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1.
Neural Regen Res ; 16(2): 382-387, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32859802

RESUMO

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.

2.
Food Chem ; 337: 128008, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920267

RESUMO

This study investigated the role of furfuryl alcohol (FFA) in the formation of furfurylthiol (FFT), the most important odorant in roasted coffee, using in-bean and spiking experiments. Green beans were spiked with FFA, and after roasting FFT was quantified by stable isotope dilution analysis. The FFT level in the roasted beans increased dose-dependently with addition of FFA. Additionally, beans were spiked with isotopically labelled d2-FFA which generated isotopically labelled d2-FFT after roasting. However, no labelled furfural was observed. The results unambiguously show that FFA serves as a precursor of FFT in coffee. On the other hand, the data indicate that furfural stems not from oxidation of FFA and plays no major role as precursor for FFT formation during coffee roasting. The suggested formation pathway leads from FFA to the furfuryl cation, then protein-bound S-furfuryl-l-cysteine and by subsequent elimination to FFT.

3.
Fitoterapia ; 147: 104739, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031867

RESUMO

Four new flavonoids (1-4) and fourteen known compounds (5-18), were isolated from the aerial part of Bupleurum chinense DC. The structural determination of the new flavonoids was accomplished using comprehensive spectroscopic methods, including 1D and 2D NMR spectra with references to the literatures, as well as high-resolution mass spectrometric analysis. The anti-proliferative activities of the flavonoids (1-18) against HeLa cells were evaluated using the MTT assay with cisplatin as the positive control.

4.
BMJ Open ; 10(10): e037829, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067281

RESUMO

INTRODUCTION: Despite the increase in the survival rate of high-risk infants (HRIs) worldwide, the prevalence of motor and neurodevelopmental sequelae in such newborns has not shown concomitant improvement. Meanwhile, there are few cohorts that explore factors related to the development of HRIs in China. Therefore, the Guangzhou High-Risk Infant Cohort (GHRIC) has been designed to examine the complex relationships among a myriad of factors influencing growth and development in such children. METHODS AND ANALYSIS: The GHRIC study is a prospective cohort study that by the year 2023 will enrol an estimated total of 3000 HRIs from Guangzhou Women and Children's Medical Center (GWCMC) in Guangzhou, China. This study is designed to assess the growth and cognitive characteristics of HRIs and the risk factors affecting their development and prognoses. Data on risk factors, neurodevelopmental and cognitive-function evaluations, laboratory results, and specimens will be collected and analysed. Information on perinatal and clinical interventions for these infants will also be recorded during regular follow-up visits until age 6. ETHICS AND DISSEMINATION: The protocol for this study has been approved by the Research Ethics Committee of GWCMC, which accepted responsibility for supervising all of the aspects of the study (No. 2017102712). Study outcomes will be disseminated through conference presentations, peer-reviewed publications, the Internet and social media. TRIAL REGISTRATION NUMBER: ChiCTR-EOC-17013236.

5.
Cancer Med ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33067881

RESUMO

BACKGROUND: It is well known that pepsinogen (PGs), as an important precursor of pepsin performing digestive function, has a good correlation with the occurrence and development of gastric cancer and it is also known that ectopic PGs expression is related to the prognosis of some cancers. However, the panoramic picture of pepsinogen gene family in human cancer is not clear. This study focused on elucidating the expression profile, activated pathway, immune cells infiltration, mutation, and copy number variation of PGs and their potential role in human cancer. METHOD: Based on the next generation sequence data from TCGA, Oncomine, and CCLE, the molecular changes and clinical correlation of PGs in 33 tumor types were analyzed systematically by R language, including the expression, mutation, and copy number variation of PGs and their correlation with cancer-related signal transduction pathway, immune cell infiltration, and prognostic potential in different cancers. RESULTS: PGs expression profiles appear different in 33 tumors. The transcriptional expression of PGs was detected in 16 of all 33 tumors. PGC was highly expressed in cholangiocarcinoma, colon adenocarcinoma, rectum adenocarcinoma, uterine corpus endometrial carcinoma, bladder urothelial carcinoma and breast cancer, while decreased in stomach adenocarcinoma, kidney renal clear cell carcinoma, prostate adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. PGA3, PGA4, and PGA5 were expressed in most normal tissues, but decreased in cancer tissues. PGs expression was significantly related to the activation or inhibition of many signal transduction pathways, in which PGC and PGA5 are more likely to be associated with cancer-related pathways. PGC participated in 33 regulatory network pathways in pan-cancer, mainly distributed in stomach adenocarcinoma, esophageal carcinoma, and lung squamous cell carcinoma, respectively. PGC and PGA3 expression were significantly correlated with immune cell infiltration. The results of survival analysis showed that different PGs expression play significantly different prognostic roles in different cancers. PGC was correlated with poor survival in brain lower grade glioma, skin cutaneous melanoma, and higher survival in kidney renal clear cell carcinoma, acute myeloid leukemia, mesothelioma, and uveal melanoma. PGA4 was only associated with higher survival in kidney renal clear cell carcinoma. Genetic variation analysis showed that PGC gene often mutated in uterine corpus endometrial carcinoma and stomach adenocarcinoma had extensive copy number amplification in various tumor types. PGC expression was upregulated with the increase of copy number in cholangiocarcinoma, esophageal carcinoma, and kidney renal papillary cell carcinoma, while in stomach adenocarcinoma, PGC was upregulated regardless of whether the copy number was increased or decreased. CONCLUSIONS: PGs was expressed unevenly in a variety of cancer tissues and was related to many carcinogenic pathways and involved in the immune regulation. PGC participated in 33 regulatory pathways in human cancer. Different PGs expression play significantly different prognostic roles in different cancers. The variation of copy number of PGC gene could affect the PGC expression. These findings suggested that PGs, especially PGC have characteristic of broad-spectrum expression in multiple cancers rather than being confined to the gastric mucosa, which may made PGs be useful biomarkers for prediction/diagnosis/prognosis and effective targets for treatment in human cancer.

6.
Biomed Pharmacother ; 132: 110809, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049584

RESUMO

Phloretin is a natural dihydrochalcone flavonoid that is mainly distributed in apple, pear and other juicy fruit peels or root peels. Phloretin exhibits several pharmacological properties, such as antidiabetic, antioxidant, anti-inflammatory, and antitumor activities. However, the poor water solubility of phloretin limits its application in the treatment of numerous diseases. To date, the underlying mechanisms of phloretin absorption have not been investigated. In this study, the pharmacokinetics of phloretin orally administered to Sprague-Dawley (SD) rats were examined, and the absorption mechanisms of phloretin were investigated in a Caco-2 cell monolayer and single-pass intestinal perfusion in SD rat. The effects measured by basic parameters, such as compound concentration, time, temperature, paracellular pathway, in different intestinal segments were analyzed, and various inhibitors, such as the P-glycoprotein (P-gp) inhibitor verapamil, the multidrug resistance protein 2 (MRP2) inhibitor indomethacin, the breast cancer resistance protein (BCRP) inhibitor reserpine, and the closely related regulator EDTA, were evaluated to determine their effects on the absorption of phloretin. The pharmacokinetics of phloretin was studied by oral and intravenous injection in rats. The bioavailability was 8.676 %.The SPIP experiments showed that P-gp, MRP2, BCRP protein inhibitor and closely related regulator, could significantly increase the apparent permeability coefficient (Papp) of phloretin. Monolayer transport experiments in Caco-2 cells showed that P-gp, MRP2 protein inhibitor and closely related regulator EDTA, significantly increased the Papp value of phloretin. In conclusion, phloretin is a substrate of P-gp and MRP2, and its modes of transport include active transport, efflux protein transport and cell bypass.

7.
Thorac Cancer ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015950

RESUMO

BACKGROUND: Plasmid construction of small fragments of interest (such as insertion of small fragment marker genes, expression of shRNA, siRNA, etc) is the basis of many biomolecular experiments. Here, we describe a method to clone short DNA into vectors by polymerase chain reaction (PCR), named one-step PCR cloning. Our method uses PCR to amplify the entire circular plasmid. The PCR was performed by the primers containing the gene of short DNA with overlapping sequences between 10-15 bp. The PCR products were then transformed into E. coli and cyclized by homologous recombination in vivo. METHODS: The pEGFP-N1-HA plasmid was constructed by one-step PCR and transformation. Cells were transfected with pEGFP-N1-HA and pEGFP-N1 plasmid using TurboFect transfection reagent. Protein expression was detected by western blotting and the HA-GFP fusion protein was detected by confocal microscopy. RESULTS: The pEGFP-N1-HA plasmid was successfully constructed and HA expression in cells. CONCLUSIONS: Free from the limitations of restriction enzyme sites and omitting the ligation process, our method offers a flexible and economical option of plasmid construction. KEY POINTS: Significant findings of the study A method to clone short DNA into plasmids was found. What this study adds Our study provides a flexible and economical option to clone short DNA into plasmids.

8.
Future Med Chem ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028090

RESUMO

Aim: With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Results & methodology: Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids 6e and 6f displayed excellent inhibitory efficacy against clinical methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration = 1 µg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule 6f could effectively interfere with MRSA membrane and insert into MRSA DNA. Conclusion: Compounds 6e and 6f could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.

9.
Acta Pharmacol Sin ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028983

RESUMO

Alcoholic liver disease (ALD) is one of the pathogenic factors of chronic liver disease with the highest clinical morbidity worldwide. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, has shown many health benefits including antioxidative, anti-inflammatory, anticancer, and hepatoprotective activities. We previously found that UA was metabolized in vivo into epoxy-modified UA containing an epoxy electrophilic group and had the potential to react with nucleophilic groups. In this study we prepared an alkynyl-modified UA (AM-UA) probe for tracing and capturing the target protein of UA from liver in mice, then investigated the mode by which UA bound to its target in vivo. By conducting proteome identification and bioinformatics analysis, we identified caspase-3 (CASP3) as the primary target protein of UA associated with liver protection. Molecule docking analysis showed that the epoxy group of the UA metabolite reacted with Cys-163 of CASP3, forming a covalent bond with CASP3. The binding mode of the UA metabolites (UA, CM-UA, and EM-UA) was verified by biochemical evaluation, demonstrating that the epoxy group produced by metabolism played an important role in the inhibition of CASP3. In alcohol-treated HepG2 cells, pretreatment with the UA metabolite (10 µM) irreversibly inhibited CASP3 activities, and subsequently decreased the cleavage of PARP and cell apoptosis. Finally, pre-administration of UA (20-80 mg· kg-1 per day, ig, for 1 week) dose-dependently alleviated alcohol-induced liver injury in mice mainly via the inhibition of CASP3. In conclusion, this study demonstrates that UA is a valuable lead compound for the treatment of ALD.

10.
Org Lett ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021799

RESUMO

By the cooperative photoredox and N-heterocyclic carbene catalysis, the γ-difluoroalkylation of γ-preoxidized enals was developed for the synthesis of γ-difluoroalkyl-α,ß-unsaturated esters with all-carbon quaternary centers. This method provides efficient catalytic C(sp3)-CF2R bond formation at the γ-position of carbonyl compounds for the first time.

11.
Sci Rep ; 10(1): 16943, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037234

RESUMO

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

12.
Arch Biochem Biophys ; : 108623, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039388

RESUMO

Renal cell carcinoma (RCC) is a frequently diagnosed cancer with high prevalence, which is inversely associated with survival benefit. Although myriad studies have shed light on disease causality, unfortunately, thus far, RCC diagnosis is faced with numerous obstacles partly due to the insufficient knowledge of effective biomarkers, hinting deeper mechanistic understanding are urgently needed. Metabolites are recognized as final proxies for gene-environment interactions and physiological homeostasis as they reflect dynamic processes that are ongoing or have been taken place, and metabolomics may therefore offer a far more productive and cost-effective route to disease discovery, particularly within the arena for new biomarker identification. In this review, we primarily expatiate recent advances in metabolomics that may be amenable to novel biomarkers or therapeutic targets for RCC, which may expand our armaments to win more bettles against RCC.

13.
Euro Surveill ; 25(40)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33034281

RESUMO

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

14.
Comput Biol Chem ; 89: 107397, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035753

RESUMO

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.

15.
Reprod Biol Endocrinol ; 18(1): 100, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046085

RESUMO

BACKGROUND: Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis. METHODS: JEG-3 cells were cocultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting. RESULTS: CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis. CONCLUSIONS: These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.

16.
Genome Biol ; 21(1): 257, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023639

RESUMO

Prime editing is a novel and universal CRISPR/Cas-derived precision genome-editing technology that has been recently developed. However, low efficiency of prime editing has been shown in transgenic rice lines. We hypothesize that enhancing pegRNA expression could improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We construct a prime editing vector harboring two pegRNA variants for W542L and S621I double mutations in ZmALS1 and ZmALS2. Compared with previous reports in rice, we achieve much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.

17.
BMC Evol Biol ; 20(1): 131, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028198

RESUMO

BACKGROUND: Leaves have highly diverse morphologies. However, with an evolutionary history of approximately 200 million years, leaves of the pine family are relatively monotonous and often collectively called "needles", although they vary in length, width and cross-section shapes. It would be of great interest to determine whether Pinaceae leaves share similar morpho-physiological features and even consistent developmental and adaptive mechanisms. RESULTS: Based on a detailed morpho-anatomical study of leaves from all 11 Pinaceae genera, we particularly investigated the expression patterns of adaxial-abaxial polarity genes in two types of leaves (needlelike and flattened) and compared their photosynthetic capacities. We found that the two types of leaves share conserved spatial patterning of vasculatures and genetic networks for adaxial-abaxial polarity, although they display different anatomical structures in the mesophyll tissue differentiation and distribution direction. In addition, the species with needlelike leaves exhibited better photosynthetic capacity than the species with flattened leaves. CONCLUSIONS: Our study provides the first evidence for the existence of a conserved genetic module controlling adaxial-abaxial polarity in the development of different Pinaceae leaves.

18.
Nat Commun ; 11(1): 4980, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020477

RESUMO

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as "Yin and Yang" partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.

19.
Cell Cycle ; : 1-14, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017570

RESUMO

The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/ß-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p. Rescue experiments were performed to determine if SUFU mediates the Wnt activation, EMT and oncogenic function of miRNA-324-5p. MiRNA-324-5p inhibitors plus SUFU siRNAs rescue partially the inhibitory effect on Wnt signaling and EMT caused by miRNA-324-5p inhibitors. Finally, the suppression of cell proliferation, migration, and colony formation ability induced by miRNA-324-5p inhibitors is alleviated by addition of SUFU siRNAs. In summary, miRNA-324-5p is overexpressed in vivo and exerts cell growth and migration-promoting effects through activating Wnt signaling and EMT by targeting SUFU in GC. It represents a potential miRNA with an oncogenic role in human gastric cancer.

20.
Medicine (Baltimore) ; 99(40): e22538, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019462

RESUMO

The current studies revealed inconsistent relationship between reproductive factors and osteoarthritis. Community-based research has not been conducted in China. The study was to examine the association of reproductive factors with the prevalence of knee osteoarthritis (OA).Through a multistage stratified random sampling method, 10 streets or villages from 5 cities in Hunan province were randomly selected, a total 2746 eligible women aged 50 to 83 were recruited in this cross-sectional study. A structured questionnaire including demographic factors, socio-economic status, reproductive factors, and knee OA was used. According to the criteria of American College of Rheumatology, clinical knee OA was assessed by doctors in community or village health clinics for knee pain, age, morning stiffness, crepitus on active motion or for knee pain, morning stiffness, crepitus on active motion, and tenderness of the bony navigation of the joint. Self-reported age of menarche, parity, abortion history, and menopausal status were collected.The prevalence of knee OA was 13.44%. Abortion is associated with knee OA (odds ratio [OR] = 1.271, 95% confidence interval [CI] = 1.007, 1.606), but age at menarche, parity, and menopausal status were not the factors. Furthermore, age (OR = 1.040, 95% CI = 1.020, 1.060), weight (OR = 1.019, 95% CI = 1.004, 1.035), higher education level (OR = 1.530, 95% CI = 1.121, 2.088), higher monthly household income (OR = .583, 95% CI = 0.441, 0.770 for 3000-4999 ¥ and OR = 0.599, 95% CI = 0.431, 0.833 for 5000 ¥ or more), and chronic gastritis (OR = 3.364, 95% CI = 2.548, 4.442) were associated with knee OA.Abortion may increase the risk of knee OA. Special attention should be paid to women with a history of abortion, and women who are planning to abort should be informed of the risk of knee OA later in life. The relationship between abortion and knee OA should be interpreted with caution and further confirmed.

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