Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.828
Filtrar
1.
Protein Expr Purif ; 177: 105750, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32920041

RESUMO

Cutaneous leishmaniasis is a parasitic and neglected tropical disease transmitted by the bites of sandflies. The emergence of cutaneous leishmaniasis in areas of war, conflict, political instability, and climate change has prompted efforts to develop a preventive vaccine. One vaccine candidate antigen is PpSP15, a 15 kDa salivary antigen from the sandfly Phlebotomus papatasi that facilitates the infection of the Leishmania parasite and has been shown to induce parasite-specific cell-mediated immunity. Previously, we developed a fermentation process for producing recombinant PpSP15 in Pichia pastoris and a two-chromatographic-step purification process at 100 mL scale. Here we expand the process design to the 10 L scale and examine its reproducibility by performing three identical process runs, an essential transition step towards technology transfer for pilot manufacture. The process was able to reproducibly recover 81% of PpSP15 recombinant protein with a yield of 0.75 g/L of fermentation supernatant, a purity level of 97% and with low variance among runs. Additionally, a freeze-thaw stability study indicated that the PpSP15 recombinant protein remains stable after undergoing three freeze-thaw cycles, and an accelerated stability study confirmed its stability at 37 °C for at least one month. A research cell bank for the expression of PpSP15 was generated and fully characterized. Collectively, the cell bank and the production process are ready for technology transfer for future cGMP pilot manufacturing.

2.
Comput Intell Neurosci ; 2020: 1246920, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014028

RESUMO

Education competitiveness is a key feature of national competitiveness. It is crucial for nations to develop and enhance student and teacher potential to increase national competitiveness. The decreasing population of children has caused a series of social problems in many developed countries, directly affecting education and com.petitiveness in an international environment. In Taiwan, a low birthrate has had a large impact on schools at every level because of a substantial decrease in enrollment and a surplus of teachers. Therefore, close attention must be paid to these trends. In this study, combining a whale optimization algorithm (WOA) and support vector regression (WOASVR) was proposed to determine trends of student and teacher numbers in Taiwan for higher accuracy in time-series forecasting analysis. To select the most suitable support vector kernel parameters, WOA was applied. Data collected from the Ministry of Education datasets of student and teacher numbers between 1991 and 2018 were used to examine the proposed method. Analysis revealed that the numbers of students and teachers decreased annually except in private primary schools. A comparison of the forecasting results obtained from WOASVR and other common models indicated that WOASVR provided the lowest mean absolute percentage error (MAPE) and root mean square error (RMSE) for all analyzed datasets. Forecasting performed using the WOASVR method can provide accurate data for use in developing education policies and responses.

3.
Cardiorenal Med ; : 1-8, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017825

RESUMO

BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk for acute kidney injury (AKI). Novel biomarkers that can predict AKI after AMI may facilitate immediate interventions. Recently, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and klotho have been established as novel AKI biomarkers. However, their effects have not been studied in patients presenting with AMI. In this study, we will measure the serum levels of these three biomarkers to find reliable biomarkers for early diagnosis of AKI in AMI patients. METHODS: This prospective observational cohort study was conducted between May 2016 and November 2017. A total of 285 consecutive patients with AMI were enrolled. The study was approved by the institutional review board of Peking University People's Hospital (No. 2016PHB 042-01). AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients was collected and serum levels of several AKI biomarkers, including cystatin C, NGAL, and klotho, were measured by ELISA. The relationship between biomarker levels of AKI were analyzed and their discrimination performances were compared. RESULTS: AKI incidence was 17.5% (50/285) during hospitalization. Compared to patients without AKI, the AKI group had higher mortality (20.0% vs. 0.4%, p < 0.001) and tended to be older, had higher incidence of chronic kidney disease, severe cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker and statins. Moreover, AKI patients experienced an increase in serum cystatin C (3,709.2 ± 2,281.5 vs. 1,918.5 ± 1,140.6 ng/mL, p < 0.001), NGAL (118.0 ± 70.3 vs. 91.8 ± 52.3 ng/mL, p = 0.003), and klotho (742.2 ± 497.4 vs. 470.3 ± 257.2 pg/mL, p <0.001). Furthermore, the areas under the receiver operating curves demonstrated that serum cystatin C levels at admission had modest discriminative powers for predicting AKI after AMI compared with serum creatinine (0.899, 95% CI, 0.855-0.944 vs. 0.734, 95% CI, 0.649-0.819, p <0.001). There was no difference between the discrimination performances of serum creatinine, NGAL, and klotho. CONCLUSION: Elevated cystatin C levels are associated with AKI in patients with AMI. This study provides reliable evidence that cystatin C levels may be superior to serum creatinine for predicting AKI after AMI at admission.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33020273

RESUMO

During the progression of ocular diseases such as retinopathy of prematurity and diabetic retinopathy, overgrowth of retinal blood vessels results in the formation of pathological neovascular tufts that impair vision. Current therapeutic options for treating these diseases include antiangiogenic strategies that can lead to the undesirable inhibition of normal vascular development. Therefore, strategies that eliminate pathological neovascular tufts while sparing normal blood vessels are needed. In this study we exploited the hyaloid vascular network in murine eyes, which naturally undergoes regression after birth, to gain mechanistic insights that could be therapeutically adapted for driving neovessel regression in ocular diseases. We found that endothelial cells of regressing hyaloid vessels underwent down-regulation of two structurally related E-26 transformation-specific (ETS) transcription factors, ETS-related gene (ERG) and Friend leukemia integration 1 (FLI1), prior to apoptosis. Moreover, the small molecule YK-4-279, which inhibits the transcriptional and biological activity of ETS factors, enhanced hyaloid regression in vivo and drove Human Umbilical Vein Endothelial Cells (HUVEC) tube regression and apoptosis in vitro. Importantly, exposure of HUVECs to sheer stress inhibited YK-4-279-induced apoptosis, indicating that low-flow vessels may be uniquely susceptible to YK-4-279-mediated regression. We tested this hypothesis by administering YK-4-279 to mice in an oxygen-induced retinopathy model that generates disorganized and poorly perfused neovascular tufts that mimic human ocular diseases. YK-4-279 treatment significantly reduced neovascular tufts while sparing healthy retinal vessels, thereby demonstrating the therapeutic potential of this inhibitor.

5.
Int J Mol Sci ; 21(19)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023006

RESUMO

Signal transducer and activator of transcription 3 (STAT3), a transcriptional factor involved in tumorigenesis and cancer stemness formation, contributes to drug resistance in cancer therapies. STAT3 not only mediates gene transcription but also participates in microRNA suppression. This study identified a STAT3-downstream micro RNA (miRNA) involved in drug resistance against regorafenib in colorectal cancer stem-like tumorspheres. Small RNAseq was used to investigate differential microRNAs in colorectal cancer cell-derived tumorspheres and in a STAT3-knockdown strain. The miRNA-mediated genes were identified by comparing RNAseq data with gene targets predicted using TargetScan. Assays for detecting cell viability and apoptosis were used to validate findings. The formation of colorectal cancer stem-like tumorspheres was inhibited by BBI608, a STAT3 inhibitor, but not by regorafenib. Additional investigations for microRNA expression demonstrated an increase in 10 miRNAs and a decrease in 13 miRNAs in HT29-derived tumorspheres. A comparison of small RNAseq results between tumorspheres and HT29shSTAT3 cells revealed the presence of four STAT3-mediated miRNAs in HT29-derived tumorspheres: hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p were upregulated, whereas miR-30a-5p was downregulated. Furthermore, hsa-miR-4521 was associated with poor overall survival probability, and miR-30a-5p was associated with better overall survival probability in patients with rectum cancer. Comparisons of RNAseq findings between HCT116- and HT29-derived tumorspheres revealed that HSPA5 were mediated by the STAT3-miR-30a-5p axis, which is overexpressed in colorectal tumorspheres associating to anti-apoptosis. In addition, the transfection of miR-30a-5p and inhibition of HSPA5 by HA15 significantly reduced cell viability and increased apoptosis in HT29 cells. In conclusion, a STAT3-miR-30a-5p-HSPA5 axis was observed against regorafenib-mediated apoptosis in colorectal cancer tumorspheres. The expression of miR-30a-5p was repressed by STAT3; in addition, HSPA5 was identified as the target gene of miR-30a-5p and contributed to both tumorsphere formation and anti-apoptosis.

6.
Neurotox Res ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025360

RESUMO

Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that DEX inhibited cell proliferation and Sirt7 expression. In addition, prenatal mouse overexposure to DEX induced the suppression of Sirt7 in the hippocampus of offspring. Sirt7 knockdown significantly decreased the percentage of proliferating cells but did not further reduce the NSC proliferation rate in the presence of DEX, whereas Sirt7 overexpression rescued DEX-induced inhibition of hippocampal NSC proliferation. Moreover, DEX inhibited Sirt7 expression through the glucocorticoid receptor (GR), and p21 was found to mediate the functional effect of DEX-induced Sirt7 suppression. In conclusion, our data demonstrate for the first time the effect of DEX on the Sirt7-p21 pathway in hippocampal NSCs, identifying a new potential therapeutic target for prenatal GC overexposure-related neurodevelopmental disorders in offspring.

7.
J Food Biochem ; : e13502, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025647

RESUMO

Bovine α-lactalbumin (α-La)/ß-lactoglobulin (ß-Lg) was pretreated through ultrasonic treatment and subsequently binding with oleic acid (OA) by heat treatment. And, the antitumor activity, IgE/IgG-binding ability, and structural modifications were investigated. After α-La/ß-Lg were treated by ultrasonic prior to binding with OA, the treated α-La/ß-Lg showed high antitumor activity and IgE/IgG-binding ability, and significantly affected the structural modifications, which reflected by the reduction in α-helix content, the increase of molecular weight, intrinsic fluorescence intensity, and surface hydrophobicity. Molecular docking studies indicated that OA bound to α-La/ß-Lg by hydrogen bonds and hydrophobic interaction. Therefore, ultrasonic prior to binding with OA could improve antitumor activity and IgE/IgG-binding ability of α-La/ß-Lg as a result of structural modifications. And, ultrasonic prior to binding with fatty acid processing of milk products alone may increase the antitumor activity, this change may enhance the risk of an allergenic reaction in milk allergy patients to some extent. PRACTICAL APPLICATIONS: Fatty acids, natural ligands associated with the bovine milk proteins, and milk protein-fatty acid complex has a variety of functional applications in the food industry. This study revealed that antitumor activity, IgE/IgG-binding ability, and structural modifications of α-La/ß-Lg induced by ultrasonic prior to binding with oleic acid. It will be beneficial to understand the mechanism of the functional changes of protein. Ultrasonic prior to binding with oleic acid will be more likely to develop a practical technology to improve the functional characteristics of milk protein and design the optimal nutritional performance of milk food.

8.
J Cardiothorac Surg ; 15(1): 289, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004056

RESUMO

BACKGROUND: Diabetes mellitus(DM) is an indicator affects postoperative mortality and morbidity after coronary artery bypass grafting (CABG). Acute kidney injury (AKI) is one of the frequent postoperative complications after CABG. This multi-centre register study designed to investigate the impact of DM on postoperative AKI in primary isolated CABG patients. METHODS: We included all patients (n = 4325) from Jiangsu Province CABG register who underwent primary isolated CABG from September 2017 to August 2019. The patients were divided into 3 groups: No-DM group(n = 3067), DM-oral group (DM with oral hypoglycemic agents, n = 706) and DM-insulin group (DM with insulin treatment, n = 552). The development and severity of AKI were based on Acute Kidney Injury Network (AKIN) criteria. RESULTS: There were totally 338, 108 and 145 patients developed AKI in No-DM, DM-oral and DM-insulin group respectively. Comparing with No-DM group, DM-oral group had a higher rate of AKI(χ2 = 10.071, p = 0.002), DM-insulin group had a higher rate(χ2 = 94.042, p<0.001) and severity of AKI(χ2 = 10.649, p = 0.005). The adjusted odds ratio for AKI was 1.26 (95% CI 1.03-1.57) in DM-oral group and 3.92 (95% CI 3.27-5.16) in DM-insulin group, in comparison with No-DM group. CONCLUSIONS: Independent of baseline renal function or cardiac function, DM was associated with an increased risk of AKI after CABG, especially in patients with insulin treatment, who also had a higher severity of AKI.

9.
Neurosurgery ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040154

RESUMO

BACKGROUND: Multiple percutaneous vertebral cement augmentation may create sandwich vertebrae. Whether the sandwich vertebra is at higher risk of further fracture remains unknown. OBJECTIVE: To compare the incidence of further fractures of sandwich vertebrae and adjacent vertebrae and to identify potential risk factors for sandwich vertebral fractures. METHODS: Patients who underwent cement augmentation for osteoporotic vertebral compression fractures (OVCFs) in a single medical center between January 2012 and December 2015 were included. A sandwich vertebra was defined as an intact vertebra located between 2 previously cemented vertebrae. Demographic data and imaging findings were recorded. All patients were followed up for at least 24 mo postoperatively. During follow-up period, if the patient reported new-onset back pain with corresponding imaging findings, a diagnosis of sandwich vertebral fracture was made. RESULTS: Among the 1347 patients who underwent vertebroplasty/kyphoplasty for OVCFs, 127 patients with 128 fracture levels met the criteria for sandwich vertebrae (females/males 100/27, mean age 77.8 ± 7.7 yr old). The fracture location was most common in the thoraco-lumbar junction (T10-L2), 68.5% (87/127). The incidence of sandwich vertebral fracture was 21.3%, whereas the incidence of adjacent level fracture of those with no sandwich vertebra was 16.4% (196/1194), P = .1879. CONCLUSION: The incidence of sandwich vertebral fracture is not higher than that at the adjacent levels. The factor associated with further sandwich vertebral fracture was male gender. Once sandwich vertebral fracture occurred, patients may seek more surgical intervention than those with only adjacent fractures.

10.
Vaccine ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33041100

RESUMO

Recent studies have revealed that the interface of gp120 and gp41 and some parts of gp41 are also critical epitopes for elicitation of broadly neutralizing antibodies. Therefore, potential trimeric gp41 or gp140 immunogen candidates are needed. Previously, we developed a trimer motif MTQ and demonstrated that it could help formation of trimeric gp120 and gp140 proteins. In the present study, we immunized Balb/c mice using trimeric gp41-expressing plasmid for prime and monomeric gp41 or trimeric gp140 protein as well as a mutant (Q577A) for boost. The antibody responses in the context of regimens with various immunization intervals and DNA adjuvants including praziquantel (PZQ), cimetidine (CIM), and amiloride (AML) were evaluated. We found that these three adjuvants were not enough to elicit remarkable specific Abs after gp41 DNA immunization, while AML could significantly promote humoral immune responses after protein boosts. Long immunization interval could induce the specific binding Abs earlier and higher and maintain a high level of Abs in the following 27 weeks after final protein boost. Moreover, two times of protein boosts with DNA adjuvant and a longer time interval achieved a higher titer of specific Abs than three times of protein boosts with a shorter time interval. Q577A mutant was benefit for trimeric gp140 boost in the production of binding Abs but harmful to inducing neutralizing Abs, while this mutant in monomeric gp41 presented the opposite trend which may be associated with the immunogen structures. This study highlights the significance of DNA adjuvant Amiloride and long immunization interval in promoting antibody responses and provides new insights into effective HIV immunization regimen design in the future.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33035392

RESUMO

Data regarding the long-term outcomes of generic antihypertensive drugs are limited. This nationwide retrospective database analysis aimed to evaluate the efficacy and safety of a generic versus brand-name nifedipine for hypertension treatment. Patients who were prescribed generic or brand-name nifedipine between January 1, 2008, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The efficacy outcomes included all-cause mortality and the composite cardiovascular (CV) outcome, including CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for heart failure. Safety outcomes included headache, peripheral edema, constipation, acute kidney injury, hypotension, syncope, new diagnosis of cancer, and cancer death. Among the 98 335 patients who were eligible for analysis, 21 087 (21.4%) were prescribed generic nifedipine. Both the generic and the brand-name groups included 21 087 patients after propensity score matching. At a mean follow-up of 4.1 years, the generic nifedipine was comparable to the brand-name drug with regard to all-cause mortality (7.2% vs. 7.1%; hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.95-1.09) and the composite CV outcomes (11.6% vs. 11.9%; HR 0.97; 95% CI 0.92-1.03). The generic nifedipine was associated with higher rates of headache, peripheral edema, and constipation but a modest reduction in the risk of newly diagnosed cancer (7.1% vs. 7.8%; subdistribution HR 0.90, 95% CI 0.84-0.97). The risks of acute kidney injury, hypotension, syncope, and cancer death were not significantly different between the two groups. In conclusion, the generic nifedipine was comparable to the brand-name drug with regard to the risks of all-cause mortality and the composite CV outcome. The finding of cancer risk could be chance and should be interpreted with caution.

13.
Scand J Immunol ; : e12988, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047375

RESUMO

The Toll-like receptor (TLR) family acts as a bridge connecting innate and acquired immunity. TLR10 remains one of the least understood members of this family. Some studies have examined TLR10 ligands, dimerization of TLR10 with other TLRs, and downstream signaling pathways and functions, but they have often arrived at conflicting conclusions. TLR10 can induce the production of proinflammatory cytokines by forming homodimers with itself or heterodimers with TLR1 or other TLRs, but it can also inhibit proinflammatory responses when co-expressed with TLR2 or potentially other TLRs. Mutations in the Toll/Interleukin 1 receptor (TIR) domain of TLR10 alter its signaling activity. Polymorphisms in the TLR10 gene can change the balance between pro- and anti-inflammatory responses, and hence modulate the susceptibility to infection and autoimmune diseases. Understanding the full range of TLR10 ligands and functions may allow the receptor to be exploited as a therapeutic target in inflammation- or immune-related diseases. Here we summarize recent findings on the pro- and anti-inflammatory roles of TLR10 and the molecular pathways in which it is implicated. Our goal is to pave the way for future studies of the only orphan TLR thought to have strong potential as a target in the treatment of inflammation-related diseases.

14.
Int J Mol Sci ; 21(19)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33008113

RESUMO

The tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockdown of Trim28 by transducing lentivirus-carrying shRNAs impairs the differentiation of 3T3-L1 preadipocytes, demonstrated by morphological observation and gene expression analysis. To understand the molecular mechanism of Trim28-mediated adipogenesis, the RNA-seq was performed to find out the possible Trim28-regulated genes. Dlk1 (delta-like homolog 1) was increased in Trim28 knockdown 3T3-L1 cells both untreated and induced to differentiation. Dlk1 is an imprinted gene and known as an inhibitor of adipogenesis. Further knockdown of Dlk1 in Trim28 knockdown 3T3-L1 would rescue cell differentiation. The epigenetic analysis showed that DNA methylation of Dlk1 promoter and differentially methylated regions (DMRs) was not altered significantly in Trim28 knockdown cells. However, compared to control cells, the histone methylation on the Dlk1 promoter was increased at H3K4 and decreased at H3K27 in Trim28 knockdown cells. Finally, we found Trim28 might be recruited by transcription factor E2f1 to regulate Dlk1 expression. The results imply Trim28-Dlk1 axis is critical for adipogenesis.

16.
EMBO Rep ; : e50283, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016573

RESUMO

A microdeletion within human chromosome 5q14.3 has been associated with the occurrence of neurodevelopmental disorders, such as autism and intellectual disability, and MEF2C haploinsufficiency was identified as main cause. Here, we report that a brain-enriched long non-coding RNA, NDIME, is located near the MEF2C locus and is required for normal neural differentiation of mouse embryonic stem cells (mESCs). NDIME interacts with EZH2, the major component of polycomb repressive complex 2 (PRC2), and blocks EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) at the Mef2c promoter, promoting MEF2C transcription. Moreover, the expression levels of both NDIME and MEF2C were strongly downregulated in the hippocampus of a mouse model of autism, and the adeno-associated virus (AAV)-mediated expression of NDIME in the hippocampus of these mice significantly increased MEF2C expression and ameliorated autism-like behaviors. The results of this study reveal an epigenetic mechanism by which NDIME regulates MEF2C transcription and neural differentiation and suggest potential effects and therapeutic approaches of the NDIME/MEF2C axis in autism.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33016860

RESUMO

A novel bacterial strain, designated CSW-10T, isolated from a freshwater pond in Taiwan, was characterized using a polyphasic taxonomic approach. Cells were Gram-stain-negative, aerobic, non-motile, rod-shaped and formed yellow-coloured colonies. Optimal growth occurred at 30 °C, pH 7, and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain CSW-10T formed a phylogenetic lineage in the genus Sphingomonas. The 16S rRNA gene sequence similarity indicated that strain CSW-10T was most closely related to Sphingomonas fonticola TNR-2T (97.6%). Strain CSW-10T showed 69.8-70.7% average nucleotide identity and 19.0-23.0% digital DNA-DNA hybridization identity with the strains of other related Sphingomonas species. The major fatty acids of strain CSW-10T were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) and C17:1 ω6c. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidyldimethylethanolamine, phosphatidylcholine, one uncharacterized sphingoglycolipid, five uncharacterized aminophospholipids, one uncharacterized phospholipid and one uncharacterized lipid. The predominant polyamines were homospermidine and spermidine. The major isoprenoid quinone was Q-10. Genomic DNA G+C content of strain CSW-10T was 62.0 mol%. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain CSW-10T should represent a novel species of the genus Sphingomonas, for which the name Sphingomonas lacunae sp. nov. is proposed. The type strain is CSW-10T (=BCRC 81190T =LMG 31340T).

18.
Artigo em Inglês | MEDLINE | ID: mdl-32998818

RESUMO

Muscle atrophy is a major character of cancer cachexia, whose mechanism remains enigmatic. During cancer cachexia, the function of endoplasmic reticulum stress (ERS), which ubiquitously exists in invasive cancer, remains unclear in muscle remodeling. In addition, ERS can be transmitted to surrounding and distant cells, terming transmissible ERS (TERS), by certain soluble factors, which have not been completely identified. In this study, tunicamycin-induced conditioned media from oral squamous cell carcinoma (OSCC) cell lines were proved to transmit ERS to muscle cells both in vivo and in vitro. We found for the first time that exosomes from the conditioned media were the key factors to mediate TERS signaling and induce muscle cell atrophy and apoptosis consequently. Next-generation RNA sequencing was applied to pinpoint exosome miR-181a-3p, which was then identified to play a critical role in regulating ERS, muscle atrophy and apoptosis pathways.

19.
Food Chem Toxicol ; 146: 111803, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035629

RESUMO

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

20.
Mol Cell Endocrinol ; 519: 111053, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035625

RESUMO

Insulin-like growth factor-1 (IGF-1) is a potent neuroprotective polypeptide that exerts neuroprotective effects via the IGF-1 receptor (IGF-1R). Our previous study reported that G protein-coupled estrogen receptor (GPER) was involved in the anti-apoptotic effect of IGF-1. The present study was designed to investigate the anti-inflammatory effect of IGF-1 in association with astrocyte activation and the molecular details of the interaction between IGF-1R and GPER. We showed that IGF-1 could improve 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits and attenuate the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) both in vivo and in vitro. The IGF-1R antagonist JB-1 and the GPER antagonist G15 could antagonize the anti-inflammatory effect of IGF-1. Silencing GPER abrogated the inhibitory effect of IGF-1 on 1-methyl-4-phenylpyridinium (MPP+)-induced upregulation of COX-2 and iNOS in primary astrocytes. Moreover, the MPP + -induced inflammatory response was related to the activation of mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathways. The inhibitory effects of IGF-1 on the phosphorylation of p38, JNK and IκB could be blocked by JB-1. G15 antagonized the inhibitory effects of IGF-1 on p-JNK and p-IκB, but not p-p38. Furthermore, IGF-1 treatment alone increased the expression of GPER, which was blocked by JB-1, the phosphatidylinositol 3-kinase (PI3-K) antagonist LY294002 and the MEK antagonist PD98059 in primary astrocytes. Overall, we show for the first time that GPER may contribute to the anti-inflammatory effect of IGF-1 against MPTP/MPP + -induced astrocyte activation. IGF-1 could regulate the expression of GPER via the IGF-1R/PI3-K/MAPK signaling pathway in primary astrocytes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA