hossein ghalehnoei

Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder characterized by the clonal and malignant proliferation of mature B-cells within the peripheral blood, bone marrow, and secondary lymphoid tissues. In chronic infections and cancers, T-cells become exhausted due to continuous antigen exposure. This uncontrolled tumor cell growth creates an environment that lacks sufficient oxygen, nutrients, and physical space for normal cells, referred to as the tumor microenvironment. The tumor microenvironment employs multiple mechanisms to suppress the immune system, affecting metabolic pathways in both T-cells and tumor cells. Consequently, inhibitory receptors on T-cells and their ligands on tumor cells are upregulated, leading to reduced proliferation, cytotoxicity, and production of effector cytokines, such as interferon-gamma, by T-cells. T-cell exhaustion presents a therapeutic challenge in treating many malignancies, including CLL. In CLL, T-cell exhaustion is observed through the simultaneous upregulation of inhibitory receptors. Given that current therapies for CLL are often associated with side effects, resistance, and relapse, studying transcript changes may assist in designing more effective treatment strategies. This study investigates the transcriptome profile of CD8+ T-cells in CLL patients compared to healthy individuals using bioinformatics platforms.

The keywords used in this study were CLL, CD8, and human. Raw data were initially searched in the SRA database using these keywords. Left and right reads were merged using CLC Genomics Workbench version 21. Following quality control of the data, sequences were assembled using human genome reference data, mRNA sequences, and coding sequences (CDS). Gene expression related to CD8+ T-cell exhaustion was then compared between CLL patients and healthy individuals. The analysis results were presented in heatmap and volcano plot formats.

In this study, genes involved in CD8+ T-cell exhaustion and differential expression were identified by comparing 11 CLL patients with 11 healthy individuals. The expression levels of 59 selected genes were displayed in volcano plot and heatmap formats. Expression changes in 42 genes were statistically significant (FDR P<0.05), with 18 genes showing increased expression and 24 showing decreased expression in CLL patients compared to healthy controls.

The study found differences in the expression levels of genes involved in CD8+ T-cell exhaustion between CLL patients and healthy individuals. Molecules encoded by genes upregulated in CLL may serve as potential targets for developing new therapies. By creating monoclonal antibodies and small molecules to inhibit these targets, it may be possible to counteract T-cell exhaustion, representing a promising advance in the treatment of this phenomenon.

Major depressive disorder is one of the most common causes of disability in people of the world, so it has imposed a heavy burden on society in terms of medicine and the economy. One of the important and valuable biomarkers in identifying major depressive disorder is the FKBP5 and SLC6A4 genes in depressed patients.

This study aimed to evaluate the sensitivity and specificity of FKBP5 and SLC6A4 genetic markers in distinguishing major depressive disorder (MDD) patients from healthy controls (HCs) and the responses to cognitive behavioral therapy (CBT) and fluoxetine therapy.

Forty patients diagnosed with MDD based on the diagnostic and statistical manual of mental disorders, fifth edition (DSM-V) criteria and 44 HCs were included in our study from patients of private clinics and Zare Hospital Sari from January 2022 to March 2022. Sampling was carried out from MDD patients and HCs. The patients were randomly assigned to CBT or fluoxetine therapy groups using a randomization block method. The CBT group (12 weeks/one session per week/90 minutes per session), the fluoxetine therapy group (3 months/20 mg daily/weekly follow-up), and relative gene expression alterations were calculated using the quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique.

The receiver operating characteristic (ROC) curve analysis showed that FKBP5 [area under the curve (AUC) = 0.724, standard error = 0.054, P < 0.001] and SLC6A4 (AUC = 0.661, standard error = 0.092, P = 0.036) genes have acceptable sensitivity and accuracy in identifying MDD from HCs. After the therapeutic intervention, a significant decrease in the Beck Depression Inventory-II (BDI-II) scores was observed in both groups (CBT group, P < 0.001, fluoxetine group, P < 0.001). Comparing before and after treatment in the CBT group, a significant decrease in FKBP5 (P < 0.001) and SLC6A4 (P < 0.001) gene expression were observed. In the fluoxetine group, SLC6A4 (P = 0.44) gene expression did not show any significant changes, but FKBP5 (P < 0.001) gene expression decreased.

The present study showed that the FKBP5 and SLC6A4 genes are appropriate biomarkers for distinguishing MDD patients from HCs and treatment response. However, more research is required to identify biomarkers in distinguishing MDD patients from HCs and treatment response.

It has long been known that Methamphetamine (MA), as a psychostimulant, leads to long-lasting cognitive deficits. Previous studies have shown that lithium, a mood stabilizer, could facilitate cognitive ability in most of brain diseases. In current study the effects of lithium on spatial memory, hippocampal apoptosis and brain edema in METH-exposed rats are investigated.

The present study 32 Wistar rats were used to examine the effects of lithium on spatial memory by the Morris water maze, hippocampal apoptosis using the TUNEL assay, and brain edema following MA administrations. 

The findings indicated that treatment with lithium significantly ameliorated spatial learning and memory impairment in MA-treated rats. In addition, the findings showed that treatment with lithium significantly reduced brain edema and apoptosis in the CA1 neurons in MA -exposed rats. 

The results show that treatment with lithium can partially ameliorate the MA –induced neurocognitive deficits in rats, which may be related to its protective effect in the hippocampus.

Mehrdad Jalalian1,
Mehdi Pourasghar2,
Ahmad Majd3,
Hossein Ghalehnoei4,
Zahra Kianmehr5

1 PhD Student in Biochemistry, Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran
2 Associate Professor,  Department of Psychiatry, Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran
3 Professor, Department of Biology, Faculty of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
4Assistant Professor, Department of Medical Biotechnology, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
5Assistant Professor, Department of Biochemistry, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran



In the article published in volume 32, issue 207, 2022, the affilifations of Mehrdad Jalalian, Ahmad Majd and Zahra Kianmehr were published incorrectly, which are now corrected.

Pancreatitis is one of the most crucial complications following endoscopic retrograde cholangiopancreatography (ERCP). The purpose of the current study was to investigate patient-related post-ERCP pancreatitis (PEP) risk factors in two groups of patients: prophylactic pancreatic stent and rectal indomethacin.

Two different prophylactic modalities were planned and complications were assessed based on the defined inclusion criteria. In this study, the patients were evaluated for the procedure and patient-related risk factors in post-ERCP pancreatitis in the recipient groups of the prophylactic pancreatic stent and rectal indomethacin.

Pancreatitis was confirmed in 27 of all 170 selected patients after ERCP. By univariate analysis, two variables were significant with the development of PEP. Regarding the patient-related risk factors, unique subjects with common bile duct (CBD) dilated 10mm were more exposed to an increased chance of PEP (P=0. 015); meanwhile, other factors did not correlate with the increased possibility of PEP in both groups. The only procedure-related risk factor for PEP was the deep cannulation of the pancreatic duct in both groups during the procedure with an incremental significant incidence of pancreatitis (P=0.005). Comparison of prophylactic pancreatic stent and rectal indomethacin showed no effects in term of post ERCP pancreatitis reduction. Additionally, there was no significant difference between these two strategies in the rate of PEP.

Prophylactic pancreatic duct stents and administration of rectal indomethacin cannot have particular approaches for reducing the possible occurrence of PEP. The increase in time of deep cannulation and the presence of CBD dilation <10mm could be considered as important risk factors.

Cutaneous leishmaniasis (CL) is an important health problem in Iran and one of the world ̛s neglected diseases which is caused by Leishmania spp. The aim of this study was to investigate the epidemiology of cutaneous leishmaniasis and its associated risk factors in an endemic center in Golestan Province.

This descriptive cross-sectional study included patients with suspected CL who had been referring to the health centers of Gonbad–e Qabus town, between 2018 and 2020. Demographic and epidemiological data of CL patients were recorded and diagnosis of Leishmania spp. was made by Giemsa staining of direct smear. PCR was also used to determine and confirm the parasite species.

From 1979 suspected CL lesions, 1704(87.4%) had positive smears. 898 (52.7%) patients were male and 806 (47.3%) were female. The highest incidence rate was observed in the patients of less than 5 (25.93%) and those between 25 and 45 years of age (25.41%). In all samples in this study, Leishmania major was the only Leishmania spp detected by ITS-PCR. Also, Critidia fasciulata was identified in three patients.

The study provided valuable data concerning the epidemiologic aspects of the CL in an old endemic focus in north of Iran, which can be used as the basis for planning future control strategies.

Background and Major depressive disorder (MDD) is a massive challenge for community mental health. Serum zinc and cortisol are suitable biomarkers for assessing the response to a given treatment. In the present study, serum concentrations of these markers were compared between two groups of patients treated with fluoxetine and cognitive behavioral therapy.
In this randomized clinical trial study, 40 female MDD (DSM-V criteria) patients were divided into two groups: fluoxetine therapy (20 mg/daily/3 months, n=20) and group CBT (90-min/once a week/12 weeks, n=20). Severity of depression was studied by Beck Depression Inventory (BDI-II) and serum cortisol and zinc concentrations were measured before and after treatments. Data were analyzed in Graphpad Prism 9.
BDI-II scores significantly reduced in both fluoxetine therapy (from 23.2±1.5 to
11.1± 1.1) and CBT (from 26.8±0.6 to 9.5±0.8) groups after treatments. Serum cortisol level did not change in patients treated with fluoxetine, but it decreased in CBT group (from 453 ± 0.09 to 386.4±0.07). Serum zinc level decreased in the fluoxetine group (from 91.6±4.8 to 72.8±2.8) and increased in the CBT group (from 78.9±2.1 to 86.5±2.6). Post intervention inter-group comparison showed greater decrease in BDI-II score and cortisol concentration in CBT group than the fluoxetine therapy group.
The decrease in BDI-II score and cortisol level and increase in serum zinc were higher in CBT group than fluoxetine group. Therefore, CBT seems to be suitable for treatment of MDD. Further studies are needed with larger sample size and longer study periods.

(Clinical Trials Registry Number: IRCT20190710044171N1)

Human blood parasites are one of the most critical infections in human that transmit by vectors. Reservoirs of the parasites are crucially important in the epidemiology and control. In the current study isolated parasites from a Rhombomys Optimus (R. opimus), rodent confirms that Crithidia is a zoonotic parasitic disease. This study aimed to find the high-risk areas of this infection by considering the distribution of reservoirs and human infection. In this study, 148 rodents from an endemic focus of Gonbad-e-Qabus city in Golestan province were trapped and then killed ethically and direct smear and culture in Novy- MacNal-Nicolle medium (NNN) were taken and finally, results were confirmed by Polymerase Chain Reaction (PCR) and Sequencing method. Out of 148 rodent, 97 (65.54%) rodent were male and 51 (34.45%) were female (P <0.05). and in smear and culture were found 8 (5.40%) T. lewisi, 6 (4.05%) L. major, and 2 (1.35%) Crithidia spp. Based on the time; 40 (27.02%), 50 (33.78%), 38 (25.67%), and 20 (13.51%) rodents were trapped in spring, summer, fall, and winter, respectively. Due to northeastern Iran (Gonbad-e-Qabus) being the endemic focus of cutaneous leishmaniasis (CL), it should be noted that the reservoirs of this disease may also be contaminated with Leishmania spp, and Crithidia. Results showed that R. opimus are the important reservoirs of CL in northeastern of Iran. Important foci of the diseases in almost all areas of Iran are dispersed. Therefore, reliable methods to control mice are essentially needed.

Methamphetamine (METH) is one of the most powerful drugs that leads to many cognitive and behavioral side effects such as anxiety. On the other hand, studies have shown that ovarian hormones such as estrogen and progesterone have neuroprotective effects on a wide range of cognitive and behavioral disorders. The aim of this study was to investigate the role of estrogen and progesterone on anxiety-like behaviors, body temperature, brain edema, and neuronal death induced by neurotoxic regimen of methamphetamine.

This study was performed in 48 ovariectomized rats divided into six groups including: control, METH (6mg / kg), vehicle (sesame oil), METH + estrogen (1mg / kg), METH + progesterone (8mg / kg), and METH + estrogen + progesterone. Body temperature and anxiety-like behaviors were investigated, then, the animals were killed and brain tissues were harvested to evaluate brain edema and neuronal death in hippocampal CA1.

Body temperature, brain water content, motor activity, and anxiety-related behaviors significantly increased in animals that received METH (P<0.001), but, treatment with estrogen and progesterone attenuated motor activity, and anxiety-related behaviors induced by METH. Brain edema, body temperature, and neuronal cell death in hippocampal CA1 area partially decreased in METH+estrogen and METH + progesterone groups.

This study suggests that ovarian hormones such as estrogen and progesterone are effective in improving behavioral deficits and neuronal death induced by METH in ovariectomized rats.

Methamphetamine (METH) as a synthetic psychostimulant is being increasingly recognized as a worldwide problem, which may induce memory impairment. On the other hand, it is well established that naloxone, an opiate antagonist, has some beneficial effects on learning and memory. The present research aimed at evaluating naloxone effects on spatial learning and memory impairment triggered by a neurotoxic regimen of METH in male rats.

The animals received the subcutaneous (sc) regimen of METH (4×6 mg/kg at 2-h intervals), intraperitoneal (ip) naloxone (4×1 mg/kg at 2-h intervals), or normal saline at four events. The Nal-METH group of rats received four naloxone injections (1 mg/ kg, ip) 30 min before each METH injection (6 mg/kg, sc) at 2-h intervals. Seven days later, they were evaluated for spatial learning and memory in the Morris Water Maze (MWM) task.

METH regimen induced hyperthermia, as well as a poor performance, in the acquisition and retention phases of the task, indicating spatial learning and memory impairment compared to the controls. Naloxone administration (1 mg/kg, ip) before each METH injection led to significant attenuations of both hyperthermia and METH adverse effects on the rat performance in the MWM task.

The results revealed that pretreatment with the opiate antagonist naloxone could prevent METH adverse effects on body temperature and memory performance. It seems that the opioidergic system and hyperthermia may, at least partially, be involved in METH effects on spatial memory.

The gastrointestinal system harbors various microorganisms, known as gut microbiota. Increase in prevalence of inflammatory bowel disease (IBD) in developed countries is associated with changes in the environment, such as decrease in incidence of parasitic infections, especially helminths, and changes in the intestinal flora. Probiotics are useful microbiota for human health. The parasitic worms (helminths) have evolved over the years with their host. Several studies have investigated the capability of helminths and probiotics to alter or control host immune responses in view of the fact that these organisms have immunomodulation effects. Given the contradictory results, further broad studies are needed to confirm the role of probiotics and helminths in the treatment of IBD.