Tehran University Medical Journal

Impact of viral oncoproteins on human genome methylation: a review article

Shahram Jalilian

Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), hepatitis B virus (HBV), human papilloma virus (HPV), Merkel cell polyomavirus (MCPyV), human lymphotropic virus type 1 (HTLV-1) and Hepatitis C virus (HCV) are among the most important viruses that cause cancer in humans. These viruses are collectively known as oncoviruses due to their potential to induce malignant transformations in host cells. Oncoviruses exert their cancer-causing effects by utilizing various viral oncoproteins and non-coding RNAs, which can drive host cells toward malignancy through multiple pathways. One critical strategy these viruses employ involves altering the host cell's regulatory mechanisms, particularly by influencing DNA methylation processes.
DNA methylation is a crucial modification that occurs on the promoter regions of genes, effectively reducing their expression levels. Under normal cellular conditions, a delicate balance of methylation and demethylation is maintained by a specific set of enzymes. Key players in this process include DNA methyltransferases (DNMTs) and TET methylcytosine dioxygenases (TETs), which are pivotal in regulating gene expression through methylation. These enzymes are prime targets for oncoviruses because, by altering their activity, viruses can hijack the host cell's regulatory machinery. Viral oncoproteins, though diverse in structure and function, often converge on disrupting the expression of these enzymes. By doing so, they induce widespread changes in DNA methylation patterns, effectively reprogramming the gene expression landscape of the host cell. This reprogramming is not random; rather, it is a calculated mechanism through which oncoviruses can manipulate the cell cycle, promoting uncontrolled cellular proliferation and progression towards cancer. By suppressing or activating specific genes, these viruses can push cells past normal checkpoints, eventually leading to tumor formation. Despite the critical role of DNA methylation in cancer development, the precise mechanisms by which oncoviruses modulate these methylation processes are not fully understood. Researchers have made significant progress in exploring the connection between viral infections and cancer, but many of the detailed pathways through which oncoviruses control methylation remain to be elucidated. As a result, this area remains a fertile ground for further research, offering potential avenues for therapeutic intervention in virus-induced cancers.

Investigating the effect of ketamine on the prevention of shivering after spinal anesthesia in lower limb orthopedic surgeries: a single-blind randomized clinical trial study

Mansour Deylami

Background: Shivering is one of the side effects of anesthesia that occurs both in general anesthesia and regional anesthesia. Ketamine, as an N-methyldiaspartate receptor antagonist, may prevent shivering after spinal anesthesia by reducing central heat distribution to the environment. Therefore, the purpose of this study is to investigate the effect of ketamine in preventing tremors after spinal anesthesia in lower limb orthopedic surgeries.
Methods: This randomized, single-blind clinical trial study was conducted on 60 patients who were candidates for orthopedic surgery of the lower limb referred to 5 Azar Hospital in Gorgan. Patients were randomly divided into two equal groups of ketamine (0.25 mg/kg) and control (placebo). The data collection tool includes a checklist containing information; Age, gender, mean arterial pressure, percentage of arterial oxygen saturation, heart rate, tremors and hallucinations. Data analysis was performed using descriptive statistics and inferential statistical tests at a significance level of P<0.05.

Results: There was no statistically significant difference in gender between the control and intervention groups. The mean age of the study subjects in the control group was 36.13±12.53 and in the intervention group was 40.30±11.96. There was no statistically significant difference in age between the control and intervention groups. There is no statistically significant difference in mean arterial pressure (MAP) between the control and intervention groups. The incidence of shivering after spinal anesthesia was 13.33% in patients receiving prophylactic ketamine and 40% in patients receiving placebo. The incidence of hallucinations in the ketamine group was 26.67%. The rate of nausea and vomiting was similar in both groups. According to this study, between the two groups in terms of hemodynamic parameters, including mean arterial pressure, heart rate, percentage of arterial oxygen saturation; There was no significant difference.
Conclusion: The incidence of shivering in spinal anesthesia in the preventive use of ketamine has been more effective than placebo. Considering the effectiveness of ketamine in reducing the incidence of shivering, its use as a prevention is suggested to reduce the incidence of shivering.

Investigating the role of vitamin D deficiency as a risk factor and prognosis of breast cancer: a case-control study

Marzieh Haghbeen

Background: Breast cancer is the most common cancer diagnosed in women. Epidemiological studies have led to the hypothesis that vitamin D may reduce the risk of breast cancer. This study aimed to investigate the association between vitamin D deficiency and breast cancer.
Methods: This case-control study was conducted on 59 patients referred to Khatam Al-Anbia Comprehensive Cancer Clinic in Jahrom city between May 2021 and March 2022. Thirty patients with pathologically confirmed ductal or lobular breast cancer in situ or invasive in one or both breasts, with no previous history of the disease and within two months of their breast cancer diagnosis, were considered as the case group. Thirty women without breast cancer who had been referred for breast screening examination were considered as the control group. Both groups were matched for demographic characteristics and age. The data collection tools in this study included demographic information and clinical history of the patients and serum vitamin D levels. Data analysis was performed using SPSS software, version 21 (IBM SPSS, Armonk, NY, USA) and descriptive statistics (mean, percentage, and standard deviation) and inferential statistical tests (logistic regression, Kolmogorov-Smirnov). The significance level was considered to be P<0.05.

Results: The mean age of the patients participating in the case group was 52.17±10.6 and in the control group was 51.24±9.7. There was no statistically significant difference in age (P=0.654). There was also no significant difference between the two groups in terms of body mass index and different body index classifications, menopause age, and age of onset of menstruation. The number of months of breastfeeding in the control group was significantly higher than the case group (P=0.001). The results of logistic regression showed that, on the other hand, there was no significant relationship between the type of pathology of the disease and serum vitamin D levels.
Conclusion: The results of the present study showed that vitamin D deficiency can be a poor prognostic factor in the course of breast cancer.

Evaluation of the impact of blue light blocking filters on visual quality after PRK surgery

Aliakbar Shafiee

Background: Problems related to blue light exposure are among the various issues experienced by individuals who have undergone Photorefractive Keratectomy (PRK).Given the growing concerns regarding blue light’s effects on visual health, this study aimed to thoroughly investigate the impacts of blue blocker filters on the improvement of vision in patients post-refractive surgery of the PRK type. The primary objective was to evaluate the overall effectiveness of these filters in enhancing visual quality and in reducing complications associated with the surgery, which can significantly affect a patient’s quality of life.
Methods: In a quasi-experimental study conducted from September 1, 2024, to the end of October 2024, individuals who had undergone PRK surgery were examined at the optometry clinic of Dr. Labbafi Nejad Hospital in Tehran. Participants were subjected to assessments both with and without the application of blue blocker filters. Key parameters, including visual acuity and contrast sensitivity among attendees, were meticulously measured under both conditions. The results were then systematically compared and analyzed to draw meaningful conclusions about the impact of blue blocker filters in this context.

Results: A total of thirty-four participants, comprising 73.5% females and 26.5% males, with an average age of 32.6 years, were incorporated into the study. Post-surgery, the average refraction measured in the right and left eyes was documented as -0.42±0.16 D and -0.30±0.16 D, respectively. Notably, visual acuity in both eyes significantly improved with the use of the blue light blocking filter (P<0.005) Moreover, contrast sensitivity at varying spatial frequencies of 1.5, 6, and 18 cycles per degree (c/d) also exhibited significant enhancement (P<0.005).
Conclusion: The incorporation of blue blocker filters for individuals with a history of PRK surgery has led to noteworthy improvements in visual acuity and enhanced contrast sensitivity. These findings underscore the critical importance of integrating blue light protection in the post-operative care of patients, as it significantly elevates the overall visual experience and may contribute to better long-term outcomes following refractive surgery.

Investigating the effect of aerobic training and Ursolic acid consumption on the expression of some genes of the sarcopenia and osteoporosis signaling pathways in type 2 diabetic model aged rats

Parvin Farzanegi

Background: Aerobic exercise and the consumption of certain supplements, such as ursolic acid, may reduce sarcopenia and osteoporosis by activating or inhibiting specific genes and signaling pathways. This study aimed to investigate the effects of aerobic exercise and ursolic acid supplementation on the expression of genes related to inflammatory and autophagy pathways in type 2 diabetes.
Methods: This experimental study was conducted from May 2023 to October 2023 at Islamic Azad University, Sari Branch. A total of 30 male Wistar rats (12 months old, mean weight 390 g) were randomly assigned to five groups: 1) healthy (normal), 2) diabetic, 3) diabetic+exercise, 4) diabetic+supplement, 5) diabetic+exercise+ supplement. Diabetes was induced via intraperitoneal injection of streptozotocin (50 mg/kg body weight). The aerobic exercise protocol was performed five days a week for eight weeks. The supplement groups received a daily intraperitoneal injection of ursolic acid (250 mg/kg body weight).

Results: Data analysis showed that there was a statistically significant difference between the groups in the expression levels of LC3, Becline-1, TNFα, IL-1β Akt, and FOXO3 genes (P=0.000). The results of the post hoc test also showed that the expression level of LC3, Becline-1, TNFα, IL-1β genes in the model group increased significantly compared to the normal group (P=0.000). A significant difference was observed between intervention groups (P<0.05). The results of the follow-up test also showed that the level of expression of Akt genes in the model group was significantly decreased compared to the normal group (P=0.000). No significant difference was observed between intervention groups (P<0.05).

Conclusion: The results of the study showed that regular aerobic training and Ursolic acid consumption can affect inflammatory and autophagy pathways. These effects reduce cell atrophy through changes in some biological signals and help improve muscle function in type 2 diabetes. Therefore, aerobic training and Ursolic acid consumption can serve as an effective strategy for improving metabolic status and preventing cellular damage in this patient population.

Prospective drug utilization evaluation of vancomycin in a specialized and sub-specialized pediatric referral hospital in Ahvaz

Farzaneh Hematian

Background: Vancomycin resistance in intensive care units has significant complications and additional costs. Given the need for rational use of this antibiotic to prevent the occurrence of antibiotic resistance, the present study was designed to evaluate how to prescribe the antibiotic vancomycin consumption pattern in a pediatric subspecialty hospital.
Methods: This cross-sectional descriptive-analytical study was conducted over a 3-month period (February, May, and June) in 2021 at the Pediatric Hospital of Jundishapur University of Medical Sciences, Ahvaz. All patients hospitalized in the intensive care unit and infectious disease ward with vancomycin prescription were included in the study. Patients who were hospitalized for less than three days or had no desire to enter the study were excluded from the study. Vancomycin prescription by clinical pharmacist was reviewed based on the latest version of Lexicomp from Wolters Kluwer and the National Health Service (NHS) guidelines.

Results: Of the 91 hospitalized patients, 70.3% (64 cases) were prescribed vancomycin without performing an antibiogram culture based on experience and 29.7% (27 cases) were based on an antibiogram culture. In 96.7% (88 cases) , the duration of intravenous vancomycin infusion did not comply with the protocol. Red Man Syndrome was observed in 8.8% (8 cases). In 91.2 % (83 cases), no adverse effects were reported. In 65.9% (60 cases), the drug dose was determined based on the correct renal function Glomerular filtration rate (GFR) and in 34.1%, the drug dose was determined regardless of the renal function of the patients. Vancomycin doses were lower and higher than the guidelines in 6 and 25 patients, respectively. Out of all patients, eighty four cases recovered and seven cases died.
Conclusion: In almost half of the patients, Vancomycin were prescribed based on experience and without performing an antibiogram test. Use of guidelines, Serum level monitoring programs and continuous medical education for doctors can be effective in rational use of antibiotics.

Comparison of the complications and results of intubation with a cuffed tracheal tube filled with alkaline lidocaine gel and filled with air in patients admitted to Baqiyatallah Al-Azam Hospital

Pourya Mashategan

Background: Intubation is normally conducted in an emergency or prior to surgery. A cuffed tracheal tube is fitted, whose inflated cuff exerts pressure on the tracheal wall. Such pressure should, therefore, be monitored every day by use of pressure gauge devices. The general guideline in this regard is that the pressure of the cuff must lie between 20 and 30 cm of water. The exaggerated pressure may cause tissue ischemia, wound, and necrosis of the tracheal wall; if it is too low, this could result in air leakage and oropharyngeal secretions, increasing the risk of insufficient ventilation and aspiration pneumonia. This study aimed at comparing the cuff pressure of an endotracheal tube inflated with alkaline lidocaine versus air for any post-extubation complications and cuff pressure changes.
Methods: This prospective cohort study was conducted on patients who were admitted to the intensive care unit of Baqiyatullah Al-Azam Hospital in Tehran between May 2023 and February 2024, underwent intubation in this unit and met the inclusion criteria for the study. This prospective study included 62 patients, and tracheal tube cuff pressure was recorded at 30 minutes, 60 minutes, 120 minutes, 6 hours, and 24 hours after intubation with a pressure gauge. Patients were randomly divided into two groups-an 'air group', whose cuff was inflated to the pressure of 20 cmH2O by air, and a 'lidocaine group,' whose cuff was filled with 2% lidocaine to the same pressure. In this study, the post-extubation complications, such as sore throat, hoarseness, and cough, were assessed immediately and 24 hours after extubation. Similarly, the tracheal tube displacement during the intubation process was monitored in both groups.
Results: The results showed that the pressure of an endotracheal tube cuff inflated with lidocaine was drastically lower than the one inflated with air, with a p-value of 0.001. On the other hand, the sore throat, cough, and hoarseness after extubation and 24 hours later were significantly fewer in the lidocaine group compared with the air group at a p-value of 0.001.
Conclusion: Cuffs inflated with alkalinized lidocaine clearly avoided high cuff pressure at induction and reduced postextubation sore throat. Hence, alkalinized lidocine-filled endotracheal tube cuffs are comparatively safer and more beneficial than conventional air-filled cuffs.

Evaluation of frequency and factors associated to cerebrospinal fluid circulation disorder after decompressive craniectomy

Morteza Taheri

Background: Decompressive craniectomy (DC) is a therapeutic approach for patients with raised intracranial pressure and cerebral edema. Although DC is not a complicated procedure, it is associated with significant complications and morbidities that significantly affect clinical outcomes. This study investigates the frequency of cerebrospinal fluid (CSF) circulation disorders after DC and evaluates related factors.
Methods: This cross-sectional analytical study was conducted on 79 patients who underwent DC at Shohadaye Haftome Tir Hospital, one of the main trauma centers in Tehran. The patients' files and the Picture Archiving and Communication System (PACS) were reviewed to collect demographic, clinical, and radiologic data. After identifying patients with post-operative (after DC) CSF circulation disorders, the relevant factors were determined using multivariate logistic regression.

Results: Overall, seventy-nine patients were studied. The mean age of patients was 40.56±12.64 years and 82.3% were male. Forty-seven patients (59.5%) underwent DC due to traumatic causes and thirty-two patients (40.5%) due to vascular pathologies. In total, 36.7% (nineteen) of patients were affected by some degree of subdural hygromas of which 13 patients (44.8%) progressed to clinical and radiologic hydrocephalus. 19% (fifteen patients) developed hydrocephalus within the first six months after surgery. Considering the clinical variables, the GCS of patients was the only one that showed a significant relationship with CSF circulation disorders. Regarding radiological variables, the presence of intraventricular hemorrhage (IVH) was the only relevant factor. In addition, from the surgical perspective, performing duraplasty (autograft or allograft) and reoperation demonstrated significant relationships with CSF circulation disorders. The results of multivariate logistic regression showed that having intraventricular hemorrhage (OR, 6.15-6.9414: CI95%, P=0.003) and reoperation (75.91: OR, 3.88-3.6, 1485/43: CI95%, P=0.004) were two independent factors associated with hydrocephalus in DC patients.

Conclusion: In patients who have undergone decompressive craniectomy, intraventricular hemorrhage (IVH) and reoperation can be independent risk factors for CSF circulation disorders. Although the incidence and presence of IVH cannot be controlled, careful and meticulous surgical technique and skill can significantly improve the outcome of decompressive craniectomy by reducing the need for reoperation

Identification of diagnostic biomarkers in kidney cancer using RNAseq data analysis and their confirmation by qRT-PCR

Seyyed Abdolhamid Angaji

Background: Clear renal cell carcinoma (ccRCC) is the most common malignant kidney tumor and has a high mortality rate. The pathogenesis of this cancer is complex and efficient biomarkers for its diagnosis and prediction are limited. This study aimed to identify predictive genes in ccRCC through analysis and laboratory validation ccRCC is the most common malignant kidney tumor and has a high mortality rate.
Methods: The present study was a case-control study in which samples were taken from patients and healthy individuals from Labafi Nejad Hospital in Tehran between October 2012 and April 2014, and laboratory tests were performed on the samples.
First, genes with differential expression in ccRCC patients were identified by bioinformatics using gene expression profile data from the Gene Expression Omnibus (GEO) database with accession number GSE213324. Data analysis was performed using Galaxy web server, protein-protein interactions were checked using Cytoscape and STRING app software, and finally two genes were selected for real-time PCR testing.

Results: Analysis identified 4,065 genes with differential expression in RCC tissues compared to healthy tissues. These genes are involved in immune responses and renal disease pathways, suggesting their potential role in disease development. After constructing the protein-protein interaction network and identifying differentially expressed genes in kidney tissue and blood, two genes, MTTP and CALCA, were selected for further investigation. In the Mann-Whitney U test, the expression of the CALCA gene decreased significantly in the patient group (P<0.05). On the other hand, the MTTP gene showed a decrease in expression, but not significantly. The AUC calculated to evaluate the diagnostic accuracy for the CALCA gene was 0.64 and significant (P<0.05), demonstrating its potential as a useful biomarker for ccRCC diagnosis. However, the AUC for the MTTP gene was not significant.
Conclusion: The reduction in CALCA expression could serve as a useful biomarker for diagnosing ccRCC.