Curcumin, a primary active ingredient extracted from the Curcuma longa, has been recently identified as a potential anti-tumor agent in multiple kinds of cancers. However, the effect of curcumin on ...retinoblastoma (Rb) is still unclear. Therefore, we attempted to reveal the functional impacts and the underlying mechanisms of curcumin in Rb cells.
Two Rb cell lines SO-Rb50 and Y79 were pre-treated with various doses of curcumin, and then cell proliferation, apoptosis, migration, and invasion were assessed, respectively. Further, regulatory effects of curcumin on miR-99a expression, as well as the activation of JAK/STAT pathway were studied.
Data showed that curcumin significantly inhibited the viability, colony formation capacity, migration and invasion, while induced apoptosis of SO-Rb50 and Y79 cells. Up-regulation of miR-99a was observed in curcumin-treated cells. Curcumin suppressed the phosphorylation levels of JAK1, STAT1, and STAT3, while curcumin did not inhibit the activation of JAK/STAT pathway when miR-99a was knocked down.
Curcumin inhibited proliferation, migration, invasion, but promoted apoptosis of Rb cells. The anti-tumor activities of curcumin on Rb cells appeared to be via up-regulation of miR-99a, and thereby inhibition of JAK/STAT pathway.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Ultrasound induced fissures and pores on rice granule surface.•Amorphous region of starch was destroyed by ultrasound rather than crystalline region.•Ultrasound treatments improved the uniformity of ...starch particle size.•Ultrasound-treated starch showed a similar pasting profiles to the native starch.
To further investigate how controlled ultrasound treatments affect the morphology, physical property and fine structure of rice starch granules, the starch suspended in water was treated with different ultrasonic power levels (150, 300, 450 and 600 W) at 25 °C for 20 min. XRD, FT-IR and Raman spectroscopy were performed to characterise the long-range and short-range ordered structure of starch granules. Results indicated that ultrasound slightly destroyed the amorphous region of starch granules, while the A-type crystalline pattern remained unchanged. The result of chain length distributions showed that the fine structure of rice starch was not significantly changed by ultrasound treatment. SEM and particle size distribution demonstrated that ultrasound induced fissures and pores on the granule surface and elevated the homogeneity of granules, with minimum effect on the granule size. In addition, the thermal and pasting properties of rice starch were also measured by DSC and RVA. Results showed that after ultrasound treatments, the peak and breakdown viscosity increased, while the peak time, pasting temperature and gelatinisation enthalpy decreased. Overall, controlled ultrasound treatments dominantly modified the morphology and physical property of rice starch rather than the fine structure, providing additional information for the application of ultrasound on starch modification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Chlorogenic acid showed a mixed-type inhibitory action on α-amylase.•Chlorogenic acid altered the secondary structure of α-amylase through hydrogen bonds.•Chlorogenic acid interacted ...with α-amylase active site or far from its catalytic site.•Chlorogenic acid is a potential inhibitor of α-amylase.
The inhibitory mechanism of chlorogenic acid (CHA) against porcine pancreatic α-amylase (PPA) was examined by enzyme kinetic analysis, circular dichroism, fluorescence quenching and molecular docking. As a result, CHA showed a mixed-type inhibitory action on PPA, with the IC50 value of 0.498 ± 0.013 mg/mL. Analysis of fluorescence and circular dichroism spectra confirmed that CHA altered the secondary structure of PPA, by interacting with the amino acid residues around or distant from the catalytic site of PPA, mainly through hydrogen bonds, and this interaction was closely associated with the enzyme’s activity. Molecular docking indicated that the best pose between CHA and PPA was achieved with the binding energy of −7.8 and −7.2 kcal/mol at the active site and inactive site of PPA, respectively. The performed study reveals that CHA has the potential to inhibit the activity of α-amylase, thereby representing a novel idea to delay the digestion of starch.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
During rice dehulling and polishing, about 14% of the rice will be broken. How to utilize those low-value broken rice effectively is a critical issue. In this study, extrusion technology was applied ...to restructure the broken rice. The morphology, molecular structure and digestibility of intact, broken and extruded rice were investigated with SEM, XRD, FT-IR as well as simulated in vitro gastrointestinal digestion technique. The extruded rice showed a rough surface and the crystalline structure transformed its diffraction type from an A-type to a mixture of B- and V-types. The equilibrium starch hydrolysis (C∞) and kinetic constant (k) of extruded rice was significantly lower than that of the broken rice, which was 76.10%, 2.91 × 10−2 (min−1) and 80.90%, 6.42 × 10−2 (min−1), respectively. Our results indicated that extrusion processing could modify the microstructure and digestibility of rice effectively, and be an optional way to produce staple rice with lower digestibility.
•The microstructure of rice was changed by extrusion processing.•Extrusion processing decreased the crystalline structure of rice.•Extrusion processing decreased the in vitro digestion of rice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this study, 5-fluorouracil (5-FU) and LY294002 (LY)-loaded PEGylated nanoliposome was prepared to target esophageal squamous cell carcinoma (ESCC). The particles were characterized in terms of ...physicochemical and biological parameters. The co-delivery of autophagy inhibitor and chemotherapeutic drug in a single carrier was successfully accomplished. The two components from 5-FU and LY-loaded PEGylated nanoliposome (FLNP) released in a controlled manner with LY relatively released faster compared to that of 5-FU. FLNP showed a receptor-mediated cellular uptake that will allow the gradual release of drug in the acidic environment. The cellular uptake of nanoparticles (NP) was further confirmed by FACS analysis. The combination of 5-FU and LY resulted in higher cytotoxic effect compared to that of individual drugs. Most importantly, FLNP exhibited a significantly higher anticancer effect in cancer cells compared to that of free cocktail combinations. The faster release of LY from FLNP leads to autophagy inhibition that improves the sensitivity of cancer cells towards 5-FU, resulting in more cell death. Consistently, FLNP induced a greater apoptosis (~ 48%) of cancer cells compared to that of any other groups. Western blot analysis clearly showed that 5-FU and LY individually increased the expression of caspase-3 and PARP, while as expected FLNP induced a remarkable expression of these protein markers indicating the superior anticancer effect. We believe that the programmed release of autophagy inhibitor and chemotherapeutic drug from a single nanocarrier will increase the prospect of anticancer therapy in ESCC.
Abstract
Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, play an indispensable role in cancer initiation, progression, metastasis, and metabolism. The ...limitations of traditional treatments can be partly attributed to the lack of understanding of the role of the tumor stroma. For this reason, CAF targeting is gradually gaining attention, and many studies are trying to overcome the limitations of tumor treatment with CAF as a breakthrough. Glutamine (GLN) has been called a “nitrogen reservoir” for cancer cells because of its role in supporting anabolic processes such as fuel proliferation and nucleotide synthesis, but ammonia is a byproduct of the metabolism of GLN and other nitrogenous compounds. Moreover, in some studies, GLN has been reported as a fundamental nitrogen source that can support tumor biomass. In this review, we discuss the latest findings on the role of GLN and ammonia in the crosstalk between CAFs and cancer cells as well as the potential therapeutic implications of nitrogen metabolism.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In order to broaden the application of potato pulp pectic polysaccharide (PPP) in stabilizing acidified milk drinks (AMDs) and investigate the stabilizing effect and physical properties of AMDs ...prepared with PPP, a comparative study was made among PPP, commercial high methoxyl pectin (HMP) and low methoxyl pectin (LMP). The zeta potential, rheology, particle size and serum separation of AMDs were evaluated after preparing with PPP, HMP and LMP, respectively. Results indicated that PPP led to lower serum separation than LMP (14.65% for AMDs prepared with 0.5% PPP compared to 25.05% for AMDs prepared with 0.5% LMP), but still higher than HMP (9.09% for AMDs prepared with 0.5% HMP). However, narrower particle size distribution and lower viscosity of AMDs was achieved by PPP than by LMP and HMP. PPP can electrostatically adsorb on the surface of casein and its abundant neutral sugar side chains would provide steric hindrance to prevent casein flocculation in AMDs. Our results might provide some new ideas for the application of PPP in improving the stability of AMDs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Since DNA damage is a first incident occurred during a tumour attack, it is rational that histone H2A.X phosphorylation on tyrosine 39 (H2A.X
Y39ph
) may act as a tumour-relevant factor. This study ...was aimed to test the authenticity of the hypothesis. Uveal melanoma MP65 cells were transfected for expression of KRas mutated. H2A.X phosphorylation and ERK1/2 was measured, and transwell experiment was performed to examine the consequents of H2A.X
Y39ph
on MP65 cells developing and migration. Regulatory relationship between H2A.X
Y39ph
and ERK1/2 downstream genes were measured. Moreover, whether JMJD6 and MDM2 are involved in H2A.X phosphorylation was studied. Mutation of Ras activated ERK1/2 signalling and inhibited H2A.X phosphorylation at Y39. Silence of H2A.X
Y39ph
contributed to the regulation of MP65 cells growth, migration and transcription of ERK1/2 downstream genes, including CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16. The repressed H2A.X phosphorylation through Ras-ERK1/2 signalling might be through MDM2-mediated JMJD6 degradation. Our study suggested that Ras-ERK1/2 signalling inhibited H2A.X phosphorylation at Y39, which led to the uncontrolled developing and migration of uveal melanoma cells. In addition, H2A.X phosphorylation was mediated possibly through JMJD6 which could be degraded by MDM2.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Colon cancer is one of the most frequent and lethal neoplasias. Altered metabolic activity is a well-known hallmark for cancer. The present study is aiming to screen key genes associated with tumor ...metabolism and construct a prognostic signature of colon cancer patients.
Glutamine- and UC- metabolism related genes were downloaded from GSEA MsigDB. Three key genes were screened by Cox regression analysis with data samples downloaded from TCGA and GSE29623 database. Consistent clustering based on the prognostic genes identified was employed to divide the colon cancer samples into two clusters with significant OS differences. The mRNA and protein expression of the key genes in colon tissues and matched adjacent noncancerous tissues of 16 patients were detected by IHC, qPCR, and Western blot to validate the constructed clustering model. GO, GSVA, and IPA were used to predict the relevant metabolic pathways.
According to the three key genes identified, i.e., ASNS, CEBPA, and CAD, the cohort can be divided into two clusters with prognosis differences. Clinical specimen results confirmed that the risk model established was effective, and the different expression pattern of ASNS and CEBPA was correlated with TNM stage and lymph node metastasis, whilst that of CAD was correlated with post-operative tumor metastasis and recurrence. Molecular mechanism prediction indicated that CREB, insulin, and RNA Pol II were the key nodes affecting CEBPA and ASNS expression. Moreover, TIDE algorithm reflected the better immune response of the cluster with shorter OS. Further immune infiltration and checkpoints analyses provided important reference for clinicians to perform individualized immunotherapy.
Differential expression profile of three aspartic acid metabolic-associated genes, ASNS, CEBPA, and CAD, can be considered as a risk model with a good evaluation effect on the prognosis of colon cancer patients.