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Abstract Trace elements, specifically magnesium (Mg), zinc (Zn), and selenium (Se) have been linked with immunomodulatory properties. This research delves into identifying the potential impression of serum levels Mg, Zn, and Se on the protective immunity arisen through Sinopharm COVID-19 vaccine in the vaccinated subjects. Levels of Mg, Zn, and Se, cytokine and antibody production as well as virus neutralization potency were investigated in 75 males and 75 females before and 2 weeks after first and second dose of vaccination. Level of Mg, Zn, and Se did not change significantly before and 2 weeks after first and second dose of vaccine administration. Concentrations of Interleukin (IL)-2, IL-6, and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum level IgG was significantly higher 2 weeks after first and second dose of vaccination compared to before vaccination. Serum level IgM was only higher after first dose of vaccination compared with before vaccine. Also, 2 weeks after both first and second dose of vaccination compared to before vaccination, FRNT50 titer was significantly higher. Levels of Mg, Zn, and Se did not significantly correlate with levels of IL-2, IL-6, IFN-γ, IgM and IgG, and FRNT50 after first and second dose of vaccination. No severe unwanted clinical symptoms were detected after vaccination. Mg, Zn, and Se do not play a role in modulating protective immunity during Sinopharm COVID-19 vaccine.

Background and purpose: This study investigated modulating the G protein-coupled estrogen receptor (GPER) on the IRElα/TXNIP pathway and its role in drug resistance in MDA-MB231 cells. Experimental approach: To determine the optimal concentrations of G1 and 4-hydroxytamoxifen (TAM), GPER expression and ERK1/2 phosphorylation were analyzed using qRT-PCR and western blotting, respectively. Cells were treated with individual concentrations of G1 (1000 nM), G15 (1000 nM), and TAM (2000 nM), as well as combinations of these treatments (G1 + G15, TAM + G15, and G1 + TAM) for 24 and 48 h. The expression levels of GPER, IRE1α, miR-17-5p, TXNIP, ABCB1, and ABCC1 genes and TXNIP protein expression were evaluated. Finally, apoptosis and cell migration were examined using flow cytometry and the wound-healing assay, respectively. Findings/Results: Activating GPER with its specific agonist G1 and TAM significantly increased IRE1α levels in MDA-MB231 cells. IRE1α through splicing XBP1 led to unfolded protein response. In addition, decreased TXNIP gene and protein expression reduced apoptosis, increased migration, and upregulated the genes associated with drug resistance. Conclusion and implication: Our investigation revealed that blocking the GPER/IRE1α/TXNIP pathway in MDA-MB231 cells could enhance treatment efficacy and improve chemotherapy responsiveness. The distinct unfolded protein response observed in MDA-MB231 cells may stem from the unique characteristics of these cells, which lack receptors for estrogen, progesterone, and HER2/neu hormones, possessing only the GPER receptor (ER-/PR-/HER2-/GPER+). This study introduced a new pathway in TNBC cells, indicating that targeting GPER could be crucial in comprehensive therapeutic strategies in TNBC cells.

Abstract Hypothyroidism has been linked to reduced mortality rate and increased lifespan and health span. Telomere shortening, enhanced oxidative stress, and reduced cellular mitochondrial content are important hallmarks of aging shown to be related to age-associated diseases. It was proposed that the status of these markers in early life can be predictive of lifespan and the predisposition to certain age-associated disease in adulthood. Animal studies indicated that prenatal injection of thyroid hormones affects postnatal telomere length. Here, we sought to determine whether thyroid hormones TSH and fT4 are related to the telomere length, mitochondrial DNA copy number (mtDNAcn), and oxidative stress resistance marker GPX in the cord blood of newborns. In this study, we analyzed 70 mothers (18–42 years) and neonate dyads born in 2022 at the Nik Nafs maternity Hospital in Rafsanjan. The relative telomere length (RTL) and mtDNAcn were measured in the genomic DNA of cord blood leukocytes using real-time PCR. GPX enzyme activity was measured in the serum using colorimetric assays. In this study the correlation between these markers and the cord blood TSH and fT4 hormones were assessed using regression models. We found a reverse relationship between TSH levels and RTL in the cord blood of neonates. Additionally, our results displayed increased TSH levels associated with enhanced GPX activity. Regarding the mitochondrial DNA copy number, we found an indirect relationship between fT4 level and mtDNAcn only in male newborns. Future analyses of various oxidative stress markers, mitochondrial biogenesis status, telomerase activity, and the level of DNA damage are warranted to demonstrate the underlying mechanism of our observations.

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

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

The low solubility of the plant-extracted agent like D-limonene in cancer therapy is a critical problem. In this study, we prepared D-limonene-loaded niosomes (D-limonene/Nio) for cancer therapy through in vitro cytotoxicity assay of HepG2, MCF-7, and A549 cell lines. The niosomal formulation was prepared by film hydration technique with Span® 40: Tween® 40: cholesterol (35:35:30 molar ratio) and characterized for vesicle distribution size, morphology, entrapment efficiency (EE%), and in vitro release behaviour. The obtained niosomes showed a nanometric size and spherical morphology with EE% about 87 ± 1.8%. Remarkably prolonged release of D-limonene from niosomes compared to free D-limonene observed. The loaded formulation showed significantly enhanced cytotoxic activity with all three cancer cell lines (HepG2, Macf-7 and A549) at the concentration of 20 μM. These results indicated that niosome loaded with phytochemicals can be a promising nano-carrier for cancer therapy applications

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 (LXR α ), 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 (PPAR γ ), and low-density lipoprotein receptor (LDLR). Results: The results showed that LXR α (P=0.003, P

Background &Objective: Resistin is an adipokin secreted from adipose tissue and immunity cells. Relationship between resistin and metabolic syndrome and its components is controversial. The aim of this study is measurement of serum resistin level, insulin resistance and other factors in subjects with and without metabolic syndrome. Materials & Methods: this cross-sectional study was conducted in 2015, 56 availableperson including; 31subjects were enrolled as the study group and 25 subjects were recruited as the control group of the study. Serum resistin concentrations were measured by ELISA and its association with metabolic syndrome markers was measured. Data were Analyzed using independent T test, Pearson correlation Test and, Chi-squared Test Results: Serum resistin levels were significantly higher in the metabolic syndrome subject compared with control group (p-value=0.002). Correlation analysis revealed body mass index (p=0.018; r=0.480), waist circumference (p=0.015; r=0.431), systolic blood pressure (p=0.008; r=0.467), diastolic blood pressure (p=0.001; r=0.562), cholesterol (p=0.018; r=0.421) and LDL (p=0.003; r=0.515) were positively correlated with plasma resistin. Conclusion: Serum resistin levels are elevated in subjects with metabolic syndrome and are associated with some of its components in metabolic syndrome patients, resistin may be associated with the severity of this syndrome and its complications.

Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area (VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats (200-250 g) were used in 5 experimental groups: 1) non morphine treat rats (control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid (i.p., for 21 d); 3) morphine treated rats (10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression (P

Background: Breast cancer is one of the most common cancers among women. Incorrect pattern of gene expression involved in epigenetic Including APOBEC3B, DNMT-1 and TET_1 can develop breast cancer. resveratrol is a natural flavonoids that antioxidant and anti-cancer properties have been reported in other studies. To investigate the mechanism of effect of resveratrol, this study examined effect of resveratrol on the expression of genes referred to the two classes of breast cancer cell lines Materials and methods: cell lines, including MCF-7 and MDA-MB-453 in separate boxes including the control group and treated groups with two doses of two doses of 25 and 100 micro molar for 24 hours of resveratrol for were cultured. RNA was extracted from the cells and then converted to cDNA. realtime PCR were used for APOBEC3B and DNMT and TET_1expression. Results: The results showed that resveratrol decrease in gene expression APOBEC3B and DNMT-1 And increased expression of TET_1 in both of cell lines. . Discussion: due to satisfactory effects of resveratrol has on breast cancer cells, probably these effects through epigenetic mechanisms applied. However, the final decision needs to be further investigation.

Background & Objectives: Adipose-derived stem cells (ADSCs) have been investigated as a promising cell source for therapeutic and engineering applications. Common proliferation protocols use fetal bovine serum (FBS) as a growth factor which is potentially a source of pathogens, and contains animal antigens that can cause an allergic reaction after transplantation in the recipient, and regarding immunity, human serum (HS) could be a suitable alternative to it. The aim of this study is to compare the culture medium enriched with FBS or HS as supplements in the proliferation and differentiation of ADSCs. Materials & Methods: Human serum was extracted from 90 ml venous blood of a healthy person, taken in respective intervals. The ADSCs were isolated according to the protocol from adipose tissue after lipolysis operation and cultured by mediums enriched with FBS or HS. Expression of the surface markers of ADSCs was investigated by flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red staining method. Results: The analysis of cell growth showed that the isolation and proliferation of ADSCs in both media (HS & FBS) were similar, but there was a significant difference in case of differentiation in the HS medium. Conclusion: This study showed that FBS could be replaced by HS in case of isolation, proliferation and differentiation of stem cells studies as supplement. Furthermore, our data suggest a fast and safe proliferation protocol by using human serum in the stem cells culture and cell-based therapies.

Background & Objectives: Adipose-derived stem cells (ADSCs) have been investigated as a promising cell source for therapeutic and engineering applications. Common proliferation protocols use fetal bovine serum (FBS) as a growth factor which is potentially a source of pathogens, and contains animal antigens that can cause an allergic reaction after transplantation in the recipient, and regarding immunity, human serum (HS) could be a suitable alternative to it. The aim of this study is to compare the culture medium enriched with FBS or HS as supplements in the proliferation and differentiation of ADSCs. Materials & Methods: Human serum was extracted from 90 ml venous blood of a healthy person, taken in respective intervals. The ADSCs were isolated according to the protocol from adipose tissue after lipolysis operation and cultured by mediums enriched with FBS or HS. Expression of the surface markers of ADSCs was investigated by flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red staining method. Results: The analysis of cell growth showed that the isolation and proliferation of ADSCs in both media (HS & FBS) were similar, but there was a significant difference in case of differentiation in the HS medium. Conclusion: This study showed that FBS could be replaced by HS in case of isolation, proliferation and differentiation of stem cells studies as supplement. Furthermore, our data suggest a fast and safe proliferation protocol by using human serum in the stem cells culture and cell-based therapies.

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

Background & Objectives: Diabetes is one of the most common diseases which is usually seen in modern societies. Due to the increased risk of the disease and its related complications, in addition to the harmless properties of sesame seeds, this research was aimed to study the effect of consuming sesame seeds on some biochemical factors in type 2 diabetic patients. Materials & Methods: This clinical trial has been carried out on 60 type 2 diabetic patients who were randomly divided into two groups of 30 sesame seeds consumers (case) and 30 non sesame seeds consumers (control).The case group was given 60 grams sesame seeds per day for 2 months and the control group did not receive any sesame seeds. The patient information was collected by questionnaire. The fasting blood serum of patients at the beginning and the end of the testing were collected and the biochemical factors of this study were measured in laboratory. For the data analysis, two independent samples t-test and paired t-test were used. Results: In this study, the mean ± SD (Standard Deviation) of the patients’ ages in the two groups, sesame seeds consumers (case) and non sesame seeds consumers (control), was 72/5 ± 40/52 and 11/6 ± 00/56 years, respectively. The results showed that fasting blood glucose, HbA1C, cholesterol, triglycerides, LDL (Low-density Lipoprotein), ALT (Alanine Transaminase) and ALP (Alkaline Phosphatase) were statistically decreased after the consumption of sesame seeds (P

Background & Objectives: Diabetes is one of the most common diseases which is usually seen in modern societies. Due to the increased risk of the disease and its related complications, in addition to the harmless properties of sesame seeds, this research was aimed to study the effect of consuming sesame seeds on some biochemical factors in type 2 diabetic patients. Materials & Methods: This clinical trial has been carried out on 60 type 2 diabetic patients who were randomly divided into two groups of 30 sesame seeds consumers (case) and 30 non sesame seeds consumers (control).The case group was given 60 grams sesame seeds per day for 2 months and the control group did not receive any sesame seeds. The patient information was collected by questionnaire. The fasting blood serum of patients at the beginning and the end of the testing were collected and the biochemical factors of this study were measured in laboratory. For the data analysis, two independent samples t-test and paired t-test were used. Results: In this study, the mean ± SD (Standard Deviation) of the patients’ ages in the two groups, sesame seeds consumers (case) and non sesame seeds consumers (control), was 72/5 ± 40/52 and 11/6 ± 00/56 years, respectively. The results showed that fasting blood glucose, HbA1C, cholesterol, triglycerides, LDL (Low-density Lipoprotein), ALT (Alanine Transaminase) and ALP (Alkaline Phosphatase) were statistically decreased after the consumption of sesame seeds (P

Background & Objectives: Non enzymatic glycation is a reaction that occurs between reducing sugars and amino groups of proteins. Advanced Glycation End-products (AGE) have been accounted for principal biological processes like aging and pathogenesis of some diseases. Accumulation of AGE during hyperglycemia can cause structural and functional changes of long-lived proteins. Therefore, it will be effective to inhibit protein glycation formation in order to reduce or to improve diabetes complications. The aim of this study is to determine the effects of hydroalcoholic extract of Allium Hirtifolium on the formation of glycated hemoglobin. Materials & Methods: In this experimental study, the effects of the various concentrations of 0.1, 0.3, and 0.5 gr/dl of hydroalcoholic extract of Allium Hirtifolium on the inhibition of hemoglobin glycation were examined. Hemoglobin A1c formation was assayed by ion exchange chromatography. The P-value < 0.05 was considered as the significant level. Results: 10 and 14 days after incubation, at the concentration of 40 millimollar glucose, hemoglobin A1c formation decreased significantly by using 0.5 gr/dl of hydroalcoholic extract of Allium Hirtifolium. Conclusion: The results revealed that Allium Hirtifolium can inhibit hemoglobin A1c formation in hyperglycemic condition. Therefore, it is suggested that Allium Hirtifolium can be useful for preventing the complications of diabetes.

Background & Objectives: Non enzymatic glycation is a reaction that occurs between reducing sugars and amino groups of proteins. Advanced Glycation End-products (AGE) have been accounted for principal biological processes like aging and pathogenesis of some diseases. Accumulation of AGE during hyperglycemia can cause structural and functional changes of long-lived proteins. Therefore, it will be effective to inhibit protein glycation formation in order to reduce or to improve diabetes complications. The aim of this study is to determine the effects of hydroalcoholic extract of Allium Hirtifolium on the formation of glycated hemoglobin. Materials & Methods: In this experimental study, the effects of the various concentrations of 0.1, 0.3, and 0.5 gr/dl of hydroalcoholic extract of Allium Hirtifolium on the inhibition of hemoglobin glycation were examined. Hemoglobin A1c formation was assayed by ion exchange chromatography. The P-value < 0.05 was considered as the significant level. Results: 10 and 14 days after incubation, at the concentration of 40 millimollar glucose, hemoglobin A1c formation decreased significantly by using 0.5 gr/dl of hydroalcoholic extract of Allium Hirtifolium. Conclusion: The results revealed that Allium Hirtifolium can inhibit hemoglobin A1c formation in hyperglycemic condition. Therefore, it is suggested that Allium Hirtifolium can be useful for preventing the complications of diabetes.

Background: It has been proposed that oxidative stress may contribute to the development of testicular abnormalities in diabetes. Morus alba leaf extract (MAE) has hypoglycemic and antioxidant properties. We, therefore, explored the impact of the administration of MAE on steroidogenesis in diabetic rats. Methods: To address this hypothesis, we measured the serum level of glucose, insulin, and free testosterone (Ts) as well as oxidative stress parameters (including glutathione peroxidase, glutathione reductase, total antioxidant capacity, and malondialdehyde) in the testis of control, untreated and MAE-treated (1 g/day/kg) diabetic rats. In order to determine the likely mechanism of MAE action on Ts levels, we analyzed the quantitative mRNA expression level of the two key steroidogenic proteins, namely steroid acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc), by real-time PCR. Results: The MAE-treated diabetic rats had significantly decreased glucose levels and on the other hand increased insulin and free Ts levels than the untreated diabetic rats. In addition, the administration of MAE to the diabetic rats restored the oxidative stress parameters toward control. Induction of diabetes decreased testicular StAR mRNA expression by 66% and MAE treatment enhanced mRNA expression to the same level of the control group. However, the expression of P540scc was not significantly decreased in the diabetic group as compared to the control group. Conclusion: Our findings indicated that MAE significantly increased Ts production in the diabetic rats, probably through the induction of StAR mRNA expression levels. Administration of MAE to experimental models of diabetes can effectively attenuate oxidative stress-mediated testosterone depletion. Please cite this article as: Hajizadeh MR, Eftekhar E, Zal F, Jaffarian A, Mostafavi-Pour Z. Mulberry Leaf Extract Attenuates Oxidative Stress-Mediated Testosterone Depletion in Streptozotocin-Induced Diabetic Rats. Iran J Med Sci. 2014;39(2):123-129.