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1.
Sci Rep ; 14(1): 11450, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769394

ABSTRACT

A mesoporous silica nanoparticle (MSN) coated with polydopamine (PDA) and loaded with umbelliprenin (UMB) was prepared and evaluated for its anti-cancer properties in this study. Then UMB-MSN-PDA was characterized by dynamic light scattering (DLS), Field emission scanning electron microscopy (FESEM), Transmission electron microscopy (TEM) and FTIR methods. UV-visible spectrometry was employed to study the percentage of encapsulation efficiency (EE%). UMB-MSN-PDA mediated cell cytotoxicity and their ability to induce programmed cell death were evaluated by MTT, real-time qPCR, flow cytometry, and AO/PI double staining methods. The size of UMB-MSN-PDA was 196.7 with a size distribution of 0.21 and a surface charge of -41.07 mV. The EE% was 91.92%. FESEM and TEM showed the spherical morphology of the UMB-MSN-PDA. FTIR also indicated the successful interaction of the UMB and MSN and PDA coating. The release study showed an initial 20% release during the first 24 h of the study and less than 40% during 168 h. The lower cytotoxicity of the UMB-MSN-PDA against HFF normal cells compared to MCF-7 carcinoma cells suggested the safety of formulation on normal cells and tissues. The induction of apoptosis in MCF-7 cells was indicated by the upregulation of P53, caspase 8, and caspase 9 genes, enhanced Sub-G1 phase cells, and the AO/PI fluorescent staining. As a result of these studies, it may be feasible to conduct preclinical studies shortly to evaluate the formulation for its potential use in cancer treatment.


Subject(s)
Antineoplastic Agents , Indoles , Nanoparticles , Polymers , Silicon Dioxide , Humans , Indoles/chemistry , Indoles/pharmacology , Silicon Dioxide/chemistry , Polymers/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Porosity , MCF-7 Cells , Umbelliferones/chemistry , Umbelliferones/pharmacology , Drug Carriers/chemistry , Cell Line, Tumor , Cell Survival/drug effects
2.
Gene ; 911: 148357, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38462023

ABSTRACT

PURPOSE: The most common malignancy among women worldwide is breast cancer. The estrogen receptor plays a vital role in this cancer. One of the most well-known mechanisms that affects the activity of this receptor is its phosphorylation by protein kinase pathways. Hesperetin, a flavonoid abundant in citrus species such as lemons, grapefruits, and oranges, is the aglycone form of hesperidin. It has undergone thorough evaluation for its potential anti-cancer properties, particularly in the context of breast cancer. Studies have shown that hesperetin has an effect on intracellular kinase pathways. The aim of this study was to investigate the effect of hesperetin on the expression, phosphorylation and activity of estrogen receptor alpha (ERα) in MCF-7 breast cancer cell line. STUDY DESIGN AND METHODS: MCF-7 cells were cultured in RPMI-1640 phenol red-free medium supplemented with charcoal-stripped FBS and treated with hesperetin. The MTT method was used to evaluate cell survival. The levels of the ERα protein and its phosphorylated form (Ser118) were determined via western blotting. A luciferase reporter vector was used to evaluate ERE activity. RESULTS: The results of this study indicated that hesperetin reduced the survival of MCF-7 cells in a dose-dependent manner. The expression and phosphorylation (at Ser118) of the ERα significantly increased and decreased, respectively, in the groups treated with hesperetin. Hesperetin increased the activity of the ERα in the absence of E2, although these differences were not statistically significant. Conversely, in the presence of E2, hesperetin caused a significant decrease in receptor activity. CONCLUSION: Based on the results of this study, it can be concluded that hesperetin has a significant effect on ERα expression, phosphorylation and activity.


Subject(s)
Breast Neoplasms , Hesperidin , Female , Humans , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , MCF-7 Cells , Hesperidin/pharmacology , Phosphorylation , Estradiol , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation
3.
J Biomol Struct Dyn ; : 1-21, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38345131

ABSTRACT

The main purpose of this research was to evaluate the role of α-lactalbumin (α-LA), ß-lactoglobulin (ß-LG), and ß-Caseins (ß-CN) in the binding interaction between Nano Resveratrol (Nano Res), as binary and ternary systems. This investigation was fulfilled through the application of multi-spectroscopic, transmission electron microscopy (TEM), field emission scanning electron microscope (FE-SEM), conductometry, isothermal titration calorimetry (ITC), and molecular dynamics (MD) simulation techniques. Fluorescence spectroscopy observations illustrated the effectiveness of Nano Res throughout the quenching of α-LA, (α-LA-ß-LG), and (α-LA-ß-CN) complexes, confirming the occurrence of interaction through the combination of static and dynamic mechanisms. An enhancement in the temperature of all three complexes caused a decrease in their Ksv and Kb values, which indicates the static and dynamic behavior of their interactions. The obtained thermodynamic parameters proved the dominance of electrostatic interaction as the binding force of both binary and ternary systems. The observed properties of Tyr or Trp residues in proteins through the data of synchronous spectroscopy at Δλ = 15 and 60 nm, respectively, demonstrated the closer positioning of (α-LA-ß-CN) complex to the proximity of Trp residues when compared to the two other cases. According to the resonance light scattering (RLS) measurements, the detection of a much greater RLS intensity in (α-LA-ß-CN) Nano Res complex suggested the production of a larger complex. Furthermore, the conductometry outcomes displayed an increase in molar conductivity and therefore approved the occurrence of interaction between Nano Res and proteins in both binary and ternary systems. The spherical shape of Nano Res was confirmed through the results of FE-SEM and TEM analyses. The conformational changes of proteins throughout the binding of Nano Res was evaluated by circular dichroism (CD) technique, while molecular docking and MD simulations affirmed the binding of Nano Res to α-LA, (α-LA-ß-LG), and (α-LA-ß-CN) complexes as binary and ternary systems. These In Silico study data confirm the results of in vitro assessments. The occurrence of changes in the secondary structure of ß-galactosidase was implied through the increased enzyme catalytic activity induced by the interaction of different lactose concentrations.Communicated by Ramaswamy H. Sarma.

4.
Bioprocess Biosyst Eng ; 46(11): 1569-1578, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37700115

ABSTRACT

Cerium oxide nanoparticles (CeO2-NPs) and Zn-Ni dual-doped CeO2-NPs were synthesized through a green approach by the implication of zucchini peel (Cucurbita pepo) extract as a capping and reduction agent. All the synthesized samples were studied by the results of FTIR, UV-Vis, XRD, and FESEM/EDAX/PSA analyses. The Zn-Ni dual-doped CeO2-NPs contained a spherical morphology and their size was observed to increase at higher temperatures. The conducted MTT assay on the Huh-7 cell line displayed 50% of cells annihilation as a result of using undoped CeO2-NPs and Zn-Ni dual-doped CeO2-NPs at the inhibitory concentrations (IC50) of 700 and 185.4 µg/mL, respectively. We also evaluated the enzymatic functionality of SOD and CAT of undoped CeO2-NPs and dual-doped NPs and found it to be dose dependent. Moreover, Zn-Ni dual-doped CeO2-NPs intensified the CAT activity without causing any changes in SOD activity in similar concentrations.


Subject(s)
Cerium , Metal Nanoparticles , Nanoparticles , Zinc Oxide , Antioxidants/pharmacology , Zinc , Nickel , Cerium/pharmacology , Superoxide Dismutase
5.
J Biomol Struct Dyn ; : 1-15, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37340682

ABSTRACT

A significant contributing factor in the development of breast cancer is the estrogens. The synthesis of estrogens is primarily facilitated by aromatase (CYP19), a cytochrome P450 enzyme. Notably, aromatase is expressed at a higher level in human breast cancer tissue compared with the normal breast tissue. Therefore, inhibiting aromatase activity is a potential strategy in hormone receptor-positive breast cancer treatment. In this study, Cellulose Nanocrystals (CNCs) were obtained from Chicory plant waste through a sulfuric acid hydrolysis method with the objective of investigating that whether the obtained CNCs could act as an inhibitor of aromatase enzyme, and prevent the conversion of androgens to estrogens. Structural analysis of CNCs was carried out using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), while morphological results were obtained using AFM, TEM, and FE-SEM. Furthermore, the nano-particles were found to be spherical in shape with a diameter range of 35-37 nm and displayed a reasonable negative surface charge. Stable transfection of MCF-7 cells with CYP19 has demonstrated the ability of CNCs to inhibit aromatase activities and prevent cell growth by interfering with the enzyme activities. Spectroscopic results revealed the binding constant of CYP19-CNCs and (CYP19-Androstenedione)-CNCs complexes to be 2.07 × 103 L/gr and 2.06 × 104 L/gr, respectively. Conductometry and CD data reported different interaction behaviors among CYP19 and CYP19-Androstenedione complexes at the presence of CNCs in the system. Moreover, the addition of CNCs to the solution in a successive manner resulted in the enhancement of the secondary structure of the CYP19-androstenedione complex. Additionally, CNCs showed a marked reduction in the viability of cancer cells compared to normal cells by enhancing the expression of Bax and p53 at protein and mRNA levels, and by decreasing mRNA levels of PI3K, AKT, and mTOP, as well as protein levels of PI3Kg-P110 and P-mTOP, in MCF-7 cells after incubation with CNCs at IC50 concentration. These findings confirm the decrease in proliferation of breast cancer cells associated with induction of apoptosis through down-regulation of the PI3K/AKT/mTOP signaling pathway. According to the provided data, the obtained CNCs are capable of inhibiting aromatase enzyme activity, which has significant implications for the treatment of cancer.Communicated by Ramaswamy H. Sarma.

6.
Bioprocess Biosyst Eng ; 46(8): 1163-1173, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37326639

ABSTRACT

The aim of this study is the green synthesis of cerium oxide nanoparticles (CeO2-NPs) using a natural capping agent and its application in water and wastewater treatment. This study presents the biosynthesis of CeO2-NPs by the exertion of a green method using zucchini (Cucurbita pepo) extract as a capping agent. Synthesized CeO2-NPs were distinguished through TGA/DTA, FT-IR, XRD, FESEM/TEM and EDX/PSA, and DRS procedures. According to the XRD pattern of NPs, the crystallinity structure was a face-centered cubic (fcc) with an Fm3m space group and the size was estimated at 30 nm. The spherical morphology of NPs was confirmed through FESEM/TEM images. In the following, the photocatalytic property of NPs was investigated by the decolorization of methylene blue (MB) dye within UV-A light. Also, the cytotoxicity of NPs on the CT26 cell line was evaluated through the MTT test, and no toxicity was observed in the results, which indicates their biocompatibility.


Subject(s)
Cerium , Metal Nanoparticles , Nanoparticles , Spectroscopy, Fourier Transform Infrared , Anti-Bacterial Agents/chemistry , Nanoparticles/chemistry , Cerium/chemistry , Plant Extracts/chemistry , Metal Nanoparticles/chemistry
7.
J Trace Elem Med Biol ; 78: 127186, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37148696

ABSTRACT

Glioblastoma multiforme (GBM) is the most aggressive kind of malignant primary brain tumor in humans. Given the limitation of Conventional therapeutic strategy, the development of nanotechnology and natural product therapy seems to be an effective method enhancing the prognosis of GBM patients. In this research, cell viability, mRNA expressions of various apoptosis-related genes apoptosis, and generation of reactive oxygen species (ROS) in human U-87 malignant GBM cell line (U87) treated with Urolithin B (UB) and CeO2-UB. Unlike CeO2-NPs, both UB and CeO2-UB caused a dose-dependent decrease in the viability of U87 cells. The half-maximal inhibitory concentration values of UB and CeO2-UB were 315 and 250 µM after 24 h, respectively. Moreover, CeO2-UB exerted significantly higher effects on U87 viability, P53 expression, and ROS generation. Furthermore, UB and CeO2-UB increased the accumulation of U87 cells in the SUB-G1 population, decreased the expression of cyclin D1, and increased the Bax/Bcl2 ratio expression. Collectively, these data indicate that CeO2-UB exhibited more substantial anti-GBM effects than UB. Although further in vivo investigations are needed, these results proposed that CeO2-NPs could be utilized as a potential novel anti-GBM agent after further studies.


Subject(s)
Glioblastoma , Nanoparticles , Humans , Reactive Oxygen Species/metabolism , Glioblastoma/drug therapy
8.
J Biomol Struct Dyn ; 41(3): 778-791, 2023 02.
Article in English | MEDLINE | ID: mdl-34919017

ABSTRACT

The current study produced Quercetin nanoemulsions (QuNEs) for the purpose of improving Quercetin solubility in an aqueous polar condition and to analyze QuNE-protein formation (QuNE-human serum albumin (HSA) and QuNE-holo-transferrin (HTF)).QuNE was produced by utilizing an ultrasound-based emulsification method and was characterized by DLS, TEM, and SEM. Its interaction with HSA and HTF proteins was studied by analyzing the results of FRET and RLS spectroscopy, Stern-Volmer plotting, the Van't Hoff equation, CD spectroscopy, and molecular docking methods. Finally, QuNE's cytotoxic impact, cell death type induction, and antioxidant properties were evaluated by applying an MTT assay on a human hepatocyte cancer cell (HepG2), measuring Cas-3 gene expression, and conducting a DPPH antioxidant test, respectively. Compared to the non-entrapped Quercetin, Quercetin-entrapped nano-emulsions formed stable complexes with HSA and HTF by improving hydrophilic-hydrophobic interactions. The binding constant (BC), ΔH0, and ΔS0 indices for both the QuNE-HSA and QuNE-HTF complexes were measured at (4.92 × 105 and 11.99 × 104 M-1), (170.96 and -131.19 KJ.mol-1), and (-464.86 and 342.83J.mol-1K-1), respectively.QuNE lowered the HepG2 viability by up-regulating Cas-3 gene expression and thus inducing apoptosis. Moreover, a notable antioxidant impact on the QuNE was detected. Due to its ability in delivering Quercetin to HSA and HTF proteins and stabilizing their protein complexes, QuNE can be used as a suitable primary transporting agent whose formation of stable bio-accessible QuNE-HSA and -HTF protein complexes creates a safe and natural secondary delivery system, which has potential to be used as an efficient anticancer compound.Communicated by Ramaswamy H. Sarma.


Subject(s)
Quercetin , Serum Albumin, Human , Humans , Serum Albumin, Human/metabolism , Quercetin/pharmacology , Olive Oil , Molecular Docking Simulation , Transferrin/chemistry , Antioxidants/pharmacology , Protein Binding , Blood Proteins/metabolism , Thermodynamics , Circular Dichroism , Spectrometry, Fluorescence/methods , Binding Sites
9.
Biofactors ; 49(2): 379-389, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36310375

ABSTRACT

One kind of brain cancer with a dismal prognosis is called glioblastoma multiforme (GBM) due to its high growth rate and widespread tumor cell invasion into various areas of the brain. To improve therapeutic approaches, the objective of this research investigates the cytotoxic, anti-metastatic, and apoptotic effect of urolithin-B (UB) as a bioactive metabolite of ellagitannins (ETs) on GBM U87 cells. The malignant GBM cell line (U87) was examined for apoptosis rate, cell cycle analysis, cell viability, mRNA expressions of several apoptotic and metastasis-associated genes, production of reactive oxygen species (ROS), MMP-2, and MMP-9 activity and protein expression, and migration ability. The findings revealed that UB decreased U87 GBM viability in a dose-dependent manner and NIH/3T3 normal cells with the IC50 value of 30 and 55 µM after 24 h, respectively. UB also induces necrosis and G0/G1 cell cycle arrest in U87 cells. UB also increases ROS production and caused down-regulation of Bcl2 and up-regulation of Bax apoptotic genes. Additionally, treatment of UB reduced the migration of U87 cells. The protein levels, mRNA expression, and the MMP-2 and MMP-9 enzyme activities also decreased concentration-dependently. So, due to the non-toxic nature of UB and its ability to induce apoptosis and reduce the U87 GBM cell invasion and migration, after more research, it can be regarded as a promising new anti-GBM compound.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Reactive Oxygen Species/pharmacology , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Apoptosis , Cell Proliferation , RNA, Messenger , Cell Line, Tumor , Cell Movement
10.
Gastroenterol Hepatol Bed Bench ; 15(2): 131-138, 2022.
Article in English | MEDLINE | ID: mdl-35845310

ABSTRACT

Aim: The present study aimed to evaluate the expression profile, prognostic value, and possible correlation of TRIM29 with ß-catenin, Cyclin D, and Bcl2 in Iranian patients with GC. Background: Tripartite Motif Containing 29 (TRIM29) has been reported to function as an oncogene or a tumor suppressor depending on the tumor type. This contextual function has created a controversial situation that needs to be fully delineated in various cancers. Although few studies have reported an elevated TRIM29 expression in gastric cancer (GC), its clinicopathological and prognostic values as well as possible molecular mechanisms are yet to be re-evaluated in different populations. Methods: Real-time quantitative PCR was used to detect TRIM29, ß-catenin, Cyclin D, and Bcl-2 expression in 40 GC and their adjacent normal tissues. Patients were further stratified into high and low expression subgroups based on their TRIM29 expression levels. The association of TRIM29 expression level with ß-catenin, Cyclin D, BCL2, some clinicopathological features, and patients' overall survival (OS) was assessed using appropriate statistical analyses. Results: The results showed a significantly higher TRIM29 expression level in GC tissues compared with their corresponding normal tissues (fold change=2.94, p=0.003). Patients with high TRIM29 expression levels exhibited poorer OS (HR=1.25, 95% CI: 1.06-1.47, p=0.007). High expression of TRIM29 was also associated with increased levels of ß-catenin, Cyclin D, and Bcl-2 genes expression. Conclusion: Overexpression of TRIM29 is associated with poor prognosis in patients with GC and is probably mediated through ß-catenin/Cyclin D/Bcl2 pathway and can be considered as a potential independent prognostic marker.

11.
J Clin Neurosci ; 101: 57-62, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35533613

ABSTRACT

BACKGROUND: Methadone and buprenorphine which are widely used for opioid maintenance treatment can affect redox status and also brain functions. The present study aimed to compare inflammation, oxidative stress, and cognitive function in methadone maintenance patients (MMP), buprenorphine maintenance patients (BMP), and healthy participants. METHOD: Oxidative- antioxidant markers, inflammatory factors were investigated in MMP (n = 30), BMP (n = 30), and healthy participants (n = 30) by evaluating the ferritin, malondialdehyde (MDA), total antioxidant capacity (TAC), and also High-sensitivity C-reactive protein (hs-CRP). Also, executive function was evaluated using Wisconsin Card Sorting Test (WCST). FINDINGS: MMP and BMP showed impairment in executive function compared to the healthy participants. Both buprenorphine and methadone treatments induced oxidative stress. The ferritin level in BMP was significantly lower compared to MMP and healthy participants (P = 0.01). There was a significant difference between control and MMP and BMP (P > 0.0001) in terms of hs-CRP level. BMP had the highest and healthy participant's lowest MDA level (P < 0.001). The TAC levels in BMP were lower than in MMP (p = 0.002) and healthy participants (p = 0.001). Finally, executive function was significantly correlated with oxidative-antioxidant status. DISCUSSION: Both methadone and buprenorphine induced severe oxidative activity (especially buprenorphine) and cognitive deficits compared to healthy participants. Stress oxidative can affect normal brain activity and consequently cognitive functions. It's suggested that concomitant antioxidant administration with buprenorphine or methadone can potentially enhance their beneficial action by regulating blood redox status.


Subject(s)
Buprenorphine , Humans , Analgesics, Opioid/therapeutic use , Antioxidants , Buprenorphine/pharmacology , Buprenorphine/therapeutic use , C-Reactive Protein , Cognition , Ferritins , Healthy Volunteers , Methadone/therapeutic use , Oxidative Stress
12.
J Gastrointest Cancer ; 53(1): 179-186, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33415720

ABSTRACT

BACKGROUND/AIMS: Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with ß-catenin, CyclinD, and BCL2 expression in patients with GC. METHODS: A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients' overall survival, some clinicopathological variables, and ß-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high. RESULTS: Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan-Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of ß-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients. CONCLUSIONS: This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker.


Subject(s)
Stomach Neoplasms , Apoptosis , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Cycle , Humans , Kaplan-Meier Estimate , Prognosis , Stomach Neoplasms/pathology
13.
Asian Pac J Cancer Prev ; 22(8): 2445-2451, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34452557

ABSTRACT

BACKGROUND AND AIM: Tripartite Motif Containing 16 (TRIM16) is a member of the TRIM protein family which is known to play a suppressor role in development of numerous tumor types. However, a positive correlation between TRIM16 expression and gastric cancer (GC) progress has created a controversial situation that need to be fully delineated.  The aim of this study was to assess the expression level of TRIM16 mRNA and its relationship with ß-catenin, CyclinD, and BCL2 expression in Iranian GC patients and to investigate its possible association with patients' overall survival.  Materials and Methods: The expression level of TRIM16 of fresh primary tumor and adjacent normal tissues in 40 GC patients was evaluated by real-time quantitative PCR method. Moreover, patients were subdivided into high or low expression subgroups based on the TRIM16 expression levels. The relationship between TRIM16 expression level, ß-catenin, Cyclin D, BCL2, some clinicopathological data and prognosis of GC patients was also analyzed. RESULTS: qPCR analysis showed a lower level of TRIM16 in GC tissues (fold change=0.351) in comparison to their matched adjacent noncancerous tissues (p <0.001). Contrary to this, the expression levels of ß-catenin, Cyclin D, and BCL2 genes were up-regulated in cancerous samples. This may explain the tumor suppressive function of TRIM16 in GC; as reduction in TRIM16 expression leads to the accumulation of mRNAs from ß-catenin, Cyclin D, and BCL2 genes and eventually cancer progression. We did not observe any significant correlation between TRIM16 expression and patients' overall survival. Univariate Cox regression analysis indicated that anemia, weight loss, bleeding, stomach ache, and smoking are statistically associated with overall survival; while, multivariate analysis did not support any correlation.  Conclusions: In sum, this study suggests a tumor suppressive role for TRIM16 in gastric cancer and proposes it as a potential candidate for GC prognosis.
.


Subject(s)
Biomarkers, Tumor/metabolism , Stomach Neoplasms/pathology , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Aged , Biomarkers, Tumor/genetics , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Survival Rate , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/genetics
14.
J Mol Model ; 27(2): 40, 2021 Jan 17.
Article in English | MEDLINE | ID: mdl-33454889

ABSTRACT

O6-methylguanine DNA methyl transferase (MGMT) is a metalloenzyme participating in the repair of alkylated DNA. In this research, we performed a comparative study for evaluating the impact of zinc metal ion on the behavior and interactions of MGMT in the both enzymatic forms of apo MGMT and holo MGMT. DNA and proliferating cell nuclear antigen (PCNA), as partners of MGMT, were utilized to evaluate molecular interactions by virtual microscopy of molecular dynamics simulation. The stability and conformational alterations of each forms (apo and holo) MGMT-PCNA, and (apo and holo) MGMT-DNA complexes were calculated by MM/PBSA method. A total of seven systems including apo MGMT, holo MGMT, free PCNA, apo MGMT-PCNA, holo MGMT-PCNA, apo MGMT-DNA, and holo MGMT-DNA complexes were simulated. In this study, we found that holo MGMT was more stable and had better folding and functional properties than that of apo MGMT. Simulation analysis of (apo and holo) MGMT-PCNA complexes displayed that the sequences of the amino acids involved in the interactions were different in the two forms of MGMT. The important amino acids of holo MGMT involved in its interaction with PCNA included E92, K101, A119, G122, N123, P124, and K125, whereas the important amino acids of apo MGMT included R128, R135, S152, N157, Y158, and L162. Virtual microscopy of molecular dynamics simulation showed that the R128 and its surrounding residues were important amino acids involved in the interaction of holo MGMT with DNA that was exactly consistent with X-ray crystallography structure. In the apo form of the protein, the N157 and its surrounding residues were important amino acids involved in the interaction with DNA. The binding free energies of - 387.976, - 396.226, - 622.227, and - 617.333 kcal/mol were obtained for holo MGMT-PCNA, apo MGMT-PCNA, holo MGMT-DNA, and apo MGMT-DNA complexes, respectively. The principle result of this research was that the area of molecular interactions differed between the two states of MGMT. Therefore, in investigations of metalloproteins, the metal ion must be preserved in their structures. Finally, it is recommended to use the holo form of metalloproteins in in vitro and in silico researches.

15.
RSC Adv ; 11(59): 37103-37111, 2021 Nov 17.
Article in English | MEDLINE | ID: mdl-35496431

ABSTRACT

The transmutation of waste into valuable materials has a special place in green chemistry. Herein, we report the preparation of quinazoline-2,4(1H,3H)-diones from 2-iodoaniline, isocyanides, and carbon dioxide in the presence of ZnO NPs stably placed on the surface of dendritic fibrous nanosilica by cellulose (DFNS/cellulose-ZnO) as a catalyst. This is a great economic strategy to create three bonds in a one-pot multicomponent reaction step employing functional groups. To prepare the catalyst, the dendritic fibrous nanosilica surface was first activated using cellulose as a substrate to support ZnO NPs. Cellulose acts as a stabilizing and reducing agent for the ZnO nanocatalyst and eliminates the need for a reducing agent. The structure of the prepared DFNS/cellulose-ZnO was examined by various methods, including thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma (ICP). The largest amount of quinazoline-2,4(1H,3H)-diones was obtained under ideal situations in the presence of 5 mg of DFNS/cellulose-ZnO under carbon dioxide (1 atm) utilizing a balloon set at 70 °C for 3 hours. The substance was reused for ten consecutive runs and the quinazoline-2,4(1H,3H)-dione content was more than 92% each time. This indicates the potential for application in the green and economic production of quinazoline-2,4(1H,3H)-diones, especially from low-cost feedstocks.

16.
J Biomol Struct Dyn ; 39(3): 1029-1043, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32000592

ABSTRACT

Berberine is widely used in traditional Iranian medicine to treat diabetes and inflammatory conditions. This study was aimed at developing a method for the preparation of Berberine nanoparticles (Nano-Ber) in order to improve its aqueous-phase solubility and its complex formation with human serum albumin (HSA) and holo-transferrin (HTF) from the viewpoint of interaction behavior. Nano-Ber was prepared with olive oil as the oil phase, Tween 80 as the surfactant and Span 60 as the co-surfactant. Nano-Ber was obtained with a spherical shape and a mean particle size of 43.7 ± 3.6 nm, with an optimal oil:surfactant:co-surfactant ratio of 1:2:2, w/w/w. The antioxidant activity of Nano-Ber in comparison with Berberine was tested using DPPH and it was found that Nano-Ber had a large antioxidant activity. The cytotoxicity effects of Nano-Ber and Berberine on HepG2 were compared by MTT assay and detected in the treated HepG2 cells at concentrations up to 0.1 mM. The binding constants of HSA-Nano-Ber and HTF-Nano-Ber complexes formation were (2.93 ± 0.02) × 104 and (9.62 ± 0.03) × 103 M -1, respectively. Hydrogen bonds and van der Waals interactions were the predominant forces in the HSA-Nano-Ber and HTF-Nano-Ber complexes, and the process of Nano-Ber binding HSA and HTF was driven by ΔH 0 = -122.76 kJ mol-1, ΔS 0 = -325.49 J mol-1K-1 for HSA and ΔH 0 = -125.09 kJ mol-1, ΔS 0 = -43.37 J mol-1K-1 for HTF. The results of the simulation demonstrated that the Nano-Ber molecules were stabilized on the surface of final aggregates through both hydrophilic and hydrophobic interactions. Communicated by Ramaswamy Sarma.


Subject(s)
Berberine , Serum Albumin, Human , Binding Sites , Humans , Iran , Olive Oil , Protein Binding , Spectrometry, Fluorescence , Thermodynamics , Transferrin , Water
17.
Med J Islam Repub Iran ; 34: 75, 2020.
Article in English | MEDLINE | ID: mdl-33306066

ABSTRACT

Background: Several environmental and genetic factors have contributed to the development of colorectal cancer (CRC). We aimed to investigate the independent and combined effects of some selected risk factors and Arg399Gln XRCC1 polymorphism on CRC. Methods: A total of 180 patients with CRC and 160 healthy individuals who were matched for sex, age, and place of residence (Northeast of Iran) participated in this case-control study. Before collecting blood samples and filling out questionnaires, a written consent form was obtained from all participants. Genotypes were determined by RFLP-PCR. The comparison of genotype and allele frequencies was performed using p value based on the results of chi-square test. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by employing a logistic regression model. All statistical calculations were performed using SPSS. Each of the 2- sided p values less than 0.05 were considered statistically significant. Results: The level of literacy, physical activity, consumption of vegetables and fruits, and tea intake of the patients were significantly lower than healthy individuals, but gastrointestinal disorders, family history of cancer, BMI, and fast food consumption were significantly higher in cases than in controls. No significant difference was observed between the 2 groups regarding smoking, opioid addiction, alcohol consumption, diet, fish consumption, and liquid intake, using the kitchen hood, diabetes, and cardiovascular disease. Arg/Gln + Gln/Gln and Arg/Gln genotypes were involved in increased CRC risk (The crude OR =1.781 with a 95% CI of 1.156-2.744 and OR = 1.690 with a 95% CI of 0.787-3.630). Also, Gln/Gln genotype was more frequent in CRC group than in control group. However, none of the risk factors interacted with polymorphism, and thus did not have an effect on CRC. Conclusion: Some risk factors, such as reducing the consumption of vegetables and fruits or reducing physical activity as well as polymorphism of the XRCC1 Arg399Gln alone, increase the risk of CRC, but they do not interact with each other.

18.
RSC Adv ; 10(26): 15044-15051, 2020 Apr 16.
Article in English | MEDLINE | ID: mdl-35495475

ABSTRACT

We studied the potential application of an efficient, reusable, and easily recoverable catalyst of dendritic fibrous nanosilica (DFNS)-supported platinum(ii) complexes (DFNS/Pt(ii) NPs) to form cyclic carbonates in the presence of epoxides by converting carbon dioxide. Cyclic carbonates from epoxides and carbon dioxide is proposed as the most appropriate way to synthesis this C1 building block. We performed FE-SEM, TEM, TGA, BET, VSM, and ICP-MS to thoroughly characterize DFNS/Pt(ii) NPs.

19.
RSC Adv ; 10(46): 27297-27304, 2020 Jul 21.
Article in English | MEDLINE | ID: mdl-35516956

ABSTRACT

Water is an essential substance for life on earth and for all living things. Plants and animals need almost pure water to live; if it is contaminated with harmful chemicals and micro organisms, it will be impossible for them to survive. This study has tried to investigate the performance of catalyst to reduce nitro-aromatic combinations in the attendance of NaBH4 solution duo to the hydrogen source. TEMPO@FeNi3/DFNS-laccase MNPs was prepared, and its features were reviewed using SEM, TEM, XRD, TGA, VSM, AFM, and FTIR. Then, its strength as a nanocatalyst for removal of nitro-aromatic combinations was tested in contact time, initial concentration, the effects of pH and nanocatalyst amount was study. The results of this research proved that TEMPO@FeNi3/DFNS-laccase MNPs has a good return in removal of nitro-aromatic combinations, as its easy synthesis and reliable recovery.

20.
Asian Pac J Cancer Prev ; 20(7): 2153-2158, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31350979

ABSTRACT

Background: Colorectal cancer (CRC) is highly prevalent cancer, which should be genetically studied among different peoples of the world. Objective: The aim of this study was to evaluate the effect of XRCC3T241M, XRCC3 A17893G and, for the first time, XRCC7 I3434T polymorphisms on CRC risk in Khorasan Razavi Province, Iran. Materials and Methods: In this case-control study, 180 patients with CRC and 160 sex- and age-matched healthy controls were studied. Genotypes were determined by RFLP-PCR and ARMS-PCR. Results: The incidence of CRC was observed to be significantly more in a heterozygous XRCC3 C/T genotype than in the CC genotype (OR 2.210, 95% CI 1.073-4.548, p=0.030). In the case of the XRCC7 I3434T polymorphism, CRC risk was significantly (4.3 fold) higher in I/T+T/T variant subjects compared to the I/I genotype (OR 4.394, 95% CI 2.721-7.096, p=0.000). Moreover, the XRCC3 A17893G polymorphism did not correlate with CRC. In addition, there was no significant difference between the distribution of genotypes of the three studied polymorphisms with demographic and clinicopathological features in the CRC patients. Conclusion: Polymorphisms of XRRC3 and XRCC7 genes are involved in CRC and should be considered as a risk factor.


Subject(s)
Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , DNA-Activated Protein Kinase/genetics , DNA-Binding Proteins/genetics , Polymorphism, Single Nucleotide , Aged , Case-Control Studies , Colorectal Neoplasms/epidemiology , Female , Follow-Up Studies , Genetic Predisposition to Disease , Genotype , Humans , Incidence , Iran/epidemiology , Male , Middle Aged , Prognosis , Risk Factors
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