The effect of topical 0.5% humic acid gel on male rats with skin ulcer.

Background: Humic derivatives have antibacterial and anti-inflammatory properties. Aim: This study aimed to assess the experimental wound-healing effect of 0.5% humic acid gel. Materials and Methods: A full-thickness skin wound was created on the dorsal side of 24 Sprague Dawley male rats (220-250 g). The animals were then randomly divided into the control, sham, and experimental groups. Skin wounds were bandaged daily using sterile gauze dipped in normal saline, carboxymethylcellulose, and 0.5% humic acid for 21 days. The wound-healing rate was evaluated grossly and histologically at various time intervals post-injury. Results: Wound-healing percentage was significantly higher in the gel treatment group at all time points (P < 0.05). The mean number of inflammatory cells was significantly lower in the humic acid gel group than in the other groups (P < 0.001). Moreover, the number of new vascular cells and fibroblasts were significantly increased in the humic acid gel compared to the control (P < 0.001). Conclusion: These data confirmed that 0.5% humic acid gel accelerates wound healing, probably by anti-inflammatory effects, as well as by promoting vascular and fibroblast proliferation. Therefore, the humic acid gel may be used to improve wound care.

The effect of combining humic and fulvic acids poultice on wound healing in male rats.

Background: Finding new compounds to accelerate wound healing is critical today. Humic substances or fulvic acid each have anti-inflammatory properties. Aims and Objectives: The purpose of this study is to determine the effects of poultice 0.5% containing humic and fulvic acids on wound healing in male rats. Materials and Methods: An animal model was arranged by making a full-thickness skin wound was created in each rat. Animals were randomly divided into control, sham, and treatment groups. To investigate the effect of humic and fulvic acids combining poultice, the wound area and histological analyses of the number of inflammatory cells, fibroblasts, and angiogenesis were evaluated for 21 days. Results: The animals in the treated group showed higher wound healing percentage, angiogenesis, and fibroblast distribution compared with the control (P < 0.001). Moreover, the topical administration of humic and fulvic acids 0.5% poultice decreased the mean number of inflammatory cells significantly than the other groups (P < 0.001). Conclusion: The topical administration of a poultice containing humic and fulvic acid accelerated wound healing by increasing angiogenesis and fibroblast and reducing inflammatory cell distribution in a rat model.

The sensory evaluation and antimicrobial efficacy of Lactobacillus acidophilus supernatant on Salmonella enteritidis in milk.

Postbiotics are metabolites derived from living probiotic bacteria like Lactobacillus strains, during the fermentation process and/or produced in pure form on laboratory scales. These compounds, depending on the type of probiotic from which they are prepared, have specific antibacterial agents such as: organic acids, bacteriocins, short-chain fatty acids, and peptides. The objective of this study was to investigate the effect of Lactobacillus acidophilus supernatant (LAS) on the growth pattern of Salmonella enteritidis at fluctuating temperatures and the sensory evaluation of milk that contains this probiotic. Baranyi and Roberts's model determined the best-fit curve for the microbial growth. According to mathematical equations, the highest and lowest specific growth (µ max) rates of S. enteritidis were obtained at 0.055 h-1 and 0.0059 h-1 and also highest and lowest maximum generation time (MGT) values were obtained at 20.06 h and 8.85 h, respectively. Sensory evaluation by the Triangel test reveals that LAS could not establish a significant (p > .05) adverse effect on milk perceptible. Regarding the results obtained in the present study, LAS, without causing adverse sensory change, could act as a safe food additive for the control of bacterial pathogens and reducing food waste, particularly in milk and milk-containing food products.

A nano-liposomal carrier containing p-coumaric acid for induction of targeted apoptosis on melanoma cells and kinetic modeling.

There has been a growth in the use of plant compounds as biological products for the prevention and treatment of various diseases, including cancer. As a phenolic compound, p-Coumaric acid (p-CA) demonstrates preferrable biological effects such as anti-cancer activities. A nano-liposomal carrier containing p-CA was designed to increase the anticancer effectiveness of this compound on melanoma cells (A375). To determine the characteristics of synthesized liposomes, encapsulation efficiency was measured. In addition, the particle size was measured utilizing DLS, FTIR, and morphology examination using SEM. In vitro release was also studied through the dialysis method, while toxicity was evaluated using the MTT assay. To determine apoptotic characteristics, biotechnology tools like flow cytometry, real time PCR, and atomic force microscopy (AFM) were employed. The findings indicated that in the cells treated with the liposomal form of p-CA, the amount of elastic modulus was higher compared to its free form. Kinetic modeling indicated that the best fitting model was zero-order.

The anticancer impacts of free and liposomal caffeic acid phenethyl ester (CAPE) on melanoma cell line (A375).

The deadliest type of skin cancer, malignant melanoma, is also the reason for the majority of skin cancer-related deaths. The objective of this article was to investigate the efficiency of free caffeic acid phenethyl ester (CAPE) and liposomal CAPE in inducing apoptosis in melanoma cells (A375) in in vitro. CAPE was loaded into liposomes made up of hydrogenated soybean phosphatidylcholine, cholesterol, and 1,2-distearoyl-sn-glycero-3 phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000], and their physicochemical properties were assessed. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was performed for comparing the cytotoxicity of free CAPE and liposomal CAPE at dosages of 10, 15, 25, 50, 75 and the highest dose of 100 µg/mL for period of 24 and 48 h on A375 cell line to calculate IC50. Apoptosis and necrosis were evaluated in A375 melanoma cancer cells using flow cytometry. Atomic force microscopy was utilized to determine the nanomechanical attributes of the membrane structure of A375 cells. To determine whether there were any effects on apoptosis, the expression of PI3K/AKT1 and BAX/BCL2 genes was analyzed using the real-time polymerase chain reaction technique. According to our results, the maximum amount of drug release from nanoliposomes was determined to be 91% and the encapsulation efficiency of CAPE in liposomes was 85.24%. Also, the release of free CAPE was assessed to be 97%. Compared with liposomal CAPE, free CAPE showed a greater effect on reducing the cancer cell survival after 24 and 48 h. Therefore, IC50 values of A375 cells treated with free and liposomal CAPE were calculated as 47.34 and 63.39 µg/mL for 24 h. After 48 h of incubation of A375 cells with free and liposomal CAPE, IC50 values were determined as 30.55 and 44.83 µg/mL, respectively. The flow cytometry analysis revealed that the apoptosis induced in A375 cancer cells was greater when treated with free CAPE than when treated with liposomal CAPE. The highest nanomechanical changes in the amount of cell adhesion forces, and elastic modulus value were seen in free CAPE. Subsequently, the greatest decrease in PI3K/AKT1 gene expression ratio occurred in free CAPE.

The Association of Methylation Status and Expression Level of MyoD1 with DNMT1 Expression Level in Breast Cancer Patients.

Background: Breast cancer (BC) is the most common malignancy in women worldwide. The methylation status of MyoD1, a tumor suppressor gene, is enrolled in various cancers, i.e., BC. Various studies showed the impact of MyoD1 epigenetic dysregulation in BC. This study aimed to investigate the methylation status and expression level of MyoD1 in BC patients and its association with the expression of DNMT1. Materials and Methods: This case-control study was conducted on 30 cases (pathology-confirmed ductal carcinoma) and 18 controls (fibroadenoma and fibrocystic masses), referred to Velayat Hospital, Qazvin, Iran. The expression of the MyoD1 and DNMT1 and the promoter methylation of the MyoD1 were evaluated in tissue blocks of BC patient masses using qRT-PCR and MS-PCR assays, respectively. SPSS 24.0 was used to analyze the data. Results: The MyoD1 promoter is hypermethylated in BC patients compared to controls (p =0.001). The expression level of MyoD1 in BC patients was significantly reduced compared to controls (fold change =0.13, p =0.042). In addition, in BC patients, the reduced expression level of MyoD1 was significantly associated with methylation of the MyoD1 promoter (p =0.001). There is no significant difference between the expression level of DNMT1 in BC patients and controls (p =0.197). A significant association is found between the expression of DNMT1 and the methylation status of the MyoD1 promoter (p =0.038). Discussion: The expression level of MyoD1 is affected by the methylation status of the promoter of this gene. Moreover, the expression level and methylation status of MyoD1 are correlated with clinical parameters.

The emerging role of LncRNA AWPPH in multiple cancers: a review study.

Long non-coding RNAs (lncRNAs) are transcribed RNA molecules longer than 200 nucleotides in length that have no protein-coding potential. They are able to react with DNA, RNA, and protein. Hence they involve in regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. LncRNAs have been proven to play an important role in human malignancies and prognostic outcomes. In this review, we will comprehensively and functionally discuss the role of a novel identified lncRNA, namely lncRNA WAPPH located on human chromosome 2q13, in various cancers. Increasing research studies have shown that lncRNA AWPPH is deregulated in different malignancies, including breast cancer, gastric cancer, colorectal cancer, ovarian cancer, bladder cancer, leukemia, and others. LncRNA WAPPH serves as an oncogene in tumorigenesis and the development of cancer. Moreover, lncRNA AWPPH is involved in numerous biological processes of solid and blood cancers. Taken together, based on our scrutiny analysis, lncRNA AWPPH can be regarded as a putative biomarker for diagnosis or therapeutic target in human malignancies.

New insights into the inhibitory effect of phenol carboxylic acid antioxidants on mushroom tyrosinase by molecular dynamic studies and experimental assessment.

The inhibitory effects of ferulic and chlorogenic acids on tyrosinase activity were investigated through multi-spectroscopic and molecular docking techniques. Ferulic and chlorogenic acids, flavonoid compounds, demonstrated inhibitory monophenolase activities of tyrosinase. The inhibitor effects against monophenolase activity were in a reversible and competitive manner with ki value equal to 6.8 and 7.5 µM respectively. The affinity between tyrosinase and L-DOPA decreased when fatty acids were added to the solution. The multi-spectroscopic techniques like UV-vis, fluorescence, and isothermal calorimetry are employed to investigate changes. Intrinsic fluorescence quenching and conformational changes of tyrosinase by hydrophobic interaction were confirmed. Tyrosinase had two and three binding sites for ferulic and chlorogenic acids with a binding constant in the order of magnitude of -6.8 and -7.2 kcal/mol. In addition, the secondary structural changes with Circular dichroism (CD) analysis, secondary structure (DSSP), radius of gyration (Rg) and analysis of hydrogen bonds (H-bonds) confirmed. Ferulic acid effect can be observed obviously and also content of α-helix decreased. Thermodynamic parameters indicated that the interaction between enzyme and ferulic and chlorogenic acids followed a spontaneous reaction dynamic manner with ΔG = -14.78 kJ/mol and ΔG = -14.61 kJ/mol (298k). The findings highlighted the potential applications of ferulic acid and chlorogenic acids in food and drug industries as potent inhibitors of tyrosinase.Communicated by Ramaswamy H. Sarma.

In silico study Ferulic and Chlorogenic Acids was performed to check the binding profile against tyrosinase.Investigate the inhibitory It inhibited tyrosinase in a competitive manner.Ferulic and Chlorogenic fatty acids for prevention of medical hyperpigmentation, and it is a good candidate for cosmetic applications.

Biomolecular interactions and binding dynamics of inhibitor arachidonic acid, with tyrosinase enzyme.

Hyperpigmentation is a disorder caused by increased melanin deposition and changes in skin pigmentation. Inhibition of tyrosinase activity contributes to the control of food browning and skin pigmentation diseases. The effects of arachidonic acid (AA) on tyrosinase activity were examined using different spectroscopy methods including UV-VIS spectrophotometry, fluorescence spectroscopy, circular dichroism (CD) differential scanning calorimetry, and molecular dynamics (MD) simulations. Based on the kinetic results, arachidonic acid showed mixed-type of inhibition with Ki = 4.7 µM. Fluorescence and CD studies showed changes of secondary and tertiary structures of enzyme and a reduction of α-helix* amino acids after its incubation with different concentrations of AA, which is also confirmed by DSSP analysis. In addition, differential scanning calorimetry (DSC) studies showed a decrease in thermodynamic stability of enzyme from Tm = 338.65k for sole enzyme after incubation with AA in comparison with complex enzyme with Tm= 334.26k, ΔH =7.52 kJ/mol, and ΔS = 0.15 kJ/mol k. Based on the theoretical methods, it was found that the interaction between enzyme and AA follows an electrostatic manner with ΔG = -8.314 kJ/mol and ΔH = -12.9 kJ/mol. The MD results showed the lowest flexibility in the complex amino acids and minimal fluctuations in AA interaction with tyrosinase in Residue 240 to 260 and 66 to 80. Thus, AA inhibitory and structural and thermodynamic instability of tyrosinase supported advantages of this fatty acid for prevention of medical hyperpigmentation. Therefore, it is a good candidate for cosmetic applications. Communicated by Ramaswamy H. Sarma.

Molecular dynamics simulations, molecular docking, and kinetics study of kaempferol interaction on Jack bean urease: Comparison of extended solvation model.

Since the urease enzyme creates gastric cancer, peptic ulcer, hepatic coma, and urinary stones in millions of people worldwide, it is essential to find strong inhibitors to help patients. Natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients, the so-called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, and cosmetic applications. Kaempferol (KPF) is an antioxidant found in many fruits and vegetables. Many reports have explained the significant effects of dietary KPF in reducing the risk of chronic diseases such as cancer, ischemia, stroke, and Parkinson's. The current study aimed at investigating the inhibitory impact of KPF on Jack bean urease (JBU) using molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations to confirm the results obtained from isothermal titration calorimetry (ITC), extended solvation model, and docking software. In addition, UV-VIS spectrophotometry was used to study the kinetics of urease inhibition. Calorimetric and spectrophotometric determinations of the kinetic parameters of this inhibition indicate the occurrence of a reversible and noncompetitive mode. Also, the docking and MD results indicated that the urease had well adapted to the kaempferol in the binding pocket, thereby forming a stable complex. Kaempferol displayed low binding energy during MMPBSA calculations. The inhibitory potential of kaempferol was confirmed by experimental and simulation data, but in vivo investigations are also recommended to validate our results.

Investigating the effects of quercetin fatty acid esters on apoptosis, mechanical properties, and expression of ERK in melanoma cell line (A375).

AIMS: Malignant melanoma (MM) is the most fatal skin cancer with a critical increase in the number of cases in the last decades. Recent studies have shown the antitumor potential of active biological phytochemical structures of flavonoids for the prevention and treatment of cancerous cells. In this study, two quercetin fatty acid esters (α-linolenic acid (ALA) and linoleic acid (LA)) compounds were evaluated in terms of inducing apoptotic human melanoma cells (A375) death in vitro. MAIN METHODS: The MTT assay was utilized for comparing the effects of quercetin, ALA, and LA on A375 cell viability concentrations of 5, 25, 35, 50, and 100µg/mL for 24 and 48 h to obtain IC50. To detect the effects on apoptosis and to determine p-ERK/ERK apoptosis-related signaling pathway proteins level, flow-cytometry and western blot were used. Finally, the nano-mechanical properties of the melanoma A375 membrane structure containing elastic modulus value and cell-cell adhesion forces were investigated using Atomic Force Microscopy (AFM). Statistical data was analyzed in GraphPad v.8.0.0. KEY FINDINGS: The most significant A375 cell viability amplified effect of Q-LA was observed with a half-maximal inhibitory concentration (IC50 = 35 µg/mL, 48 h), proportional to dose. Ester compounds, especially Q-LA, showed the highest cell proliferation inhibition with improved elastic modulus, cell-cell adhesion forces (253 ± 11.2), and elevated apoptosis-inducing effect (p < 0.01**). Moreover, Q-LA significantly decreased the mean levels of p-ERK phosphorylation (0.1439) and, subsequently, apoptosis in A375 cells. SIGNIFICANCE: The data presented in this study confirmed the antitumor activity of ester compounds against A375 cells, high-lighting the ability of the tested compounds to induce apoptosis.

Ivermectin-Induced Clinical Improvement and Alleviation of Significant Symptoms of COVID-19 Outpatients: A Cross-Sectional Study.

Although several drugs have been proposed and used to treat the COVID-19 virus, but recent clinical trials have concentrated on ivermectin. It appears that ivermectin can potentially act against COVID-19 and stop the development in its infancy. The purpose of this study was to determine the effect of ivermectin on the recovery of outpatients with COVID-19. In this cross-sectional study, we compared the symptoms reduction in COVID-19 disease in two groups of patients by administering ivermectin. A total of 347 mild outpatients in the Iranian provinces of Qazvin and Khuzestan with a confirmed PCR were enrolled. The symptoms of outpatients with COVID-19 were analyzed using SPSS (V23). In this cross-sectional study, the sex ratio was 0.64 (female/male: 37.9/59.8) and most patients were under 50 years old (72.8%). The results of this study demonstrated a significant decrease in several COVID-19 disease symptoms, including fever, chills, dyspnea, headache, cough, fatigue, and myalgia in the group administered ivermectin compared to the control group. In addition, the odds ratio of the above symptoms was significantly lower in patients who received ivermectin than in patients who did not receive the drug (OR = 0.16, 95% CI = 0.09, 0.27).

Predicting Efficacy of 5-Fluorouracil Therapy via a Mathematical Model with Fuzzy Uncertain Parameters.

Background: Due to imprecise/missing data used for parameterization of ordinary differential equations (ODEs), model parameters are uncertain. Uncertainty of parameters has hindered the application of ODEs that require accurate parameters. Methods: We extended an available ODE model of tumor-immune system interactions via fuzzy logic to illustrate the fuzzification procedure of an ODE model. The fuzzy ODE (FODE) model assigns a fuzzy number to the parameters, to capture parametric uncertainty. We used the FODE model to predict tumor and immune cell dynamics and to assess the efficacy of 5-fluorouracil (5-FU) chemotherapy. Result: FODE model investigates how parametric uncertainty affects the uncertainty band of cell dynamics in the presence and absence of 5-FU treatment. In silico experiments revealed that the frequent 5-FU injection created a beneficial tumor microenvironment that exerted detrimental effects on tumor cells by enhancing the infiltration of CD8+ T cells, and natural killer cells, and decreasing that of myeloid-derived suppressor cells. The global sensitivity analysis was proved model robustness against random perturbation to parameters. Conclusion: ODE models with fuzzy uncertain kinetic parameters cope with insufficient/imprecise experimental data in the field of mathematical oncology and can predict cell dynamics uncertainty band.

Evaluation of Healing Effects of Poultice Containing 0.5% Fulvic Acid on Male White-Male Rats with Skin Ulcer.

Background: Chronic and acute skin wounds are an important health concern because they are very frequent during human life and affect millions of people worldwide. Shortening the wound healing process reduces treatment costs and hospitalization. Therefore, researchers have been looking for new treatment approaches to shorten the wound healing process. Aims and Objectives: The aim of this study was to evaluate the wound healing properties of poultice containing 0.5% fulvic acid. Materials and Methods: In this experimental study, a full-thickness skin wound was created on the dorsal side of 24 male rats. The animals were then randomly assigned to control, sham, and experiment groups. The skin defects were daily bandaged by using sterile gauze dipped in normal saline, carboxymethylcellulose, and 0.5% fulvic acid for 21 days, respectively. The wound healing rate was evaluated grossly and histologically at various time intervals post injury. Both descriptive and statistical analysis methods were applied (P < 0.05). Results: The wound healing percentage was significantly higher in the poultice treatment group at all time intervals (P < 0.001). The wound was completely closed in this group compared with other groups at the end of week 4 post treatment. The mean numbers of inflammatory cells were statistically lower, and fibroblasts and vessels were higher in the poultice group than in the other groups at various time intervals post injury (P < 0.001). Conclusion: Fulvic acid (0.5%) could be used as an effective therapeutic approach to improve the wound healing process because of its unique anti-inflammatory and neovascularization properties at the skin wound site.

Activation of apoptosis and G0/G1 cell cycle arrest along with inhibition of melanogenesis by humic acid and fulvic acid: BAX/BCL-2 and Tyr genes expression and evaluation of nanomechanical properties in A375 human melanoma cell line.

Objectives: Humic acid (HA) and Fulvic acid (FA) are major members of humic substances, which are extracted from organic sources including soil and peat. The pro-apoptotic and anti-melanogenic effects of HA and FA at the cellular and molecular levels in the A375 human melanoma cell line were examined in this study. Materials and Methods: The cytotoxicity effect of HA and FA were evaluated by cell viability assay. Apoptosis and cell cycle were investigated by flow cytometry. Real-time PCR was carried out to measure the expression of BAX, BCL-2, and Tyr genes. Moreover, the changes in nanomechanical properties were determined through atomic force microscopy (AFM). Results: It was found that HA and FA decrease cell viability with an IC50 value of 50 µg/ml (dose-dependent) for 14 hr, arrested cells in the G0/G1 phase, and increased the sub-G1 phase (induce apoptosis). Based on the AFM analysis, Young's modulus and adhesion force values were increased, also ultrastructural characteristics of cells were changed. Results of Real-time PCR revealed that HA and FA lead to a decrease in the expressions of BCL-2 and Tyr genes, and increase the BAX gene expression. Conclusion: These results exhibited that HA and FA possess pro-apoptotic effects through increasing the BAX/ BCL-2 expression in A375 cells. These molecular reports were confirmed by cellular nanomechanical assessments using AFM and flow cytometry. In addition, HA and FA inhibited melanogenesis by decreasing the expression of the Tyr gene. It is worthwhile to note that, HA and FA can be regarded to design new anti-cancer and anti-melanogenesis products.

Rhenium Perrhenate (188ReO4) Induced Apoptosis and Reduced Cancerous Phenotype in Liver Cancer Cells.

Recurrence in hepatocellular carcinoma (HCC) after conventional treatments is a crucial challenge. Despite the promising progress in advanced targeted therapies, HCC is the fourth leading cause of cancer death worldwide. Radionuclide therapy can potentially be a practical targeted approach to address this concern. Rhenium-188 (188Re) is a ß-emitting radionuclide used in the clinic to induce apoptosis and inhibit cell proliferation. Although adherent cell cultures are efficient and reliable, appropriate cell-cell and cell-extracellular matrix (ECM) contact is still lacking. Thus, we herein aimed to assess 188Re as a potential therapeutic component for HCC in 2D and 3D models. The death rate in treated Huh7 and HepG2 lines was significantly higher than in untreated control groups using viability assay. After treatment with 188ReO4, Annexin/PI data indicated considerable apoptosis induction in HepG2 cells after 48 h but not Huh7 cells. Quantitative RT-PCR and western blotting data also showed increased apoptosis in response to 188ReO4 treatment. In Huh7 cells, exposure to an effective dose of 188ReO4 led to cell cycle arrest in the G2 phase. Moreover, colony formation assay confirmed post-exposure growth suppression in Huh7 and HepG2 cells. Then, the immunostaining displayed proliferation inhibition in the 188ReO4-treated cells on 3D scaffolds of liver ECM. The PI3-AKT signaling pathway was activated in 3D culture but not in 2D culture. In nude mice, Huh7 cells treated with an effective dose of 188ReO4 lost their tumor formation ability compared to the control group. These findings suggest that 188ReO4 can be a potential new therapeutic agent against HCC through induction of apoptosis and cell cycle arrest and inhibition of tumor formation. This approach can be effectively combined with antibodies and peptides for more selective and personalized therapy.

Evaluation of expression level and methylation profile of CXX1 gene in breast cancer tissue blocks.

AIMS: The hypermethylation of CpG islands in the promoter of tumor-suppressor genes (TSGs) leads to silencing the transcription of tumor suppressors, which lead to the development of cancer. The hypermethylation of CXX1 and CDH1 genes, as TSGs, plays an essential role in the development of various types of cancer, i.e., colorectal and gastric cancer. This study aims at evaluating the expression level of CXX1 and CDH1 genes and the methylation status of CXX1 CpG island's promoter in breast cancer (BC). MATERIALS AND METHODS: In this study, the expression level of the CXX1 and CDH1 genes and the promoter methylation status of the CXX1 gene were evaluated in 30 paraffin-embedded tissue blocks of malignant BC and 18 benign breast lesions, using quantitative reverse transcription-PCR and methylation-specific (MS)-PCR assays, respectively. RESULTS: The CXX1 gene was downregulated in the malignant tissues due to the hypermethylation of the CpG islands in the promoter, compared to the control group (P = 0.031). The downregulation of CDH1 gene expression was observed in the patient group compared to control, but this reduction was not statistically significant. The results show that the risk of BC is increased with aging (P < 0.001). Furthermore, the benign breast lesions (controls) had more mobility in comparison with the malignant breast tumors (P < 0.001). In the malignant samples, the size of the mass was larger than control's mass samples (P = 0.006). CONCLUSIONS: In the pathophysiological state of BC, the aberrant DNA hypermethylation in CpG island of CXX1 promoter is responsible for the reduction of its expression level in BC patients.

Cytotoxicity and Genotoxicity of Calcium Hydroxide and Two Antibiotic Pastes on Human Stem Cells of The Apical Papilla.

OBJECTIVE: This study aimed to assess the cytotoxicity and genotoxicity of triple antibiotic paste, double antibiotic paste and calcium hydroxide medicaments on human stem cells of the apical papilla. METHODS: In this experimental study, stem cells were isolated from the apical papilla and cultured. They are treated with different concentrations 0.1, 0.5, 1, 10 and 100 mg/ml of medicaments for 24, 48 and 72 hours. The cytotoxicity and genotoxicity of the medicaments were determined using methyl thiazolyl tetrazolium assay and Comet test, respectively. RESULTS: Results showed all tested concentrations of the calcium hydroxide had no significant effect on stem cells at any time point. Triple antibiotic paste showed cytotoxicity in 10 and 100 mg/mL concentrations at all-time points and in 1, 10 and 100 mg/ml concentrations at 72 hours. In addition, its genotoxicity was significantly higher than that of other groups (P<0.05). Double antibiotic paste showed cytotoxic effects only in 100 mg/ml concentration at 24 hours and 10 and 100 mg/ml concentrations at 48 and 72 hours. And also, its genotoxicity in these concentrations was significantly higher than that of control and calcium hydroxide groups (P<0.05). CONCLUSION: In contrast to calcium hydroxide, triple antibiotic paste and double antibiotic paste, especially in their higher concentrations, induced cytotoxicity and genotoxicity on human stem cells of the apical papilla.

The effects of the esterified Quercetin with omega3 and omega6 fatty acids on viability, nanomechanical properties, and BAX/BCL-2 gene expression in MCF-7 cells.

Quercetin is one of the major flavonoids and it appears to have cytotoxic effects on various cancer cells through regulating the apoptosis pathway genes such as BAX and BCL2. Combination of Quercetin (Q) with other compounds can increase its effectiveness. In the present study, the effects of the Quercetin and its esterified derivatives on viability, nanomechanical properties of cells, and BAX/BCL-2 gene expression were investigated. Using the MTT and flow cytometry assays, the cytotoxic potential, apoptosis, and necrosis were investigated. The AFM assay was performed to find the nanomechanical properties of cells as the elastic modulus value and cellular adhesion forces. The BAX/BCL2 gene expression was investigated through the Real-Time PCR. The results showed that the esterification of Quercetin with linoleic acid (Q-LA) and α-linolenic acid (Q-ALA) increased the cytotoxic potential of Q. The elastic modulus value and cellular adhesion forces were increased using the esterified derivatives and the highest ratio of BAX/BCL2 gene expression was observed in Q-LA. Esterified Quercetin derivatives have a higher cytotoxic effect than the un-esterified form in a dose-dependent manner. Esterified derivatives caused the nanomechanical changes and pores formation on the cytoplasmic membrane. One of the internal apoptosis pathway regulation mechanisms of these compounds is increasing the BAX/BCL2 gene expression ratio.