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Nooshin Ghavidel,1 Fariba Khodagholi,1 Abolhassan Ahmadiani,1 Reza Khosrowabadi,2 Sareh Asadi,3 Jamal Shams4 1Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran, Iran; 3NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Behavioral Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Sareh AsadiNeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Evin, Daneshjoo Blvd, P.O. Box 19615-1178, Tehran, IranTel + 98-21-22429768Fax + 98-21- 22432047Email s.asadi@sbmu.ac.ir Jamal ShamsBehavioral Research Center, Imam Hossain Educational Hospital, Shahid Beheshti University of Medical Sciences, Madani Ave, P.O. Box 1617763141, Tehran, IranTel/Fax + 98-21-77553074Email J_shams@sbmu.ac.irIntroduction: Studies have been reported that frequent use of methamphetamine (MA) is associated with brain function impairment, mood disorders and excessive free radical production accompanied by the decreased level of the antioxidant response elements, but no study investigated their correlations simultaneously. In the current study, the correlation of brain function, depression and anxiety levels, and the serum levels of PON1 (an antioxidant) in MA-dependent patients were investigated.Methods: Nineteen active MA abusers and 18 control subjects performed color-word Stroop task during fMRI and the state of their depression, anxiety, and stress were measured by the Depression, Anxiety and Stress Scale-21 Items (DASS-21) questionnaire. Their blood samples were collected to measure the level of PON1 by the human enzyme-linked immunosorbent assay (ELISA) kit and its correlation with the measured variables was studied.Results: Analysis of fMRI findings showed frontocingulate dysfunction in Stroop effect condition, including left anterior cingulate cortex, paracingulate gyrus, superior frontal gyrus, and frontal pole in MA-dependent patients, which was associated with a higher level of depression and decreased level of serum PON1 in these patients.Discussion: The results of the current study showed that MA-dependency is associated with frontocingulate dysfunction, decreased serum PON1 concentration, and increased depression/anxiety, which is worth to be more studied to elucidate their roles in the pathophysiology of MA addiction.Keywords: anxiety, depression, fMRI, PON1, Stroop task

Hesam Hasanpour,1 Ramak Ghavamizadeh Meibodi,1 Keivan Navi,1 Jamal Shams,2 Sareh Asadi,3 Abolhassan Ahmadiani4 1Faculty of Computer Science and Engineering, Shahid Beheshti University, Tehran, Iran; 2Behavioral Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive thoughts or repetitive behaviors. Clinicians use serotonin reuptake inhibitors (SRIs) for OCD treatment, but 40%–60% of the patients do not respond to them adequately. Here, we described an association rule mining approach for treatment response prediction using an Iranian OCD data set.Patients and methods: Three hundred and thirty OCD patients fulfilling DSM-5 criteria were initially included, but 151 subjects completed their pharmacotherapy which was defined as 12-week treatment with fluvoxamine (150–300 mg). Treatment response was considered as >35% reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score. Apriori algorithm was applied to the OCD data set for extraction of the association rules predicting response to fluvoxamine pharmacotherapy in OCD patients. We considered the association of each attribute with treatment response using interestingness measures and found important attributes that associated with treatment response.Results: Results showed that low obsession and compulsion severities, family history of mental illness, illness duration less than 5 years, being married, and female were the most associated variables with responsiveness to fluvoxamine pharmacotherapy. Meanwhile, if an OCD patient reported a family history of mental illness and his/her illness duration was less than 5 years, he/she responded to 12-week fluvoxamine pharmacotherapy with the probability of 91%. We also found useful and applicable rules for resistant and refractory patients.Conclusion: This is the first study where association rule mining approach was used to extract predicting rules for treatment response in OCD. Application of this method in personalized medicine may help clinicians in taking the right therapeutic decision. Keywords: data mining, apriori algorithm, family history, refractory patients

Marzie Sina,1 Abolhassan Ahmadiani,1 Sareh Asadi,2 Jamal Shams3 1Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction: Obsessive–compulsive disorder (OCD) is a debilitating psychiatric disorder causing intrusive thoughts or repetitive behaviors. Serotonin reuptake inhibitors are used for OCD treatment, but 40%–60% of patients do not respond to them adequately. In this study, the associations of serotonin receptor 2a polymorphisms rs6311 and rs6313 with OCD, its familial form and fluvoxamine treatment response in Iranian population were investigated. Patients and methods: Association analyses were conducted in 293 OCD cases fulfilling the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR and 245 controls. Pharmacotherapy was defined as 12 weeks of treatment with fluvoxamine (150–300 mg). Treatment response was considered as >25% reduction in Yale–Brown Obsessive Compulsive Scale score. Genotyping was performed by means of PCR-RFLP. Results: The results showed no association of rs6311 or rs6313 with OCD, but their haplotypes had different distribution patterns in cases and controls. Moreover, rs6313 was associated with the familial form of OCD in females significantly (P=0.005) under the recessive genetic model. Moreover, rs6311–rs6313 haplotypes were associated with fluvoxamine treatment response in OCD patients with more AC and less AT in responders. Conclusion: HTR2A haplotypes are associated with OCD and its treatment response with a fluvoxamine in Iranian patients. Furthermore, the observed association of rs6313 with the familial form of OCD in females suggests different genetic background of OCD familial and non-familial forms, which needs further investigation. Keywords: family history, fluvoxamine, treatment response, rs6311, rs6313

Abstract Alzheimer’s disease (AD) is the most prevalent type of dementia. Its causes are not fully understood, but it is now known that factors like mitochondrial dysfunction, oxidative stress, and compromised ion channels contribute to its onset and progression. Flickering light therapy has shown promise in AD treatment, though its mechanisms remain unclear. In this study, we used a rat model of streptozotocin (STZ)-induced AD to evaluate the effects of 40 Hz flickering light therapy. Rats received intracerebroventricular (ICV) STZ injections, and 7 days after, they were exposed to 40 Hz flickering light for 15 min daily over seven days. Cognitive and memory functions were assessed using Morris water maze, novel object recognition, and passive avoidance tests. STZ-induced AD rats exhibited cognitive decline, elevated reactive oxygen species, amyloid beta accumulation, decreased serotonin and dopamine levels, and impaired mitochondrial function. However, light therapy prevented these effects, preserving cognitive function and synaptic plasticity. Additionally, flickering light restored mitochondrial metabolites and normalized ATP-insensitive mitochondrial calcium-sensitive potassium (mitoBKCa) channel activity, which was otherwise downregulated in AD rats. Our findings suggest that 40 Hz flickering light therapy could be a promising treatment for neurodegenerative disorders like AD by preserving synaptic and mitochondrial function.

"nBackground: There is a growing interest in understanding the biological effects of time-tested folk medicinal plants including the green leafy vegetables, which supply minerals and vitamins to the diet. Trigonella foenum-graecum L (fenugreek) is a dietary vegetable and there are reports concerning its antinociceptive effects in Iranian traditional medicine. Its seeds are also known for their carminative, tonic, antidiabetic, antineoplastic and restorative properties. These reports and the hypoglycemic effect of fenugreek leaf extract encouraged us to assay fenugreek aqueous extract for cytotoxicity on NIH3T3 mouse fibroblast cells. "nMethods: The NIH3T3cell line was purchased from National Research Center for Genetic Engineering and Biotechnology of Iran. The cells were plated in 24-well microtiter plates with DMEM+F12 medium containing 10% fetal calf serum supplemented with 445 mg/L L-glutamine and maintained at 37oC with 5% CO2/95% air. Following a 24-hr incubation period, various concentrations (0.01-20 mg) of the extract to the culture wells. Cell viability was assessed using trypan blue and MTT assays after five days of incubation. "nResults: The results show that the IC50 of the fenugreek extract as calculated from the trypan blue and MTT assays were 1.25 and 2.5 mg/mL, respectively. "nConclusions: Our findings, therefore, suggest that the aqueous extract of fenugreek is classified as nontoxic. This observed cytotoxicity is not specific and could be due to membrane disturbances.

Abstract Background Glioblastoma multiforme (GBM) is a type of fast-growing brain glioma associated with a very poor prognosis. This study aims to identify key genes whose expression is associated with the overall survival (OS) in patients with GBM. Methods A systematic review was performed using PubMed, Scopus, Cochrane, and Web of Science up to Journey 2024. Two researchers independently extracted the data and assessed the study quality according to the New Castle Ottawa scale (NOS). The genes whose expression was found to be associated with survival were identified and considered in a subsequent bioinformatic study. The products of these genes were also analyzed considering protein-protein interaction (PPI) relationship analysis using STRING. Additionally, the most important genes associated with GBM patients’ survival were also identified using the Cytoscape 3.9.0 software. For final validation, GEPIA and CGGA (mRNAseq_325 and mRNAseq_693) databases were used to conduct OS analyses. Gene set enrichment analysis was performed with GO Biological Process 2023. Results From an initial search of 4104 articles, 255 studies were included from 24 countries. Studies described 613 unique genes whose mRNAs were significantly associated with OS in GBM patients, of which 107 were described in 2 or more studies. Based on the NOS, 131 studies were of high quality, while 124 were considered as low-quality studies. According to the PPI network, 31 key target genes were identified. Pathway analysis revealed five hub genes (IL6, NOTCH1, TGFB1, EGFR, and KDR). However, in the validation study, only, the FN1 gene was significant in three cohorts. Conclusion We successfully identified the most important 31 genes whose products may be considered as potential prognosis biomarkers as well as candidate target genes for innovative therapy of GBM tumors.

The well-known fluorimetric method for histamine measurement which is one of the common methods in diagnostic laboratories was modified to accelerate and facilitate measurement of serum histamine levels and decrease the costs and restrictions. The modified method needs only 1 ml of whole blood (or serum) instead of about 10 ml in original method which is difficult almost or impossible specially for children. In addition, very small amounts of the expensive materials are needed and the samples are saved for about 15 days in -20°C which makes no significant changes. Because in most cases, sample can not be read at sampling day, the saving possibility is an advantage for improved method.

Abstract Background: Ovarian hyperstimulation syndrome (OHSS) as a known complication in women with polycystic ovarian syndrome (PCOS) may occur following inducible fertility treatments such as in vitro fertilization (IVF) and can affect the sequels of these treatments. Objective: This study aimed to assess the effects of OHSS on pregnancy outcomes through IVF in women with PCOS. Also, we assessed the value of baseline sexual hormones to predict the pregnancy's success. Materials and Methods: This case-control study was conducted on 180 consecutive women suffering from PCOS who were candidates for IVF at Fatemieh hospital in Hamadan, Iran, from May-July 2022. The women were assigned to the case group (with OHSS, n = 129) and the control group (without OHSS, n = 51). Measuring the sexual hormones was performed using the enzyme-linked immunosorbent technique. Results: In the multivariable logistic regression model, OHSS could not predict the likelihood of clinical or chemical pregnancy following IVF. None of the baseline sexual hormones could predict the successful chemical or clinical pregnancy in PCOS women following IVF. Conclusion: OHSS may not influence IVF-related outcomes in PCOS women. The values of sexual hormones may not also determine the pointed outcome.

Contemporary English physicist, Stephen Hawking, by authoring The Big Plan and introducing the M-theory, brought the long-running conflict between science and religion to a new level. Despite Hawking's claim of the ‘death of philosophy’, he has used some philosophical principles in his M-theory. This paper, using the descriptive-analytical method, seeks to evaluate these principles. The most important philosophical foundations on which M-theory is based are: (1) Scientism, as the most fundamental basis of M-theory; (2) Instrumentalism, ccording to which laws and theories are merely some instruments for predicting phenomena, lacking any physical reality; (3) Denial of causality, which has been inferred from the ‘uncertainty principle’ and the ‘principle of accident.’ After explaining these foundations, some significant objections have been directed to them, the most important of which are: scientism neglects the limitations of the empirical-experimental method and excludes other epistemological sources; instrumentalism, besides denying the scientific realism, results in accepting contradicting theories; Denial of causality, which is due to a misunderstanding of this philosophical concept, destroys any real connections between the objects in the world. Finally, it is concluded that these fundamental criticisms really challenge M-theory’s validity.

This study investigates enhancing energy efficiency in desalination by introducing a novel combined ejector-solar vacuum tube collector cycle. The cycle utilizes a two-phase state and lower-temperature saturated steam generation to overcome the energy consumption hurdle, particularly by compressors. Water enters the ejector's primary nozzle in a liquid phase, while steam from the solar collector aids in separation, yielding desalinated water in a variable phase. Fluent software's computational fluid dynamics assesses the ejector's performance, considering primary and secondary inlet pressures' impact on hydrodynamic characteristics. TRNSYS software models the cycle transiently over a year in Tehran, exploring different pressures' effects on fluid behavior. Results indicate that increasing secondary nozzle pressure at constant primary pressure significantly boosts steam flow rate and inlet velocity. The investigation covers secondary inlet pressures ranging from 7000 Pa to 39,000 Pa and primary nozzle pressures between 200,000 Pa and 500,000 Pa, studying their impact on fluid behavior. Under Tehran's climatic conditions, the proposed cycle achieves a peak output rate of 1.35 kg/m2/h, a maximum daily yield of 8.47 kg/m2, and a total annual output of 767 kg/m2 for desalinated water. This innovative approach showcases promise for energy-efficient desalination, especially in regions with solar potential like Tehran.

The color of food is critical to the food and beverage industries, as it influences many properties beyond eye-pleasing visuals including flavor, safety, and nutritional value. Blue is one of the rarest colors in nature's food palette-especially a cyan blue-giving scientists few sources for natural blue food colorants. Finding a natural cyan blue dye equivalent to FD&C Blue No. 1 remains an industry-wide challenge and the subject of several research programs worldwide. Computational simulations and large-array spectroscopic techniques were used to determine the 3D chemical structure, color expression, and stability of this previously uncharacterized cyan blue anthocyanin-based colorant. Synthetic biology and computational protein design tools were leveraged to develop an enzymatic transformation of red cabbage anthocyanins into the desired anthocyanin. More broadly, this research demonstrates the power of a multidisciplinary strategy to solve a long-standing challenge in the food industry.

Introduction: Midbrain dopaminergic neurons are involved in various brain functions, including motor behavior, reinforcement, motivation, learning, and cognition. Primary dopaminergic neurons and also several lines of these cells are extensively used in cell culture studies. Primary dopaminergic neurons prepared from rodents have been cultured in both DMEM/F12 and neurobasal mediums in several studies. However, there is no document reporting the comparison of these two mediums. So in this study, we evaluated the neurons and astroglial cells in primary midbrain neurons from rat embryos cultured in DMEM/F12 and neurobasal mediums. Methods: Primary mesencephalon cells were prepared from the E14.5 rat embryo. Then they were seeded in two different mediums ( Dulbeccochr('39')s Modified Eagle Medium/Nutrient Mixture F-12 [DMEM/F12] and neurobasal). On day 3 and day 5, half of the medium was replaced with a fresh medium. On day 7, β3-tubulin-, GFAP (Glial fibrillary acidic protein)- and Tyrosine Hydroxylase TH-positive cells were characterized as neurons, astrocytes, and dopaminergic neurons, respectively, using immunohistochemistry. Furthermore, the morphology of the cells in both mediums was observed under light microscopy on days 1, 3, and 5. Results: The cells cultured in both mediums were similar under light microscopy regarding the cell number, but in a neurobasal medium, the cells have aggregated and formed clustering structures. Although GFAP-immunoreactive cells were lower in neurobasal compared to DMEM/F12, the number of β3-tubulin- and TH-positive cells in both cultures was the same. Conclusion: This study’s findings demonstrated that primary midbrain cells from the E14.5 rat embryo could grow in both DMEM/F12 and neurobasal mediums. Therefore, considering the high price of a neurobasal medium, it can be replaced with DMEM/F12 for culturing primary dopaminergic neurons.

The risk of cardiovascular and respiratory diseases attributed to satellite-based PM2.5 has been less investigated. In this study, the attributable risk was estimated in an area of Iran. The predicted air PM2.5 using satellite data and a two-stage regression model was used as the predictor of the diseases. The dose-response linkage between the bias-corrected predictor employing a strong statistical approach and the outcomes was evaluated using the distributed lag nonlinear model. We considered two distinct scenarios of PM2.5 for the risk estimation. Alongside the risk, the attributable risk and number were estimated for different levels of PM2.5 by age and gender categories. The cumulative influence of PM2.5 particles on respiratory illnesses was statistically significant at 13–16 µg/m3 relative to the reference value (median), mostly apparent in the middle delays. The cumulative relative risk of 90th and 95th percentiles were 2.03 (CI 95%: 1.28, 3.19) and 2.25 (CI 95%: 1.28, 3.96), respectively. Nearly 600 cases of the diseases were attributable to the non-optimum values of the pollutant during 2017–2022, of which more than 400 cases were attributed to high values range. The predictor's influence on cardiovascular illnesses was along with uncertainty, indicating that additional research into their relationship is needed. The bias-corrected PM2.5 played an essential role in the prediction of respiratory illnesses, and it may likely be employed as a trigger for a preventative strategy. [ABSTRACT FROM AUTHOR]

Introduction: A 40-Hz white light emitting diode (WLED) has emerged as an alternative nonpharmacological and noninvasive approach to Alzheimer disease (AD). Here, we investigated the therapeutic effects of 40-Hz WLED on psychiatric symptoms (PS) and the contribution of mitochondrial factors in the early stages of sporadic AD (sAD) in rats. Methods: In male Wistar rats, the AD model was induced via intracerebroventricular (ICV) injection of streptozotocin (STZ). After recovering (7 days) from stereotaxic surgery, 40-Hz WLED exposure was performed for 7 consecutive days lasting 15 min/d. Behavioral (elevated plus maze (EPM), force swim test, and social interaction test), enzymatic, and molecular assays were conducted 24 hours after the last 40-Hz WLED exposure. Results: Behavioral tasks revealed that 40-Hz WLED exposure in STZ-induced toxicity rats lowered anxiety and depression and increased social interaction. Furthermore, the 40-Hz WLED therapy in STZ-induced toxicity rats increased catalase (CAT) activity in the amygdala, decreased the activity of monoamine oxidases A and B in the whole brain, and increased mitochondrial DNA in the hippocampus. Conclusion: The current study supports that 40-Hz WLED therapy improved PS and biomarkers in the early stages of sAD. Also, a potential relationship between PS and alterations in mitochondrial markers in certain brain regions seems to exist. [ABSTRACT FROM AUTHOR]

Introduction: Toll-like receptor (TLR) 4 is involved in neuroinflammatory processes in peripheral tissues and central nervous system. Pro-inflammatory cytokines production, due to over activation of TLR4, interfere with insulin signaling elements lead to insulin resistance. Regarding the critical roles of TLR4 and insulin in the pathogenesis of Parkinson’s disease (PD), in the present study the TLR4/insulin receptor interaction was assessed in a neuroinflammation model of PD. Methods: LPS was injected into the right striatum of male Wistar rats (20µg/rat). Insulin (2.5IU/ day), insulin receptor antagonist (S961; 6.5nM/kg), or TLR4 antibody (Resatorvid (TAK242); 0.01µg/rat) were administered intracerebroventricularly (ICV) for 14 days. Insulin and TAK242 were also simultaneously injected in a distinct group. Behavioral assessments were performed using rotarod, apomorphine-induced rotation, and cylinder tests. The levels of α-synuclein, TLR4, and elements of the insulin signaling pathway were measured in the striatum. Results: LPS impaired motor performance of the animals and increased the levels of α-synuclein and TLR4. Furthermore, it reduced mRNA levels of IRS1 and IRS2 and enhanced GSK3β mRNA and protein levels, indicating the development of insulin resistance. Treatment with insulin and TAK 242 improved motor deficits, restored insulin signaling pathway, and reduced α-synuclein and TLR4 levels. Conclusion: The findings indicate that LPS impaired motor function, at least in part, via α-synuclein and TLR4 overexpression, leading to insulin resistance. Suppression of TLR4 and activation of insulin receptors attenuated motor deficits, suggesting that TLR4 and insulin receptors are promising therapeutic targets for PD modification. [ABSTRACT FROM AUTHOR]

Deciphering the lncRNA‐associated competitive endogenous RNA (ceRNA) network is essential in decoding glioblastoma multiforme (GBM) pathogenesis by regulating miRNA availability and controlling mRNA stability. This study aimed to explore novel biomarkers for GBM by constructing a lncRNA‐miRNA‐mRNA network. A ceRNA network in GBM was constructed using lncRNA, mRNA and miRNA expression profiles from the TCGA and GEO datasets. Seed nodes were identified by protein–protein interaction (PPI) network analysis of deregulated‐mRNAs (DEmRNAs) in the ceRNA network. A lncRNA‐miRNA‐seed network was constructed by mapping the seed nodes into the preliminary ceRNA network. The impact of the seed nodes on the overall survival (OS) of patients was assessed by the GSCA database. Functional enrichment analysis of the deregulated‐lncRNAs (DElncRNA) in the ceRNA network and genes interacting with OS‐related genes in the PPI network were performed. Finally, the positive correlation between seed nodes and their associated lncRNAs and the expression level of these molecules in GBM tissue compared with normal samples was validated using the GEPIA database. Our analyzes revealed that three novel regulatory axes AL161785.1/miR‐139‐5p/MS4A6A, LINC02611/miR‐139‐5p/MS4A6A and PCED1B‐AS1/miR‐433‐3p/MS4A6A may play essential roles in GBM pathogenesis. MS4A6A is upregulated in GBM and closely associated with shorter survival time of patients. We also identified that MS4A6A expression positively correlates with genes related to tumour‐associated macrophages, which induce macrophage infiltration and immune suppression. The functional enrichment analysis demonstrated that DElncRNAs are mainly involved in neuroactive ligand–receptor interaction, calcium/MAPK signalling pathway, ribosome, GABAergic/Serotonergic/Glutamatergic synapse and immune system process. In addition, genes related to MS4A6A contribute to immune and inflammatory‐related biological processes. Our findings provide novel insights to understand the ceRNA regulation in GBM and identify novel prognostic biomarkers or therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: It is well documented that insulin has neuroprotective and neuromodulator effects and can protect against different models of memory loss. Furthermore, cholinergic activity plays a significant role in memory, and scopolamine-induced memory loss is widely used as an experimental model of dementia. The current study aimed at investigating the possible effects of insulin against scopolamine-induced memory impairment in Wistar rat and its underlying molecular mechanisms. Methods: Accordingly, animals were bilaterally cannulated in CA1, hippocampus. Intrahippocampal administration of insulin 6 MU and 12 MU in CA1 per day was performed during first 6 days after surgery. During next four days, the animal’s spatial learning and memory were assessed in Morris water maze test (three days of learning and one day of retention test). The animals received scopolamine (1 mg/kg) Intraperitoneally (IP) 30 minutes before the onset of behavioral tests in each day. In the last day, the hippocampi were dissected and the levels of MAPK (mitogen-activated protein kinases) and caspase-3 activation were analyzed by Western blot technique. Results: The behavioral results showed that scopolamine impaired spatial learning and memory without activating casapase-3, P38, and JNK, but chronic pretreatment by both doses of insulin was unable to restore this spatial memory impairment. In addition, scopolamine significantly reduced Extracellular signal-Regulated Kinases (ERKs) activity and insulin was unable to restore this reduction. Results revealed that scopolamine-mediated memory loss was not associated with hippocampal damage. Conclusion: Insulin as a neuroprotective agent cannot restore memory when there is no hippocampal damage. In addition, the neuromodulator effect of insulin is not potent enough to overwhelm scopolamine-mediated disruptions of synaptic neurotransmission.