Comparison of serum levels of IL-10 and IL-11 and mRNA expression of IL-10, IL-11, COX-2, BCL6, and ZEB Family in peripheral blood mononuclear cells (PBMC) of women with polycystic ovary syndrome and healthy individuals.

BACKGROUND: The roles of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 genes in the potential correlation between polycystic ovary syndrome (PCOS), inflammation, and cancer remain controversial. AIMS: This study aimed to compare serum levels of IL-10 and IL-11 and gene expression of IL-10, IL-11, COX-2, BCL6, ZEB1, and ZEB2 in PBMCs of women with PCOS and healthy controls. METHODS: A case-control study included 40 women with PCOS as the case group and 40 healthy women as controls. Group matching for age and BMI was performed. Serum levels of IL-10 and IL-11 were assessed using ELISA, while gene expression was measured using real-time PCR. Parameters were compared between groups, and correlations among gene expression and serum levels were explored. RESULTS: In comparison to healthy women, women with PCOS exhibited a significant decrease in the expression of COX-2 and IL-10 genes (p<0.001), alongside a significant increase in ZEB2 gene expression (p<0.001). There were no significant differences observed in the expression of IL-11, BCL6, and ZEB1 genes. Furthermore, the serum level of IL-10 was significantly lower in women with PCOS compared to the control group (p<0.001), while no significant difference was found in IL-11 levels. Additionally, no significant correlations were identified between gene expression and serum levels. CONCLUSION: In women with PCOS, reduced IL-10 gene expression may indicate inflammation and serve as a diagnostic biomarker. However, conflicting findings on COX-2 expression complicate understanding. Elevated ZEB2 expression in PCOS women may lead to infertility, epithelial-mesenchymal transition, and aggressive phenotypes.

Iron chelators: as therapeutic agents in diseases.

The concentration of iron is tightly regulated, making it an essential element. Various cellular processes in the body rely on iron, such as oxygen sensing, oxygen transport, electron transfer, and DNA synthesis. Iron excess can be toxic because it participates in redox reactions that catalyze the production of reactive oxygen species and elevate oxidative stress. Iron chelators are chemically diverse; they can coordinate six ligands in an octagonal sequence. Because of the ability of chelators to trap essential metals, including iron, they may be involved in diseases caused by oxidative stress, such as infectious diseases, cardiovascular diseases, neurodegenerative diseases, and cancer. Iron-chelating agents, by tightly binding to iron, prohibit it from functioning as a catalyst in redox reactions and transfer iron and excrete it from the body. Thus, the use of iron chelators as therapeutic agents has received increasing attention. This review investigates the function of various iron chelators in treating iron overload in different clinical conditions.

Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis.

Frequent exposure to various external and internal adverse forces (stresses) disrupts cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.

Evaluation of epigenetic-related gene expression (DNMT, HDAC1) in Iranian patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. AIMS: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and histone deacetylase 1 (HDAC1) in Iranian patients with SLE. METHODS: This matched case-control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjani rheumatology clinic, in southeast Iran. The expression of DNMT and HDAC1 genes was measured through a real-time PCR assay of blood samples. RESULTS: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94). CONCLUSION: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes related to SLE disease is essential and may help to make an accurate diagnosis of the disease.

Evaluation of epigenetic-related gene expression (DNMT, HDAC1) in Iranian patients with systemic lupus erythematosus / Evaluación de la expresión de los genes relacionados con la epigenética (DNMT, HDAC1) en pacientes iraníes con lupus eritematoso sistémico

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. Aims: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and histone deacetylase 1 (HDAC1) in Iranian patients with SLE. Methods: This matched case–control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjani rheumatology clinic, in southeast Iran. The expression of DNMT and HDAC1 genes was measured through a real-time PCR assay of blood samples. Results: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94). Conclusion: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes related to SLE disease is essential and may help to make an accurate diagnosis of the disease.(AU)

Antecedentes: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, en la cual el sistema inmunitario reacciona de manera anormal frente a las células y tejidos causantes de la inflamación. Las alteraciones epigenéticas, incluyendo la metilación del ADN y la modificación de la histona, tienen efectos críticos en la enfermedad autoinmune y la patogenia del LES, a través de la desregulación de los genes críticos. Objetivo: El objetivo de este estudio fue evaluar la expresión del gen relacionado con la epigenética de ADN metiltransferasa (DNMT) e histona deacetilasa 1 (HDAC1) en los pacientes iraníes afectados de LES. Métodos: Este estudio pareado caso-control incluyó 16 personas con LES y 16 personas sanas, derivadas a la clínica de reumatología de Rafsanjan, en el sudeste de Irán. La expresión de los genes DNMT y HDAC1 se midió mediante una PCR a tiempo real de muestras de sangre.Resultados: La expresión del gen DNMT no difirió significativamente entre los grupos de pacientes de LES y de controles sanos (p=0,21). Por contra, la expresión del gen HDAC1 se incrementó en el grupo LES, aunque dicho incremento no alcanzó significación estadística (p=0,94). Conclusión: Los resultados de este estudio sugieren que la sobreexpresión de HDAC1 podría servir para diagnosticar el LES. Son necesarios estudios adicionales con muestras de mayor tamaño para confirmar nuestros hallazgos. Es esencial la evaluación de otros genes relacionados con el LES, pudiendo ayudar a realizar un diagnóstico preciso de la enfermedad.(AU)

The Effect of Changes in the Angular Position of Implants on Metal Artifact Reduction in Cone-Beam Computed Tomography Images: A Scoping Review.

Objective: Dental implant artifacts can compromise the quality of cone-beam computed tomography (CBCT) scans and challenge radiographic detection in surrounding regions. This literature review was conducted to examine the impact of implant angle modification on reducing metal artifacts in CBCT scans. Materials and Methods: A scoping review of literature was carried out in PubMed, Embase, Scopus, and Cochrane databases. Results: Different spatial planes, including alpha, beta, gamma, and phi, along with 0°, 5.2°, 9.8°, 14.5°, 15°, 30°, 45°, 60°, 75°, and 90° angles were studied. Changes in the angular position of implants may reduce metal artifacts and improve the quality of CBCT scans. Conclusions: Rotating implants within the alpha plane and angling them at 90° in the alpha plane enables reducing dental implant artifacts.

The Glucose-Regulated Protein78 (GRP78) in the Unfolded Protein Response (UPR) Pathway: A Potential Therapeutic Target for Breast Cancer.

Amongst all types of cancers, breast cancer is recognized as the most common cancer and a principal cause of morbidity and mortality in women. Endoplasmic reticulum (ER) stress pathways are primarily activated in cancer cells and activate a signaling network called the unfolded protein response (UPR). Many tumors, by activating the UPR pathway, allow them to adapt and grow under stressful conditions. UPR is usually inactive in non-tumor cells, while it is active in tumor cells, so it is appropriate to develop new breast cancer therapies. A protein that regulates UPR is 78 KDa Glucose-Regulated Protein (GRP78). Usually, the GRP78 level in the cell is relatively low but increases significantly under stresses that affect the ER and calcium homeostasis, and increases resistance to chemotherapy. GRP78 drug suppressors could provide promising anticancer therapeutics. Therefore, understanding the molecular mechanism of GRP78 in cancer and identifying drugs that target GRP78 is essential for the treatment of breast cancer. In this review, we investigate the role of GRP78 in the pathogenesis of breast cancer.

Diosgenin and 4-Hydroxyisoleucine from Fenugreek Are Regulators of Genes Involved in Lipid Metabolism in The Human Colorectal Cancer Cell Line SW480.

OBJECTIVE: Diosignin and 4-hydroxy-L-isulosine (4-OH-Ile) are the two active ingredients of Fenugreek (Trigonella foenumgraecum). Thus, in this study, we examined the effects of hydroalcoholic extract of fenugreek seeds (HEFS), diosgenin and 4-OH-Ile on the expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ) and low-density lipoprotein (LDL) receptor (LDLR) which are involved in lipid metabolism in SW480 cell line. MATERIALS AND METHODS: In this experimental study, SW480 cells were cultured in RPMI-1640 medium and treated with HEFS, diosignin, 4-OH-Ile or orlistat for 24 and 48 hours. Inhibitory concentration of 20% (IC20) was calculated using MTT method and cells were then pre-treated with the IC20 concentrations for 24 and 48 hours before RNA extraction and cDNA synthesis. Changes in the expression of ACC, FAS, PPARγ and LDLR genes were assayed by employing the real time-polymerase chain reaction (PCR) method. RESULTS: Our results showed a significant down-regulation in the expression of ACC (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and FAS genes (P<0.001 and P<0.001 after 24 and 48 hours, respectively) in SW480 cells treated with HEFS, diosignin, 4-OH-Ile, or orlistat, but significant up-regulation in the expression of PPARγ (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and LDLR (P=0.005 and P=0.001 after 24 and 48 hours, respectively). CONCLUSION: According to the results of the present study, HEFS, diosgenin and 4-OH-Ile up or down-regulate the expression of some predominant genes involved in lipid metabolism pathway, similar to that observed for orlistat. These types of regulatory effects are presumably proper for the treatment of obesity and overweight.

The Effects of Hydro-Alcoholic Extract of Fenugreek Seeds on the Lipid Profile and Oxidative Stress in Fructose-Fed Rats.

BACKGROUND: Metabolic syndrome (MetS) is a complex clinical disorder that can lead to an increase in oxidative stress. Patients with this syndrome are at risk of diabetes and cardiovascular disease. The Trigonella foenum-graecum L. (fenugreek) plant has many therapeutic effects, including anti-diabetic and antioxidant. The present study aimed to investigate the effects of the hydro-alcoholic extract of fenugreek seeds (HEFS) on dyslipidemia and oxidative stress due to high-fructose diet-induced MetS. METHODS: In this experimental study, to induce MetS, animals received water containing 20% fructose for 8 weeks. After induction of MetS, 48 male Wistar rats (200-250 g) were randomized into six groups. HEFS was administered to animals at doses of 100 and 200 mg/kg orally for 4 weeks. Animal blood samples were collected to measure biochemical and antioxidant parameters of fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC). RESULTS: The findings showed that the serum levels of FPG, TC, LDL-C, TG, and MDA were significantly reduced in HEFS-exposed groups compared with the control group (P<0.05). Also, significant increases in HDL-C, GPX, CAT, and TAC levels (P<0.05) were observed. CONCLUSION: Our results revealed that treatment with HEFS increases the levels of antioxidant enzymes, decreases FPG level, and at the same time, modifies the lipid profile in MetS. Therefore, HEFS may help to alleviate the risk of some chronic complications of this disease.

The effect of hydroalcoholic Berberis integerrima fruits extract on the lipid profile, antioxidant parameters and liver and kidney function tests in patients with nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the hepatic disorders which is characterized by increasing fat deposits in the liver. This disorder may lead to elevation the activity of liver enzymes and is associated with obesity, dyslipidemia, hypertension, and type II diabetes. The aim of present study was to investigate the effect of Berberis integerrima extract on NAFLD patients compare to placebo. METHODS: The present clinical trial was performed on 42 NAFLD patients who were randomly divided into two groups. The case group received a capsule (750 mg) containing hydro-alcoholic extract of Berberis integerrima extract every 12 h for 2 months, while the control (placebo) group received a capsule containing cellulose. Baseline characteristics, biochemical factors, antioxidant parameter, functional liver and renal test were evaluated before and after the treatment. RESULTS: Comparison rate of different parameters in case group before and after treatment demonstrated that BMI, cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal parameters such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly decreased while HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly elevated. The comparison of the mean parameters difference in two groups indicated that cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal factors were significantly decreased, however HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly increased in case group compared to control group. CONCLUSION: The study findings revealed that the Berberis integerrima extract could reduce biochemical factors of blood, except HDL-C and increases total antioxidant capacity and glutathione peroxidase enzyme. Therefore, hydro-alcoholic extract of Berberis integerrima may be used as a great supplementary medicine in treating NAFLD.

Trigonella foenum-graecum seed extract modulates expression of lipid metabolism-related genes in HepG2 cells

Objective: To investigate anti-dyslipidemic effects of hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile on HepG2 cell line. Methods: HepG2 cells were treated with hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat. IC20 was calculated using the MTT method. The cells were then pre-treated with IC20 concentrations for 24 and 48 h. Real time PCR was employed to measure expression of liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1C (SREBP-1C), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fibroblast growth factor 21 (FGF21), peroxisome proliferator-activated receptor gamma (PPARγ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXRα (P=0.003, P<0.001), SREBP-1C (P<0.001, P<0.001), ACC (P=0.002, P=0.006), and FAS (P<0.001, P<0.001) were downregulated significantly, while FGF21 (P<0.001, P<0.001), PPARγ (P=0.004, P<0.001), and LDLR (P<0.001, P<0.001) were upregulated significantly in HepG2 cells treated with the IC20 of hydroalcoholic fenugreek seed extracts, diosgenin, 4-OH-Ile, and orlistat in 24 and 48 h, respectively. Conclusions: Hydroalcoholic fenugreek seed extracts, diosgenin, and 4-OH-Ile significantly modulate the expression of some important lipid metabolism related genes, which is similar to orlistat. Trigonella foenum-graecum seed extract or its derivatives should be further investigated for their dyslipidemia effects and its complications.

Friendship Network and Dental Brushing Behavior among Middle School Students: An Agent Based Modeling Approach.

By using a standard questionnaire, the level of dental brushing frequency was assessed among 201 adolescent female middle school students in Tehran. The initial assessment was repeated after 5 months, in order to observe the dynamics in dental health behavior level. Logistic Regression model was used to evaluate the correlation among individuals' dental health behavior in their social network. A significant correlation on dental brushing habits was detected among groups of friends. This correlation was further spread over the network within the 5 months period. Moreover, it was identified that the average brushing level was improved within the 5 months period. Given that there was a significant correlation between social network's nodes' in-degree value, and brushing level, it was suggested that the observed improvement was partially due to more popularity of individuals with better tooth brushing habit. Agent Based Modeling (ABM) was used to demonstrate the dynamics of dental brushing frequency within a sample of friendship network. Two models with static and dynamic assumptions for the network structure were proposed. The model with dynamic network structure successfully described the dynamics of dental health behavior. Based on this model, on average, every 43 weeks a student changes her brushing habit due to learning from her friends. Finally, three training scenarios were tested by these models in order to evaluate their effectiveness. When training more popular students, considerable improvement in total students' brushing frequency was demonstrated by simulation results.