This study aimed to observe the differential expression of Annexin-A1 in esophageal squamous cell carcinoma (ESCC) and explored the effect of small interfering ribonucleic acid (RNAi)-Annexin-A1 on the biological behavior of CE81T-0 cells. An immunohistochemical approach was used to detect the expression of Annexin-A1 in 86 pairs of ESCC samples. Quantitative reverse transcription polymerase chain reaction was used to detect the expression of Annexin-A1 in CE81T-0 and CE81T-4 cells, and the expression of Annexin-A1 in CE81T-0 cells was knocked out by RNAi. A methyl-thiazolyl-tetrazolium assay was used to observe the effect of Annexin-A1 on cell proliferation, and flow cytometry was conducted to analyze its effect on cell cycles and apoptosis. A scratch assay and a Transwell chamber were used to detect changes in cell migration and invasion. From the results, compared with the Annexin-A1 expression rate of 59.3% in para-carcinoma tissues, the expression of Annexin-A1 in cancer was reduced to only 32.6% in ESCC cells. Annexin-A1 was strongly expressed in highly differentiated ESCC cells without lymphatic metastasis and highly expressed in the CE81T-0 cell group with low metastasis. Annexin-A1 gene silencing promoted cell proliferation and inhibited apoptosis, blocked cells in the S-phase, and increased cell migration, leading to an increase in the number of invaded cells. Above all, Annexin-A1 could reflect the differentiation degree and lymph node metastasis of ESCC cells to some extent and was involved in the invasion, metastasis, proliferation, and other biological behaviors of ESCC cells, indicating an experimental basis for Annexin-A1 as a molecular marker in the early diagnosis of ESCC and the prediction of cell metastasis, invasion, and differentiation degree.
The liver is the focus of research on the effects of estrogen on cholesterol metabolism. Few studies have investigated the effects of estrogen on macrophages despite the significance of cells in atherosclerosis. The purpose of this study is to examine the effect of estrogen on macrophage cholesterol efflux. Macrophage cholesterol efflux, oil red O staining, RT-qPCR, Western blotting analyses were used to determine cholesterol metabolize and the expressions of adenosine triphosphate (ATP)-binding cassette transporter G1 (ABCG1) and ATP-binding cassette transporter A1 (ABCA1) in J774A.1 cells, and the effect of these treatments was compared to without adding 17β-estradiol (E2). Gain and loss of estrogen receptor alpha (ERα), liver X receptor α (LXRα) were conducted to study interactions between E2, ERα, LXRα and ABCA. Finally, in mice, we validate the relationship between ERα and ABCA1. E2 increases cholesterol efflux from macrophages and decreases the formation of lipid droplets and positively regulates the expression of ABCA1. This suggests that estrogen receptors (ERs) directly regulate ABCA1 translation. We suppressed ERα, which decreased the mRNA and protein expression of ABCA1. At the mRNA level, E2 treatment could partially counteract these phenomena, but not at the protein level. ABCA1 expression decreased after LXRα was inhibited. This suggests that ABCA1 translation is directly regulated by ERα. In the ovariectomized mouse model of ABCA1 protein expression was significantly reduced in the peritoneal macrophages of the ovariectomy (OVX) group. ABCA1 protein expression was greater in the E2+OVX group than in the OVX group. E2 contributes to the positive regulation of ABCA1 expression and promotes cholesterol efflux in macrophages by binding to ERα. The effect is independent of ABCA1 transcription regulation by LXRα.
Seventeen young healthy physically active males (age 23 ±3 years; body mass (BM) 72.5 ±7.9 kg; height 178 ±4 cm, (mean ±SD)), not specifically trained in cycling, participated in this study. The subjects performed two cycling incremental tests at the pedalling rate of 60 rev x min-1. The first test, with the power output (PO) increases of 30 W every 3 min, was to determine the maximal oxygen uptake (V'O2max) and the power output (PO) at V'O2max, while the second test (series of 6 minutes bouts of increasing intensity) was to determine energy expenditure (EE (V'O2)), gross efficiency (GE (V'O2/PO)) and delta efficiency (DE(ΔV'O2/DPO)) during sub-lactate threshold (LT) PO. V'O2max was 3.79 ±0.40 L x min-1 and the PO at V'O2max was 288 ±27 W. In order to calculate GE and DE the V'O2 was expressed in W, by standard calculations. GE measured at 30 W, 60 W, 90 W and 120 W was 11.6 ±1.4%, 17.0 ±1.4%, 19.6 ±1.2% and 21.4 ±1.1%, respectively. DE was 29.8 ±1.9%. The subjects' BM (range 59-87 kg) was positively correlated with V'O2 at rest (p<0.01) and with the intercept of the linear V'O2 vs. PO relationship (p<0.01), whereas no correlation was found between BM and the slope of V'O2 vs. PO. No correlation was found between BM and DE, whereas GE was negatively correlated with BM (p<0.01). GE was also negatively correlated with V'O2max and the PO at V'O2max (p<0.01). We conclude that: V'O2 at rest affects GE during moderate-intensity cycling and GE negatively corelates with V'O2max and the PO at V'O2max in young healthy men.
Clove plant (Syzygium aromaticum) is one of the Myrtaceae family. It's a common flavor in food and the traditional medicine. The study's objective was to ascertain whether the clove bud aqueous extract (CAE) and CAE + nanosilver have any biological effects on immune cells and HT-29 colon cancer cell line. Nanosilver was produced through green synthesis approach using CAE. Produced nanosilver was characterized via electron microscope (scanning, SEM) and ultraviolet-visible spectroscopy. CAE and CAE + nanosilver were examined for their active biomolecules using FTIR analysis, p53 contents using real-time PCR, apoptosis and cell cycle arrest power on HT-29 cancer cell line via flow cytometerty and immunomodulatory potential utilizing MTT assay. Results cleared that a spherical nanosilver with a diameter range of 53 nm was formed by CAE. There were several active biomolecules in CAE and CAE + nanosilver. CAE and CAE + nanosilver increased the p53 protein expression and apoptotic cell number in HT-29 colon cancer cells. CAE and CAE + nanosilver could arrest HT-29 cells at the phase G2/M. CAE and CAE + nanosilver stimulated quiescent and PHA-pre-treated splenic cells at higher concentrations, and CAE suppressed quiescent splenic cell when diluted. In conclusion, the safe edible Syzygium aromaticum plant can be utilized to make anti-tumor agent, essentially for colon tumor. As Syzygium aromaticum plant could stimulate immune cells, it can be used as immune-stimulatory agent that can help fight tumor and tumor development.
Spent hops extract (SHE) is a plant extract containing compounds with proven anti-inflammatory and anti-angiogenic activities. However, extract may exert synergic effects compared to its individual polyphenol components. Inflammatory diseases of the retina may lead to visual impairment, a reduction of the comfort of life, and even blindness due to the formation of new pathological blood vessels. More effective therapeutic options are being sought. The goal of the present study was to investigate the anti-inflammatory and anti-angiogenic potentials of SHE on human retinal pigment epithelial cells (ARPE-19) stimulated by lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The SHE (250 μg/mL) was found to downregulate the gene expression of interleukin 6 (IL-6) to 33% in LPS-triggered cells; it also reduced both matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) mRNA expression to 13% and 43% respectively, and their activity to 82% (MMP-2) and 57% (MMP-9), compared to TNF-α-stimulated cells. Also, SHE modulated the TNF-α-induced expression of vascular endothelial growth factor (VEGF) and endothelial growth factor receptor 2 (VEGFR2). It is possible that SHE inhibited retinal inflammation and angiogenesis by suppressing the nuclear factor kappa B (NF-κB), protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways. Our results demonstrate that SHE has anti-inflammatory and anti-angiogenic potential against retinal diseases. This is the first such study to report on the efficacy of SHE on retinal inflammatory diseases.
Tumor-derived exosomes (TDEs) play critical roles in many aspects of cancer progression. There have been several advances in cancer immunotherapy in recent years. A major challenge, however, has been addressed to the role of TDEs in tumor cell immune escape through their influence on the antitumor immunity of natural killer (NK) cells, a key type of immune cell. In this review, we present our overview of the effects of different TDEs on NK cell activation and NK cell toxicity. Studies on mechanism suggest that TDEs mainly affect the immune response of NK cells by inhibiting activated receptors on the surface of NK cells and downregulating the NK recognition ligand MICA/B on the tumor cell surface. In addition, a summary was documented on how to restore the cytotoxicity of NK cells and improve the drug's ability to recognize tumor cells, and a detailed explanation was also provided on the mechanism of action of the drug.
The multi-markers combined detection can make up for the deficiency of single marker detection and significantly increase the positive detection rates of tumors. This study aimed to assess the performance of serum HER-2 extracellular domain (HER-2/neu ECD), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA15-3) in early screening and auxiliary diagnosis of breast cancer. The HER-2, CEA, and CA15-3 serum levels were measured in 164 healthy volunteers, 111 patients with benign nodules (BN), 123 with early breast cancer (EBC), and 25 with advanced breast cancer. In distinguishing health and EBC, the sensitivity and specificity of joint detection of HER-2, CEA, and CA15-3 were 96.75% and 96.95%, respectively; the accuracy was up to 96.19%, and the AUC was 0.994. In the cohort for distinguishing BN from EBC, serum HER-2, CEA, and CA15-3 sensitivities were 77.03%, 75.27%, and 48.65%, respectively. Combined with three markers, the sensitivity was increased to 84.46%, the AUC was 0.834. All in all, through the combined detection of serum HER-2, CEA and CA15-3 levels in healthy volunteers, BN and EBC, our study found that this method can significantly improve the diagnosis level of breast cancer, suggesting that the three markers panel can be used as an effective tool to improve the early screening level, early diagnosis, and clinical intervention of breast cancer.
Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein.
Breast cancer (BRCA) is a serious life-threatening cancer, especially triple-negative breast cancer (TNBC). Alcohol dehydrogenase-1B (ADH1B) has recently been revealed to be associated with poor prognosis of BRCA patients. This study identified the exact function of ADH1B on the progression of BRCA and TNBC. ADH1B effect on the prognosis of BRCA and TNBC patients was researched based on online databases and clinical samples. The function of ADH1B on the proliferation, invasion and migration, and growth of BRCA and TNBC cells was investigated by cell counting kit-8, Transwell, and in vivo assays. Western blot was utilized to determine the effect of ADH1B on the mitogen-activated protein kinase (MAPK) signalling pathway activity. As a result, ADH1B was down-regulated in BRCA and TNBC patients and cells, predicting unfavorable prognosis (P<0.05). ADH1B overexpression suppressed the proliferation, invasion and migration, and inactivated the MAPK signalling pathway in BRCA and TNBC cells (P<0.01). ADH1B synergized with Selumetinib (inhibitor of the MAPK signalling pathway) to attenuate the proliferation, invasion and migration of BRCA and TNBC cells (P<0.001). Conversely, Vacquinol-1 (activator of the MAPK signalling pathway) abolished the suppression of ADH1B on the proliferation, invasion and migration of BRCA and TNBC cells (P<0.05). ADH1B suppressed in vivo growth of TNBC cells (P<0.001). Thus, ADH1B may inhibit the proliferation, invasion and migration of BRCA and TNBC cells by inactivating the MAPK signalling pathway. It may be a promising target for the clinical treatment of BRCA and TNBC.
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