The antioxidant and anti-apoptotic properties of vitamins A, C and E in heart tissue of rats exposed to zinc oxide nanoparticles.

BACKGROUND: The rapidly increasing applications of zinc oxide nanoparticles (ZnO NPs) in various industries have led to growing concerns about their damaging influence on human health. The present research was designed to determine the protective action of vitamins (Vits) A, C and E on the heart toxicity induced by ZnO NPs. METHODS: Fifty-four male Wistar rats were allocated into 9 groups of 6 and then exposed to ZnO NPs (200 mg/kg), water (Control1), olive oil (Control2), Vit A (1000 IU/kg), Vit C (200 mg/kg), Vit E (100 IU/kg) and three groups were co-treated with ZnO and one of the Vits A, C or E. The oxidative stress situation was evaluated by measuring oxidative stress markers and the tissue antioxidant enzyme activity. Besides, the mRNA expression of Bcl-2 and Bax and caspase 3,7 activity were assessed. A histopathological examination was also performed to determine the rate of cardiac injury. RESULTS: The results indicated that co-administration of ZnO NPs and the aforementioned Vits significantly reduced the total oxidant status and lipid peroxidation relative to the ZnO group (P < 0.05). Furthermore, the supplementation of vitamins, notably Vit E, decreased the ZnO NPs-induced oxidative damage by enhancing the activity of antioxidant enzymes compared to the ZnO NPs-fed rats (P < 0.05). Data also showed the mitigating effects of Vits against ZnO NPs-mediated apoptosis by suppressing the ratio of Bax/Bcl-2 expression and caspase 3,7 activity. CONCLUSION: This study highlights the protective role of Vits A, C and E against ZnO NPs cardiotoxicity, though at different levels of effectiveness.

The protective effects of vitamins A, C, and E on zinc oxide nanoparticles (ZnO NPs)-induced liver oxidative stress in male Wistar rats.

The ever-increasing use of zinc oxide nanoparticles (ZnO NPs) in industrial and consumer products leads to concerns about their safety. Liver is one of the most important target organs of nanoparticles after entering the body. As such, the aim of this study was to evaluate the protective effects of vitamins (Vit) A, C, and E on ZnO NPs-induced liver oxidative stress. For this task, 54 male Wistar rats were randomly divided into nine groups of six: control 1 (water), control 2 (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. The animals received ZnO for 2 weeks while treatment with Vit started one week before the ZnO administration. In order to specify oxidative stress status, total antioxidant capacity (TAC), total oxidative status and malondialdehyde were determined by colorimetric assay. In addition, the activity and gene expression of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were evaluated by colorimetric assay kit and qRT-PCR, respectively. Moreover, histological analysis was conducted to estimate the extent of liver damage. Our results indicate that the oxidative parameters are increased while the content of TAC, antioxidant enzymes activity, and gene expression of SOD, GPX, and CAT show a significant reduction in the liver of ZnO-treated rats compared to the control (p< 0.05). In contrast, the administration of Vit could significantly modulate the aforementioned changes. Overall, Vit A, E, and C can mitigate oxidative stress caused by ZnO NPs.

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.

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.

Higher circulating levels of ANGPTL8 are associated with body mass index, triglycerides, and endothelial dysfunction in patients with coronary artery disease.

Bac Coronary artery disease (CAD) is the leading cause of death worldwide and most commonly develops as a result of atherosclerosis. ANGPTL8 is a secreted adipokine that regulates lipid metabolism and is associated with cardiometabolic diseases, including type 2 diabetes and CAD. However, the association between circulating ANGPTL8 levels and CAD is inconsistent among studies and the mechanism by which ANGPTL8 contributes to CAD development remains poorly understood. Here we sought to evaluate the relationship between ANGPTL8 levels and endothelial dysfunction and adipose tissue inflammation in CAD patients. Concentrations of ANGPTL8, adiponectin, TNF-α, IL6, hsCRP, ICAM-1, and VCAM-1 were measured by ELISA in serum samples from 192 CAD patients diagnosed with stenosis > 50% in at least one coronary artery by angiography and 71 individuals with normal heart function. Serum ANGPTL8 levels were significantly higher in CAD patients compared to controls (83.84 ± 23.25 ng/mL vs. 50.45 ± 17.73; p < 0.001), independent of adjustment for age, sex, BMI, smoking and statin use. ANGPTL8 could also differentiate CAD patients from controls with 82.3% specificity and 81.4% sensitivity (p < 0.001). Adiponectin levels were lower in CAD patients, while ICAM-1, VCAM-1, TNF-α, IL6, and hsCRP levels were higher compared to non-CAD controls (all p < 0.001). ANGPTL8 levels were associated with BMI in controls and with BMI, TG, and ICAM-1 in CAD patients. The presence of elevated ANGPTL8 levels in CAD patients and independent association with TG and ICAM-1 suggest a possible role related to endothelial dysfunction in the pathogenesis of atherosclerosis.

Palmitate-induced IL6 expression ameliorated by chicoric acid through AMPK and SIRT1-mediated pathway in the PBMCs of newly diagnosed type 2 diabetes patients and healthy subjects.

Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.

Effects of vitamin A and vitamin E on attenuation of titanium dioxide nanoparticles-induced toxicity in the liver of male Wistar rats.

The increasing application of titanium dioxide nanoparticles (NTiO2) in life and the toxicity potential of these nanoparticles have raised concerns about their detrimental effects on human health. This study was conducted to investigate the hepatoprotective effects of vitamin E and vitamin A against hepatotoxicity induced by NTiO2 in rats. Thirty-six male Wistar rats were randomly divided into six groups of six rats each. Intoxicated group received 300 mg/kg NTiO2 for two weeks by gavage. Groups treated with vitamin E (100 IU/kg), vitamin A (100 IU/kg) and mixture of these vitamins were orally administered for 3 weeks (started 7 days before NTiO2 administration). In order to investigate the redox changes, total antioxidant capacity, total oxidant status, and lipid peroxidation were determined in liver tissue as well as activity of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, and catalase. In addition, inflammatory responses were assessed by measuring the expression of NF-κB (mRNA) and TNF-α (mRNA and protein). Histopathological analysis and measurement of liver enzymes (ALP, ALT, AST, and LDH in serum) were also done to determine hepatic injury. In liver, NTiO2 caused hepatic injury, redox perturbation, and reduction of antioxidant enzymes and elevation of inflammatory mediators, significantly. However, treatment with vitamins was able to significantly ameliorate these alterations. This study highlights the antioxidant and anti-inflammatory properties of vitamins A and E against toxicity of NTiO2 and poses the use of these vitamins to mitigate the toxic effects of this nanoparticles in NTiO2-contained products.

Study of Insulin-Loaded Chitosan Nanoparticle Effects on TGF-ß1 and Fibronectin Expression in Kidney Tissue of Type 1 Diabetic Rats.

In diabetes, the increasing blood glucose levels through oxidative stress, with increase in inflammatory cytokines and growth factors, such as TGF-ß1, can cause long-term complications, including nephropathy. Subcutaneous injection of insulin is a common method used to treat Type 1 diabetes, which can lead to problems such as hypoglycemia and edema. In the present study, we examined the effect of insulin in its two injectable and oral forms on the expression of TGF-ß1 and fibronectin in kidney tissue of STZ diabetic rats. A total of 25 male Wistar rats were randomly divided into 5 groups: C: normal control, D: diabetic control, D+NP, oral insulin-loaded trimethyl chitosan nanoparticles (8 IU/kg), and subcutaneously injected insulin (8 IU/kg). The groups were treated from 8th to 10th weeks. After 10 weeks, FBS was measured. Also, the TGF-ß1 and fibronectin mRNA expression and serum TGF-ß1 protein were examined in the kidney tissue. Structural changes in the kidney tissue were studied using H&E staining. After 10 weeks of diabetes induction, the rats showed significant change in blood glucose, weight, serum TGF-ß1, Fibronectin and TGF-ß1 expression of kidney in diabetic groups (p < 0.05). Oral insulin-loaded trimethyl chitosan nanoparticles treatment, similar to injected insulin, significantly ameliorate blood glucose and rats' weight (p < 0.05). However, the reduction in fibronectin and TGF-ß1 expression and serum TGF-ß1 protein by both treatments was not statistically significant (p > 0.05). These data showed that oral insulin-loaded trimethyl chitosan nanoparticles were better therapeutic intervention than injected insulin for Type 1 diabetes.

Ameliorative Effects of Allium sativum Extract on iNOS Gene Expression and NO Production in Liver of Streptozotocin + Nicotinamide-Induced Diabetic Rats.

Diabetes mellitus (DM) is one of the most prevalent diseases in the world, which is strongly associated with liver dysfunction. Hyperglycemia, through an oxidative stress pathway, damages various tissues. Herbal medicine is a good candidate to ameliorate hyperglycemia and oxidative stress. In this study, the effects of aqueous Allium sativum (garlic) extract (AGE) on gene expression of inducible nitric oxide synthases (iNOS) and production of nitric oxide (NO) were evaluated in the liver tissue of diabetic rats. Four groups of rats contained normal control rats, garlic control rats (AGE), Streptozotocin (STZ) + nicotinamide-induced diabetic rats (DM), and diabetic rats treated with garlic (DM + AGE). Glucose levels and liver enzymes activities were determined by colorimetric assay in the serum. Gene expression of iNOS by real-time PCR, NO levels by Griess method, oxidative stress parameters by spectrophotometric method and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Glucose levels, activities of liver enzymes, oxidative stress markers, iNOS gene expression, and NO production increased significantly in diabetic rats in comparison with control rats, whereas after oral administration of garlic, these parameters decreased significantly, close to the normal levels. Hence, the beneficial effects of garlic on the liver injury of diabetes could be included in the hypoglycaemic and antioxidant properties of garlic via a decrease in gene expression of iNOS and subsequent NO production.

In-silico and in-vitro investigation on the phenylalanine metabolites' interactions with hexokinase of Rat's brain mitochondria.

Hexokinase (HK) is the first enzyme of glycolysis pathway. In brain, most dominant form of HK, HK-I, binds reversibly to the outer mitochondria membrane. Those metabolites that affect binding or releasing of the enzyme from the mitochondria have regulatory effect on glucose consumption of the cell. In this study destructive effect of phenylalanine and its metabolites in relation to glucose metabolism in brain have been studied. The results show that phenylpyruvic acid decreases the activity of enzyme in the presence and absence of glucose-6-phosphate (G6P) and increases the release of the enzyme from mitochondria, whereas phenylalanine and phenyllactic acid have no such effects. Obtained Interactions and elicited binding energies of docking and MD simulations also showed more affinity for phenylpyruvic acid compared with the other potent inhibitors for hexokinase after the natural product of G6P. It is possible that phenylpyruvic acid is the cause of the reduction of glucose consumption by decreasing hexokinase activity and the higher inhibitory function. Therefore, production of ATP declines in brain cells.

Effect of Cichorium intybus L. seed extract on renal parameters in experimentally induced early and late diabetes type 2 in rats.

Blood and urine biochemistry screening tests are important for initial detection of diabetes, determination of severity of its complications, and monitoring of therapy. We evaluated the effects of aqueous chicory seed extract (CSE), on renal biochemical parameters, histology, and Na+/glucose cotansporters, SGLT1 and SGLT2 expression levels using metformin, and aspirin as controls. Late stage type 2 diabetes (LT2D; FBS, >300 mg/dl) and early stage type 2 diabetes (ET2D; FBS, 140-220 mg/dl) were induced in rats by streptozotocin (STZ group) and a combination of STZ and niacinamide (NIA/STZ group), respectively. A non-diabetic group was included as control. Treatment included daily intraperitoneal injections of either CSE (125 mg/kg b.w.) or metformin (100 mg/kg b.w.) and oral aspirin (120 mg/kg b.w.) for 21 days. At the end, blood and 24 h urine samples were collected; and kidneys were saved at -80 ËšC. CSE reduced urinary α1-microgobulin excretion in ET2D (p = .043), and serum uric acid (p = .045), and glomerular diameter (p < .01) in LT2D. Metformin appeared to be more effective in LT2D with respect to serum uric acid, urea, and BUN (< .05). Both CSE and metformin improved histology. Aspirin improved several blood and urine variables, but appeared to aggravate morphological damages to the kidney tissue. The absolute values of albumin, α1-microglobulin or total protein in urine rather than their creatinine ratios seemed more useful in the detection of early kidney damage; CSE was able to repair the kidney damage and α1-microglobulin was sensitive enough to allow monitoring of the improvements caused by the treatment.

Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes.

CONTEXT: Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia. OBJECTIVE: The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ) + nicotinamide-induced diabetes. MATERIALS AND METHODS: Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ + nicotinamide-induced diabetes that received a single dose of STZ (65 mg/kg) and nicotinamide (110 mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2 g/kg/d, gavage), and normal rats that received garlic (2 g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats. RESULTS: The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p < 0.05). MDA, TOS and NO increased (p < 0.001) in diabetic rats compared with the control group, and decreased in garlic-treated diabetic rats compared with diabetic rats (p < 0.01). The level of TNF-α mRNA did not differ between groups but the TNF-α protein level in diabetic rats was higher than in the control rats (p < 0.01), whereas after treatment with garlic, it was close to the normal level (p < 0.01). DISCUSSION AND CONCLUSION: These results indicate that garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.

Beneficial Effect of Aqueous Garlic Extract on Inflammation and Oxidative Stress Status in the Kidneys of Type 1 Diabetic Rats.

One of the most important complications of diabetes is nephropathy. This study investigates the effects of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of diabetic rats. Male rats were divided into four groups- control rats, diabetic rats, garlic extract-treated diabetic rats, garlic extract-treated normal rats. The glucose, urea, uric acid, and creatinine levels were measured in sera using colorimetric methods. To determine the oxidative stress condition in the kidney tissues, total antioxidant capacity (TAC), malondialdehyde (MDA), and total oxidant status (TOS) were measured using colorimetric methods. Inflammation status was evaluated by the determination of tumor necrosis factor-alpha (TNF-α) gene and protein expression using qRT-PCR and ELISA respectively, while nitric oxide (NO) level in these tissues was measured using the Griess method. Histological examination of Kidneys was carried out by H&E staining. The levels of glucose, urea, and uric acid were found to increase in the serum of diabetic rats and decrease in that of diabetic rats after treatment with garlic. Measurement of MDA, TOS, and TAC revealed oxidative stress in diabetic rats, which improved after receiving the extract. The NO and TNF-α protein levels in diabetic rats were higher than those in control rats. After treatment with garlic, the levels of TNF-α protein and NO became close to the normal levels. Histological results confirmed certain other data as well. Garlic has antioxidant properties; therefore, it can reduce oxidative stress, which plays an important role in the development of diabetic nephropathy. Reduction in oxidative stress has beneficial effects on inflammation because it leads to a decrease in the level of TNF-α.

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.

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.

Immune Response to COVID-19 Vaccination in Hematologic Malignancies: A Mini-Review.

The outbreak of the COVID-19 infection has led to the rapidity of vaccine usage in recent years. Emerging data indicate that the efficacy of vaccination against COVID-19 was about 95% in the general population, though its impact is impaired in patients with hematologic malignancies. As such, we decided to research the publications in which the authors reported the impacts of COVID-19 vaccination in patients suffering from hematologic malignancies. We concluded that patients with hematologic malignancies have lower responses, antibody titers as well as an impaired humoral response following vaccination, notably in patients with chronic lymphocytic leukemia (CLL) and lymphoma. Furthermore, it seems that the status of treatment can significantly affect the responses to the COVID-19 vaccination.