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1.
BMJ Open Respir Res ; 11(1)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834332

ABSTRACT

OBJECTIVE: This study aims to explore the common genetic basis between respiratory diseases and to identify shared molecular and biological mechanisms. METHODS: This genome-wide pleiotropic association study uses multiple statistical methods to systematically analyse the shared genetic basis between five respiratory diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer and snoring) using the largest publicly available genome wide association studies summary statistics. The missions of this study are to evaluate global and local genetic correlations, to identify pleiotropic loci, to elucidate biological pathways at the multiomics level and to explore causal relationships between respiratory diseases. Data were collected from 27 November 2022 to 30 March 2023 and analysed from 14 April 2023 to 13 July 2023. MAIN OUTCOMES AND MEASURES: The primary outcomes are shared genetic loci, pleiotropic genes, biological pathways and estimates of genetic correlations and causal effects. RESULTS: Significant genetic correlations were found for 10 paired traits in 5 respiratory diseases. Cross-Phenotype Association identified 12 400 significant potential pleiotropic single-nucleotide polymorphism at 156 independent pleiotropic loci. In addition, multitrait colocalisation analysis identified 15 colocalised loci and a subset of colocalised traits. Gene-based analyses identified 432 potential pleiotropic genes and were further validated at the transcriptome and protein levels. Both pathway enrichment and single-cell enrichment analyses supported the role of the immune system in respiratory diseases. Additionally, five pairs of respiratory diseases have a causal relationship. CONCLUSIONS AND RELEVANCE: This study reveals the common genetic basis and pleiotropic genes among respiratory diseases. It provides strong evidence for further therapeutic strategies and risk prediction for the phenomenon of respiratory disease comorbidity.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Respiratory Tract Diseases/genetics , Genetic Pleiotropy , Pulmonary Disease, Chronic Obstructive/genetics , Asthma/genetics
2.
Arch Dermatol Res ; 316(5): 176, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758283

ABSTRACT

Psoriasis is a chronic immune mediated inflammatory skin disease with systemic manifestations. It has been reported that caloric restriction could improve severity of psoriasis patients. However, the mechanism of intermittent fasting effects on psoriasis has not been investigated. Caloric restriction is known to reduce the number of circulating inflammatory monocytes in a CCL2-dependent manner. However, it is still unknown whether caloric restriction can improve psoriasis by regulating monocytes through CCL2. In this study, we used imiquimod (IMQ)-induced psoriasis-like mouse model to explore the effects and the mechanisms of intermittent fasting on psoriasis-like dermatitis. We found that intermittent fasting could significantly improve IMQ-induced psoriasis-like dermatitis, and reduce the number of γδT17 cells and IL-17 production in draining lymph nodes and psoriatic lesion via inhibiting proliferation and increasing death of γδT17 cells. Furthermore, intermittent fasting could significantly decrease monocytes in blood, and this was associated with decreased monocytes, macrophages and DC in psoriasis-like skin inflammation. Reduced monocytes in circulation and increased monocytes in BM of fasting IMQ-induced psoriasis-like mice is through reducing the production of CCL2 from BM to inhibit monocyte egress to the periphery. Our above data shads light on the mechanisms of intermittent fasting on psoriasis.


Subject(s)
Chemokine CCL2 , Disease Models, Animal , Fasting , Imiquimod , Monocytes , Psoriasis , Animals , Psoriasis/immunology , Psoriasis/chemically induced , Psoriasis/pathology , Monocytes/immunology , Monocytes/metabolism , Mice , Fasting/blood , Chemokine CCL2/metabolism , Th17 Cells/immunology , Interleukin-17/metabolism , Skin/pathology , Skin/immunology , Humans , Mice, Inbred C57BL , Male , Cell Proliferation , Caloric Restriction , Intermittent Fasting
3.
Int Rev Immunol ; : 1-25, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37882232

ABSTRACT

Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg cells have been involved in the pathogenesis of various autoimmune diseases and allograft rejection. Therefore, the approaches that increase the pool or suppressive function of Treg cells in vivo could be a general strategy to treat different autoimmune diseases and allograft rejection. Interleukin-2 (IL-2) is essential for the development, survival, maintenance, and function of Treg cells, constitutively expressing the high-affinity receptor of IL-2 and sensitive response to IL-2 in vivo. And low-dose IL-2 therapy in vivo could restore the imbalance between autoimmune response and self-tolerance toward self-tolerance via promoting Treg cell expansion and inhibiting follicular helper T (Tfh) and IL-17-producing helper T (Th17) cell differentiation. Currently, low-dose IL-2 treatment is receiving extensive attention in autoimmune disease and transplantation treatment. In this review, we summarize the biology of IL-2/IL-2 receptor, the mechanisms of low-dose IL-2 therapy in autoimmune diseases, the application in the progress of different autoimmune diseases, including Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Autoimmune Hepatitis (AIH), Alopecia Areata (AA), Immune Thrombocytopenia (ITP) and Chronic graft-versus-host-disease (GVHD). We also discuss the future directions to optimize low-dose IL-2 treatments.


Low-dose interleukin-2 (IL-2) is a potential treatment for autoimmune diseases. IL-2 is a protein that helps regulate the immune system, and low doses of it can activate regulatory T cells (Tregs), which help control the immune response. This can be beneficial in autoimmune diseases where the immune system attacks healthy tissues. We discuss several clinical trials that have investigated the effectiveness of low-dose IL-2 in treating autoimmune diseases. These trials have shown promising results, with some patients experiencing improvements in symptoms and disease progression. However, more research is needed to determine the safety and effectiveness of low-dose IL-2 as a treatment for autoimmune diseases. IL-2 can also activate other immune cells, which may cause unwanted side effects. Therefore, careful monitoring and dosing are necessary when using this treatment. We should also take note of some of the challenges associated with using low-dose IL-2 as a treatment for autoimmune diseases. For example, it can be difficult to determine the optimal dose and dosing schedule for each patient. In addition, there may be individual differences in how patients respond to low-dose IL-2 treatment. Overall, we believe that low-dose IL-2 shows promise as a treatment for autoimmune diseases, but more research is needed to fully understand its potential benefits and risks.

4.
J Sep Sci ; 46(19): e2300435, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37548124

ABSTRACT

A reliable method for determination of six α-dicarbonyl compounds in traditional Chinese medicines was first developed and validated by high-performance liquid chromatography-fluorescence detector with pre-column derivatization. α-Dicarbonyl compounds in traditional Chinese medicines were extracted and derivatized with 2,3-diaminaphthalene. The derivatization procedure of six α-dicarbonyl compounds was confirmed by high-resolution mass spectrometry. The limits of quantitation for six α-dicarbonyl compounds ranged from 3.70 × 10-3 to 2.21 × 10-2  µM. The established method showed good linearity (regression coefficient > 0.9990), precision (relative standard deviation < 3.37%), and high recovery (97.8%∼113.1%). The developed method was successfully applied to detect the six α-dicarbonyl compounds in traditional Chinese medicines. The result exhibited six α-dicarbonyl compounds was found in the 15 kinds of traditional Chinese medicines, which suggested us that the determination of α-dicarbonyl compounds should be paid more attention in the quality control of traditional Chinese medicines.


Subject(s)
Medicine, Chinese Traditional , Chromatography, High Pressure Liquid/methods , Mass Spectrometry
5.
Poult Sci ; 102(10): 102924, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37542941

ABSTRACT

The paper aimed to evaluate the effects of dietary inclusion of green tea powder (GTP) on laying performance, egg quality, and blood biochemical parameters of laying hens. A total of 240 Jingfen No. 6 laying hens (age, 24 wk) were randomly allocated into 4 groups: control group (CON, basal diet), GTP0.5, GTP0.75, and GTP1.0 (basal diet included 0.5, 0.75, and 1.0% GTP, respectively). Each group has 5 replicates with 12 birds each. The feeding trial lasted 8 wk. The results showed that the hen-day egg production rate in GTP0.5 and GTP 0.75 group was higher than that of GTP1.0 group (P < 0.05), hen-day egg production rate in the GTP1.0 group was lower compared to the CON group (P > 0.05), the feed conversion ratio (FCR) in the GTP0.75 group was lower than that in CON and GTP 1.0 group (P < 0.05) during the entire experimental period. Albumen height and Haugh unit were higher in the GTP0.75 and GTP1.0 group compared to the CON group at d 56 (P < 0.05). At the end of experiment, plasma TG content in the GTP0.75 and GTP1.0 group was lower than that in the CON group (P < 0.05), the T-CH concentration in the GTP0.5 and GTP0.75 group was lower compared to the CON group (P < 0.05), plasma LDL-C and CORT concentrations were decreased by dietary GTP supplementation (P < 0.05), the HDL-C and BUN concentrations in the GTP0.75 and GTP1.0 group were higher than that in the CON group (P < 0.05). The antibody titers of H5N1 in the GTP0.75 and GTP1.0 group, and H7N9 in the GTP1.0 group were lower than that in the CON group (P < 0.05). In conclusion, dietary GTP inclusion could affect laying performance, regulate lipid metabolism, and have no favorable influence on antibody titers of H5N1 and H7N9, herein, dietary 0.5% GTP inclusion is suggested for Jingfen No. 6 laying hens during the peak laying period.


Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza A Virus, H7N9 Subtype , Animals , Female , Dietary Supplements , Chickens/physiology , Powders , Tea , Ovum , Diet/veterinary , Guanosine Triphosphate , Animal Feed/analysis
6.
Molecules ; 27(23)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36500290

ABSTRACT

Diterpenoids are considered the major bioactive components in Scutellaria barbata to treat cancer and inflammation, but few comprehensive profiling studies of diterpenoids have been reported. Herein, a stepwise diagnostic product ions (DPIs) filtering strategy for efficient and targeted profiling of diterpenoids in Scutellaria barbata was developed using UHPLC-Q-Exactive-Orbitrap-MS. After UHPLC-HRMS/MS analysis of six diterpenoid reference standards, fragmentation behaviors of these references were studied to provide DPIs. Then, stepwise DPIs filtering aimed to reduce the potential interferences of matrix ions and achieve more chromatographic peaks was conducted to rapidly screen the diterpenoids. The results demonstrated that stepwise DPIs were capable of simplifying the workload in data post-processing and the effective acquisition of low abundance compounds. Subsequently, DPIs and MS/MS fragment patterns were adopted to identify the targeted diterpenoids. As a result, 381 diterpenoids were unambiguously or tentatively identified, while 141 of them with completely new molecular weights were potential new diterpenoids for Scutellaria barbata. These results demonstrate that the developed stepwise DPIs filtering method could be employed as an efficient, reliable, and valuable strategy to screen and identify the diterpenoid profile in Scutellaria barbata. This might accelerate and simplify target constituent profiling from traditional Chinese medicine (TCM) extracts.


Subject(s)
Diterpenes , Drugs, Chinese Herbal , Scutellaria , Scutellaria/chemistry , Tandem Mass Spectrometry/methods , Diterpenes/chemistry , Medicine, Chinese Traditional , Drugs, Chinese Herbal/chemistry , Ions , Chromatography, High Pressure Liquid/methods
7.
Front Oncol ; 12: 905230, 2022.
Article in English | MEDLINE | ID: mdl-36147922

ABSTRACT

Objective: In contrast to normal cells, in which reactive oxygen species (ROS) are maintained in redox equilibrium, cancer cells are characterized by ectopic ROS accumulation. Myoferlin, a newly identified oncogene, has been associated with tumor metastasis, intracellular ROS production, and energy metabolism. The mechanism by which myoferlin regulates gastric cancer cell migration and ROS accumulation has not been determined. Methods: Myoferlin expression, intracellular ROS levels, the ratios of reduced to oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) and migratory ability were measured in gastric cancer cells in vitro and in the TCGA and GEO databases in silico. Results: Myoferlin was found to be more highly expressed in tumor than in normal tissues of gastric cancer patients, with higher expression of Myoferlin associated with shorter survival time. Myoferlin was associated with significantly higher intracellular ROS levels and enhanced migration of gastric cancer cells. N-acetyl-L-cysteine (NAC), a potent inhibitor of ROS, inhibited Myoferlin-induced ROS accumulation and cell migration. Conclusions: Myoferlin is a candidate prognostic biomarker for gastric cancer and plays an essential role in regulating redox equilibrium and gastric cancer cell migration. Myoferlin may also be a new target for treatment of patients with gastric cancer.

8.
Front Immunol ; 13: 880201, 2022.
Article in English | MEDLINE | ID: mdl-35757712

ABSTRACT

Psoriasis is a chronic autoimmune inflammatory disease that remains active for a long period, even for life in most patients. The impact of psoriasis on health is not only limited to the skin, but also influences multiple systems of the body, even mental health. With the increasing of literature on the association between psoriasis and extracutaneous systems, a better understanding of psoriasis as an autoimmune disease with systemic inflammation is created. Except for cardiometabolic diseases, gastrointestinal diseases, chronic kidney diseases, malignancy, and infections that have received much attention, the association between psoriasis and more systemic diseases, including the skin system, reproductive system, and oral and ocular systems has also been revealed, and mental health diseases draw more attention not just because of the negative mental and mood influence caused by skin lesions, but a common immune-inflammatory mechanism identified of the two systemic diseases. This review summarizes the epidemiological evidence supporting the association between psoriasis and important and/or newly reported systemic diseases in the past 5 years, and may help to comprehensively recognize the comorbidity burden related to psoriasis, further to improve the management of people with psoriasis.


Subject(s)
Psoriasis , Renal Insufficiency, Chronic , Chronic Disease , Comorbidity , Humans , Inflammation/epidemiology , Renal Insufficiency, Chronic/epidemiology , Skin/pathology
9.
Int J Cancer ; 151(4): 607-615, 2022 08 15.
Article in English | MEDLINE | ID: mdl-35419831

ABSTRACT

This randomized, multicenter, phase II clinical trial was performed to compare the safety and efficacy of concurrent chemoradiotherapy using S-1 (CCRT) with radiotherapy alone (RT) for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). All eligible patients were randomly assigned to the CCRT group or the RT group at a 1:1 ratio. The CCRT group received 50.4 Gy radiotherapy concurrent with S-1 and the RT group received 59.4 Gy radiotherapy alone. The primary endpoints were toxicity and the overall response rate (ORR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). In total, 157 elderly patients with ESCC were recruited from December 2016 to March 2020. By June 2021, the median follow-up duration had reached 38 months. No grade 5 toxicities occurred in either group and the overall rate of severe toxicities (≥grade 3) was higher in the CCRT group (19.2% vs 7.6%; P = .037), particularly neutropenia (7.7% vs 1.3%; P = .06). The CCRT group presented a significantly higher ORR (83.3% vs 68.4%; P = .009) and prolonged PFS (25.7 vs 13.9 months; P = .026) than the RT group. The median OS was 27.3 months in the CCRT group and 19.1 months in the RT group (P = .59). For patients older than 70 years with locally advanced ESCC, concurrent chemoradiotherapy with S-1 had tolerable adverse effects and improved ORR and PFS compared to radiotherapy alone.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/adverse effects , Cisplatin/therapeutic use , Epithelial Cells/pathology , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Esophageal Squamous Cell Carcinoma/drug therapy , Humans
10.
Materials (Basel) ; 15(2)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35057292

ABSTRACT

In this article, we performed symmetry analysis of perovskite-based multiferroics: bismuth ferrite (BiFeO3)-like, orthochromites (RCrO3), and Ruddlesden-Popper perovskites (Ca3Mn2O7-like), being the typical representatives of multiferroics of the trigonal, orthorhombic, and tetragonal crystal families, and we explored the effect of crystallographic distortions on magnetoelectric properties. We determined the principal order parameters for each of the considered structures and obtained their invariant combinations consistent with the particular symmetry. This approach allowed us to analyze the features of the magnetoelectric effect observed during structural phase transitions in BixR1-xFeO3 compounds and to show that the rare-earth sublattice has an impact on the linear magnetoelectric effect allowed by the symmetry of the new structure. It was shown that the magnetoelectric properties of orthochromites are attributed to the couplings between the magnetic and electric dipole moments arising near Cr3+ ions due to distortions linked with rotations and deformations of the CrO6 octahedra. For the first time, such a symmetry consideration was implemented in the analysis of the Ruddlesden-Popper structures, which demonstrates the possibility of realizing the magnetoelectric effect in the Ruddlesden-Popper phases containing magnetically active cations, and allows the estimation of the conditions required for its optimization.

11.
Food Res Int ; 144: 110360, 2021 06.
Article in English | MEDLINE | ID: mdl-34053553

ABSTRACT

Obesity is regarded to be associated with fat accumulation, chronic inflammation, and gut microbiota dysbiosis. Raw and ripened pu-erh tea extract (PETe) have the effect of reducing body weight gain and fat accumulation, which are associated with gut microbiota. However, little is known about the difference of raw and ripened PETe on the regulation of gut microbiota. Here, our results suggested that supplementation of raw and ripened PETe displayed similar anti-obesogenic effect in high fat diet (HFD)-induced obesity mice, by attenuating the body weight gain, fat accumulation, oxidative injury, and low-grade inflammation, improving the glucose tolerance, alleviating the metabolic endotoxemia, and regulating the mRNA and protein expression levels of the lipid metabolism-related genes. 16S rRNA sequencing of fecal samples indicated that raw and ripened PETe intervention displayed different regulatory effect on the HFD-induced gut microbiota dysbiosis at different taxonomic levels. The microbial diversity, the relative abundance of Firmicutes and Bacteroidetes as well as F/B ratio were reversed more closer to normal by ripened PETe. Phylotypes of Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, Muribaculaceae, and Rikenellaceae which are negatively correlated with obesity were enhanced notably by the intervention of ripened PETe, while Erysipelotrichaceae and Lactobacillaceae which have positive correlation with obesity were decreased dramatically. In addition, the treatment of ripened PETe had better effect on the increase of benefical Bacteroides, Alistipes, and Akkemansia and decrease of obesity associated Faecalibaculum and Erysipelatoclostridium (p < 0.05). These findings suggested that pu-erh tea especially ripened pu-erh tea could serve as a great candidate for alleviation of obesity in association with the modulation of gut microbiota.


Subject(s)
Gastrointestinal Microbiome , Animals , Diet, High-Fat , Mice , Obesity , RNA, Ribosomal, 16S , Tea
13.
Sci Rep ; 10(1): 3990, 2020 03 04.
Article in English | MEDLINE | ID: mdl-32132642

ABSTRACT

An excellent pre-column fluorescent derivatization reagent N-acetylhydrazine acridone for the quantitative determination of malondialdehyde was synthesized. Malondialdehyde was derivatized at 80 °C for 30 min in the presence of trichloroacetic acid. The separation of the derivative was performed on an Agilent ZORBAX SB-C18 column in conjunction with gradient elution. The excitation and emission wavelengths were 370 nm and 420 nm, respectively. The developed method demonstrated good linear relationship in the range of 0.02 pmol to 2.5 pmol (r = 0.9998). The calculated limit of detection and limit of quantification were 2.5 fmol and 8.3 fmol, respectively. The analytical precisions of the method were in the range of 1.36-2.27% (intra-day) and 2.36-3.92% (inter-day) respectively. The method was sensitive, specific and simple. It was successfully implemented to analysis the malondialdehyde in rat prostate.


Subject(s)
Limit of Detection , Malondialdehyde/analysis , Prostate/chemistry , Animals , Chromatography, High Pressure Liquid , Linear Models , Male , Malondialdehyde/chemistry , Malondialdehyde/isolation & purification , Rats , Spectrometry, Fluorescence
14.
Thorac Cancer ; 10(12): 2236-2242, 2019 12.
Article in English | MEDLINE | ID: mdl-31679181

ABSTRACT

BACKGROUND: Previous studies have documented the therapeutic value of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for early-stage non-small cell lung cancer (NSCLC). However, few studies have focused on patients aged 80 years and older. This retrospective study aimed to evaluate the safety and clinical outcomes of CT-guided percutaneous MWA in patients aged 80 years and older with early-stage peripheral NSCLC. METHODS: A retrospective analysis of 63 patients aged 80 years and older with cT1a-2bN0M0 peripheral NSCLC who underwent CT-guided percutaneous MWA was performed between January 2008 and January 2018 at 11 hospitals in Shandong Province, China. RESULTS: The median follow-up time was 21.0 months. The overall median survival time was 50 months. The cancer-specific median survival time was not reached in five years. The one-, two-, three-, four-, and five-year overall survival rates were 97.1%, 92.6%, 63.4%, 54.4%, and 32.6%, respectively. The one-, two-, and three-year cancer-specific survival (CSS) rates were 97.9%, 97.9%, and 69.4%, respectively. The four- and five-year CSS rates were not achieved. A total of 14 patients (22.2%) had local progression. The one-, two-, three-, four-, and five-year local control rates were 88.8%, 78.8%, 70.3%, 63.9%, and 63.9%, respectively. The mortality rate was 0% within 30 days after the procedure. Major complications included pneumothorax requiring drainage (21.1%), pulmonary infection (4.2%), and pleural effusions requiring drainage (2.8%). CONCLUSIONS: CT-guided percutaneous MWA is a safe and effective modality for treating patients aged 80 years and older with early-stage peripheral NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Catheter Ablation/methods , Lung Neoplasms/therapy , Microwaves/therapeutic use , Surgery, Computer-Assisted/methods , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , Comorbidity , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Male , Prognosis , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome
15.
RSC Adv ; 9(12): 6717-6723, 2019 Feb 22.
Article in English | MEDLINE | ID: mdl-35518507

ABSTRACT

A novel fluorescence labeling reagent N-acetylhydrazine acridone (AHAD) was designed and synthesized. A highly sensitive high performance liquid chromatography (HPLC) method coupled with fluorescence detection to determine benzaldehyde after derivatization with AHAD was developed. Optimum derivatization was obtained at 40 °C for 30 min with trichloroacetic acid as catalyst. Benzaldehyde derivative was separated on a reversed-phase SB-C18 column in conjunction with a gradient elution and detected by fluorescence detection at excitation and emission wavelengths of 371 nm and 421 nm. The established method exhibited excellent linearity over the injected amount of benzaldehyde of 0.003 to 5 nmol mL-1. The method was successfully applied to the determination of serum semicarbazide-sensitive amine oxidase (SSAO) activity in humans. SSAO is a significant biomarker because serum SSAO activity is elevated in patients with Alzheimer's disease, vascular disorders, heart disease and diabetes mellitus. It was demonstrated that the SSAO activity of the hyperglycemic group (60 ± 4 nmol mL-1 h-1) was significantly higher than that of normal blood sugar group (44 ± 4 nmol mL-1 h-1) with P < 0.05.

16.
Sci Rep ; 8(1): 5183, 2018 03 26.
Article in English | MEDLINE | ID: mdl-29581534

ABSTRACT

MicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.


Subject(s)
Biomarkers, Tumor/genetics , Esophageal Squamous Cell Carcinoma/genetics , MicroRNAs/genetics , Receptor, Notch2/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Esophageal Squamous Cell Carcinoma/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis , Male , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , RNA, Messenger/genetics , Signal Transduction
17.
Oncol Lett ; 15(1): 984-990, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29387242

ABSTRACT

Breast cancer (BC) is the leading cause of cancer-associated mortality among women worldwide, with a poor 5-year survival rate, particularly among patients with metastatic BC. Previous studies have indicated that the dysregulation of microRNAs (miRNAs/miRs) is associated with carcinogenesis and metastasis. Thus, investigating the underlying molecular mechanisms by which miRNAs mediate their effects may aid in the improvement of BC treatment. In the present study, reverse transcription-quantitative polymerase chain reaction analyses were performed to investigate miR-124-3p expression in BC tissues. The expression of miR-124-3p was significantly decreased in primary BC tissues compared with that in adjacent non-tumor tissues. Downregulated miR-124-3p was correlated with lymph node metastasis and a low overall survival time. Wound-healing and Transwell assays revealed that MDA-MB-231 and MCF-7 cell motility was inhibited by miR-124-3p, but was promoted by a miR-124-3p inhibitor. Overexpression of miR-124-3p increased levels of E-cadherin, and decreased levels of N-cadherin and Vimentin, indicating that miR-124-3p inhibits the epithelial-mesenchymal transition. In addition, a bioinformatics analysis and subsequent in vitro experiments identified programmed cell death protein 6 (PDCD6) as a direct target of miR-124-3p. Restoration of PDCD6 expression impaired the metastasis inhibitor role of miR-124-3p by promoting cell invasion. Furthermore, the expression of miR-124-3p was inversely associated with PDCD6 mRNA levels in clinical breast tumors. Taken together, these data suggest that miR-124-3p inhibits tumor metastasis by inhibiting PDCD6 expression, and that the miR-124-3p/PDCD6 signaling axis may be a potential target for novel treatments in patients with advanced BC.

18.
RSC Adv ; 8(33): 18549-18559, 2018 May 17.
Article in English | MEDLINE | ID: mdl-35541139

ABSTRACT

A novel fluorescent labeling reagent toluene-4-sulfonic acid 2-(2-thiophen-2-yl-phenanthro[9,10-d]imidazol-1-yl)-ethyl ester has been designed and synthesized. It was used to label twenty-six fatty acids (C5-C30) successfully in the presence of K2CO3 catalyst in N,N-dimethylformamide solvent. The reaction conditions were optimized by employing a three-factor, three-level Box-Behnken design. Derivatives were sufficiently stable to be efficiently analyzed by high-performance liquid chromatography with fluorescence detection. All fatty acid derivatives were separated on a hypersil BDS-C8 column in conjunction with a gradient elution with a good baseline resolution. Good linear correlations were observed for all fatty acids with correlation coefficients > 0.993. The established method exhibited high sensitivity and excellent repeatability. The limit of detection (at a signal-to-noise ratio of 3 : 1) was 8.8-45.5 fmol. The method was used to quantify free fatty acids in ginkgo nut and ginkgo leaf samples with satisfactory results.

19.
Oncol Lett ; 14(3): 2677-2682, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28927030

ABSTRACT

Radiotherapy, particularly the target delineation of cancer based on scanned images, plays a key role in the planning of cancer treatment. Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) has emerged as a prospective superior procedure compared with intensified computed tomography (CT) and positron emission tomography (PET) in the target delineation of cancer. However, the implication of DW-MRI in lung cancer, the leading cause of cancer-associated mortality worldwide, has not been extensively evaluated. In the present study, the gross target volumes of lung cancer masses delineated using the DW-MRI, CT and PET procedures were compared in a pairwise manner in a group of 27 lung cancer patients accompanied with atelectasis of various levels. The data showed that compared with CT and PET procedures, DW-MRI has a more precise delineation of lung cancer while exhibiting higher reproducibility. Together with the fact that it is non-invasive and cost-effective, these data demonstrate the great application potential of the DW-MRI procedure in cancer precision radiotherapy.

20.
Biomed Chromatogr ; 31(11)2017 Nov.
Article in English | MEDLINE | ID: mdl-28474782

ABSTRACT

A simple, fast and reliable high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C18 column (4.6 × 150 mm, 5 µm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity (r > 0.99), intra-/inter-day precision (1.0-10.1%), accuracy (relative error, <7.6%), stability (0.6-13.2%), extract recovery (74.9-91.9%) and matrix effect (89.1-109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet.


Subject(s)
Anthraquinones , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/administration & dosage , Flavonoids , Gastrointestinal Diseases/metabolism , Tandem Mass Spectrometry/methods , Administration, Oral , Animals , Anthraquinones/blood , Anthraquinones/chemistry , Anthraquinones/pharmacokinetics , Drug Stability , Drugs, Chinese Herbal/pharmacokinetics , Flavonoids/blood , Flavonoids/chemistry , Flavonoids/pharmacokinetics , Gastrointestinal Motility , Limit of Detection , Linear Models , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results
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