Comparison of plasma mitochondrial DNA copy number in asymptomatic and symptomatic COVID-19 patients

IntroductionSince the beginning of the COVID-19 pandemic, a wide clinical spectrum, from asymptomatic infection to mild or severe disease and death, have been reported in COVID-19 patients. Studies have suggested several possible factors, which may affect the clinical outcome of COVID-19. A pro-inflammatory state and impaired antiviral response have been suggested as major contributing factors in severe COVID-19. Considering that mitochondria have an important role in regulating the immune responses to pathogens, pro-inflammatory signaling, and cell death, it has received much attention in SARS-CoV-2 infection. Recent studies have demonstrated that high levels of cell-free mitochondrial DNA (cf-mtDNA) are associated with an increased risk of COVID-19 intensive care unit (ICU) admission and mortality. However, there have been few studies on cf-mtDNA in SARS-CoV-2 infection, mainly focusing on critically ill COVID-19 cases. In the present study, we investigated cf-mtDNA copy number in COVID-19 patients and compared between asymptomatic and symptomatic cases, and assessed the clinical values. We also determined the cf-nuclear DNA (cf-nDNA) copy number and mitochondrial transcription factor A (TFAM) mRNA level in the studied groups.Materials and methodsPlasma and buffy coat samples were collected from 37 COVID-19 patients and 33 controls. Briefly, after total DNA extraction, plasma cf-mtDNA, and cf-nDNA copy numbers were measured by absolute qPCR using a standard curve method. Furthermore, after total RNA extraction from buffy coat and cDNA synthesis, TFAM mRNA levels were evaluated by qPCR.ResultsThe results showed that cf-mtDNA levels in asymptomatic COVID-19 patients were statistically significantly higher than in symptomatic cases (p value = 0.01). However, cf-nDNA levels were higher in symptomatic patients than in asymptomatic cases (p value = 0.00). There was no significant difference between TFAM levels in the buffy coat of these two groups (p value > 0.05). Also, cf-mtDNA levels showed good diagnostic potential in COVID-19 subgroups.Conclusioncf-mtDNA is probably important in the outcome of SARS-CoV-2 infection due to its role in inflammation and immune response. It can also be a promising candidate biomarker for the diagnosis of COVID-19 subgroups. Further investigation will help understanding the COVID-19 pathophysiology and effective diagnostic and therapeutic strategies

Moyamoya Syndrome Associated with Henoch-Schönlein Purpura

How to Cite This Article: Shiari R, Tabatabaei Nodushan SMH, Mohebbi MM, Karimzadeh P, Javadzadeh M. Moyamoya Syndrome Associated with Henoch-Schönlein Purpura. Iran J Child Neurol. Autumn 2016; 10(4):71-74.AbstractSome reports have shown the association between Moyamoya syndrome andautoimmune diseases. Herewith, we present a 3.5 yr old girl with Henoch-Schönleinpurpura (HSP) who was treated with steroids because of severcolicky abdominal pain. However, central nervous system manifestations suchas headache, ataxia and vision impairment developed during 6 months of heroutpatient follow-up. More evaluation using MRA revealed intracranial stenosisof internal carotid artery and arterial collaterals that were in favor of Moyamoyasyndrome. To our knowledge, this is the first report of Moyamoya syndromefollowing henoch-schönleinpurpura.References1. Aicardi J. Diseases of the nervous system in childhood, 2nd ed. London: Mac Keith Press, 1998. pp. 554–556.2. Currie S, Raghavan A, Batty R, Connolly DJ, Griffiths PD. Childhood moyamoya disease and moyamoya syndrome: a pictorial review. Pediatr Neurol 2011; 44:401–13.3. Suzuki J, Takaku A. Cerebrovascular, “moyamoya” disease. Disease showing abnormal net-like vessels in  base of brain. Arch Neurol 1969; 20:288–99.4. Smith ER, Scott RM. Spontaneous occlusion of the circle of Willis in children: pediatric moyamoya summary with proposed evidence-based practice guidelines. A review. J Neurosurg Pediatr. 2012 Apr;9(4):353-60.5. Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 2006; 65(7): 936-941.6. Gardner-Medwin JM, Dolezolova P, Cummins C, Southwood TR. Incidence of Henoch-Schonleinpurpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. 2002; 360: 1197-1202.7. Aalberse J, Dolman K, Ramnath G, Periera RR, Davin JC. Henoch-Schönleinpurpura in children: an epidemiological study among Dutch paediatricians on incidence and diagnostic criteria. Ann Rheum Dis. 2007; 66(12): 1648-1650.8. Saulsbury FT. Henoch-Schönleinpurpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore). 1999; 78(6): 395-409.9. Tarvin SE, Ballinger S. Henoch-Schonleinpurpura. Current Paediatrics. 2006; 16: 259-263.10. Cahide Y, Hu¨seyin, Şükrü Arslan C et al. Bilateral brachial plexopathy complicating henoch-schönleinpurpura. Brain & Development 28 (2006) 326–328.11. Bellman AL, Leicher CR, Moshe SL, Mezey AP. Neurologic manifestations of henoch–schönleinpurpura: Report of three cases and review of the literature. Pediatrics 1985; 75:687-92.12. Reza Shiari. Neurologic Manifestations of Childhood Rheumatic Diseases. Iran J Child Neurol 2012; 6(4): 1-7.13. Lee YJ, Yeon GM, Nam SO, Kim SY. Moyamoya syndrome occurred in a girl with an inactive systemic lupus erythematosus. Korean J Pediatr 2013; 56(12): 545–549.14. Seol HJ, Wang KC, Kim SK, Hwang YS, Kim KJ, Cho BK. Headache in pediatric moyamoya disease: review of 204 consecutive cases. J Neurosurg 2005; 103: Suppl: 439-42.15. Suzuki J, Kodama N. Moyamoyadisease — a review. Stroke 1983; 14:104-9.16. Baba T, Houkin K, Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry 2008; 79:900-4.17. Tanghetti B, Capra R, Giunta F, Marini G, Orlandini A. Moyamoya syndrome in only one of two identical twins: case report. J Neurosurg 1983; 59:1092-4.18. Guey S, Tournier-Lasserve E, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet 2015; 8: 49–68.19. Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pialsynangiosis. J Neurosurg 2004; 100: Suppl: 142-9.20. Lubman DI, Pantelis C, Desmond P, Proffitt TM, Velakoulis D. Moyamoya disease in a patient with schizophrenia. J Int Neuropsychol Soc 2003; 9:806-10.21. Smith ER, Scott RM. Moyamoya Disease and Moyamoya Syndrome. N Engl J Med 2009; 360:1226-37.22. Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis. Guidelines for diagnosis and treatment of moyamoya disease Neurol Med Chir (Tokyo) 2012; 52(5):245–266.23. Fung LW, Thompson D, Ganesan V. Revascularisation surgery for paediatricmoyamoya: a review of the literature. Childs Nerv Syst 2005; 21(5):358–364

The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways

Hepatocellular carcinoma (HCC) is a significant global health issue, with a high prevalence in many regions. There are variations in the etiology of HCC in different regions, but most cases are due to long-term infection with viral hepatitis. Hepatitis B virus (HBV) is responsible for more than 50% of virus-related HCC, which highlights the importance of HBV in pathogenesis of the disease. The development and progression of HBV-related HCC is a complex multistep process that can involve host, viral, and environmental factors. Several studies have suggested that some HBV genome mutations as well as HBV proteins can dysregulate cell signaling pathways involved in the development of HCC. Furthermore, it seems that the pathogenicity, progression of liver diseases, response to treatment and also viral replication are different among HBV mutants. Understanding the relationship between HBV genome variations and host signaling pathway alteration will improve our understanding of the molecular pathogenesis of HBV-related HCC. Furthermore, investigating commonly dysregulated pathways in HBV-related HCC is necessary to discover more specific therapeutic targets and develop more effective strategies for HCC treatment. The objective of this review is to address the role of HBV in the HCC progression and primarily focus on the impacts of HBV genome variations on HCC-related signaling pathways

Antihyperglycemic activity of quince (Cydonia oblonga Mill.) fruit extract and its fractions in the rat model of diabetes

Introduction: Diabetes mellitus is a metabolic disease that has affected approximately 10% of population worldwide. Cydonia oblonga Mill. (C. oblonga), commonly called quince, contains diverse phytochemical constituents with a broad range of pharmacological activities. The current study is aimed to investigate the antihyperglycemic effect of aqueous extract of Cydonia oblonga Mill. fruit (ACO) in streptozotocin-induced diabetic rats and to identify the active fraction. Methods and Results: Diabetes was induced in rats by a single intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin. The antihyperglycemic activity of different concentrations of ACO (80, 160 and 240 mg/kg body weight daily for a period of 28 days) was evaluated in the diabetic rats by measuring their fasting blood glucose (FBG). Furthermore, the antihyperglycemic effects of two major fractions of ACO were evaluated for the identification of active fraction. Finally, the chemical composition of the active fraction, methanolic fraction (MF), was examined by gas chromatography-mass spectrometry (GC-MS) assay. The oral administration of ACO on diabetic rats resulted in a significant collapse in FBG in a dose-dependent manner. In addition, the MF was the active fraction and exhibited antihyperglycemic activity in diabetic rats during the experiment. The main component of MF was identified as 5-hydroxymethylfurfural or 5-HMF (a well-known natural compound) that may be responsible, at least partly, for the antidiabetic and antihyperglycemic effects of quince. Conclusion: Our results have demonstrated for the first time that quince possesses antihyperglycemic effect in diabetic rats and the MF of the aqueous extract is active fraction

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies

Hematological and biochemical evaluation of goats naturally infected with contagious ecthyma

Contagious ecthyma (CE) is a zoonotic skin disease of small ruminants, caused by an epitheliotropic parapoxvirus and has a worldwide distribution with significant economic importance. The objective of this study was to determine clinicopathlogic abnormalities in goats naturally infected with CE. Thirty two goats, 16 affected with CE and 16 normal healthy goats were used in this study. CE was confirmed by histopathology and PCR. Blood samples were collected from jugular veins for hematological and biochemical analysis. The PCV, WBC and neutrophil counts of CE affected goats were significantly higher than those in the unaffected goats (p < 0.05). Serum biochemical analysis revealed significantly higher levels of BUN, glucose, MDA and iron concentrations as well as CK, AST, GGT and catalase activities in CE affected goats than healthy animals (p < 0.05). The serum activity of catalase, SOD and GPx in goats with CE were significantly lower than those in normal goats. Creatinine concentration in serum of goats with CE was significantly lower than that in heathy ones (p < 0.05). There was no significant difference in serum total protein, albumin, total and direct bilirubin, and cholesterol concentrations between CE affected and healthy goats. The alterations observed in hematological and biochemical parameters of CE affected goats could be related to weight loss, subnutrition, oxidative stress and pathological changes including inflammation and secondary bacterial infection. These findings could be useful for the management of cases of sheep and goats with CE

Comparison of the Effects of Media-based and Face-to-face Cardiac Rehabilitation Training Programs on Self-efficacy in Patients Undergoing Coronary Artery Bypass Grafting

Background: Several complications may occur in patients after coronary artery bypass grafting (CABG) leading to decreased self-efficacy. Rehabilitation training is the best method for reducing the complications and increasing self-efficacy. Various educational techniques lead to different rehabilitation results and levels of self-efficacy. Improving these measures requires the selection of the most appropriate educational technique. Aim: This study aimed to compare the effect of two media-based and face-to-face cardiac rehabilitation training methods on self-efficacy in patients undergoing CABG. Method: This clinical trial was conducted among 60 patients, who were randomly assigned into two groups, in Imam Reza Hospital, Mashhad, Iran, 2017. Cardiac rehabilitation training program was implemented face-to-face or using a researcher-made multimedia upon admission, discharge, at the start of cardiac rehabilitation, and at the end of the 10th session for half-hour. A researcher-constructed questionnaire on self-efficacy was completed by the participants in the mentioned stages. Data analysis was performed in SPSS software, version 16. Results: The mean ages of the participants in the face-to-face and multimedia groups were 56.0±8.1 and 57.5±7.3 years old, respectively. No significant difference was observed in the self-efficacy scores of the patients upon admission (P=0.36). However, there was a significant difference between the groups at the post-intervention stage (