Dengue viruses and promising envelope protein domain III-based vaccines

Abstract Dengue viruses are emerging mosquito-borne pathogens belonging to Flaviviridae family which are transmitted to humans via the bites of infected mosquitoes Aedes aegypti and Aedes albopictus. Because of the wide distribution of these mosquito vectors, more than 2.5 billion people are approximately at risk of dengue infection. Dengue viruses cause dengue fever and severe life-threatening illnesses as well as dengue hemorrhagic fever and dengue shock syndrome. All four serotypes of dengue virus can cause dengue diseases, but the manifestations are nearly different depending on type of the virus in consequent infections. Infection by any serotype creates life-long immunity against the corresponding serotype and temporary immunity to the others. This transient immunity declines after a while (6 months to 2 years) and is not protective against other serotypes, even may enhance the severity of a secondary heterotypic infection with a different serotype through a phenomenon known as antibody-depended enhancement (ADE). Although, it can be one of the possible explanations for more severe dengue diseases in individuals infected with a different serotype after primary infection. The envelope protein (E protein) of dengue virus is responsible for a wide range of biological activities, including binding to host cell receptors and fusion to and entry into host cells. The E protein, and especially its domain III (EDIII), stimulates host immunity responses by inducing protective and neutralizing antibodies. Therefore, the dengue E protein is an important antigen for vaccine development and diagnostic purposes. Here, we have provided a comprehensive review of dengue disease, vaccine design challenges, and various approaches in dengue vaccine development with emphasizing on newly developed envelope domain III-based dengue vaccine candidates. Keywords: Dengue virus Envelope protein Chimeric vaccine Disease Immunogenicit

Prevention of methylprednisolone acetate-induced osteoporosis with calcium administration in rat model

Glucocorticoid steroids are widely used as anti-inflammatory and immunosuppressive medications and are well known to induce osteoporosis. In Present study 24 rats were randomly divided into four groups (n=6): Group A (control), Group B (sham)that was treated only by normal saline for 1 month.Group C that was treated by methylprednisolone acetate alone (0.2 mg/kg) for 1 month. Group D that was treated by methylprednisolone acetate (0.2 mg/kg) and oral calcium supplementation (15 mg/kg) for 1 month. Changes in concentration of bone metabolic markers such as osteocalcine, acid phosphatase and calcium were evaluated before and after treatment. Bone mineral density (BMD) of lumbar vertebrae was also measured by dual energy X ray absorptiometry (DEXA). The results showed that concentration mean of serum acid phosphatase was increased significantly (P � 0.05) in C and D groups in compared to A and B groups. The concentration mean of serum osteocalcine in group C was decreased significantly (P � 0.05) in comparison to A and B groups but increased significantly in the group D in comparison to group C. The concentration mean of serum calcium was decreased significantly (P � 0.05) in C and D groups in compared to A and B groups. The bone mineral density (g/cm2) was decreased significantly (P � 0.05) in group C in compared to A and B groups. This increased significantly in group D in compared to group C. These results are compatible with the view that low doses of methylprednisolone acetate decreases bone formation and increase bone resorption in the lumbar vertebrae of rats. Calcium administration decreased effects of methylprednisolone. © 2009 Tehran University of Medical Sciences. All rights reserved

Quality of Life Among Veterans With Chronic Spinal Cord Injury and Related Variables

Background: In recent decades, the incidence of spinal cord injuries has increased. In a systemic review on epidemiology of traumatic spinal cord injury in developing countries reported 25.5/million cases per year. Objectives: To assess the quality of life (QOL) of the veterans among Iran-Iraq war with chronic spinal cord injuries (SCI) and to evaluate long-term impressions of SCI on their quality of life. Patients and Methods: Fifty-two veterans, all male, with chronic spinal cord injury from Iran-Iraq war (1980-1988) were interviewed and examined. The mean age of veterans at the time of interview was 49.3 years (38 to 80 years). Veterans were assessed by using a 36-item short-form (SF-36), hospital anxiety and depression scale (HADS) and the Barthel index. The presence or absence of pressure sores and spasticity were documented as well. Results: The mean age of veterans at the time of study was 49.3 years. Pearson's correlation test showed that depression and anxiety have a reverse association with mental component summary (MCS) scale and physical component summary (PCS) scale scores, respectively. Regression analysis showed a negative effect of depression and pressure sore on PCS. Moreover, no association was found between the duration of injury and age with quality of life. Conclusions: Lower QOL was found among veterans with chronic SCI. More researches on health-related quality of life (HRQOL) are needed to give us a better understanding of changes in life of patients with SCI and the ways to improve them

The effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis: A randomized, double-blind, placebo-controlled trial

Objective: This study was carried out to determine the effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis (HD) patients. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either vitamin D supplements at a dosage of 50,000 IU (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of diabetic HD patients with RT-PCR method. Results: Results of RT-PCR indicated that after the 12-week intervention, compared to the placebo, vitamin D supplementation downregulated gene expression of interleukin (IL)-1β (P = 0.02), tumor necrosis factor alpha (TNF-α) (P = 0.02) and interferon gamma (IFN-γ) (P = 0.03) in PBMCs of diabetic HD patients. Additionally, vitamin D supplementation, compared to the placebo, downregulated gene expression of transforming growth factor beta (TGF-β) (P = 0.04), protein kinase C (PKC) (P = 0.001), and mitogen-activated protein kinases 1 (MAPK1) (P = 0.02) in PBMCs of diabetic HD patients. Although not significant, vitamin D supplementation let to a reduction of nuclear factor kappa B (NF-kB) (p = 0.75) expression in PBMCs isolated from diabetic patients compared to the placebo group. There was no statistically significant change following supplementation with vitamin D on gene expression of interleukin (IL)-4, IL-6, and vascular endothelial growth factor (VEGF) in PBMCs of diabetic HD patients. Conclusions: Overall, we found that vitamin D supplementation for 12 weeks among diabetic HD patients had beneficial effects on few gene expression related to inflammation and oxidative stress. © 2018 Haddad Kashani, Seyed Hosseini, Nikzad, Soleimani, Soleimani, Tamadon, Keneshlou and Asemi

The protective effect of coenzyme Q10 and berberine on sperm parameters, with and without varicocelectomy in rats with surgically induced varicoceles

The current study aimed to investigate the protective effects of coenzyme Q10 (Co Q10) and berberine (BB) with and without varicocelectomy on sperm parameters in postoperative varicocele rats. For the current purpose, a total of 60 mature male Wistar rats were randomly divided into control (n = 6 rats), control-sham (n = 6 rats), and experimental (n = 6 rats) groups. The animals in the experimental groups were undergone experimental varicocele, and simple laparotomy was performed in control-sham group. The experimental group was subdivided into the following groups 60 days after varicocele (VCL) induction: non-treated VCL-induced rats (n = 6 rats), VCL-induced rats administered 100 mg (kg per day) BB (n = 6 rats), VCL-induced rats administered Co Q10 75 mg (kg per day) (n = 6 rats), VCL-induced rats administered 100 mg (kg per day) BB + Co Q10 75 mg (kg per day) (n = 6 rats), varicocelectomy rats (n = 6 rats), varicocelectomy rats administered 100 mg (kg per day) BB (n = 6 rats), varicocelectomy rats administered Co Q10 75 mg (kg per day) (n = 6 rats), varicocelectomy rats administered 100 mg (kg per day) BB + Co Q10 75 mg (kg per day) (n = 6 rats). Following 60 days, the animals were euthanized and sperm parameters were evaluated. Non-treated VCL-induced animals indicated a significant (P < 0.05) decrease in sperm parameters and a significant (P < 0.05) increase in sperm DNA damage compared to control and control-sham groups. Insignificant changes were found between control and control-sham groups. Meanwhile, each treatment group showed a remarkable (P < 0.05) increase in sperm parameters as well as a significant (P < 0.05) decrease in sperm DNA damage. Based on current results, BB and Co Q10 alone and/or together could improve sperm parameters and reduce sperm DNA damage in varicocele-induced rats compared to control and control-sham groups. Varicocelectomy alone will improve sperm parameters, but this recovery will be greater when combined with Co Q10 and BB. © 2018, Springer-Verlag London Ltd., part of Springer Nature

The Effectiveness of Integrative Group Therapy on the Sexual Function of Women with Systemic Scleroderma

Aims: Systemic scleroderma is a multiple chronic autoimmune disease that has important clinical and psychological consequences, including sexual dysfunction. The purpose of this study was to determine the efficacy of integrated treatment group on sexual function and its domains in women with scleroderma. Materials & Methods: This research was a semi-experimental design with pre-test, post-test, and follow-up with the experimental and control groups. The statistical population included women with scleroderma referred to Shariati Hospital in Tehran and Iran's Rheumatism Center in the second half of 2017. Of these, 30 patients were selected as available samples and randomly were placed in the control and the experimental groups. The experimental group was subjected to an integrated approach intervention in 9 sessions of 90-minutes, where as the control group did not receive such an intervention. The instrument of this study was the Female Sexual Function Index (FSFI) Questionnaire. Data were analyzed using SPSS24 software and repeated measures ANOVA. Findings: Unilateral psychotherapy intervention significantly increased the mean post-test of sexual function and its six sub-components in both control and experimental groups (p<0.01, F=19.59). The satisfaction component with 0.82 (p<0.01, F=125.35) and psychological stimulation with 0.74 (F=77.9, p<0.01) had the most effect on intervention, and the component of orgasm with 0.33 (F=13.54, p<0.01) had the least effect among the components. After three months, there was no statistically significant difference between the post-test and the follow-up of the experimental group, which indicated the stability of intervention effects. Conclusion: Unified psychotherapy is effective in increasing the sexual function of patients with systemic sclerosis and can play a significant role in improving the quality of life of these people

Radiographic outcome of surgical treatment of adolescent idiopathic scoliosis in males versus females

Background: Studies on adolescent idiopathic scoliosis have well documented the differences between natural history of male and female patients. There are also differences in responses to nonoperative treatment, but the results of operative treatment in male patients compared with females have not been widely reported. Only few studies had compared the outcomes of operative treatment between male and female patients with different results. Methods: We retrospectively reviewed the outcome of 150 (112 girls and 38 boys) consecutive patients with diagnosis of adolescent idiopathic scoliosis who were managed surgically between May 1996 and September 2005. Next, male radiographic parameters were compared with female ones pre- and postoperatively. Then, a subgroup of 38 matched girls was compared regarding the age, curve type, curve magnitude, and the instrumentation we used. Results: In comparing male patients with unmatched girls, the boys had greater mean age (17.3 ± 2.3 vs. 16.3 ± 2.9; p = 0.049), greater primary curve (71.4 ± 21.3° vs. 62.7 ± 17.5°; p = 0.013), less flexibility (30.1 ± 13.5 vs. 40.3 ± 17.8; p = 0.01), and less correction percentage (51.3 ± 12.9 vs. 58.8 ± 16.5; p = 0/013). The loss of correction was comparable between the two groups. In the matched comparison, the flexibility in boys was less than girls (30.1 ± 13.5 vs. 38.1 ± 17.5; p = 0.027). Also, the boys had a smaller correction percentage compared to the girls, but this finding was not statistically significant. Conclusion: There was similar distribution curve pattern between male and female patients with AIS. Males had more rigid primary curves compared to females but a similar degree of postoperative scoliosis correction. Male AIS patients were older at the time of surgery. These preoperative gender differences, however; did not compromise the radiological outcomes of surgical treatment and the results were comparable between the genders. © 2008 Ameri et al; licensee BioMed Central Ltd

Evaluation of the serum sex hormones levels and alkaline phosphatase activity in rats� testis after administering of berberine in experimental varicocele

Current study was aimed to investigate the protective effect of berberine (BB) on the serum gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B (INHB), testosterone (T) and alkaline phosphatase (Alk-p) activity in the testis of experimental varicocele-induced animals. For the current objective, 30 mature-male Wistar rats were randomly divided into control (n = 6 rats), control-sham (n = 6 rats) and experimental groups (n = 18 rats). The animals in the experimental groups were undergone experimental varicocele and simple laparotomy was conducted in control-sham group. 60 days after varicocele (VCL) induction the experimental group subdivided into: non-treated VCL-induced and 50 mg/kg and 100 mg/kg BB-treated groups (intra-peritoneally). Following 60 days, the animals were euthanized and serum levels of testosterone and testicular activity of alkaline phosphatase were measured. Non-treated VCL-induced animals indicated a significant (P < 0.05) reduction in serum levels of T and INHB and a remarkable (P < 0.05) increase in GnRH, FSH, LH and Alk-p activity compared to control and control-sham groups. Insignificant changes were found between control and control-sham groups. Meanwhile, each BB administered group showed a remarkable (P < 0.05) increase in serum levels of T and INHB and a significant (P < 0.05) decrease in GnRH, FSH, LH and alkaline phosphatase activity in testis tissue. According to the current findings, BB by increasing serum levels of testosterone and INHB increases the testicular endocrine capacity and protects Leydig cell against inflammatory and oxidant injury of varicocele. In addition, BB by inhibiting GnRH, FSH, LH and alkaline phosphatase activity, regulate the levels of serum sex hormones in experimental varicocele and reduces varicocele-induced inflammatory reactions. © 2019, Institute of Korean Medicine, Kyung Hee University

Open string wavefunctions in flux compactifications

We consider compactifications of type I supergravity on manifolds with SU(3) structure, in the presence of RR fluxes and magnetized D9-branes, and analyze the generalized Dirac and Laplace-Beltrami operators associated to the D9-brane worldvolume fields. These compactifications are T-dual to standard type IIB toroidal orientifolds with NSNS and RR 3-form fluxes and D3/D7 branes. By using techniques of representation theory and harmonic analysis, the spectrum of open string wavefunctions can be computed for Lie groups and their quotients, as we illustrate with explicit twisted tori examples. We find a correspondence between irreducible unitary representations of the Kaloper-Myers algebra and families of Kaluza-Klein excitations. We perform the computation of 2- and 3-point couplings for matter fields in the above flux compactifications, and compare our results with those of 4d effective supergravity.Comment: 89 pages, 4 figures. v3: more typos corrected, version published in JHE