heidar tayebinia

Antibody mediated rejection (AMR) is a major challenge in kidney transplantation and adversely affects allograft survival. Oxidative stress (OS) is implicated in AMR pathogenesis by triggering inflammation, apoptosis and fibrosis in the graft tissue. However, the status of OS and antioxidant defense in AMR patients remains unclear. We aimed to evaluate the levels of OS markers and antioxidant enzymes in AMR patients. 

We conducted a case-control study involving 22 biopsy-proven AMR patients (test group) and 14 kidney recipients with stable graft function (control group). Serum total oxidant status (TOS), total antioxidant capacity (TAC), total thiol groups, nitric oxide (NO), 8-isoprostane (8-IP) were determined and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were measured by spectrophotometric methods.

 Data analysis showed significant increases in TOS, TAC and 8-IP levels together with marked reductions in NO and total thiol groups in AMR patients. CAT and GPx activities did not differ between groups, however SOD activity was significantly lower in AMR patients.

Our study showed increased OS and impaired antioxidant defense in AMR patients. NO level may serve as a potential biomarker of OS severity and immune response in AMR. Further studies are required to elucidate the mechanisms and consequences of OS in AMR and to explore the therapeutic potential of antioxidants.

The impaired functions of granulosa cells (GCs) in the delayed development and immaturity of oocytes have been reported in polycystic ovary syndrome (PCOs). Even with ovarian stimulation, a large number of oocytes in these patients are still in the stage germinal vesicle (GV).

The levels of Smad2/3, phosphorylated Smad2/3 (P-Smad2/3), the expression of SARA, Smad4, and SMURF2 genes in the GCs surrounding metaphase II (MII) or GV oocytes in PCOs women were investigated.

GCs of MII and GV oocytes were isolated from 38 women with PCOs and the expression levels of SARA, Smad4, and SMURF2 in surrounding GCs of MII and GV oocytes were determined using reverse-transcription polymerase chain reaction. Also, Smad2/3 and P-Smad2/3 proteins were determined using western blotting.

The expression level of SMURF2 was significantly higher in GCs surrounding GV oocytes compared with that of GCs encompassing MII oocytes (p < 0.001). At the same time, no significant differences were observed in SARA and Smad4 expression levels in GCs surrounding GV and MII oocytes. A lower level of P-Smad2/3 was also found in GCs GV oocytes compared with GCs of MII oocytes (p < 0.001).

It seems that P-Smad2/3 plays a role in oocyte development, and the downregulation of this protein is associated with a defect in the maturation of GV oocytes. On the other hand, the upregulation of the SMURF2 gene also affects the growth process of GCs and the maturation of GV oocytes.

Granulosa cells (GCs) play key roles in oocyte maturation by providing required estradiol (E2). Since the presence of immature oocytes has been reported in cases with polycystic ovary syndrome (PCOS), in this study, the levels of mitochondrial membrane transporter proteins involved in E2 synthesis were determined. E2 concentration and parameters of oxidative status were also measured in follicular fluids of PCOS women.

Forty-three women with PCOS and 43 healthy women who were candidates for IVF procedure due to their husbands' infertility were enrolled in this case-control study. The gene expression and protein levels of mitochondrial translocator protein (TSPO) and voltage-dependent anion channel 1 (VDAC1) were determined in GCs using RT-qPCR and immunocytochemistry assay, respectively. E2 level was measured with electrochemiluminescence, whereas total cholesterol, total antioxidant capacity (TAC), total oxidant status (TOS), and malondialdehyde (MDA) were determined using colorimetric methods in follicular fluids. Data were analyzed using unpaired t-test or Mann-Whitney U test, and Spearman’s correlation coefficient.

VDAC1 and TSPO were significantly lower in mRNA (p<0.05) and protein levels (p<0.001) of PCOS patients. PCOS patients had lower cholesterol, estradiol, and TAC levels, and higher TOS and MDA contents. E2 level had direct correlation with VDAC1, TSPO, and TAC while it was negatively correlated with TOS, oxidative stress index (OSI), and MDA (p<0.001). Higher E2 levels were associated with higher numbers of high-quality oocytes and conceived embryos (p<0.001).

Decreased E2 levels and increased oxidative stress in the follicular fluid may be the cause of immature oocytes in PCOS cases.

Genistein is an isoflavone that has been reported to have various anti-cancer properties.

This study aimed to reveal whether or not the anti-cancer properties of genistein in AGS gastric cancer cell line were mediated through caspase-3 enzyme.

AGS gastric cancer cells were treated with different concentrations of genistein for 12, 24, and 48 hours and, then, the viability of the cells and IC50 were determined. To determine the effect of genistein on AGS cell migration potency, the wound healing assay was performed. The genistein-induced apoptosis in AGS gastric cells was evaluated by flow cytometry. Caspase-3 gene (CASP3) expression level and its enzyme activity level were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and colorimetric techniques, respectively.

The IC50 value was calculated as 70 µM concentration for 24 hours of incubation with genistein. Genistein significantly reduced AGS cell migration compared to the untreated control cells (P<0.001). Genistein increased the early and late apoptosis of the cells (P<0.001) and upregulated the caspase-3 gene expression (P<0.001), but did not significantly enhance the caspase-3 enzyme activity in treated cells.

Genistein exhibited anti-cancer effects on AGS cells to some extent by reducing cellular migration, increasing apoptosis, and upregulating CASP3 gene expression; however, it did not alter the caspse-3 activity. Therefore, it was recommended that more studies should be carried out to delineate the role of caspase-3 in health benefits attributed to the genistein.

Diabetes affects the central nervous system associated with cognition, especially memory and learning. The present study aimed to investigate the effects of probiotics (living microorganisms that provide health benefits) and resveratrol (a polyphenol with potential antioxidant activity) combination on oxidative stress, glucagon-like peptide-1 (GLP-1), memory, and learning in diabetic rats.

Male Wistar rats were randomly divided into five groups (six animals per group) of control, diabetic, probiotic-treated diabetic (50×109CFU/kg in drinking water), resveratrol-treated diabetic (10 mg/kg, oral gavage), as well as probiotics and resveratrol-treated diabetic. The treatment procedures lasted for four weeks, and a Shuttle Box test was then performed to evaluate memory and learning. At the end of the study, animals were sacrificed, and the hippocampus was removed to perform biochemical studies.

The levels of malondialdehyde and total oxidative status significantly decreased in the diabetic group treated with combined resveratrol and probiotics (P<0.05). Furthermore, the levels of superoxide dismutase, catalase, and glutathione peroxidase significantly increased in the hippocampus of the diabetic group treated with combined resveratrol and probiotics (P<0.05). According to the results, the combined therapy improved memory and learning (P<0.05). In addition, the level of GLP-1 increased in the treatment groups (P<0.05).

Treatment with resveratrol and probiotics significantly normalized pyramidal cell densities in the hippocampus of diabetic rats. This combination also reduced oxidative stress and activated the gut-brain axis in diabetic animals.

Gastric Cancer (GC) is one of the deadliest cancers in the world. Recently, LINC00961, TPT1-AS1, and SAMMSON Long non-coding RNA (lncRNAs)have been discovered, which significantly contribute to the occurrence of various cancers. This study aimed to determine the expression levels of these genes in GC tissues, compared to healthy adjacent tissues, and the relationship of their expressions with clinical characteristics.

In this case-control study, the expression of LINC00961, SAMMSON, and TPT1-AS1 were evaluated in 40 pairs of cancerous and adjacent non-cancerous tissue samples in GC patients using qRT-PCR. Statistical analysis and graphing of the relationship between RNA levels and the clinic-pathological characteristics of GC were carried out using SPSS and Prism 5.00 software. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn to represent the sensitivity and specificity of LINC00961, SAMMSON, and TPT1-AS1 expression as biomarkers of GC.

The expression of TPT1-AS1 and SAMMSON were significantly up-regulated, and the expression of LINC00961 was significantly decreased in GC specimens, compared to adjacent control samples. Our results showed that TPT1-AS1 and SAMMSON RNA levels in GC were significantly related to the tumor size and histopathological grade. Moreover, the ROC curve analysis of LINC00961 and SAMMSON RNA level demonstrated that these two lncRNAs had an appropriate sensitivity and specificity for the diagnosis goals.

Based on the results, LINC00961, SAMMSON, and TPT1-AS1 may play critical roles in exacerbating and even initiating GC due to their cellular pathways.

Since activation of NLRP3 inflammasome results in the production of interleukin-1β (IL 1β) and initiation of inflammation as the key players in development of cancer, this study investigated possible activation of NLRP3 inflammasome during the progression of colorectal cancer (CRC) and evaluated the role of NLRP3 inflammasome in epithelial-mesenchymal transition (EMT) process.   Tissue samples were collected from cancerous (test) and adjacent normal tissues (control) of forty-three male CRC patients (18 grade I and 25 grade III).  The gene expression and protein levels were determined by qRT PCR and Western blotting, respectively, and tissue morphological was examined by histopathology.   The gene and protein expression levels of transforming growth factor-β (TGF β), IL 1β, nuclear factor κB (NF κB), NLRP3, and caspase-1, as well as the enzyme activity of caspase-1, were significantly increased in CRC.  mRNA and protein levels of TGF-β, mature IL 1β, NF κB, and NLRP3 were higher in patients with grade III. EMT markers N cadherin, vimentin, and MMP 9 markedly increased in CRC, and were higher in grade III than grade I, whereas expression of E-cadherin declined by the progression of CRC.  NLRP3 protein level was inversely correlated with E-cadherin whereas it positively was correlated with IL 1β, active NF κB, N cadherin, vimentin, and MMP 9.   This study for the first time showed that activation of NLRP3 inflammasome contributed to the progression of CRC and is correlated with the EMT process.  Although the present study showed that EMT markers are positively correlated with tumor grade, further investigations are required to strongly link the EMT markers to the progression of CRC.

Hypercholesterolemia is correlated with brain amyloid-β (Aβ) deposition and impaired cognitive functions and contributes to Alzheimer’s disease. Effects of cholesterol-lowering dill tablets and aqueous extract of Ocimum basilicum L. (basil) on learning and memory and hippocampus fatty acid composition were examined.  mRNA levels of the genes involved in cholesterol homeostasis were also determined in high-cholesterol diet (HCD) fed rats.   Forty male Wistar rats were allocated to 4 groups: rats fed chow diet (C); rats fed high-cholesterol (2%) diet (HCD); rats treated with HCD+300 mg/kg dill tablets (HCD+Dill); and finally, rats fed HCD and treated with 400 mg/kg basil aqueous extract (HCD+basil).  Treatment was carried out for 16 weeks.  Hippocampus Aβ(1-42) level was determined. Spatial and passive avoidance tests were used to examine cognitive functions.  Hippocampal FA composition was assessed by gas chromatography. Basil aqueous extract was analyzed by GC-double mass spectroscopy (GC-MS/MS) and expression of LXR-α, LXR-β, and ABCA1 genes was assessed by qRT-PCR.   Dill tablets and basil extract remarkably ameliorated serum cholesterol (p <0.001), retarded hippocampal accumulation of Aβ, and attenuated HCD-induced memory impairment.  Hippocampus FA composition did not change but serum cholesterol was found positively correlated with hippocampus Aβ(1-42) (p <0.001), total n 6 PUFA (P=0.013), and Aβ(1-42) showed correlation with the ratio of n6 to n3 PUFA.  At least 70 components were identified in basil aqueous extract.   Dill tablets and aqueous extract of basil attenuated the hypercholesterolemia-induced memory impairment by lowering serum cholesterol and hippocampus amyloid deposits, and probably beneficial in AD adjuvant therapy.

Matrix metalloproteinases-2 and -9 play important roles in the development of breast cancer by hydrolyzing the extracellular matrix. Since −1306C/T and −1562C/T polymorphisms are located at the promoter regions of the matrix metalloproteinase- 2 and -9 genes, respectively, C to T substitution may affect promoter activity and impact the rate of extracellular matrix degradation and cancerous cell proliferation. Therefore, we aimed to determine the genotype and allele frequencies of these polymorphisms in Iranian healthy women and women with breast cancer. We have also examined the correlation of genotypes with clinicopathological parameters such as tumor type, tumor size, and metastasis to lymph nodes.
This case-control study enrolled 200 women with breast cancer and 200 age-matched healthy women. DNA was extracted, and we determined the genotype and allele frequencies of −1306C/T matrix metalloproteinase-2 and −1562C/T matrix metalloproteinase-9 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method. Additionally, tumor size (20 mm), tumor type (ductal/non-ductal), and metastasis (yes/no) were determined.
Genotype and allele frequencies of the −1306C/T matrix metalloproteinase- 2 polymorphism showed no significant association with the occurrence of breast cancer. Genotype and allele distribution differed in the −1562C/T matrix metalloproteinase- 9 polymorphism and indicated a 4.83-fold increase in the risk of breast cancer for T allele carriers. There was no likelihood of any interaction found between the two polymorphisms and susceptibility to breast cancer. In addition, the −1562C/T matrix metalloproteinase-9 T allele showed an association with metastasis to lymph nodes but we observed no association between the −1306C/T matrix metalloproteinase- 2 polymorphism and clinicopathological features.
The ‒1562C/T matrix metalloproteinase-9 polymorphism is involved in the pathogenesis of breast cancer in Iranian women. The T allele may increase the risk of disease.

Ammonia, urea, uric acid, and creatinine are the major non-protein nitrogenous compounds (NPNs). It is reported that the concentration of NPNs in the seminal plasma of normal and infertile individuals is different and sperm is affected by NPNs.
The aim of this study was to determine the quantities of ammonia, urea, uric acid, and creatinine in seminal plasma and the correlation of these compounds with the fertilization rate after an intracytoplasmic sperm injection (ICSI).
The levels of ammonia, urea, uric acid, and creatinine were determined in seminal plasma collected from 50 men. The ammonia and urea were determined by L-glutamate dehydrogenase and diacetyl monoxime method, respectively. Uric acid and creatinine were detected by enzymatic method and Jaffe reaction, respectively. The fertilization was evaluated around 16–18 hours post-ICSI on the appearance of 2 pronuclei and 2 polar bodies. The fertilization rate was calculated by the number of fertilized oocytes per the number of oocytes injected.
There was a significant negative correlation between seminal ammonia and sperm motility (P The findings of the present study showed that urea and uric acid in seminal plasma have a negative impact on the fertilization rate.

Urinary tract stones are one of the most common causes of kidney disease. There is evidence for the possible involvement of oxidative stress in the formation of kidney stones and renal cell injury.
In this study, we aimed to determine the total antioxidant capacity (TAC), malondialdehyde (MDA), serum thiol group, ceruloplasmin (CP) levels and catalase (CAT) activity in the serum of the patients with kidney stones.
This study was conducted as a case-control study. A total of 31 patients (16 males and 15 females) with kidney stone(s) and a comparative normal control group including 21 (12 males and 9 females) healthy subjects were included.
The present study revealed that TAC level was significantly higher in the control group (P=0.004), and the mean thiol group was remarkably decreased in the patient group (P It can be concluded that the reduction of antioxidant indices in the patients with kidney stones can damage the renal tubular cells and strengthen the accumulation of crystals and the formation of kidney stones