mohammad reza ashrafi

Aminoglycosides like gentamicin can cause nephrotoxicity by increasing reactive oxygen species (ROS) and reducing antioxidants. The transcription factor Nrf2 regulates antioxidant genes like NQO1 to combat oxidative stress. This study evaluated Nrf2/NQO1 involvement in gentamicin renal toxicity and vitamin E protection.

24 rats were divided into control, gentamicin, vitamin E, and gentamicin plus vitamin E groups. Gentamicin (100 mg/kg) and vitamin E (250 mg/kg) were given intraperitoneally for 8 days. Kidney function, oxidative stress, Nrf2/NQO1 expression, and histology were analyzed.

Gentamicin significantly increased serum creatinine by 1.98-fold (1.43 ± 0.49 vs 0.72 ± 0.16 mg/dl, p <0.01) and BUN by 5.58-fold (252.3 ± 78.13 vs 45.18 ± 7.26 mg/dl, p <0.0001) compared to control. Gentamicin also markedly suppressed renal Nrf2 mRNA expression by 83% and NQO1 by 79% versus control (p <0.0001). Vitamin E partially alleviated the functional impairment and downregulation of Nrf2 and NQO1 caused by gentamicin. The vitamin E group displayed the highest Nrf2 (2.8-fold vs control) and NQO1 (1.6-fold vs control) expression among all groups (p <0.0001).

Gentamicin appears to cause nephrotoxicity partly by suppressing Nrf2/NQO1 antioxidant defense. Vitamin E provided renoprotection by scavenging ROS and potentially reactivating Nrf2/NQO1. The study suggests oxidative stress is an important mechanism in aminoglycoside kidney toxicity that may be mitigated by appropriate antioxidants. Evaluating Nrf2/NQO1 modulation provides insights into gentamicin nephrotoxicity and related kidney injuries.

Methylation alterations of tumor suppressor gene promoters are essential aspects of epigenetic changes in gastric cancer (GC). Cadherin1 (CDH1) encodes a protein with essential roles in cell-cell adhesions. In this study association of organochlorine pesticides (OCPs) serum levels with the methylation profile of this gene was investigated in gastric cancer (GC), intestinal metaplasia (IM), and functional dyspepsia (FD) patients.

GC (n=34), IM (n=8), and FD (n=48) patient serums were analyzed for the determination of OCP levels by gas chromatography equipment. The methylation status of the CDH1 gene promoter was examined by methylation-specific PCR (MSP) method. In order to confirm reduced protein expression of this gene in methylated samples, immunohistochemistry (IHC) was used.

Our findings revealed significant hypermethylation of CDH1 gene promoter along with reduced expression in GC patients compared with IM and FD patients. Furthermore, there was significant association between CDH1 promoter hypermethylation and 2,4-DDT (odds ratio [OR]:1.183;95%CI:1.001-1.398, p=0.048) serum levels in GC patients.

Our results could suggest the association of 2,4-DDT OCP levels in the GC patient serums with CDH1 gene promoter hypermethylation. Additionally, this gene promoter methylation may play a role in the progression of pre-cancerous IM towards GC.

Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system.

Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels.

Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2–related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively.

The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.

Thyroid cancer is the most prevalent type of endocrine malignancy with the highest incidence rate among women under 45 years old. Ethinylestradiol (EE) and levonorgestrel (LNG) are two steroid components of low-dose oral contraceptives used all over the world. In this study, we aimed to examine the possible effects of the combination of these two steroids on metastasis and angiogenic factors in BCPAP papillary thyroid cancer (PTC) cell line. After treatment of BCPAP cells with the combination of 20 nM EE and 90 nM LNG, mRNA expression levels of long noncoding RNAs HOTAIR and MALAT1, angiogenic and antiangiogenic gene markers VEGFA and THBS1, and epithelial-mesenchymal transition (EMT) biomarkers CDH1, CDH2, FN1, and VIM were analyzed by real-time PCR. Additionally, the protein expression of VEGFA was semiquantified by Western blotting. Results showed that the combination of LNG and EE significantly elevated the level of VEGFA protein and mRNA expression of VEGFA, MALAT1, HOTAIR, CDH2, FN1, and VIM genes while decreased CDH1 gene expression but had no marked effect on the expression of THBS1 gene in comparison with the control group. Also, our results suggest that LNG and EE may increase the metastatic and migratory properties of BCPAP cells via modulating angiogenic and EMT biomarkers. These data may highlight the potential of exogenous steroids in the advancement of PTC tumors.

Background and Changing the quality of groundwater and saltinating of water resources are Concerning a major threat for country's agricultural development, especially in arid and semi-arid lands. Preparing maps of both Same amount maps for salinity and salts can be an important step in the proper utilization of water resources. This research was carried out in Firoozabad plain in west of Fars province to evaluate the hydrogeochemical processes affecting groundwater quality.
Preparation of the map of the chemical parameters (isochromic) of Firoozabad plain using hydrodynamic data of wells measured in East and West of Firoozabad plain. Preparation of similar maps using Shooler and Wilcox methods to produce coincidence lines it placed.
Findings : Based on the maps of the chemical parameters in the studied areas and the diagrams of the changes and classification of the data based on the Schuler and Wilcox diagrams, the irrigation water classification according to Wilcox's diagram in 2004 and 2011 showed a decline trend in agricultural quality. Based on the results of the classification of drinking water, there were generally no significant changes in drinking quality except in 2011.
The amount of chlorine and electrical conductivity parameters in the west and east of the Firoozabad plain increased from north and northwest to the center and eastern plain from east to center, respectively, in the east and west of the plain, the highest values ​​were observed. Also, the results showed that the groundwater of the area based on the Schuler diagram was classified into three classes: good, acceptable and moderate, and quality, for use in agriculture in 2011 in C3S1, C1S1, C2S1 C3S2, C3S4, C3S3 and in the first period, 2004, in C3S1, C1S1, and C2S1 classes. The irrigation water classification according to Wilcox, in terms of 2004 and 2010, indicates a decrease in agricultural quality. The results of the classification of drinking water (Shooler classification) show that overall there is no significant change in the quality of drinking water and only in 2011, reduced quality.

Polyphenol oxidase (PPO), also known as tyrosinase (EC 1.14.18.1), is a copper-containing enzyme widely distributed in microorganisms, animals, and plants. This enzyme is responsible not only for browning in plants but also for melanization in animals. Thus, tyrosinase inhibitors have a huge impact on industry and the economy. In the current study, we first purified the enzyme, then evaluated inhibitory potency of three benzaldehyde derivatives: 2,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde and 4-dimethylaminobenzaldehyde on diphenolase activity of the purified mushroom tyrosinase, compared to kojic acid. Despite their close structural similarity, 2,4-dihydroxybenzaldehyde was found as potent competitive inhibitor while uncompetitive inhibition was observed for 4-dimethylaminobenzaldehyde. Further complementary studies on these types of inhibitors, as potential drugs for treating abnormal melanin pigmentation, are needed.

Interaction of drugs with serum albumin, the most abundant protein in plasma, has a great significance in pharmaceutical sciences. It can affect the biological activity, toxicity, and pharmacokinetics of drugs and design of dosages. Determination of the impact of chemical modifications of albumin and its structural changes upon interaction with drugs are very important when drugs bind with albumin to a significant degree. Hypochlorite is naturally produced by activated phagocytes in vivo at inflammatory conditions. In current study, the effects of hypochlorite-mediated oxidation on the albumin stability, surface hydrophobicity and its interaction with furosemide were investigated using intrinsic and extrinsic fluorescence techniques. Bovine serum albumin (BSA) was chemically modified with sodium hypochlorite under nondenaturing conditions. The Job’s plot indicated that the drug binds to the unmodified and modified BSAs with a 1:1 stoichiometry. Fluorescence quenching data showed that the albumin affinity for the drug as well as its surface hydrophobicity increases under the effect of protein oxidation. Measurement of conformational stability indicated that oxidized BSA is less stable compared to the unmodified protein. Thermodynamic analyses of the binding process showed that the major forces involved in the interaction of furosemide to the unmodified and oxidized BSA are same (hydrophobic). Increment of protein surface hydrophobicity (PSH) as well as the decrement of protein stability may reminiscent of higher protein structural flexibility upon oxidation which may affect the drug binding site.

Febrile convulsion (FC) is the most common seizure disorder in childhood. white blood cell (WBC) and erythrocyte sedimentation rate (ESR) are commonly measured in FC. Trauma, vomiting and bleeding can also lead to WBC and ESR so the blood tests must carefully be interpreted by the clinician. In this cross sectional study 410 children(163 with FC), aged 6 months to 5 years, admitted to Bahrami Children hospital in the first 48 hours of their febrile disease, either with or without seizure, were evaluated over an 18 months period. Age, sex, temperature; history of vomiting, bleeding or trauma; WBC, ESR and hemoglobin were recorded in all children. There was a significant increase of WBC (P<0.001) in children with FC so we can deduct that leukocytosis encountered in children with FC can be due to convulsion in itself. There was no significant difference regarding ESR (P=0.113) between the two groups. In fact, elevated ESR is a result of underlying pathology. In stable patients who dont have any indication of lumbar puncture, there's no need to assess WBC and ESR as an indicator of underlying infection. If the patient is transferred to pediatric ward and still there's no reason to suspect a bacterial infection, there is no need for WBC test.