Tehran University of Medical Sciences
Recent publications
•Malignant cardiac tumors are extremely rare. •25% of primary cardiac tumors are malignant. •Most malignant cardiac tumors are metastatic (from breast, lung, melanoma, soft tissue sarcoma, etc.). •Sarcoma, lymphoma, and malignant pericardial mesothelioma are three main primary malignant cardiac tumors. •Usual imaging studies consist of TTE, CMR, and contrast TTE that are helpful noninvasive tools to diagnose suspicious cardiac masses. •Generally, despite multimodal treatment strategies, prognosis of malignant cardiac tumors is poor.
Background: In the posttransplant period, recipients face a complex phenomenon called the new heart, which is a symbol of physical and emotional life. They use different methods to get used to the new heart. Objective: The aim of this study was to explore the integration process with a donated heart in heart transplant patients. Methods: A qualitative study design with a grounded theory approach following Corbin and Strauss was used. Purposive and then theoretical sampling led to the inclusion of 15 heart transplant patients with diverse characteristics. Observations and semistructured interviews were conducted during a 1-year period in 2019 to 2020. Data collection and analysis occurred simultaneously. Results: The process of integration with the new heart in the transplant patients or the core category in this study was "rebirth." The process involved thre3 sequential and overlapping phases, which over time led to toleration and management of the situation. Religious issues, emotional chaos, additional worries, and sense of duality in the early stages after transplantation form a cycle, and the person is moving in this cycle. Discussion: The results of this study indicated that the patients experienced several emotional and psychological changes after heart transplantation. It was also shown that the participants experienced a change in the emotions and feelings over time. On the basis of the findings of this study, it can be suggested that health care providers need to improve their knowledge about posttransplant changes, recipients' feelings, and adaptation strategies.
Objective Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator ( AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000–200,000 worldwide and 1/6500–9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families. Methods We sequenced the coding regions of the AIRE gene and documented mutations which were further confirmed in respective parents. Results In total, 11 cases from 8 independent families were recruited. Mucosal candidiasis, Addison’s disease and hypoparathyroidism were the most common clinical manifestations in these patients. One novel homozygous splice acceptor mutation (c.308-1G>C), and one novel heterozygous stop-gain mutation (c.1496delC) combined with a known heterozygous c.232T>C missense mutation were found. Moreover, we observed previously described splice donor (c.1095+2T>A), frameshift (c.967-979del), stop-gain (c.415C>T), and missense (c.62C>T) mutations among the patients. All results were co-segregated in parents. Conclusion Here, we reported two novel mutations in the AIRE gene leading to APECED. Our data could provide insight into the phenotypic and genotypic spectrum of APECED in the non-Jewish Iranian population. These findings, in addition to future functional assays, can elucidate disease-causing mechanisms related to the AIRE gene and assist in genetic counseling and diagnosis.
Background: Several inflammatory and vascular molecules, and neurotrophins have been suggested to have a possible role in the development of migraine. However, pathophysiological events leading to migraine onset and transformation of episodic migraine (EM) to chronic migraine (CM) are not fully understood. Thus, we aimed to assess peripheral levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2) in EM and CM patients, and controls. Methods: From September 2017 to June 2020, 89 subjects were enrolled in a case-control study; 23 and 36 EM and CM patients, respectively, and 30 age and sex-matched controls. Demographic data and medical history were obtained from all patients. Headache characteristics were recorded at baseline visit and ensuing 30 days for persons with migraine disease. Serum levels of NGF, BDNF, VEGF, and PGE2 were measured once for controls and EM and CM patients, and adjusted for age, sex, and body mass index. Results: Serum levels of NGF were significantly lower in EM patients compared to controls and CM patients (P-value=0.003 and 0.042, respectively). Serum levels of BDNF were significantly lower in EM and CM patients as opposed to controls (P-value<0.001), but comparable between EM and CM patients (P-value=0.715). Peripheral blood levels of VEGF were significantly higher in EM and CM patients as opposed to controls (P-value<0.001), but not different between EM and CM patients (P-value=0.859). Serum levels of PGE2 were significantly lower in EM patients compared to controls (P-value=0.011), however similar between EM and CM patients (P-value=0.086). In migraine patients, serum levels of NGF and PGE2 positively correlated with headache frequency (NGF: ρ = 0.476 and P-value<0.001; PGE2: ρ = 0.286 and P-value=0.028), while corresponding levels of BDNF and VEGF did not correlate with headache frequency (BDNF: ρ = 0.037 and P-value=0.778; VEGF: ρ= -0.025 and P-value=0.850). Conclusions: Our findings suggest that NGF, BDNF, PGE2, and VEGF may play a significant role in migraine pathogenesis and/or chronification, and therefore might bear potential value for novel targeted abortive and prophylactic migraine therapy. Further prospective cohort studies with larger sample sizes can more robustly evaluate the implications of these findings.
Objective Musculoskeletal pain conditions (MPs) are a widespread public problem that can affect 13.5% to 47% of the total population. Dietary changes can have strong effects on person’s health; for instance, Sulfur amino acids (SAAs) can act as a precursor of neurotransmitters, antioxidative metabolic intermediates, such as glutathione, impact inflammation, and play a role in severity and frequency of MPs. We evaluated the relationship between dietary SAAs intake with severity and frequency of pain in patients with MPs. Results This cross-sectional study consisted of 175 men and woman. Anthropometric measurements and pain assessments were conducted via questionnaires. Dietary data were collected using 7 days 24-h recall. ANOVA and Spearman correlation coefficients were used to examine the relationship and correlation, respectively, between exposure and outcome variables. There was a significant correlation between age, weight, waist circumference (WC), waist circumference to height (WHtR), body mass index (BMI), and severity and frequency of MPs among women. There was a correlation between age and severity of pain in men. The present study highlights a positive association between the dietary SAAs and severity of pain, even after adjusting for confounding variables.
The Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPPs) are novel therapeutic targets for the restoration of β-cell survival and function in diabetes. Their upregulation and activation in β-cells under conditions of both type 1 and type 2 diabetes directly correlates with β-cell failure; β-cell death and loss of insulin secretory function through disturbance of cell survival control mechanisms. PHLPPs directly dephosphorylate and regulate activities of β-cell survival-dependent kinases AKT and MST1 constituting a regulatory triangle loop to control β-cell apoptosis. PHLPP1 deletion in severely diabetic leptin receptor-deficient db/db mice restored normoglycemia and β-cell area through increased β-cell proliferation and reduced β-cell apoptosis. The beneficial effects of PHLPP1 deficiency in a severe mouse model of obesity and diabetes make PHLPP a new target for β-cell-directed diabetes therapy.
Objective The endothelial cells overexpress the adhesion molecules in the leukocyte diapedesis pathway, developing vessel subendothelial molecular events. In this study, miR-194 and miR-27a were predicted and investigated on the expression of adhesion molecules in HUVEC cells. The SELE, SELP, and JAM-B adhesion molecules involved in the leukocyte tethering were predicted on the GO-enriched gene network. Following transfection of PEI-miRNA particles into HUVEC cells, the SELE, SELP, and JAM-B gene expression levels were evaluated by real-time qPCR. Furthermore, the monocyte-endothelial adhesion was performed using adhesion assay kit. Results In agreement with the prediction results, the cellular data showed that miR-27a and miR-194 decrease significantly the SELP and JAM-B expression levels in HUVECs (P < 0.05). Moreover, both the miRNAs suppressed the monocyte adhesion to endothelial cells. Since the miR-27a inhibited significantly the monocyte-endothelial adhesion (P = 0.0001) through the suppression of SELP and JAM-B thus it might relate to the leukocyte diapedesis pathway.
Background Nasopharyngeal cancer (NPC) is showing an increasing incidence in Iran . Radiation is the main treatment of this cancer. Use of new techniques such as intensity-modulated radiotherapy (IMRT) is on the rise. Here, we aimed to evaluate the oncological outcomes of NPC patients treated with three-dimensional conformal radiotherapy (3DCRT) for a more reliable comparison with IMRT in the future. Results We reviewed the medical records of 106 patients with NPC treated by definitive radiotherapy from 2007 to 2016. Patients were treated with 70 Gy in 2-Gy fractions. Twenty-one patients died during the follow-up period. Twenty-nine patients suffered from locoregional or distant recurrences. Of these, 6 recurred after 2 years of treatment completion. The 2-year and 5-year overall survival rates were 81% and 76%, respectively. The 2-year and 5-year progression-free survival rates were 72% and 63%, respectively. The 5-year locoregional recurrence and distant metastasis-free survival rates were 68% and 69%, respectively. Conclusion Due to high survival rates of NPC and the importance of receiving planned total dose of RT, the treatment-related toxicity and quality of life are critical considerations both for patients during active treatment and for survivors.
Background The mutations in the ATRX gene have been shown to cause two types of disorders: inherited mutations lead to alpha thalassemia X-linked mental retardation (ATR-X) syndrome and acquired somatic mutations cause alpha thalassemia myelodysplastic syndrome (ATMDS). Here we report a case of ATRX gene mutation without completely features of ATR-X or ATMDS syndromes. Moreover we review previous reports of ATRX gene mutations in both ATR-X syndrome and ATMDS. Methods After sample collection and DNA extraction, whole exome sequencing was performed using Illumina HiSeq PE150 apparatus. The results were confirmed using Sanger sequencing for the patients and his relatives. Literature review was performed based on the published data in Web of science, Science direct, Springer link and Pubmed databases. Results We identified a hemizygous missense ATRX gene mutation ( ATRX, c.2388A > C, p. K796N) as a new disease-causing variant in the patient, heterozygous situation for his mother and his father was hemizygous for wild type allele. The literatures of patients were reviewed regarding the ATR-X syndrome. Conclusions According to previous findings, inherited ATRX mutations are associated with a broad spectrum of clinical presentations. Therefore a person with a mild α-thalassemia phenotype may also has mutation in ATRX gene. Accordingly, it is critical for geneticist and physicians to increase awareness in molecular diagnosis of α-thalassemia patients.
Variegate Porphyria (VP) is an inherited rare disorder that is caused by mutations in the protoporphyrinogen oxidase ( PPOX ) gene. This deficiency is associated with the accumulation of porphyrins and porphyrin precursors in the body, which, in turn, can potentially result in a variety of skin and neurological symptoms. Here, we reported a 7-year-old boy with homozygous VP and novel mutation on PPOX gene. He was admitted with three episodes of generalized tonic-clonic seizure in the last 6 months. He was presented with lesions, hyperpigmentation, fragility, and blistering of sun-exposed skin. The weakness of limbs and brachydactyly were observed. In the follow-up, he had aggressive behavior, learning disability and abdominal pain, particularly around the navel. Eventually, the whole exome sequencing (WES) result reported a novel homozygous pathogenic variant (c.1072G > A p.G358R) in PPOX gene which confirmed the VP. He had been advised to be away from the sun and use sunscreen regularly.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus is a highly contagious microorganism, and despite substantial investigation, no progress has been achieved in treating post-COVID complications. However, the virus has made various mutations and has spread around the world. Researchers have tried different treatments to reduce the side effects of the COVID-19 symptoms. One of the most common and effective treatments now used is steroid therapy to reduce the complications of this disease. Long-term steroid therapy for chronic inflammation following COVID-19 is harmful and increases the risk of secondary infection, and effective treatment remains challenging owing to fibrosis and severe inflammation and infection. Sometimes our immune system can severely damage ourselves in disease. In the past, many researchers have conducted various studies on the immunomodulatory properties of stem cells. This property of stem cells led them to modulate the immune system of autoimmune diseases like diabetes, multiple sclerosis, and Parkinson's. Because of their immunomodulatory properties, stem cell-based therapy employing mesenchymal or hematopoietic stem cells may be a viable alternative treatment option in some patients. By priming the immune system and providing cytokines, chemokines, and growth factors, stem cells can be employed to build a long-term regenerative and protective response. This review addresses the latest trends and rapid progress in stem cell treatment for Acute Respiratory Distress Syndrome (ARDS) following COVID-19.
Background Anti-vascular endothelial growth factor (Anti-VEGF) therapy is now considered as one of standard therapies in approaching infants with retinopathy of prematurity (ROP). The purpose of this study was to assess the time to full retinal vascularization in infants with ROP who were treated with intravitreal bevacizumab (IVB). Methods This retrospective cohort study evaluated premature infants with ROP who were treated with IVB between 2012 and 2019. Demographic and clinical data were collected from the medical records and analyzed. Main outcomes were defined as time to complete vascularization and time of zone shift. Results Eight hundred sixty-five eyes from 441 patients were included. Average gestational age and birth weight were 28 ± 4 weeks and 1121 ± 624 g, respectively. Primary treatment failure and reactivation occurred in 35 eyes (4.0%) and 33 eyes (3.8%), respectively. Recurrent ROP occurred significantly more frequently in infants with pre-treatment zone 1 ROP compared to those with zone 2 ROP (7.6% versus 3%, p < 0.01). Patients with pre-treatment zone 2 reached zone 3 faster than those with pre-treatment zone 1 (142 ± 152 days versus 181 ± 174 days, p < 0.01); however, the time until full retinal vascularization did not significantly differ between the groups (p = 0.10). Conclusion This study revealed that pre-treatment ROP zone was associated with ROP reactivation rate but not with time to full vascularization in those treated with IVB. Trial registration Retrospectively registered; IR.TUMS.FARABI.REC.1399.040
Alzheimer’s disease (AD), a critical neurodegenerative condition, has a wide range of effects on brain activity. Synaptic plasticity and neuronal circuits are the most vulnerable in Alzheimer’s disease, but the exact mechanism is unknown. Incorporating optogenetics into the study of AD has resulted in a significant leap in this field during the last decades, kicking off a revolution in our knowledge of the networks that underpin cognitive functions. In Alzheimer's disease, optogenetics can help to reduce and reverse neural circuit and memory impairments. Here we review how optogenetically driven methods have helped expand our knowledge of Alzheimer's disease, and how optogenetic interventions hint at a future translation into therapeutic possibilities for further utilization in clinical settings. In conclusion, neuroscience has witnessed one of its largest revolutions following the introduction of optogenetics into the field.
Introduction: There is no study on the effectiveness of hyaluronic acid (HA) placement either with or without absorbable collagen sponge (ACS) in reducing or preventing bisphosphonate-related osteonecrosis of the jaws (BRONJ). This preliminary animal study examined the efficacy of this clinically important treatment. Methods: For simulating BRONJ, zoledronic acid was administered to 40 rats for 5 weeks. Two weeks later, a right first molar was extracted from each rat. The rats were randomized into four groups of socket treatments: control (empty extraction socket) or with sockets filled with ACS, HA, or HA+ACS (n=4×10). After 2 weeks, 5 rats in each group were sacrificed and subjected to histopathologic and histomorphometric evaluation. Eight weeks post-surgically, the rest of rats were euthanized and histologically examined. The Kruskal-Wallis test was used to compare the four treatments at each time point (α=0.05). Results: Six rats were lost overall. In the second week, vascularization was higher in ACS group (P<0.05); osteoclast activity was not different between groups (P>0.05); empty lacunae were the most and fewest in control and HA+ACS groups, respectively (P<0.05); eosinophil infiltration was maximum in HA group (P<0.05); lymphocyte counts were maximum and minimum in the HA+ACS and ACS groups, respectively (P<0.05); the highest and lowest neutrophil counts were seen in ACS and control groups, respectively (P<0.05); and the extent of live bone did not differ between groups (P>0.05). In the eighth week, vascularization was not different in groups (P>0.05); the highest and lowest osteoclast activities were seen in the control and HA+ACS groups, respectively (P<0.05); empty lacunae were the most and fewest in control and HA+ACS, respectively (P<0.05); maximum and minimum numbers of eosinophils were in control and HA+ACS groups, respectively (P<0.05); HA and control groups exhibited the highest and lowest lymphocyte counts, respectively (P<0.05); the lowest and highest neutrophil counts were observed in HA+ACs and control groups, respectively (P<0.05); and the highest and lowest extents of the live bone were observed in HA+ACS and control groups, respectively (P<0.05). Conclusions: Within the limitations of this preliminary animal study, HA and especially HA+ACS seem a proper method for preventing or treating BRONJ.
Mesenchymal stem/stromal cells (MSCs) are known as the issue in biology because of some unpredictable characteristics in the different microenvironments especially in their bone marrow niche. MSCs are used in the regenerative medicine because of their unique potentials for trans-differentiation, immunomodulation, and paracrine capacity. But, their pathogenic and pro-survival effects in tumors/cancers including hematologic malignancies are indisputable. MSCs and/or their derivatives might be involved in tumor growth, metastasis and drug resistance in the leukemias. One of important relationship is MSCs and hematologic malignancy-derived cells which affects markedly the outcome of disease. The communication between these two cells may be contact-dependent and/or contact-independent. In this review, we studied the crosstalk between MSCs and malignant hematologic cells which results the final feedback either the progression or suppression of blood cell malignancy. Graphical abstract
Background Congenital heart disease CHD is a significant cause of mortality and morbidity in children worldwide. Patients with congenital heart disease may develop hematological problems, including thrombocytopenia and neutropenia. In addition, several studies indicate the higher frailty of patients with CHDs to infections and malignancies. Nevertheless, the mechanisms of immune system changes in these patients have remained in the shadow of uncertainty. Moreover, very few studies have worked on cytopenia in CHD. This study has assessed the frequency of thrombocytopenia, neutropenia, lymphopenia, and anemia in pediatric patients with acyanotic congenital heart disease ACHD prior to open-heart surgery. Methods This cross-sectional study was handled in the Pediatric Cardiology Clinic, Tehran University of Medical Sciences, during pre-operation visits from 2014 till 2019. Two hundred forty-eight children and adolescents with acyanotic congenital heart disease before open-heart surgery met the criteria to enter the study. Results A total of 191 (76.7%) patients with Ventricular Septal Defects (VSD), 37 (14.85%) patients with Atrial Septal Defects (ASD), and 20 (8.11%) patients with Patent Ductus Arteriosus (PDA) were enrolled in this study. The median age was 23.87 months. Thrombocytopenia and neutropenia were found, respectively, in 3 (1.2) and 23 (9.2%) patients. Hemoglobin level and lymphocyte count were significantly lower in patients with neutropenia than patients with normal neutrophil count ( P value = 0.024 and P value = 0.000). Significant positive correlations were found between neutropenia and anemia. There were no correlations between neutrophil count and Platelets. Also, anemia was found in 48 patients (19.3%). The study also found a statistically significant correlation between the co-existence of VSD and neutropenia in the patients ( P value = 0.000). Conclusion Although most were mildly neutropenic, there was a significant correlation between neutropenia and Ventricular Septal Defect compared to PDA and ASD groups. Regarding the importance of neutropenia to affect the prognosis of congenital heart defects in infections, it is important to consider further studies on the status of immune system function in these patients.
Long non-coding RNAs (LncRNAs) are widely known for their various functions in cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classified into grades I to IV according to their malignant histological features with grade IV, also known as glioblastoma multiforme (GBM), displaying the highest level of malignancy. Thus, the search for differentially expressed LncRNAs in GBM versus low-grade glioma to uncover new insights into the molecular mechanisms of glioma progression have intensified. Bulk RNA sequencing pinpointed decreased expression of OBI1-AS1 in GBM compared to low-grade glioma samples. Subsequent single nuclei RNA sequencing revealed OBI1-AS1 to be a super-exclusive astrocyte marker with AUC = 0.99 and the potential to fully differentiate astrocytes from other brain cell types. Additional supplementary bioinformatics analysis exhibited OBI1-AS1 role in synaptic signal transduction and glutamatergic signaling. In addition, ChIP-Seq data were analyzed to explore transcription factors that can regulate OBI1-AS1 expression in neural cells. Results of Hi-C, methylation and ChIP-Seq analysis strongly suggest methylation of the CTCF binding site serving a central role in regulation of OBI1-AS1 expression via managing chromatin interactions. Our study indicated that lncRNAs, like OBI1-AS1, could be extremely precise in identifying the astrocyte cluster in the single-cell transcriptome and demonstrating superiority to well-established astrocyte markers such as GFAP , S100B , ALDH1L1, and AQP4 . Graphical abstract
Systematic reviews cling to the doctrine that science has an updating databank and attempt to identify all available evidence by featured eligibility criteria to find the answer to a unique scientific question. Therefore, to reach this aim, these researches should use a wise method and comprehensive search strategy, as they are widely used to guide clinical and political decisions and the establishment of future researches. We would like to appreciate Jenny Carè, Amie Steel, and Jon Wardle for the valuable article “Stakeholder attitudes to the regulation of traditional and complementary medicine professions: a systematic review”. Some important missed search terms in the field of traditional medicine names and traditional and complementary medicine (T&CM) regulation concepts were discussed in the article.
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6,322 members
Fateme Rajabi
  • Center for Research and Training in Skin Diseases and Leprosy
Akbar Shafiee
  • Tehran Heart Centre
District 6, Keshavarz Boulevard and Ghods St. crossing, Tehran, Tehran, Iran
Head of institution
Abbas Karimi, MD
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