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The genus Aeromonas is a widespread pathogen that includes more than 30 Gram-negative species, many of which are opportunistic bacteria. Aeromonas species are naturally distributed in various aquatic sources. Infectious processes in marine animals such as fish usually develop under stressful conditions, and when their immune systems are weakened. MicroRNAs (miRNAs/miRs) are short, non-coding RNAs that post-transcriptionally regulate gene expression. Their diverse biological functions, such as influencing cell development, proliferation, differentiation, tumorigenesis, metabolism, and apoptosis have been studied in various animals. Fish is the most important source of aquatic nutrients throughout the world, and its market is constantly growing. Overpopulation in aquaculture brings infectious diseases that threaten the development of aquaculture around the world. There is extensive evidence that microRNAs are involved in modulating infectious processes and regulating the inflammatory response to major bacterial fish infections, including Aeromonas. Here, we review the current literature on the fish microRNA repertoire and outline the physiological roles assigned to microRNAs to provide a foundation for future research during Aeromonas infection. Understanding the interaction between microRNAs and Aeromonas may provide clues to a remarkable strategy for preventing Aeromonas infections in fish. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the significant expression of Peptidyl prolyl cis-trans isomerase (PIN1) as a key regulator of COVID-19 cycle. A quantitative real-time polymerase chain reaction (qRT-PCR) measured the expression levels of PIN1 in the serum of mild and severe patients and evaluated its association with clinical parameters. ROC curve analysis was performed to evaluate the expression of PIN1 for the diagnosis of COVID-19 between mild and severe patients. Expression of the PIN1 gene in severe patients (0.89±0.43) was higher than in mild patients (-2.28±0.34), and this difference was statistically significant between the two groups regardless of other factors (P‑value<0.0001). ROC curve analysis showed that high PIN1 levels in the discrimination of severe from mild patients could be useful. PIN1 expression levels were significantly associated with shortness of breath and cough. PIN1 can be considered an effective factor in the intensification of the symptoms of COVID-19., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Saeideh Gholamzadeh Khoei reports financial support was provided by Qazvin University of Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Propolis is a natural product used in cancer treatment, which is produced by bees via different sources. The chemical composition of Propolis is determined based on the climatic and geographical conditions, as well as harvesting time and method. This compound has been the subject of numerous investigational endeavors due to its expansive therapeutic capacity which includes antibacterial, anti-fungal, anti-inflammatory, anti-oxidant, anti-viral, and anti-cancer effects. The growing incidence rate of different cancers necessitates the need for developing novel preventive and therapeutic strategies. Chemotherapy, radiotherapy, and stem cell therapy have proved effective in cancer treatment, regardless of the adverse events associated with these modalities. Clinical application of natural compounds such as Propolis may confer promise as an adjuvant therapeutic intervention, particularly in certain subpopulations of patients that develop adverse events associated with anticancer regimens. The diverse biologically active compounds of propolis are believed to confer anti-cancer potential by modulation of critical signaling cascades such as caffeic acid phenethyl ester, Galangin, Artepillin C, Chrysin, Quercetin, Caffeic acid, Nymphaeols A and C, Frondoside A, Genistein, p-coumaric acid, and Propolin C. This review article aims to deliver a mechanistic account of anti-cancer effects of propolis and its components. Propolis can prevent angiogenesis by downregulating pathways involving Jun-N terminal kinase, ERK1/2, Akt and NF-ƘB, while counteracting metastatic progression of cancer by inhibiting Wtn2 and FAK, and MAPK and PI3K/AKT signaling pathways. Moreover, propolis or its main components show regulatory effects on cyclin D, CDK2/4/6, and their inhibitors. Additionally, propolis-induced up-regulation of p21 and p27 may result in cell cycle arrest at G2/M or G0/G1. The broad anti-apoptotic effects of propolis are mediated through upregulation of TRAIL, Bax, p53, and downregulation of the ERK1/2 signaling pathway. Considering the growing body of evidence regarding different anti-cancers effects of propolis and its active components, this natural compound could be considered an effective adjuvant therapy aimed at reducing related side effects associated with chemotherapy and radiotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Hematological abnormalities in COVID-19 infection included quantitative and qualitative changes and should be further characterized. Evaluation for myelodysplastic syndromes (MDS) is usually prompted by abnormal hematologic findings and the presence of dysplastic morphologies. Viral infections are considered to be the cause of dysplastic morphologies and should be considered by morphologists. There are few reports of dysplastic abnormal morphologies in patients with COVID-19 infection. However, such correlations still have to be clarified. Materials and Methods: In the present study, we examined the granulocyte lineage morphological abnormalities in symptomatic RT-PCR-confirmed COVID patients. Peripheral blood samples were collected from 82 patients with symptomatic COVID-19. Blood smears were prepared according to the standard Wright-Giemsa staining procedure. The morphological examination was carried out by two laboratory experts. Results: Blood smear examination revealed common myelodysplastic syndrome (MDS) type abnormalities including but not limited to pseudo-pelger nuclear lobulation (4.8%), hypogranulation (7.3%), Howell-Jolly-like bodies or detached nuclear segments (6.0%) and elongated and thin nuclear filaments (6.0%). One case of abnormal immature granulocyte and ring form nucleus is also evident. Conclusion: Our results accounted for the possibility of active COVID-19 infection in all subjects with granulocyte dysplasia. These results are of practical importance for patients suspected of having myelodysplastic syndromes or disease processes associated with myeloid malignancies., (Copyright © 2024 Tehran University of Medical Sciences.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

Introduction: Crimean-Congo hemorrhagic fever (CCHF) is the widest emerging severe viral tick-borne disease affecting humans. Crimean-Congo haemorrhagic fever virus (CCHFV) circulates by routine enzootic tick-vertebrate hosts-tick transmission cycles. We aimed to evaluate the molecular prevalence of CCHFV in ticks on a global scale., Methods: A systematic procedure was used to perform this review and meta-analysis using PubMed, Google Scholar, and Web of Science databases from 1 January 2000 through 12 April 2023. Of the 2310 papers identified, 43 articles met the inclusion criteria for this study., Results: The overall prevalence of CCHFV was 4.0% (95%CI: 2.7-6.0%) in ticks on the global scale, with heterogeneity (I 2 =96.387; p=0.0001). The genus Hyalomma was shown as the most frequent tick infected with CCHFV 5.4% (95%CI: 3.3-8.7%). We found that the pooled prevalence of CCHFV was higher in Hyalomma aegyptium 27.6% (95%CI: 22.7-33.2%). The pooled prevalence was higher in Asia 5.1% (95%CI: 3.3-7.7%), and Spain 21.0% (95%CI: 3.4-66.9). The locations with annual rainfall of 401-1000 mm 6.1% (95%CI: 2.6-13.5%) and latitude of 31-40° 6.0% (95%CI: 4.1-8.9%) were associated with the greatest pooled prevalence of CCHFV in ticks., Conclusions: Surveillance of CCHFV in ticks will give a better comprehension for the future implementation of public health interventions. The question of whether Hyalomma aegyptium is a plausible or certain vector should be the subject of further investigation., Competing Interests: Conflicts of interest: All authors – none to declare., (GERMS.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 John Wiley & Sons Ltd.)

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., Competing Interests: All the authors have declared no conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: There are no conflicts of interest/competing interests in this manuscript., (Copyright © 2023 Tehran University of Medical Sciences.)

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.

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.

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., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Medical Signals & Sensors.)

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., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Objective: Epigenetic alterations, including any change in DNA methylation pattern, could be the missing link of understanding radiation-induced genomic instability. Dapper, Dishevelled-associated antagonist of β-catenin homolog 2 ( DACT2 ) is a tumor suppressor gene regulating Wnt/β-catenin. In hepatocellular carcinoma (HCC), DACT2 is hypermethylated, while methylation status of its promoter regulates the corresponding expression. Radionuclides have been used to reduce proliferation and induce apoptosis in cancerous cells. Epigenetic impact of radionuclides as therapeutic agents for treatment of HCC is still unknown. The aim of this study was to evaluate epigenetic impact of 188Rhenium perrhenate ( 188 ReO 4 ) on HCC cells., Materials and Methods: In this in vitro experimental study, HepG2 and Huh7 cells were treated with 188ReO4, receiving 55 and 73 Mega Becquerel (MBq) exposures, respectively. For cell viability measurement, live/dead staining was carried out 18, 24, and 48 hours post-exposure. mRNA expression level of β-Catenin, Wnt1, DNMT1, DACT2 and WIF- 1 genes were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Then, possible regulatory impact of DACT2 upregulation was investigated through evaluating methylation-specific PCR (MS-PCR)., Results: Results showed that viability of both cells was reduced after treatment with 188 ReO 4 at three time points postexposure compared to the control groups. The qRT-PCR results showed that DACT2 mRNA level was significantly increased at 24, and 48 hours post-exposure in HepG2 cells compared to the control group, while, no significant change was observed in Huh7 cells. Methylation pattern of DACT2 promoter remained unchanged in HepG2 and Huh7 cells., Conclusion: Treatment with 188 ReO 4 reduced viability of HepG2 and Huh7 cells. Although DACT2 expression was increased after 188 ReO 4 exposure in HepG2 cells, methylation pattern of its promoter remained unchanged. This study assessed impacts of the 188 ReO 4 β-irradiation on expression and induction of DACT2 epigenetic aberrations as well as the correlation of this agent with viability of cells., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

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 IC 50 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., Competing Interests: The authors of this study have no conflicts of interests.