This study investigated the effects of the ethanolic extract of propolis (EEP) in the absence and presence of aspirin on the glycation-induced structural changes of human hemoglobin (Hb). Hb samples ...were incubated in the presence and absence of glucose (40 mM) for 5 weeks in the absence and presence of various concentrations of EEP and aspirin. Sampling was conducted at the end of each week, and the extent of glycation was evaluated by spectrophotometry, Thioflavin-T test, and by measuring free amino group contents and heme degradation products. Results showed that Hb was glycated by glucose after various incubation times reduced free amino group content, downturn absorption of and induced blue shifting in the UV–visible spectrum of Hb as well as increased amyloid structures and heme degradation. EEP prevented these changes and decreased the extent of glycation in a concentration-dependent manner. Aspirin also prevented glycation with the same efficacy as EEP (20 μg/ml). Surprisingly, the simultaneous presence of aspirin and EEP resulted in the extensive inhibition of glycation; in the 40 μg/ml concentration of EEP and aspirin, glycation was fully prevented in a synergic way. It is probable that EEP exerts its anti-glycation effect via its potent antioxidant and radical scavenging properties which decrease glycation-produced oxidative stress. In conclusion, EEP is to be introduced as an anti-glycation agent for the first time in this study. It could be developed as a natural agent for the design of new anti-glycation drugs aimed at reducing protein glycation as well as diabetic complications.
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•Preparation of the hollow capsule via the LbL method and subsequent core removal.•Higher release of the trapped drug at acidic pH.•Potential cytotoxicity effect of the prepared drug ...carrier on the HCT-116 cells.
The utilization of hollow structures for encapsulation and controlled release of drugs has attracted considerable attention in recent years. Among the different methods reported for fabrication of hollow polymer microcapsules, the layer-by-layer (LbL) assembly of oppositely charged polymers is of special importance. The pH-responsive capsules have attracted special interest as anti-cancer drug delivery systems due to the difference between normal and cancerous tissue. In this work, new pH-sensitive and biodegradable capsules were prepared based on the layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes, chitosan (CS), and poly(ethylene glycol dimethacrylate-co-methacrylic acid) (EM). The obtained microcapsules were used for the delivery of two types of anticancer drugs including gemcitabine (Gem) and curcumin (Cur). The removal of the core was proved with transmission electron microscopy (TEM) confirming the spherical shape of the prepared hollow structure. The high performance of microcapsules was proven by encapsulation efficiency (EE%) and releasing efficiency (RE%) of above 84% and 82%, respectively. The high pH sensitivity of prepared microcapsules is due to the solubility of chitosan in acidic media. These microcapsules exhibit high cytotoxicity in a dose-dependent manner on the HCT-116 colorectal carcinoma cells. On the other hand, the desired results for the drug delivery of Gem and Cur demonstrate the applicability of prepared microcapsules for different drugs.
Multilayered pH-responsive hollow microcapsules with non-toxicity and biological specificity advantages were prepared from two kinds of polymers i.e., chitosan (CH) and poly (ethylene glycol ...dimethacrylate-co-methacrylic acid) (PE) via layer-by-layer (LbL) method, which is followed by subsequent removal of silica core. The hollow nature of obtained spherical microcapsules was found by transmission electron microscopy (TEM). The microcapsules were prepared as gemcitabine (GM) and curcumin (CR) carriers. The drugs have been loaded within the microcapsules during or after the synthetic procedure. Although acceptable loading efficiencies (LE) were obtained in both methods, the amount of drug loaded during the synthesis method is relatively higher. Values above 78% and 87%, for releasing efficiency (RE%) and encapsulation efficiency (EE%), respectively, demonstrate the high potential of the prepared microcapsules for drug delivery. In addition, the difference between the amount of drug released in acidic and neutral pH indicates the pH-responsivity of the prepared microcapsules. Moreover, the dose-dependent high cytotoxicity effect of the prepared microcapsules was observed on the HCT116 colorectal carcinoma cells.
•Three new mixed-ligand Schiff-base complexes with Cu(SB)L1–3ClO4 formulae were synthesized.•Anticancer studies were performed on three human carcinoma cell lines that showed promising results.•The ...results revealed that the complex with bpy co-ligand was the most effective against all the three cell lines.•Molecular docking was also used that further supported the experimental results.
New mixed-ligand Cu(II) complexes, Cu(SB)L1–3ClO4, that contain a tridentate NN'O type unsymmetrical Schiff-base main ligand (SB) and a heterocyclic co-ligand (L) (py in (1), bpy in (2) and phen in (3)) were synthesized and characterized. The SB is the product of 1:1 condensation between 1,3-propanediamine with 2‑hydroxy-4-methoxybenzaldehyde, which was formed during the template synthesis of complex (1). Complexes (2) and (3) were obtained by the exchange of monodentate py with bidentate bpy or phen, respectively. The crystal structure of (2) was obtained by single-crystal x-ray crystallography (SCXRC). From the crystal structure, (2) is pentacoordinated with square-based pyramidal geometry around Cu(II). The anticancer activity of the complexes was studied against three human carcinoma cell lines. All the complexes showed a potent cytotoxic effect on the Human colorectal (HCT116), lung (A549) and breast (MCF7) cancerous cells that exert their cytotoxicity in a dose and time dependent manner. Among these complexes, (2) had the highest cytotoxicity that made it a promising candidate for developing new anticancer drugs. The IC50 values for (2) were 4.16, 4.97 and 7.82 μM against A549, MCF7 and HCT116, respectively, after 48 h of incubation. The IC50 values order were (2)<(1)<(3) in each cell line. Molecular docking studies were also performed on A549 (PDB ID: 4zxt), HCT116 (PDB ID: 3ruk) and MCF-7 (PDB ID: 4zvm) human carcinoma cells' proteins. Based on the estimated free binding energy (EFBE) good correlation was observed with the obtained experimental data.
Recently, biocompatible and high-performance drug carriers have revolutionized drug delivery systems. This study aims to design and develop a slow, targeted delivery system of curcumin (C) and ...gemcitabine (G) as two types of anticancer drugs. Three-layer shells containing two types of biodegradable polymers i.e. chitosan (CHI) and poly (methacrylic acid-coethyleneglycol dimethacrylate) (ME) were coated on Fe3O4 (MG) and/or MG@SiO2 cores. Silica removal in the next stage produced core-shell and yolk-shell structures, as confirmed via transmission electron microscopy (TEM). The loading and releasing of drugs in phosphate buffer saline (PBS) with pH = 5.5 and pH = 7.4 were examined via UV–Vis spectroscopy. In both types of microparticles, acceptable loading (LE%) and encapsulation (EE%) efficiencies were obtained. Nevertheless, the LE% values of yolk-shell microparticles (H-MG@CHI.ME.CHI) were significantly higher than those of the core-shell microparticles (MG@CHI.ME.CHI). This higher loading capacity arises from the presence of cavities in the yolk-shell structure. Both microcapsules showed a release rate of over 80% for both drugs at acidic pH, while the release of drugs was relatively lower in the neutral environment. Further, the cytotoxic effect of microparticles, determined through the MTT method, was consistent with the results of drug release.
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•BLG can bind simultaneously to 5-FU and Irinotecan and formed a complex.•5-FU and Irinotecan have different binding site on the BLG and there is no change in the number of binding ...sites.•5-FU and Irinotecan can locate simultaneously in the β-barrel cavity of the BLG.•Simultaneous delivery ability of the BLG makes it an attractive candidate for oral drug delivery systems.
Drug delivery system optimization is an issue that dramatically affects toxicity properties. We aim to assess the simultaneous binding effects of the two main chemotherapy drugs of 5-Fluorouracil (5-FU) and Irinotecan with milk globular whey protein, β-lactoglobulin (BLG), which is a promising candidate for oral drug delivery systems. BLG interaction with 5-FU and Irinotecan examined using spectroscopy, molecular docking, and molecular dynamics (MD) simulation methods. The experimental findings confirmed molecular docking calculations, according to which 5-FU and Irinotecan interacted with the BLG in the β-barrel cavity with two different locations. MD simulations also showed that the drugs penetrate the cavity and the amino acids at the top of the calyx fix the drugs. In addition, the results showed that the BLG intrinsic fluorescence was quenched upon interaction with the drugs under individual and simultaneous conditions which leads to the BLG secondary structural changes that were indicated by CD spectroscopy. The experimental findings cross-validate with the theoretical results since there is no difference between the number of the 5-FU and Irinotecan binding sites on BLG under individual and simultaneous conditions. MD results also verify that the densification of the BLG is not affected by the complexation process. 5-FU and Irinotecan make also a complex with the BLG at the Förster Theory distance that was in agreement with the MD data. Consequently, this work shows that the BLG can be a promising carrier for 5-FU and Irinotecan simultaneously. Considering BLG's remarkable features, it is an outstanding candidate to make an oral drug delivery system for the targeted cancer treatment in the combination therapy strategy.
In this study, we have successfully synthesized magnetic Fe3O4 nanoparticles adorned with samarium (Sm-MNPs) utilizing ginger extract for the very first time. Furthermore, a comprehensive ...characterization of the nanoparticles along with an exploration of their physicochemical attributes was conducted. The biological functionalities of the synthesized nanoparticles were investigated through a thorough examination of their interaction with calf thymus DNA (ctDNA) using diverse spectroscopic techniques encompassing ultraviolet-visible (UV-Vis) and fluorescence spectroscopy at varying temperatures. Subsequently, we evaluated the cytotoxicity of the magnetic nanoparticles using a colorectal cancer cell model (HCT116 cells) and a tetrazolium colorimetric assay (MTT assay). The characterization of the ginger extract-coated magnetic nanoparticles (ginger-Sm-MNPs) revealed their superparamagnetic nature, nanocrystalline structure, spherical morphology, hydrodynamic size of 155 nm, and uniform distribution. The outcomes from UV-Vis and fluorescence spectroscopy affirmed the binding of ginger-Sm-MNPs with ctDNA. Additionally, the MTT assay demonstrated that the cytotoxicity of ginger-Sm-MNPs surpassed that of both magnetite nanoparticles and ginger extract. Notably, the inhibitory concentrations (IC50) for the green-synthesized nanoparticles after 24 and 48 h of incubation were determined as 198.1 and 135.8 μg/mL, respectively. In conclusion, our study findings suggest the potential utility of ginger-Sm-MNPs as a promising candidate for various biomedical applications.Communicated by Ramaswamy H. Sarma.
Long noncoding RNAs (lncRNAs) are emerging as the master regulators of tumor initiation, proliferation, and metastasis; however, their diagnostic value as potential biomarkers should be clarified. ...Vitamin D influences the expression of several genes in various pathways, including the CYP24A1 gene in the vitamin D metabolism pathway. In the present research, we surveyed the expression levels and clinical significance of novel lncRNAs related to CYP24A1 and PFDN4 genes in colorectal cancer (CRC) using real‐time polymerase chain reaction. Furthermore, we assessed the expression of these genes after vitamin D treatment in HCT‐116 and HT‐29 colon cancer cell lines. Our results indicated that the transcription of CYP24A1, PFDN4, and nearby lncRNAs was affected by vitamin D treatment in HCT‐116 and HT‐29 cell lines. Moreover, CYP24A1, PFDN4, lnc‐CYP24A1‐3:1, and lnc‐TSHZ2‐19:1 were upregulated and had the potential to distinguish colorectal cancer tissues from the adjacent tissues by the large area under the receiver operating characteristic curve (0.94, 0.66, 0.70, and 0.60, respectively). lnc‐TSHZ2‐19:1 expression level significantly correlated with gender (p = .03). In conclusion, CYP24A1, PFDN4, lnc‐CYP24A1‐3:1, and lnc‐TSHZ2‐19:1 can be used as potential diagnostic biomarkers in the specific and sensitive assessment of CRC. Besides this, vitamin D treatment may modulate the expression of these genes in a cell‐specific manner.
Background
The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25‐dihydroxyvitamin D3. These enzymes contribute to the ...formation of 1,25‐dihydroxyvitamin D3, which starts with a 25‐hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α‐hydroxylation via CYP27B1.
Methods
By using quantitative real‐time polymerase chain reaction (qRT‐PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non‐cancer controls. The genotyping was performed using tetra‐primer amplification refractory mutation system polymerase chain reaction (TP‐ARMS–PCR) method.
Results
The results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039).
Conclusion
CYP2R1 and CYP27B1 genes were over‐expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.
Patients and controls were recruited into this case‐control study, from Gastroenterology and Liver Diseases Research Center. Then, for the first step, total RNA was extracted from fresh frozen CRC tissues and the noncancerous tissues and the qRT‐PCR reaction was performed in 96‐well plates. The qRT‐PCR amplification efficiency was assessed using LinRegPCR software. In the second step, Genomic DNA was extracted from peripheral blood and SNPs frequencies were carried out by TP ARMS PCR. Analysis of inheritance models was performed using the online software.
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