Resveratrol prevents cognitive impairment and hippocampal inflammatory response induced by lipopolysaccharide in a mouse model of chronic neuroinflammation.

BACKGROUND: Neurodegenerative disorders are associated with chronic neuroinflammation, which contributes to their pathogenesis and progression. Resveratrol (RSV) is a polyphenolic compound with strong antioxidant and anti-inflammatory properties. In the present study, we investigated whether RSV could protect against cognitive impairment and inflammatory response in a mouse model of chronic neuroinflammation induced by lipopolysaccharide (LPS). METHOD: Mice received oral RSV (30 mg/kg) or vehicle for two weeks, and injected with LPS (0.75 mg/kg) or saline daily for the last seven days. After two weeks, mice were subjected to behavioral assessments using the Morris water maze and Y-maze. Moreover, mRNA expression of several inflammatory markers, neuronal loss, and glial density were evaluated in the hippocampus of treated mice. RESULTS: Our findings showed that RSV treatment effectively improved spatial and working memory impairments induced by LPS. In addition, RSV significantly reduced hippocampal glial densities and neuronal loss in LPS-injected mice. Moreover, RSV treatment suppressed LPS-induced upregulation of NF-κB, IL-6, IL-1ß, and GFAP in the hippocampus of treated mice. CONCLUSION: Taken together, our results highlight the detrimental effect of systemic inflammation on the hippocampus and the potential of natural products with anti-inflammatory effects to counteract this impact.

Extrapulmonary Tuberculosis Leading to Abdominal Wall Mass in Young Patient.

Background: Tuberculosis is a bacterial infection that is caused by Mycobacterium tuberculosis. Tuberculosis has arguably been the largest killer of humans historically, and it remains one of the most important infectious causes of death in the world. Tuberculosis can be classified into different forms and it manifests as pulmonary and out pulmonary, respectively, in 85% and 15% of cases. Only a few cases of tuberculosis with abdominal wall involvement have been reported. Case Presentation. Herein, we present a 27-year-old Persian woman, presented with asymmetric abdominal bulging in the right side of the periumbilical area since 6 months before admission that has no pain or secretion. The patient was oriented and not ill or toxic in general appearance. Vital signs were within normal ranges. An abdominal physical examination revealed a mobile, well-bordered, nontender mass 3 × 3 centimeter (cm) in diameter palpated in the right periumbilical area. The patient underwent surgery which revealed a cystic lesion that was carefully resected. In histopathology examination of the specimen resection, tuberculosis was confirmed. Conclusion: We report a rare case of extrapulmonary tuberculosis that was identified at the abdominal wall. Due to the high number of cases of TB and the development of extrapulmonary forms that can present in an unusual location as an abdominal wall which are difficult to diagnose, it is very important to keep in mind the differential diagnosis of tuberculosis.

Prenatal Zinc Supplementation Ameliorates Hippocampal Astrocytes Activation and Inflammatory Cytokines Expression Induced by Lipopolysaccharide in a Rat Model of Maternal Immune Activation.

Introduction: Evidence suggests that gestational exposure to Lipopolysaccharide (LPS) results in fetal zinc deficiency and eventually neurodevelopmental abnormalities. In this study, we utilized a rat model of Maternal Immune Activation (MIA) to investigate the possible neuroprotective effects of zinc supplementation during pregnancy on hippocampal astrocytes activation as well as inflammatory cytokines expression in adult offspring. Methods: Pregnant rats received intraperitoneal injections of either LPS (0.5 mg/kg) or saline on Gestational Days (GD) 15 and 16, and orally gavaged with zinc sulfate (30 mg/kg) during pregnancy. Astrocyte density and histological assessment were evaluated in the hippocampus of adult offspring on Postnatal Days (PND) 60 to 62. Also, the mRNA levels of IL-6, TNF-α, IL-1ß, NF-κB, and GFAP were measured using qPCR analysis. Results: Prenatal exposure to LPS resulted in upregulated expression levels of IL-6, TNF-α, NF-κB, and GFAP in the hippocampus of adult pups. Moreover, the offspring from the LPS group showed an increased astrocyte density in the CA1 region with no histological alterations in CA1 and CA3 areas. However, maternal zinc supplementation ameliorated the LPS-induced inflammatory alterations. Conclusion: This study supports the premise that zinc supplementation during pregnancy might be an early treatment option to inhibit hippocampal inflammation induced by the maternal immune response to infectious agents. Highlights: Maternal immune activation induced mild hippocampal inflammation in adult offspring.Zinc supplementation suppressed LPS-induced hippocampal inflammation in offspring.Zinc might be an early therapeutic option to inhibit neurodevelopmental impairments. Plain Language Summary: Schizophrenia is a chronic and disabling psychiatric disorder, affecting an estimated one percent of the world's population. To date, the biological mechanisms underlying this mental disorder remain largely elusive, however, research has demonstrated the involvement of both genetic and environmental factors. Of environmental factors, gestational exposure to rubella, influenza, and genital-reproductive infections have gained particular interest among researchers. Based on this evidence, in the present study, we used an animal model of schizophrenia and showed the beneficial effect of zinc supplementation during pregnancy to protect against LPS-induced inflammation in the hippocampus of adult offspring. Collectively, our study provides support for the premise that early treatment might be a suitable option to prevent schizophrenia risk in progeny.

A Pediatric Parathyroid Carcinoma: An Unusual Clinical Presentation and Mini-review.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a rare condition in the pediatric population. Parathyroid carcinoma (PC) is a very uncommon cause of PHPT, accounting for < 1% of pediatric PHPT cases. It is challenging to distinguish between parathyroid adenoma (PA), the most common cause of PHPT, and PC. In this report, we described a young female who presented with a history of progressive limping and was finally diagnosed with PC. CASE PRESENTATION: A 15-year-old girl presented with progressive limping and bone pain for 8 years. She was referred by an orthopedic surgeon because of elevated intact parathyroid hormone (iPTH) for further evaluation. Physical examination revealed a large, firm, and non-tender neck mass, left hip tenderness, and limited range of motion. The initial biochemistry tests showed a borderline high calcium level of 10.8 mg/dl, an elevated iPTH level of 2876 pg/mL, and a decreased phosphorus level of 2.4 mg/dL. The 99mTechnetium (Tc) sestamibi scan displayed early intense activity in the right thyroid lobe persisting in the three-hour repeat scan, compatible with a parathyroid lesion. The patient underwent right-sided neck exploration and parathyroidectomy. Intraoperative and pathology findings confirmed the diagnosis of PC. Immunohistochemistry (IHC) staining revealed creatine kinase (CK) and CD31 in endothelial cells of the tumor. Ki67 staining was also positive in 2% - 3% of tumor cells. The whole exome sequencing (WES) study was negative for cell division cycle 73 (CDC73) and multiple endocrine neoplasia 1 (MEN1) genes. CONCLUSIONS: PC should be considered as a differential diagnosis of PHPT in the pediatric population, even in the presence of mild hypercalcemia.

The impact of variations in transcription of DICER and AGO2 on exacerbation of childhood B-cell lineage acute lymphoblastic leukaemia.

The expression of microRNA in eukaryotic cells is subject to tightly regulated processing. The altered expression of microRNAs in a number of cancers suggests their contribution to disease pathogenesis, where processing pathways may be involved in disease pathogenesis. In the present study, we evaluated changes in the profile of two main components of microRNA biogenesis, AGO2 and DICER, and assessed their correlation with disease progression in childhood acute lymphoblastic leukaemia (ALL). To achieve this aim, 25 patients afflicted with ALL were included in the study along with 25 healthy subjects as control. The expression level of AGO2 and DICER was evaluated by real-time PCR. The results revealed an increase in the expression of DICER and a decrease in AGO2 in patients. The correlation between the alteration levels of these genes with pathologic events was also studied. This increase or decrease proved to be directly correlated with the progression of the disease particularly in L1 to L2. According to the obtained results, it can be deduced that dysregulation in transcription of DICER and AGO2, involved in the formation of mature microRNAs in cytoplasm of ALL cancer cells, is a part of the pathological molecular mechanism implicated in the exacerbation of this malignancy. Therefore, the genes involved in microRNAs biogenesis that have been studied here could be considered as candidate prognostic markers especially in childhood ALL which will help towards a better understanding of the molecular basis of ALL.

Additional cytogenetic aberrations in chronic myeloid leukemia: a single-center experience in the Middle East.

BACKGROUND: Additional cytogenetic aberrations are associated with disease progression in chronic myeloid leukemia (CML). This study was conducted to determine the type and frequency of these aberrations and their relationship with hematologic and molecular findings in the Middle East. METHODS: In this retrospective study, 134 well-established cases of CML were selected from 2010 to 2016. Their hematologic phase and type of fusion gene were determined. Finally, their karyotypes were analyzed and reported according to ISCN 2013. RESULTS: Patients had a mean age of 44 years. Twenty-two patients (16.4%) showed additional cytogenetic aberrations. Nine patients (6.7%) harbored a variant Philadelphia chromosome, and most were in the chronic phase. Seventeen patients (12.7%) had major and minor route abnormalities. There was a significant relationship between additional cytogenetic aberrations and major molecular response (P=0.032). Patient survival in the group with additional cytogenetic aberrations was significantly lower (49.7±11.1 mo) than that in the group without additional cytogenetic aberrations (77.3±3.1 mo) (P=0.031). CONCLUSION: This study revealed the same frequency of additional cytogenetic aberrations in CML as found in previous studies. Additional chromosomal aberrations led to shorter survival and lower rates of achievement of a major molecular response.

Accuracy of Soluble Endoglin for Diagnosis of Preeclampsia and its Severity

Background: The use of biomarkers for diagnosis of Preeclampsia (PE), a life-threatening pregnancy disorder, could reduce serious complications of this disease. In this study, we investigated dysregulation of endoglin (Eng) expression and diagnostic accuracy of soluble endoglin (sEng) in PE patients. Methods: For this case-control study, 26 mild and 15 severe preeclamptic women along with 20 normotensive controls were recruited. The expression level of Eng (the co-receptor of TGF-ß1) was evaluated using qRT-PCR. Also, the serum concentration of soluble Eng and expression of membranous Eng were determined by ELISA and immunohistochemistry. Results: A significant up-regulation in Eng mRNA and sEng levels was observed in PE patients versus normal controls. Immunohistochemistry (IHC) showed up-regulation of membranous Eng staining in syncytiotrophoblast and cytotrophoblast cells of PE patients. The serum levels of sEng were significantly increased in all patients (mild, sever, early- and late-onset) as compared to healthy pregnant women (P˂0.001). Receiver-operating characteristic (ROC) curve analysis revealed that sEng had the highest accuracy in distinguishing PE from normal pregnancies with cut-off value of 20.4, sensitivity of 92.1%, specificity of 90%, and area under the curve (AUC) of 0.94 (95% CI: 0.88-1.00). Conclusion: Our data showed that the up-regulation of Eng mRNA along with its membranous and soluble form in PE patients leads to defect in angiogenesis pathway. Also, the results of this study revealed sEng potential as a marker for diagnosis of PE and its severity.

A report of outbreaks of measles on the southern coast of Iran from 2009 to 2015.

INTRODUCTION: Immunogenicity assessment figures of the measles vaccine is approximately 90%, and decreases over time. Therefore, the immunity level of measles vaccine is variable which can result in outbreaks of measles in a population. The aim of current study was to report the outbreaks of measles in Hormozgan province from 2009 to 2015. METHODS: This cross-sectional study was carried out in Hormozgan Province on the southern coast of Iran. The documented data of all cases suspected of measles are included in this study. We used a checklist including gender, age, area, place of residence, contact history, and vaccination status to extract required data. Data was analyzed using IBM SPSS statistics software version 21.0. RESULTS: Eight hundred fifty-one suspicious cases of measles were determined from 2006 to 2015. Of those, 135 infected cases were reported. Among patients, 49% were male, 79% were Iranian, 18% were Afghans, and 3 % were Indians or Pakistanis. Also, 31% of cases were reported from Bandar Abbas, 25% were reported from Minab, 18% from Qeshm, 17 % from Jask and other cases were reported from other areas of the Hormozgan Province. Thirty percent of the cases were reported from urban areas. CONCLUSION: A high percentage of cases with measles in rural areas were reported in the areas which were covered by complete vaccination. This shows interruption of cold continuum. Also, increasing the number of under one-years-old cases reported, could be due to poor nutritional status of the children and insufficient immunization of mothers. Further studies are required for identifying the causes of cold continuum interruption. Further studies are required for the assessment of immunization in children and mothers and various vaccination protocols.