Archives of Razi Institute最新文献

Prolonged use of antiretroviral agents has been clearly associated with nephrotoxicity, suggesting deterioration of renal function in patients receiving Highly Active Antiretroviral Therapy (HAART). The present study was designed to investigate the therapeutic efficacy of resveratrol (RV) in the treatment toxins-induced renal impairment. Twenty-four adult male Wistar rats weighing 70-90 g were divided into four groups and subjected to the following treatments: Control A (distilled water), B (HAART), C (RV-2.5 mg/kg), D (RV- 2.5 mg/kg) + HAART. Assessment included renal histological examination; renal function indicators such as serum creatinine and blood urea nitrogen; serum electrolyte levels including sodium, chloride, potassium, bicarbonate; and oxidative stress biomarkers such as malondialdehyde, catalase and glutathione and superoxide dismutase. Adverse effects of HAART include adverse histological changes, such as tubular atrophy, vacuolization, tubular granular degeneration and glomerular capillaries abnormalities. Compared to the other treatment cohorts, serum creatinine, blood urea nitrogen (BUN), sodium, chloride and malondialdehyde (MDA) levels were significantly increased, while antioxidant enzyme activities such as catalase (CAT) and superoxide dismutase (SOD) and glutathione (GSH) levels were notably decreased. Renal structure remained largely unchanged after RV administration, with some recovery in histological abnormalities. Visible improvements, including reduced inflammation, reduced necrosis, reduced vacuolization and improved tubule and glomerular configuration, were also observed. In addition, RV notably increased antioxidant enzyme levels (SOD, CAT, and GSH) and decreased BUN, serum creatinine and MDA levels. RV helped mitigate HAART-induced structural abnormalities and renal dysfunction, while improving renal morphology. However, further investigation of these mechanisms is needed.

The present experimental study aimed to assess the in vitro wound healing and anti-inflammatory effects of green synthesized copper nanoparticles (CuNPs) by the methanol extract of Ferula macrecolea (Boiss), as a plant with various pharmacological effects, such as anti-inflammatory and antimicrobial effects, in traditional and modern medicine. The precipitation approach was used for the green synthesis of CuNPs by mixing the methanol and copper sulfate solution. Cell viability and fibroblast proliferation assay were performed by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The migration abilities of fibroblast cells were evaluated using the in vitro scratch assay for wound healing. The effects of CuNPs on gene expression of inducible nitric oxide synthesis (iNOS) were also examined by real-time polymerase chain reaction (PCR). In vitro antibacterial susceptibility test of CuNPs was carried out according to the standards protocol of the National Committee for Clinical Laboratory Standards. The scanning electron microscope analysis revealed that the green synthesized CNP exhibited a globular shape with a size ranging from 15 to 90 nm, while the majority were at 40-60 nm. The results of the MTT assay demonstrated that the calculated 50% cytotoxic concentration (CC₅₀) value of green synthesized CuNPs was 236.3 μg/mL. The optimum concentrations of the CuNPs were selected based on the CC₅₀, which dose-dependently increased the proliferation of fibroblast cells. The CuNPs dose-dependently increased the rate of wound closure after 16 and 24 h. The results of the real-time PCR illustrated that CuNPs caused upregulation in the expression level of the iNOS gene in RAW 264.7 cells. CuNPs showed promising antimicrobial effects against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The present study highlighted the high potency of green CuNPs synthesized by F. macrecolea for wound healing through their antimicrobial properties, proliferation of fibroblast cells, and provoking iNOS.

There is always a concern about the quality of cell-based products in terms of the contamination of the cells and their lack of efficiency. Therefore, it is of prime importance to ensure these cells' identity, purity, efficacy, and suitability for the production of biological products and diagnostic uses. Hence, cells must be identified, evaluated, documented, and stored to be used consistently and efficiently. With these conditions, vaccine manufacturers have a suitable reserve of efficient and valuable cells for the production and quality control of biological products. In this review article, a strategic plan was drawn for cell-substrate well-characterization and identification according to scientific principles, the author's work experience, and regulatory guidance for the optimal use of that cell in research and diagnostic studies especially for the biological product production process. For this purpose, all aspects of cell identification, cell evaluation, and cell characterization are discussed. Because of the importance of cell identity in the competence of a cell substrate, in the cell identification section, all aspects of cell identification, including general cell information and specific cell characteristics, especially in terms of cell passage history, cell storage conditions, and cell coding and labeling, were studied. In the part of cell evaluation and determination of cell characteristics, all required tests to determine cell characteristics from various aspects, including determination of cell identity, cell growth conditions, cell quality, efficiency, and the possibility of cell contamination with adventitious agents, including cellular, viral, bacterial, mycoplasma, and mycobacterial agents were introduced. Due to the importance of endogenous virus contamination, this topic is specially discussed. In addition, the stability of the cell both from the aspect of genetic stability and from the aspect of stability of cell efficiency, were discussed. In the end, while reviewing the necessary documents to be under the control of the cell for use in the laboratory, based on the studies conducted, the certificate of the cell has been compiled. Therefore, on this basis, the studied cell can be used for research and diagnostic studies of virology, especially for the production and quality control of biological products.

In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system. Scopolamine injection increases dopamine by inhibiting M2/4 muscarinic autoreceptors. These autoreceptors are located on dopaminergic presynaptic neurons, and their activation reduces the release of dopamine. Therefore, blocking these autoreceptors by scopolamine can increase the release of dopamine. Both D1 and D2 receptors are involved in learning and memory processes. In general, stimulation of dopamine D1 receptors follows an inverted U-shaped dose-response curve, meaning that both insufficient and excessive amounts of dopamine cause memory impairment. Therefore, an indirect effect on the dopaminergic system can be one of the scopolamine-induced memory impairment mechanisms. Effects on cell membrane potential and neuron plasticity, and interaction with acetylcholine are among other mechanisms. Serotonin plays a complex role in memory and learning. Serotonin receptors (5-HT2A) also play a role in memory function by affecting calcium transport. This action is similar to dopamine and other G-protein-coupled receptors, which activate phospholipase C, enter calcium into the cell, and activate calcineurin. Activation of 5-HT2A and 5-HT4 receptors by specific agonists of these receptors enhances long-term potentiation (LTP), which plays a significant role in memory. On the other hand, specific 5-HT3 receptor antagonist improves LTP. The 5-HT6 receptor antagonist can improve memory function. Therefore, different serotonin receptors have different roles in memory function, and the interaction between scopolamine and these receptors needs further study. It has been shown that histamine increases the secretion of acetylcholine in the hippocampus, and postsynaptic H1 and presynaptic H3 receptors play a major role in memory and learning; however, whether scopolamine can cause memory impairment through interaction with histamine receptors has been not reviewed.

Lipases are triacylglycerol hydrolases with various potential applications because of their different physical properties. Most lipase producers are extracellular in nature and are created using solid-state fermentation and submerged fermentation methods. The fungal, mycelial, and yeast lipases are produced using various solid substrates through the solid-state fermentation method. This method is cost-effective and widely used in industries to produce lipase using fungi. However, lipases from bacteria are produced using submerged fermentation. The optimization of media is a main requirement for increasing the quantitative yield by the overproduction of enzymes. The optimization of media is a main requirement for increasing the quantitative yield by overproduction of enzymes. Different parameters, such as pH, temperature, agitation speed, inoculum size, incubation time, and carbon and nitrogen sources, have been of great importance for researchers in designing economical media. The optimization by one factor at a time (OFAT) is a one-dimensional approach that is laborious and time-consuming and does not consider interactions between the factors. The limitations of OFAT method can be alleviated by employing some techniques, such as Plackett-Burman design (PBD) and response surface methodology (RSM). The PBD is a method to screen the variables that influence production and remove the non-significant factors to attain a smaller and manageable set of factors. Subsequently, the chosen significant factors are optimized by RSM that assists to study the interactions of different factors. The RSM comprises of central composite design (CCD) to fit a second-order polynomial equation. In this study, the effect of temperature, tryptone, inoculum size, and incubation time on the lipase production were analysed by PBD screening experiments. The experiments were designed using a CCD with four variables as part of RSM, utilizing the Design Expert software. This model predicted optimal activity of lipase at 58.53 U/mL when using 1.5% tryptone, a 10 mL inoculum size, and an incubation period of 48 h at 34°C. This experiment was further validated and optimal activity of lipase of 57.85 U/mL was observed. Thus, RSM model enhanced the production of lipase and can be applied for the maximum yield of lipase.

Cancer, a disease threatening human life, is caused by the disturbance of the normal cell cycle, which results in the spontaneous growth of normal and malignant cells, the lack of differentiation between the two, and consequently malignant growths. Nowadays, various synthetic agents are applied for cancer therapy; nevertheless, reports have confirmed that these chemical agents are associated with various adverse complications. This experimental study was designed to assess the anti-tumor activities of zinc nanoparticles (ZnNPs) green synthesized by the Astragalus maximus (A. maximus) extract against Ehrlich solid tumors (EST) in mice. To induce the EST model, 0.2 ml of cell suspension was intramuscularly injected into the right thigh of the mice. Five days post-injection, the mice were assigned to five groups (eight mice each): EST mice treated with normal saline, EST mice orally treated with ZnNPs 10 mg/kg/day, EST mice orally treated with ZnNPs 25 mg/kg/day, and EST mice orally treated with ZnNPs 50 mg/kg/day for 14 days. Afterward, the volume of the tumor, tumor growth inhibition, body weight, tumor markers, oxidant/antioxidant markers, and tumor necrosis factor-alpha level were assessed in the tested mice. The results showed that after the treatment of EST mice with cyclophosphamide and ZnNPs at 10, 25, and 50 mg/kg, the volume of the tumor, and the serum amount of tumor markers (alpha-fetoprotein and carcinoembryonic antigen) were significantly reduced (P<0.001). It was found that ZnNPs at 10, 25, and 50 mg/kg markedly declined oxidative markers and increased the level of antioxidant enzymes (superoxide dismutase and glutathione peroxidase), compared to the control group, which received normal saline (P<0.001). To conclude, this study reported the unveiling of the anti-tumor activity of ZnNPs green synthesized by the A. maximus extract, mainly at a dose of 50 mg/kg against EST in mice. However, further supplementary studies are required to clarify all the anti-tumor aspects of these nanoparticles.

Intestinal protozoan parasitic infections are considered one of the most frequent types of infection caused by these parasites and remain a major health problem for communities. This study aims to detect the frequency of intestinal protozoan infections infection among Zakho general population from October 2018 to June 2022. This cross-sectional study was performed on 2,118 patients referring to private medical diagnostic laboratories in Zakho, Kurdistan Region, Iraq. Samples of fecal matter were collected and subjected to analysis using two different techniques: direct observation under the microscope (wet mount) and formalin-ether concentration methods. Morphological characteristics of trophozoites and cysts were used to identify E. histolytica using microscopical examination. Out of 2,118 recruited samples, 1,155 (54.53%) were male, and 963 (45.47%) were female. The mean age of participants was 20.41 (±19.12), with ages ranging from 1 to 63 years. The overall prevalence of protozoan infections was 395/2118 (18.65%). Out of these, Entamoeba histolytica was the predominant pathogenic protozoa infection 271 (68.61%), followed by Giardia lamblia 100 (25.31%). A significant association was seen between Entamoeba histolytica and age groups (P=0.003) and gender (P=0.004). The highest infection rate was reported among the age group <15 years (55.72%). We also found a higher rate of Giardia infection among age group < 15 years (46%) with significant differences (P=0.002) and a higher rate of Giardia seen in females (55%) with significant association (P=0.014). The frequency of Giardia lamblia and E. histolytica infections in our study was higher than other studies reported in Iraq and other countries, and these infections continue to pose a difficult public health issue and necessitate the implementation of stronger and more effective preventative measures.

Highly pathogenic avian influenza (HPAI) is a viral disease caused by some H5 and H7 subtypes of influenza virus type A in most species of birds, especially poultry. HPAI viruses are among the most challenging viruses that threaten both human and animal health. Consequently, various strategies, such as the use of vaccines have been proposed to control the disease. After a catastrophic pandemic and the failure of conventional methods (elimination and extermination) in Iran, multiple vaccines have been used to control the disease. This study investigates the immunogenicity of two recombinant inactivated commercial vaccines of H5N1 and H5N3 subtypes in laying pullet flocks in Tehran Province, Iran. From 32 halls in six breeding units of laying pullets, 3,200 sera, and 800 tracheal and cloacal swabs were collected. After collecting the samples, Serum neutralisation (SN) and hemagglutination inhibition (HI) tests were conducted on sera to determine the serum titers of H5 specific antibody obtained from vaccine inoculation in three steps: before, after the first vaccination, and after the second vaccination (booster). The SN and HI tests were carried out by the alpha and beta methods on the pooled samples by the vaccine type (as antigen for HI and SN), and the results were compared. The PCR was performed on the tracheal and cloacal swab samples to possibly detect the HA (H5) virus in the studied flocks. The HI test results showed that both vaccines had a Serum antibody titre above 5 (log₂) after two vaccination rounds, indicating a desirable immunogenic response. The SN test results also showed a neutralisation index above 10^4.5 for both vaccines, indicating more than 50% reduction in antigenicity of the virus. The PCR results were negative. This study was the first investigation of immunogenicity following two-time vaccination against H5 subtype vaccines in Iranian poultry flocks, indicating suitable antibody titer against the influenza virus in vaccinated flocks.

In this case report, we present a 63-year-old man with a history of diabetes mellitus and kidney transplantation who was diagnosed with nasal myiasis. The patient presented with symptoms of nasal myiasis infestation, including epistaxis, nasal obstruction, nasal discharge, and the presence of larvae. The patient had risk factors for poor wound healing, such as hyperglycemia, and the presence of diabetes mellitus, hypertension, and kidney transplantation indicated the presence of predisposing factors for myiasis. The myiasis was observed subsequent to the traumatic insertion of a nasogastric tube. The patient exhibit[ed symptoms of myiasis infestation in the nasal region, including epistaxis, nasal obstruction, and nasal discharge, along with the presence of larvae. Our findings highlight the occurrence of nasal myiasis in a patient with a complex medical history, and emphasize the need for clinicians to remain vigilant for this infection. Axial CT scan showed no mucosal thickening, and T1 weighted cervical MRI showed no abnormal signal intensity, except for spondylopathy and modic changes. Diffusion Weighted-MRI (DWI) revealed no abnormal signal in the brain parenchyma. Our findings suggest the importance of clinicians being vigilant for nasal myiasis in patients with predisposing risk factors, such as diabetes mellitus and kidney transplantation. Managing nasal myiasis can be challenging, particularly in patients with multiple conditions. The management of nasal myiasis can be challenging, particularly in patients with multiple comorbidities.

Hepatic encephalopathy (HE) is a clinical syndrome that can result from acute and chronic liver disorders, such as hepatitis, liver failure caused by alcohol or drugs, autoimmune diseases, metabolic diseases, cirrhosis, different types of tumors, and infections. This study aimed to investigate the effects of different doses of Beta-myrcene (β-myrcene) on the improvement of HE caused by thioacetamide (TAC) in male rats. To induce liver failure and acute damage in the studied animals, TAC was administered to rats at a dose of 100 mg/kg of body weight through an intraperitoneal (IP) injection with 24-hour intervals for seven consecutive days. After the oral treatment of rats with β-myrcene at doses of 10, 25, and 50 mg/kg/day for seven days, the cerebral edema (brain water content, BWC), the serum level of liver enzymes (aspartate aminotransferase, alanine transferase, alkaline transferase, total protein, and bilirubin), ammonia, and the level of oxidant-antioxidant factors (lipid peroxidation [MDA], glutathione peroxidase [GPx], catalase [CAT], and superoxide dismutase enzymes [SOD]), were evaluated. β-myrcene dose-dependently reduced BWC in TAC-induced acute HE in rats. In TAC rats treated with β-myrcene, especially at doses of 25 and 50 mg/kg, the serum levels of these liver enzymes and ammonia were significantly moderated (P<0.001), compared to the untreated TAC rats. The analysis of the obtained results revealed that the treatment of TAC rats with β-myrcene, especially at doses of 25 and 50 mg/kg, significantly reduced the oxidative stress marker MDA (P<0.001), whereas it significantly increased the antioxidant enzymes SOD, CAT, and GPx (P<0.001). Therefore, it can be concluded that the treatment of TAC rats with β-myrcene, especially at doses of 25 and 50 mg/kg, significantly reduced the oxidative stress marker MDA, whereas it significantly increased antioxidant enzymes and subsequently improved TAC-induced acute HE in rats.