The role of miR-133a in silibinin-mediated inhibition of the PI3K/AKT/mTOR pathway in MCF-7 breast carcinoma cells.

Breast cancer is particularly severe in women. Research highlights the crucial role of miRNAs in key cellular processes, showcasing their intricate interactions with the oncogenic PI3K/AKT/mTOR (PAM) signaling pathway and underscoring their significant role as tumor suppressors. The effect of silibinin on cell growth and survival was evaluated using an MTT assay. Bioinformatics analysis identified putative miR-133a targets inside the PAM pathway. After incubating MCF-7 cells with silibinin, we measured miR-133a, EGFR, PI3K, AKT, PTEN, and mTOR expression levels using qRT-PCR. Furthermore, protein expression levels of mTOR were assessed using Western blotting. The MTT experiment displayed that silibinin effectively inhibits MCF-7 cell proliferation in a time- and dose-dependent manner. Silibinin's IC50 value, determined at 370 µM after 48 hours, was established. qRT-PCR analysis at this IC50 concentration highlighted reduced expression of EGFR, PI3K, AKT, PTEN, and mTOR mRNAs, alongside increased miR-133a expression. Notably, miR-133a exhibited a negative correlation with both EGFR and PIK3C2A expression. Furthermore, western blotting confirmed silibinin's capacity to diminish p-mTOR protein levels, the ultimate element of the PAM signaling pathway. The findings enhance comprehension of silibinin's impact on PAM signaling and miR-133a expression, offering promise for targeted therapies in disrupting oncogenic pathways in MCF-7 breast cancer cells. This insight could advance breast cancer treatment strategies.

Anticancer Action of Silver Nanoparticles in SKBR3 Breast Cancer Cells through Promotion of Oxidative Stress and Apoptosis.

Silver nanoparticles (AgNPs) are known as one of the highly utilized NPs owing to their unique characteristics in the field of cancer research. The goal of this research was to explore the oxidative stress, apoptosis, and angiogenesis in SKBR3 breast cancer cells after exposure to AgNPs. The survival rate of SKBR3 cancer cells and MCF-10A normal breast cells was assessed under the effects of different concentrations (0, 32, 64, 128, and 250 µg/ml) by MTT method. The oxidative condition was assessed by measuring reactive oxygen species (ROS) production, total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), and antioxidant enzyme activity (CAT, GPx, and CAT) using colorimetric-based kits. Flow cytometry and Hoechst 33258 staining were performed to investigate the induction of apoptosis. Furthermore, the expression of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3 and 7 activity was measured. The cell migration and vascular endothelial growth factor-A (VEGF-A) gene expression, protein kinase B (AKT), phosphatidylinositol 3-kinase (PI3K) were also studied. The MTT results indicated that AgNPs inhibit the SKBR3 cells' viability in a concentration-dependent way. Besides, AgNPs markedly induced oxidative stress via increasing TOS content, MDA production, reduction of TAC, and regulation of antioxidant enzyme level. Additionally, AgNPs promoted apoptosis as revealed by an enhancement in Bax/Bcl-2 expression ratio. Findings also indicated that AgNPs suppress the expression of genes (VEGF-A, AKT, and PI3K) involved in angiogenesis. Altogether, our data revealed that AgNPs initiate oxidative stress and apoptosis in SKBR3 breast cancer cells, dose dependently.

Association between Metabolic Syndrome Risk Factors and Immunohistochemical Profile in Women with Breast Cancer.

Background: The association between metabolic syndrome (MetS) and breast cancer may significantly impact the mortality and incidence of breast cancer. This study aimed to assess the association between MetS risk factors and immunohistochemical (IHC) profiles in women with breast cancer. Methods: This cross-sectional study used the medical records of 300 breast cancer patients with an average age of 53.11±12.97 years in the Chemotherapy and Radiation Therapy Clinic of Dr. Anbiai, Tehran, Iran (2020-2021). The cases were divided into five subgroups including luminal A, luminal B (HER-2-), luminal B (HER-2+), HER-2 overexpressing, and triple negative. Results: There was no difference in the prognostic indicators between the presence and absence of MetS in women with breast cancer. A higher proportion of luminal A tumors (39.3%), luminal B (HER-2+) (25%), triple-negative (17%), luminal B (HER-2-) (10.7%), HER-2 overexpression (8%) was observed in women with MetS than those without MetS. Multivariate logistic regression analysis showed that patients with MetS had a 41% higher chance of developing luminal A than those without MetS, and patients with a BMI≥30 Kg/m2 had an 80% higher chance of developing luminal B (HER-2+) than those with a BMI<30 Kg/m2. Moreover, women with a waist circumference higher than 88 cm had a 14 % lower chance of developing Luminal B (HER-2+) than those with a waist circumference less than 88 cm. Conclusion: There was no difference in prognostic indicators and IHC profile in patients with and without MetS.

Correlation of Wilms' Tumor 1 (WT1) with Oxidative Stress Markers and Expression of miR-361-5p; New Aspect of WT1 in Breast Cancer.

Breast carcinoma is a heterogeneous disease that affects millions of women worldwide. Wilms' tumor 1 (WT1) is an oncogene that promotes proliferation, metastasis and reduces apoptosis. MicroRNAs (miR) are short noncoding RNAs with a major role in cancer metastasis. In present study, we investigated the association of serum level of WT1 with oxidative stress and expression of miR-361-5p in breast cancer. Serum samples of 45 patients and of 45 healthy women analyzed for protein level of WT1, malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant capacity (TAC). Serum and tissue expression of miR-361-5p in 45 tumor tissues and 45 paired non-tumor adjacent tissues and 45 serum samples of patients and healthy women analyzed by qRT-PCR. Protein levels of WT1 not significantly difference in serum of patients compared to healthy controls. Serum levels of MDA and TOS in patients were higher, but TAC level was lower than healthy controls (p < 0.001). There was a positive correlation between WT1 with MDA and TOS, and a negative correlation between WT1 with TAC in patients. miR-361-5p expression in tumor tissues and serum of patients was lower than non-tumor adjacent tissues and serum of healthy controls, respectively (p < 0.001). Moreover, there was a negative correlation between miR-361-5p and WT1 in patients. The positive correlation between WT1 with MDA and TOS and negative correlation between TAC and miR-361-5p suggests that this gene can play an important role in worse prognoses in breast cancer. Additionally, miR-361-5p may serve as an invasive biomarker for early detection of breast cancer.

Vitamins A, C, and E Exert Anti-apoptotic Function in the Testis of Rats After Exposure to Zinc Oxide Nanoparticles.

Some reports emphasize that zinc oxide nanoparticles (ZnO NPs) are detrimental to the reproductive organs of animals. As such, this research aimed at exploring the apoptotic potential of ZnO NPs on testis along with the beneficial role of Vitamins (V) A, C, and E against ZnO NP-induced damage. To this aim, a population of 54 healthy, male Wistar rats were used in this work and then assigned into nine groups of 6 rats as G1: Control 1 (Water); G2: Control 2 (Olive oil); G3: VA (1000 IU/kg), G4: VC (200 mg/kg), G5: VE (100 IU/kg), G6: ZnO NPs exposed animals (200 mg/kg); and G7, 8 and 9: ZnO NPs-exposed animals that were pre-treated with either VA, C, or E. Apoptosis rates were estimated by measuring the level of apoptotic regulatory markers including Bcl-2-associated X (Bax) and B-cell lymphoma protein 2 (Bcl-2) using western blotting and qRT-PCR assays. The data indicated that ZnO NPs exposure elevates the level of Bax protein and gene expression, whereas the protein and gene expression of Bcl-2 was reduced. Further, the activation of caspase-3,7 occurred after exposure to ZnO NPs, while the above alterations were significantly alleviated in the rats that were co-treated with VA, C, or E and ZnO NPs relative to the rats in the ZnO NPs group. In summary, VA, C, and E exerted anti-apoptotic functions in the testis of rats following administration of ZnO NPs.

Investigation of miR-133a, miR-637 and miR-944 genes expression and their relationship with PI3K/AKT signaling in women with breast cancer.

PURPOSE: MicroRNAs (miRNAs) are regulatory molecules capable of positively or negatively regulating signaling pathways, and are involved in tumorigenesis as well as various aspects of cancer. The purpose of this study was to investigate the expression levels of miR-133a, miR-637, and miR-944 in serum and tumor tissues as well as their relationship with the expression level of phosphatidylinositol-3-kinase (PI3K) and protein kinase-B (AKT) genes and proteins along with their clinical significance in breast cancer. METHODS: The expressions of miR-133a, miR-637, miR-944, PI3K, and AKT genes were examined in the tumor and tumor margin tissues of 40 patients with breast cancer, as well as the serum levels of miR-133a, miR-637, and miR-944 in these patients and 40 healthy groups by quantitative real-time PCR (qRT-PCR). PI3K and AKT proteins expression in tumor and tumor margin tissues were detected using immunohistochemistry (IHC). RESULTS: The expression levels of miR-133a and miR-637 in the tumor tissue and serum of patients were lower than those in the tumor margin tissue and serum of the healthy group, respectively. In addition, the expression level of miR-944 in the tumor tissue was lower than that in the tumor margin tissue, but its expression increased in the serum of cancer patients compared to that in the healthy group. The expression of miR-637 was correlated with tumor location and Her2 receptors, and the expression of miR-944 was correlated with tumor location and family history. PI3K and AKT mRNA and protein levels were higher in the tumor tissues than in the tumor margin tissues (p < 0.05). CONCLUSION: The results of our study revealed that miR-637 has a better diagnostic value in breast cancer than miR-133a and miR-944.

Fish oil and chicoric acid combination protects better against palmitate-induced lipid accumulation via regulating AMPK-mediated SREBP-1/FAS and PPARα/UCP2 pathways.

Non-alcoholic fatty liver disease (NAFLD) is associated with lipid accumulation and lipotoxicity. The main aim of this study is to evaluate the synergistic treatment effect of fish oils (FOs) and chicoric acid (CA) in palmitate (PA)-induced NAFLD HepG2 model. HepG2 cells were pre-treated with palmitate (0.75 mM) for 24 h, and then were exposed to CA, FOs and combination of these chemicals for another 24 h. Gene expression and protein levels were determined using qRT-PCR and western blotting or ELISA analysing, respectively. The combination index (CI) values of FOs and CA in HepG2 cells were calculated according to the Chou-Talalay equation using the CompuSyn software. FOs and CA acid together synergistically reduced lipid accumulation as indicated by decreased oil red O staining (vehicle-treated control: 1 ± 0.1; PA-treated control: 4.7 ± 0.4; PA + CA100: 3.9 ± 0.4; PA + CA200: 2.4 ± 0.3; PA + FOs: 2.7 ± 0.1; PA + CA200 + FOs: 1.5 ± 0.1) and triglyceride (vehicle-treatedcontrol:10 ± 1.2; PA-treated control: 25.8 ± 2.7; PA + CA100: 18.9 ± 2.5; PA + CA200: 14.4 ± 1.8; PA + FOs: 15.2 ± 2.4; PA + CA200 + FOs: 11.9 ± 1.5) levels in PA-treated HepG2 cells. Gene expression and Immunoblotting analysis confirmed the combination effect of FOs and CA in up-regulation of AMPK-mediated PPARα/UCP2 and down-regulation of AMPK-mediated SREBP-1/FAS signalling pathways. Collectively, these results suggest that combining FOs with CA can serve as a potential combination therapy for NAFLD.

The Alleviative Efficacy of Vitamins A, C, and E Against Zinc Oxide Nanoparticles-Induced Hepatic Damage by Reducing Apoptosis in Rats.

Nanoparticles are vastly exploited in today's technology. However, it is realized that exposure to high concentrations of nanoparticles (NPs) may have adverse effects on human health. According to previous reports, zinc oxide (ZnO) NPs cause toxic effects in tissues via inducing apoptosis. The current work was designed to evaluate possible protective activities of vitamins (Vits) A, C, and E against ZnO NPs-induced apoptosis in the liver of rats. To this aim, fifty-four adult male Wistar rats were randomly distributed into nine groups (n = 6 rats for each group), namely, Control1 (water), Control2 (olive oil), Vit A (1000 IU/kg), Vit C (200 mg/kg), Vit E (100 IU/kg), ZnO (200 mg/kg), ZnO + VitA, ZnO + VitC, and ZnO + VitE. To investigate apoptosis, the mRNA and protein expression of Bcl-2-associated X (Bax) and B-cell lymphoma protein 2 (Bcl-2) were examined by qRT-PCR and western blot techniques. The mRNA and protein expression of TNF-α as well as the activity of caspase 3,7 were also measured. The results revealed that ZnO NPs considerably enhance the ratio of Bax to Bcl-2 mRNA and protein expression as well as the activity of caspase 3,7 compared to the control group. Furthermore, the findings implied that the elevated level of TNF-α may link with ZnO NPs-mediated apoptosis in the liver of rats. More importantly, Vits A, C, and E exhibited ameliorative properties against apoptosis-inducing effects of ZnO NPs. Thus, administration of Vits A, C, and E may be effective in preventing liver damage and apoptosis caused by ZnO NPs.

Copper Nanoparticles Induce Apoptosis and Oxidative Stress in SW480 Human Colon Cancer Cell Line.

Cu nanoparticles (CuNPs) have various applications in biomedicine, owing to their unique properties. As the effect of CuNPs on the induction of oxidative stress and apoptosis in the human colorectal cancer cell line SW480 has not yet been studied, we investigated the toxicity and mechanism of action of these NPs in SW480 cells. MTT assay was performed to assess the effect of the particles on the viability of SW480 cells. The levels of oxidative stress were assessed after 24 h of treatment with CuNPs by evaluating the Reactive Oxygen Specious (ROS) production. The antioxidant enzyme activity was assessed using a colorimetric method. To investigate the effect of NPs on cellular apoptosis, Hoechst33258 staining was performed, and the expression of Bax, Bcl-2, and p53 was evaluated by qRT-PCR. The MTT assay results showed that CuNPs inhibited the viability of SW480 cells. Moreover, the increase in ROS production at all three concentrations (31, 68, and 100 µg/ml) was significant. It has been observed that CuNPs lead to increased expression of Bax and p53, and decreased expression of Bcl-2. Hoechst staining was performed to confirm apoptosis. In conclusion, the induction of apoptosis demonstrated the anticancer potential of the CuNPs.

Assessment of Tissue Oxidative Stress, Antioxidant Parameters, and Zinc and Copper Levels in Patients with Breast Cancer.

Breast cancer is a multifactorial disease, and among the many factors which are involved in the onset, progression, and invasion of the disease, oxidative stress plays a significant role. The concentration and activity of enzymatic antioxidants are proportional to the concentration of trace elements, and the concentration of trace elements is often deficient in malignancies. Therefore, in the present study, we studied the tissue levels of oxidative stress, antioxidant status, zinc (Zn), and copper (Cu) in breast cancer patients. Tissue samples were collected from 40 patients with breast cancer and 40 tumor margin tissue as a control group. All subjects gave their informed consent. The tissue samples were measured for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), total antioxidants capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA), Zn, and Cu. Data of all biochemical parameters of two groups were statistically analyzed by SPSS software, t test, and GraphPad Prism. Concentrations of MDA, TOS, and OSI in tumor tissue were significantly higher than tumor margin tissue, but the level of TAC and CAT, SOD, and GPX activities was significantly reduced in tumor tissue (p<0.05). It was found that the concentrations of Zn and Cu in breast cancer patients were higher than tumor margin tissue. Patients with breast cancer have a rise in oxidative stress indicators and a decrease in antioxidant stress markers. Since oxidative stress is a significant contributor to the development and progression of breast cancer, more research might lead to a more effective method of breast cancer treatment. Considering the dual role of oxidative stress in cancer, which can both cause survival and adaptation, and the death of cancer cells, and with more information, it can be used to manage the treatment and destruction of cancer cells.

Silver Nanoparticles Exert Apoptotic Activity in Bladder Cancer 5637 Cells Through Alteration of Bax/Bcl-2 Genes Expression.

Bladder cancer is defined as a urinary tract malignancy that threatens men's and women's health. Due to the side effects of common chemotherapies, novel therapeutic strategies are necessary to overcome the issues concerning bladder cancer treatments. Nanotechnology has been suggested as a means to develop the next-generation objectives of cancer diagnosis and treatment among various novel therapies. Owing to the special characteristics that they can offer, silver nanoparticles (AgNPs) were investigated in this study to evaluate their apoptotic impact on bladder cancer 5637 cells. In this study, an MTT assay was conducted and appropriate concentrations of AgNPs were selected. Moreover, reactive oxygen species (ROS) production and apoptosis levels were determined using fluorimetric and Annexin/PI flow cytometry assays, respectively. Moreover, the activity of caspase 3,7, mRNA expression of Bax (Bcl-2-associated X) and Bcl-2 (B-cell lymphoma 2) were assessed based on colorimetric and qRT-PCR methods, respectively. The results indicated that AgNPs can significantly reduce the viability of 5637 cells in a dose-dependent mode as well as having the ability to elevate ROS production. Flow cytometry data showed that AgNPs lead to a remarkable increase in the apoptosis rate as compared with the control. Consistent with this, the induction of apoptosis was revealed by the overexpression of Bax, accompanied by a reduction in Bcl-2 expression compared to the control. Furthermore, AgNPs remarkably stimulated caspase 3,7 activation. In summary, AgNPs can mediate apoptosis in 5637 cells via excessive ROS formation, up-regulating Bax/Bcl-2 expression, and caspase 3,7 activation.

Association between Oxidative Stress Parameters and Hematological Indices in Breast Cancer Patients.

Background: Breast cancer is one of the leading causes of death in women worldwide. This causes an increase in free radicals, resulting in oxidative stress. The aim of this study was to determine the effect of breast cancer on oxidative stress and its relationship with hematological indices. Methods: This case-control study included 43 women with breast cancer and 37 age-matched healthy controls. Oxidative stress and its correlation with hematological profiles over seven months were evaluated. Finally, the data were compared between the two groups using the t-test and Pearson's test, and the results were analyzed using the SPSS 24 software. Results: The results revealed that patients with breast cancer had significantly increased hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels compared with healthy subjects (p < 0.05). In addition, oxidative stress parameters, such as superoxide dismutase (SOD), catalase (CAT), total oxidant status (TOS), and total antioxidant capacity (TAC), were significantly elevated. Glutathione peroxidase (GPX) and malondialdehyde (MDA) were significantly lower in patients with breast cancer than in the control group (p < 0.05). Statistical significance in hematological indices showed a positive or negative correlation with oxidative stress parameters. Conclusion: Women with breast cancer showed a deranged complete blood count (CBC) pattern compared to healthy individuals.

Antitumor Activities of Aqueous Cinnamon Extract on 5637 Cell Line of Bladder Cancer through Glycolytic Pathway.

Background: Pharmacotherapy with medicinal plants is a promising approach to treat cancer. Cinnamon is a medicinal plant whose properties have been proven in various fields of medical sciences. Among its biological activities, its antioxidant and antiviral effects can be mentioned. In this study, the antitumor effects of Cinnamon with a focus on glucose metabolism in bladder cancer carcinoma cell-line 5637 were investigated. Methods: Aqueous extract of Cinnamon was prepared from Cinnamon bark. Bladder cancer 5637cell line were treated with different concentrations of aqueous extract of Cinnamon. MTT was used to evaluate cell viability at 24, 48, and 72 h. The concentration of 1.25, 2.50, and 5 mg/ml was used. Apoptosis was assessed with Hochest33258 staining. For evaluating of aqueous extract of Cinnamon effect on glycolysis, the gene expression of epidermal growth factor receptor 2 (ErbB2), heat shock protein transcription factor1 (HSF1), and lactate dehydrogenase A (LDHA), as well as protein levels of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production, were measured. Results: Aqueous extract of Cinnamon significantly decreased ErbB2, HSF1, and LDHA gene expression and also decreased the protein level of HSF1 and LDHA, LDH activity, glucose consumption, and lactate production dose-dependently (p < 0.05). Conclusion: Our finding showed that the aqueous extract of Cinnamon can inhibit proliferation in 5637 cells by inhibition of glycolysis and induction of apoptosis.

Effects of gold nanoparticles on oxidative stress status in bladder cancer 5637 cells.

INTRODUCTION: Nanomedicine has recently been known as an emerging research area with promising applications in cancer diagnosis and treatment. Aside from this, gold nanoparticles (AuNPs), as one of the important components of nanomedicine, have attracted considerable attention due to their special physicochemical properties and lower toxicity than other nanoparticles. Despite the impressive advantages of AuNPs, it has not been yet determined whether oxidative stress contributes to the toxicity of AuNPs on bladder cancer. AIM: The aim of this study was to address this issue by conducting experiments in order to investigate the effects of 20 nm AuNPs on human bladder cancer 5637 cells. MATERIALS AND METHODS: The viability of 5637 cells was evaluated upon 24 hour exposure to different concentrations of AuNPs (0- 50 µg/ml) by 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. In order to evaluate oxidative stress status, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and also activities of antioxidant enzymes including glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were all determined by colorimetric assay kits. RESULTS: The results from our experiment showed that the cytotoxicity caused by AuNPs was dose-dependent and the IC50 value was found to be 43.14 µg/ml after 24-hour exposure. Furthermore, MDA and TOS levels were significantly increased in treated cells compared to untreated cells (p.

Is human umbilical cord mesenchymal stem cell-derived conditioned medium effective against oxidative and inflammatory status in CCl4-induced acute liver injury?

INTRODUCTION: Acute liver injury (ALI) is diagnosed by detection of elevated liver enzymes within six months after liver damage. Mesenchymal stem cells (MSCs) have recently been considered a beneficial strategy for treating various diseases due to healing secretory factors. Therapeutic effects of human umbilical cord MSCs-derived conditioned medium (hMSC-CM) were evaluated on CCl4-induced ALI. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into groups including N (received saline), ALI (received CCl4), RPMI (received CCl4 and RPMI medium), and ALI-CM (received CCl4 and hMSC-CM) groups. The expression of TNF-α and TGFß-1 genes was evaluated with qPCR. Hepatic levels of TNF-α and TGF-ß were measured by ELISA. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), glutathione peroxidase (GPx) activity, and catalase (CAT) activity were also assayed. Hematoxylin-eosin (H&E), Masson's trichrome, reticulin, and Periodic Acid-Schiff (PAS) stainings were conducted to evaluate tissue lesions. RESULTS: CCl4 increased expression of TNF-α and TGF-1ß at both mRNA and protein levels, while hMSC-CM decreased these parameters in the ALI-CM group. TAC levels significantly decreased in the ALI group, and CCl4 increased TOS and MDA levels compared with the N group. hMSC-CM treatment led to the return of these parameters to their baseline levels. GPx and CAT activity in the ALI group were significantly lower than in the N group and hMSC-CM reduced these parameters to the baseline in the ALI-CM group. hMSC-CM modulated CCl4-induced tissue lesions. CONCLUSION: The present study suggests hMSC-CM probably improves CCl4-induced ALI through its antioxidant and anti-inflammatory effects.

Gold nanoparticles induce apoptosis in HCT-116 colon cancer cell line.

INTRODUCTION: This study aimed to investigate the apoptotic and anti-cancer effect of gold nanoparticles (AuNPs) on apoptosis in HCT-116 colon cancer cells. MATERIALS AND METHODS: The level of ROS and apoptosis were determined by fluorimetric method and flow cytometry and Hoechst 33,258 staining, respectively. Furthermore, the mRNA expression of Bax, Bcl-2, CCNB1, P53 genes was evaluated by qRT-PCR method in HCT116 cells. RESULTS: The experimental results of this study showed that treatment with nanoparticles led to a significant increase in expression of Bax, P53 genes and a significant decrease in the expression of Bcl-2, CCNB1 genes at concentrations of 25 and 50 µg/ml during 48 h of incubation, compared to control cells (p < 0.05). The flow cytometric results (Annexin-pI) and Hoechst 33,258 staining also showed a significant increase in the level of apoptosis in the treated cells, depending on the concentration and time. CONCLUSIONS: The results of this study showed that AuNPs cause apoptosis at the half-maximal inhibitory concentration in the HCT-116 tumor cells during 48 h of incubation.

The influence of gastric bypass surgery on the concentration of high mobility group box 1, nuclear factor erythroid 2-related factor 2 and the genes expression of high mobility group box 1, nuclear factor erythroid2-related factor 2, interleukin 6, and tumor necrosis factor-alpha in the peripheral blood mononuclear cells of patients with morbid obesity.

BACKGROUND AND OBJECTIVES: Obesity is known as a disease with a chronic low-grade state of inflammation and high levels of oxidative stress. Given the challenges and consequences caused by obesity, obesity therapy is an essential subject to address. For sustainable weight loss, gastric bypass surgery is the most successful and essential option. METHODS: This prospective cohort study was performed on 35 patients aged (18-54) with morbid obesity (BMI: 42.06 kg/m2). Volunteers blood was taken, and peripheral blood mononuclear cells (PBMCs) were isolated, high mobility group box 1(HMGB1), nuclear factor erythroid2-related factor 2(Nrf2), Interleukin 6(IL-6), tumor necrosis factor-alpha (TNF-α), and biochemical factors were determined one day before and 4 months after surgery. RESULTS: Four months following surgery, the BMI, hip and waist circumferences, and waist-to-hip ratio (WHR) all decreased significantly. The lipid profile and antioxidant power were dramatically enhanced after surgery. IL-6 and TNF-α expression in PBMC patients showed a significant decrease after surgery. HMGB1 and Nrf2 expression in PBMC of postoperative patients decreased compared to before surgery, and HMGB1, and Nrf2 protein levels also decreased after surgery. CONCLUSION: Weight loss indicated the significant function of adipose tissue in the induction of oxidative stress and inflammatory factors. Gastric bypass reduced the inflammation conditions and improved the metabolic status and living situations in the patients with morbid obesity.

Anticancer Effects of Cinnamaldehyde Through Inhibition of ErbB2/HSF1/LDHA Pathway in 5637 Cell Line of Bladder Cancer.

BACKGROUND AND OBJECTIVE: The growing prevalence of bladder cancer worldwide has become a major concern for researchers, and the side effects of chemotherapy drugs have always been a major problem in cancer treatment. Cinnamaldehyde, the active ingredient in the Cinnamon plant, has long been considered with anti-oxidant and anti-inflammatory effects. METHODS: Bladder cancer 5637 cell lines were treated with the different concentrations of Cinnamaldehyde. MTT assay was performed to evaluate cell viability at 24, 48, and 72 hours. The concentration of 0.02, 0.04, and 0.08 mg/ml of Cinnamaldehyde was selected. Apoptosis was assessed with Annexin V-FITC/PI and Hochest33258 staining. Cell migration was performed by the scratch test. To evaluate Cinnamaldehyde effect on glycolysis, the gene expression of epidermal growth factor receptor 2 (ErbB2), Heat Shock Protein Transcription Factor-1 (HSF1) and lactate dehydrogenase A (LDHA), as well as the protein levels of HSF1 and LDHA, LDH activity and finally glucose consumption and lactate production, were measured. RESULTS: Cinnamaldehyde significantly increased apoptosis rate in the 5637 cells (p<0.05). Furthermore, it significantly reduced the gene expression of ErbB2, HSF1, and LDHA, protein level of HSF1 and LDHA, LDH activity, as well as cell migration, glucose consumption, and lactate production (p<0.05). These changes were dose-dependent. CONCLUSION: Thus, Cinnamaldehyde induced apoptosis and decreased growth in 5637 cells by reducing ErbB2-HSF1- LDHA pathway.

Anticancer Effects of Gold Nanoparticles by Inducing Apoptosis in Bladder Cancer 5637 Cells.

Nanotechnology is a developing and revolutionary science that has been widely recommended for diagnosis and treatment of cancer. Among the various nanoparticles used in nanotechnology, gold nanoparticles (AuNPs) have attracted much attentions due to their promising anticancer properties. Despite the potential advantages of AuNPs, their apoptotic and anti-angiogenic effects have not yet been reported on human bladder cancer 5637 cells. This motivated us to evaluate (reactive oxygen species) ROS-mediated apoptosis in 5637 cells. For this task, inhibitory effect of AuNPs was investigated after 24-h exposure to different concentrations of AuNPs by MTT assay. Also, apoptosis level was assessed by ROS production, flow cytometry, and Hoechst 33,258 staining. Besides, mRNA expression of B-cell lymphoma protein 2 (Bcl-2), Bcl-2-associated X (Bax), vascular endothelial growth factor A (VEGFA) genes, and caspase-3,7 activity were determined by qRT-PCR and colorimetric assay, respectively. Moreover, migration rate was evaluated by wound healing assay. MTT results demonstrate that AuNPs can reduce 5637-cell viability in a dose-dependent manner, while fluorimetric assay data show significant increased ROS production in 25 and 50 µg/ml-treated cells. It is also observed that AuNPs lead to Bax overexpression and downregulation of Bcl-2 and VEGFA genes. In line with this, flow cytometry results show increased levels of apoptosis in 25 and 50 µg/ml AuNP-treated cells (p < 0.05). Similarly, Hoechst staining indicates a remarkable increase in cells with apoptotic morphology after treating with AuNPs. Overall, our findings show that AuNPs significantly provoke ROS production, induce apoptosis, and suppress cell migration in bladder cancer 5637 cells.

The Restoring Effect of Human Umbilical Cord-Derived Mesenchymal Cell-Conditioned Medium (hMSC-CM) against Carbon Tetrachloride-Induced Pulmonary Fibrosis in Male Wistar Rats.

Objective: Pulmonary toxicity induced by CCl4, a model of idiopathic pulmonary fibrosis (IPF), leads to tissue remodeling and inflammation. Human umbilical cord mesenchymal cell-conditioned medium (hMSC-CM) is a potent anti-inflammatory, antioxidative, and antifibrotic agent. Methods: Forty male Wistar rats were assigned to the control (C), olive oil control (C.O) (hMSC-CM), control (C.Ms), fibrosis (fb), and fibrosis with hMSC-CM (f.Ms) treatment groups. The groups C, C.O, and C.Ms received PBS (200 µl), olive oil (1 ml/kg), and hMSC-CM (100 µg protein/kg), respectively. The fibrosis group was administered with only CCl4 (1 ml/kg). The last group, f.Ms was treated with CCl4 (1 ml/kg) and 100 µg protein/kg IV hMSC-CM. While the treatment with olive oil and CCl4 was performed for 2 days/week from the first week for 12 weeks, the treatment with PBS and hMSC-CM was carried out 2 days/week from week 4th to week 12th. The effect of the UC-MSC culture medium treatment on the lung was evaluated by assessing lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1) genes, and proteins expression by real-time RCR and western blotting, respectively. Results: Lysyl oxidase (LOX), tumor necrosis factor-alpha (TNF-α), transforming growth factor-b1 (TGF-ß1), malondialdehyde (MDA), and oxidative stress levels were markedly higher in the fibrosis group than in the control groups (p ≤ 0.001). Additionally, glutathione (GSH) in the fibrosis group was markedly lower than those in the control groups (p ≤ 0.001). Fibrosis in the UC-MSC treatment group had milder histopathological injuries than in the fibrosis group. Conclusion: hMSC-MSC as a strong anti-inflammatory, antioxidative, and antifibrotic decreases the level of oxidative stress, proinflammatory cytokines, and MDA causing a restoring effect against CCl4-induced pulmonary fibrosis.