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Disease Markers 2022LINC01140 has been known to be involved in various cancers. However, its underlying molecular mechanism in breast cancer (BC) needs further exploration.
BACKGROUND
LINC01140 has been known to be involved in various cancers. However, its underlying molecular mechanism in breast cancer (BC) needs further exploration.
METHODS
The LINC01140, miR-452-5p, and RGS2 levels in BC cells and tissues were evaluated by means of RT-qPCR and western blotting. The variations in the biological functions of BC cells were analyzed through CCK-8, transwell, western blotting, and xenograft experiments to observe cell viability, migration, levels of apoptosis-related proteins (Bax and Bcl-2), and tumor growth. The correlations existing among LINC01140, miR-452-5p, and RGS2 were validated through luciferase reporter and RIP assays.
RESULTS
LINC01140 and RGS2 were remarkably downregulated in BC cells and tissues, whereas miR-452-5p was upregulated. LINC01140 overexpression diminished BC cell viability, migration, and tumor growth and facilitated apoptosis. MiR-452-5p upregulation enhanced cell viability and migration and suppressed apoptosis. Nevertheless, the additional upregulation of LINC01140 could reverse the promotive effects of miR-452-5p upregulation. Additionally, RGS2 overexpression inhibited the malignant phenotypes of BC cells, but miR-452-5p upregulation abolished this effect. In terms of mechanisms, LINC01140 acted as a miR-452-5p sponge. Moreover, RGS2 was determined to be miR-452-5p's downstream target gene in BC.
CONCLUSION
LINC01140 functioned as an antitumor agent in BC by sponging miR-452-5p to release RGS2. This hints that LINC01140 is a promising therapeutic target for BC.
Topics: Humans; Female; MicroRNAs; Cell Proliferation; Cell Movement; Cell Line, Tumor; Sincalide; bcl-2-Associated X Protein; Breast Neoplasms; Apoptosis Regulatory Proteins; Carcinogenesis; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; RGS Proteins
PubMed: 36299824
DOI: 10.1155/2022/2434938 -
Journal of Nuclear Medicine Technology Sep 2014Enterogastric reflux (EGR) is the reflux of duodenal contents into the stomach. Hepatobiliary scintigraphy provides physiologic assessment of the biliary system and was...
UNLABELLED
Enterogastric reflux (EGR) is the reflux of duodenal contents into the stomach. Hepatobiliary scintigraphy provides physiologic assessment of the biliary system and was used to test the hypothesis that presence and timing of EGR may be associated with infusion of sincalide, a surrogate of endogenous cholecystokinin.
METHODS
One hundred fifty-seven hepatobiliary scintigraphy studies were retrospectively reviewed. Data included EGR incidence on initial reports, incidence after masked second reads, and time of EGR onset in relation to sincalide infusion. EGR cases were then classified according to onset on pre-, post-, or both presincalide and postsincalide imaging.
RESULTS
Time of EGR onset at 19-24 minutes after start of a 15-min sincalide infusion differed significantly from normal (p<0.0001). EGR was initially reported in 14 of 157 cases (8.9%) but found in 38 of 157 cases on masked second reads (24.2%), corresponding to a 15.3% discrepancy rate.
CONCLUSION
The temporal association of EGR onset with sincalide infusion may identify patients with EGR mimicking chronic cholecystitis or biliary dyskinesia. A novel classification schema was therefore developed as a framework for future research, utilizing EGR onset in relation to pre-, post-, or both presincalide and postsincalide imaging as a hypothetical biomarker of clinically significant EGR.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Biliary Tract; Duodenogastric Reflux; Female; Gastrointestinal Agents; Humans; Liver; Male; Middle Aged; Radionuclide Imaging; Retrospective Studies; Sincalide; Young Adult
PubMed: 25033884
DOI: 10.2967/jnmt.114.141168 -
Contrast Media & Molecular Imaging 2022Esophageal cancer is the most prevalent digestive system tumor. Due to a lack of characteristic symptoms and early diagnosis, a confirmed esophageal cancer is typically...
BACKGROUND
Esophageal cancer is the most prevalent digestive system tumor. Due to a lack of characteristic symptoms and early diagnosis, a confirmed esophageal cancer is typically detected at a progressively harmful stage. Therefore, it is critical to investigate the molecular mechanisms governing the formation and progression of esophageal cancer in order to identify new treatment targets for esophageal cancer early detection.
METHODS
We first screened the differentially expressed gene LINC00240 in the TCGA database. Multivariate analysis and Cox regression were performed, and a nomogram was constructed for internal validation. The correlation between LINC00240 and immune cells was analyzed using the TIMER database. The possible mechanism of action was explored through GSEA enrichment analysis. Then, in 43 esophageal cancer tissues, paracancour tissues, and cell lines, the LINC00240 expression was found. Transwell assays, CCK-8, and clone formation assays were utilized to assess the impact of LINC00240 on the metastasis of esophageal cancer cells. The binding activity of LINC00240 to downstream miRNAs was assessed using the luciferase reporter gene.
RESULTS
TCGA database showed that LINC00240 expression was increased in cancer tissues compared to adjacent tissues. The -index of the nomogram is 0.712 (0.666-0.758), and the prediction model has good accuracy. According to the TIMER database, the LINC00240 expression is linked to immune infiltration and may be crucial in encouraging the immune escape of tumor cells. Gene enrichment analysis depicts that LINC00240 could influence the biological events of esophageal cancer by taking part in pathways such as affecting the cell cycle. LINC00240 expression was substantially greater in the plasma of esophageal cancer patients (3.94 ± 1.55) than in the normal control group (2.13 ± 0.89). Plasma expression of LINC00240 was linked to the degree of differentiation (=0.0345) and TNM stage (=0.0409). Knocked down LINC00240 inhibited esophageal cancer cells proliferation, lone formation, and invasion. LINC00240 might bind itself to miR-26a-5p and influence its expression. MiR-26a-5p inhibitor can dramatically limit the ability of LINC00240 knockdown on plate colony formation and relocation of esophageal cancerous cells was demonstrated in colony formation and migration experiments.
CONCLUSION
LINC00240 expression is elevated in esophageal cancerous tissues, and knocking down LINC00240 decreases esophageal cancer cell proliferation, clone formation, invasion, and migration via miR-26a-5p. As a result, LINC00240 could be a novel target for esophageal cancer patients' early diagnosis and treatment.
Topics: Humans; RNA, Long Noncoding; Sincalide; Cell Line, Tumor; Esophageal Neoplasms; MicroRNAs; Cell Proliferation; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 36262998
DOI: 10.1155/2022/1071627 -
Nature Chemical Biology Dec 2021Cholecystokinin A receptor (CCKR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an...
Cholecystokinin A receptor (CCKR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including G, G and G. However, the basis for G-protein coupling promiscuity and ligand recognition by CCKR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKR in complex with G, G and G heterotrimers, respectively. CCKR presents a similar conformation in the three structures, whereas conformational differences in the 'wavy hook' of the Gα subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKR and uncover the mechanism of receptor recognition by sulfated CCK-8.
Topics: Amino Acid Sequence; Benzodiazepinones; Cholecystokinin; Cryoelectron Microscopy; Humans; Ligands; Models, Molecular; Protein Binding; Protein Conformation; Protein Multimerization; Receptor, Cholecystokinin A; Receptors, G-Protein-Coupled; Sincalide; Triazoles
PubMed: 34556862
DOI: 10.1038/s41589-021-00841-3 -
International Journal of Neural Systems Nov 2018Vagus Nerve Stimulation (VNS) has shown great promise as a potential therapy for a number of conditions, such as epilepsy, depression and for Neurometabolic Therapies,...
OBJECTIVE
Vagus Nerve Stimulation (VNS) has shown great promise as a potential therapy for a number of conditions, such as epilepsy, depression and for Neurometabolic Therapies, especially for treating obesity. The objective of this study was to characterize the left ventral subdiaphragmatic gastric trunk of vagus nerve (SubDiaGVN) and to analyze the influence of intravenous injection of gut hormone cholecystokinin octapeptide (CCK-8) on compound nerve action potential (CNAP) observed on the same branch, with the aim of understanding the impact of hormones on VNS and incorporating the methods and results into closed loop implant design.
METHODS
The cervical region of the left vagus nerve (CerVN) of male Wistar rats was stimulated with electric current and the elicited CNAPs were recorded on the SubDiaGVN under four different conditions: Control (no injection), Saline, CCK1 (100[Formula: see text]pmol/kg) and CCK2 (1000[Formula: see text]pmol/kg) injections.
RESULTS
We identified the presence of A[Formula: see text], B, C1, C2, C3 and C4 fibers with their respective velocity ranges. Intravenous administration of CCK in vivo results in selective, statistically significant reduction of CNAP components originating from A and B fibers, but with no discernible effect on the C fibers in [Formula: see text] animals. The affected CNAP components exhibit statistically significant ([Formula: see text] and [Formula: see text]) higher normalized stimulation thresholds.
CONCLUSION
This approach of characterizing the vagus nerve can be used in closed loop systems to determine when to initiate VNS and also to tune the stimulation dose, which is patient-specific and changes over time.
Topics: Action Potentials; Animals; Male; Peripheral Nervous System Agents; Rats, Wistar; Sincalide; Stomach; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 29631504
DOI: 10.1142/S0129065718500065 -
Disease Markers 2022Breast cancer (BC) is the most common cancer and the most frequent cause of cancer death among women worldwide. The aim of the present study was to identify the critical...
Breast cancer (BC) is the most common cancer and the most frequent cause of cancer death among women worldwide. The aim of the present study was to identify the critical genes for the diagnosis and prognosis of BC. Two mRNA expression data (GSE29431 and GSE42568) were acquired from the GEO database. The determination of differently expressed genes (DEGs) between BC specimens and nontumor specimens was completed via the LIMMA package of R. GO annotation and KEGG pathway enrichment analyses were applied to explore the function of DEGs. Kaplan-Meier methods were used to determine the prognostic value of DEGs in BC using TCGA datasets. The diagnostic value of the survival-related DGEs were confirmed using ROC assays in two GEO datasets. RT-PCR was used to examine the expression of the critical genes in BC cells and normal breast cells. CCK-8 experiments were applied to explore the function of the critical genes in BC cells. In this study, we identified 31 DEGs between BC specimens and nontumor specimens. KEGG analysis revealed 31 DEGs were involved in PPAR signal path, AMPK signal path, glycerolipid metabolism, adipocytokine signaling pathway, phenylalanine metabolism, tyrosine metabolic process, and glycine, serine, and threonine metabolic process. Four DEGs including CRYAB, DEFB132, MAOA, and RBP4 were observed to be associated with clinical outcome of BC patients. Their diagnostic values were also confirmed in both GSE29431 and GSE42568 datasets. In addition, we analyzed TCGA datasets and confirmed that the results were consistent with GEO datasets. Finally, the results of RT-PCR confirmed that the expression of CRYAB and RBP4 was distinctly downregulated in BC cells. CCK-8 analysis revealed that overexpression of CRYAB and RBP4 distinctly suppressed the proliferation of BC cells. Overall, our findings suggested CRYAB and RBP4 as critical genes for the diagnosis and prognosis of BC patients. They may be used as novel biomarkers for BC patients.
Topics: Biomarkers, Tumor; Breast Neoplasms; Computational Biology; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Retinol-Binding Proteins, Plasma; Sincalide
PubMed: 35686034
DOI: 10.1155/2022/9041466 -
Gut Feb 1999
Topics: Animals; Gastric Mucosa; Humans; Leptin; Proteins; Rats; Sincalide
PubMed: 9895370
DOI: 10.1136/gut.44.2.153 -
Aging Jan 2024Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory...
Approximately 10% of gastric cancers are associated with Epstein-Barr virus (EBV). polysaccharides (TFPs) are characterized by antioxidative and anti-inflammatory effects in different diseases. However, whether TFP improves EBV-associated gastric cancer (EBVaGC) has never been explored. The effects of TFP on EBV-infected GC cell viability were determined using a CCK-8 assay and flow cytometry. Western blotting and RT-qPCR were performed to explore the expression of ferroptosis-related proteins. The CCK-8 assay showed that TFP decreased EBV-infected GC cell viability in a dose- and time-dependent manner. Flow cytometry assays indicated that TFP significantly induced EBV-infected GC cell death. TFP also reduced the migratory capacity of EBV-infected GC cells. Furthermore, treatment with TFP significantly increased the mRNA levels of PTGS2 and Chac1 in EBV-infected GC cells. Western blot assays indicated that TFP suppressed the expression of NRF2, HO-1, GPX4 and xCT in EBV-infected GC cells. More importantly, overexpression of NRF2 could obviously rescue TFP-induced downregulation of GPX4 and xCT in EBV-infected GC cells. In summary, we showed novel data that TFP induced ferroptosis in EBV-infected GC cells by inhibiting NRF2/HO-1 signaling. The current findings may shed light on the potential clinical application of TFP in the treatment of EBVaGC.
Topics: Humans; Herpesvirus 4, Human; Stomach Neoplasms; Epstein-Barr Virus Infections; NF-E2-Related Factor 2; Ferroptosis; Sincalide; Basidiomycota
PubMed: 38244583
DOI: 10.18632/aging.205457 -
Journal of Nuclear Medicine : Official... Feb 2010Sincalide-stimulated cholescintigraphy is performed to quantify gallbladder contraction and emptying. However, different infusion methods are used for this study. Our... (Clinical Trial)
Clinical Trial
UNLABELLED
Sincalide-stimulated cholescintigraphy is performed to quantify gallbladder contraction and emptying. However, different infusion methods are used for this study. Our purpose was to determine the infusion method with the least variability (smallest coefficient of variation [CV]) for calculation of the gallbladder ejection fraction (GBEF) in healthy subjects and to establish normal values.
METHODS
Sixty healthy volunteers at 4 medical centers were injected intravenously with (99m)Tc-mebrofenin. After gallbladder visualization had been confirmed at 60 min, 0.02 microg of sincalide per kilogram was administered using 3 different infusion durations, 15, 30, and 60 min, each performed on separate days. The CV, mean, SD, first to 99th percentile, and fifth to 95th percentile were calculated. GBEF normal values were determined for the different infusion durations.
RESULTS
The CV was smallest for the 60-min infusion at 60 min (19%; 95% confidence interval [CI], 16%-23%), compared with the 30-min infusion at 30 min (35%; 95% CI, 29.2%-42.1%) and the 15-min infusion at 15 min (52%; 95% CI, 44%-63%). These were all significantly different (P < 0.0007). For the 60-min infusion at 60 min, the lower limit of normal for the GBEF was 38% defined at the 1% CI.
CONCLUSION
The GBEF at 60 min has the lowest CV in healthy subjects, compared with shorter infusions of 15 or 30 min. This multicenter trial establishes a GBEF lower limit of normal of 38% (first percentile) for a 60-min infusion of 0.02 microg of sincalide per kilogram, quantified at 60 min. Using this infusion method minimizes the variability in measured GBEFs. This sincalide infusion method should become the standard for routine clinical use.
Topics: Adult; Aniline Compounds; Female; Gallbladder; Gallbladder Emptying; Gastrointestinal Agents; Glycine; Humans; Imino Acids; Infusions, Intravenous; Male; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Reference Values; Sincalide; Young Adult
PubMed: 20080900
DOI: 10.2967/jnumed.109.069393 -
Molecular Medicine (Cambridge, Mass.) Sep 2022This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia.
BACKGROUND
This study aimed to investigate the effects of LINC00240/miR-155/Nrf2 axis on trophoblast function and macrophage polarization in the pathogenesis of preeclampsia.
METHODS
Bindings between LINC00240, miR-155 and Nrf2 were validated by dual luciferase reporter assay or RNA-immunoprecipitation. Cell proliferation, migration, invasion, and pyroptosis were detected by CCK-8, clone formation, wound healing, Transwell system, and flow cytometry, respectively. Macrophage polarization was tested by flow cytometry. The expression levels of LINC00240, miR-155, Nrf2, and oxidative stress and pyroptosis-related markers in in vitro and in vivo preeclampsia models were analyzed by qPCR, western blot, or ELISA assays. Blood pressure, urine protein levels, liver and kidney damages, and trophoblast markers in placenta tissues were further studied in vivo.
RESULTS
Placenta tissues from preeclampsia patients and animals showed decreased LINC00240 and Nrf2 and increased miR-155 expression levels, and the decreased M2 macrophage polarization. LINC00240 directly bound and inhibited expression of miR-155, which then inhibited oxidative stress-induced pyroptosis, promoting proliferation, migration and invasion abilities of trophoblasts, and M2 macrophage polarization. Inhibition of miR-155 led to increased Nrf2 expression and similar changes as LINC00240 overexpression in trophoblast function and macrophage polarization. Overexpression of LINC00240 in in vivo preeclampsia model decreased blood pressure, urine protein, liver and kidney damages, increased fetal weight and length, and induced trophoblast function and M2 macrophage polarization.
CONCLUSION
LINC00240 inhibited symptoms of preeclampsia through regulation on miR-155/Nrf2 axis, which suppressed oxidative stress-induced pyroptosis to improve trophoblast function and M2 macrophage polarization. LINC00240 could be a potential therapeutic target for preeclampsia.
Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Female; Humans; Macrophages; MicroRNAs; NF-E2-Related Factor 2; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pyroptosis; RNA, Long Noncoding; Sincalide; Trophoblasts
PubMed: 36153499
DOI: 10.1186/s10020-022-00531-3