. The hydrodynamic diameters of PSPm were within 210-270 nm, depending on pH values. Changes in morphology and size of PSPm were clearly observed before and after exposure to a reducing agent. Paclitaxel (PTX) was encapsulated into the core and cisplatin (CDDP) was chelated on the shell of PSPm, with both PTX and CDDP being efficiently released from PSPm in the presence of a reducing agent in an acid condition. MTT and annexin V/propidium iodide dual staining results demonstrated that co-loading of CDDP and PTX into PSPm had a synergistic effect in killing lung cancer cells and exerted superior antitumor activity over the combination of single drug-loaded PSPm or the combination of free-CDDP and free-PTX at equivalent drug amounts. Hence, encapsulating the dual drugs into PSPm exhibits a synergistic effect for potential lung cancer therapy.

18.
Lab Invest ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203894

RESUMO

Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease with poor clinical outcomes. Podocyte loss via apoptosis is one important mechanism underlying the pathogenesis of FSGS. Recently, Yes-associated-protein (YAP), a key downstream protein in the Hippo pathway, was identified as an activator for multiple gene transcriptional factors in the nucleus to control cell proliferation and apoptosis. To investigate the potential role of YAP in the progression of FSGS, we examined kidney samples from patients with minimal change disease or FSGS and found that increases in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in human FSGS. Utilizing an established mT/mG transgenic mouse model and primary cultured podocytes, we found that YAP was distributed uniformly in nucleus and cytoplasm in the podocytes of control animals. Adriamycin treatment induced gradual nuclear exclusion of YAP with enhanced phospho-YAP/YAP ratio, accompanied by the induction of podocyte apoptosis both in vivo and in vitro. Moreover, we used verteporfin to treat an Adriamycin-induced FSGS mouse model, and found YAP inhibition by verteporfin induced nuclear exclusion of YAP, thus increasing podocyte apoptosis and accelerating disease progression. Therefore, our findings suggest that YAP nuclear distribution and activation in podocytes is an important endogenous anti-apoptotic mechanism during the progression of FSGS.

19.
Biogerontology ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159806

RESUMO

Aging animals accumulate insoluble proteins as a consequence of a decline of proteostatic maintenance with age. In Caenorhabditis elegans, for instance, levels of detergent-insoluble proteins increase with age. In longer-lived strains of C. elegans, this accumulation occurs more slowly, implying a link to lifespan determination. We further explored this link and found that detergent-insoluble proteins accumulate more rapidly at higher temperatures, a condition where lifespan is short. We employed a C. elegans strain carrying a GFP transcriptional reporter under the control of a heat shock (hsp-16.2) promoter to investigate the dynamics of proteostatic failure in individual nematodes. We found that early, sporadic activation of hsp-16.2 was predictive of shorter remaining lifespan in individual nematodes. Exposure to rapamycin, resulting in reduced mTOR signaling, delayed spurious expression, extended lifespan, and delayed accumulation of insoluble proteins, suggesting that targets downstream of the mTOR pathway regulate the accumulation of insoluble proteins. We specifically explored ribosomal S6 kinase (rsks-1) as one such candidate and found that RNAi against rsks-1 also resulted in less age-dependent accumulation of insoluble proteins and extended lifespan. Our results demonstrate that inhibition of protein translation via reduced mTOR signaling resulted in slower accumulation of insoluble proteins, delayed proteostatic crisis, and extended lifespan in C. elegans.

20.
Cell Death Dis ; 11(11): 1002, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33223519

RESUMO

Numerous studies have reported the association of long non-coding RNAs (lncRNAs) in cancers, yet the function of lncRNA high expressed in hepatocellular carcinoma (HEIH) in esophageal carcinoma (EC) has seldom been explored. Here, we aimed to explore the mechanism of HEIH on EC via microRNA-185 (miR-185)/kallikrein-related peptidase 5 (KLK5) modulation. Cancer and non-tumoral tissues were collected, in which HEIH, miR-185 and KLK5 expression were detected, as well as their correlations. Also, the relation between the prognosis of EC patients and HEIH/miR-185/KLK5 expression was clarified. EC cells (KYSE-30 and TE-1) were screened for subsequent gain- and loss-of-function assays and their biological functions were further monitored. Tumor volume and weight in EC mice were also measured. Results from this study indicated that HEIH and KLK5 were elevated and miR-185 was declined in EC. The positive correlation was seen in HEIH and KLK5 expression, while the negative correlation was observed in HEIH or KLK5 and miR-185 expression. High HEIH and KLK5 indicated worse prognosis and high miR-185 suggested better prognosis of EC patients. Depleting HEIH or restoring miR-185 suppressed the malignant phenotypes of EC cells, and delayed tumor growth in EC mice. HEIH was found to bind with miR-185 to regulate KLK5 expression. Overexpressing KLK5 alone promoted EC cell progression while up-regulating miR-185 reversed such effects on EC cells. Collectively, we reveal that HEIH depletion dampens EC progression by upregulating miR-185 and downregulating KLK5, which provides novel treatments for EC.

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