Regulatory T cells for amyotrophic lateral sclerosis/motor neuron disease: A clinical and preclinical systematic review

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by neuronal degeneration and inflammation in the nerves. The role of the immune system has been concentrated by researchers in the etiopathogenesis of the disease. Given the inhibitory roles of regulatory T cells (Tregs), it is expected that increasing or activating their populations in patients with ALS can have significant therapeutic effects. Here we searched databases, including CENTRAL, MEDLINE, CINAHL Plus, clinicaltrials.gov , and ICTRP for randomized clinical trials (RCTs) and non-RCTs until March 2019. For preclinical studies, we searched PubMed, Scopus, and Google Scholar up to June 2019. We also included preclinical studies, due to the lack of clinical information available, which used Tregs (or directly targeting them) for treating mice models of ALS. We identified 29 records (CENTRAL 7, MEDLINE 4, CINAHL Plus 8, and clinicaltrials.gov 10) and removed 10 duplicated publications. After screening, we identified one RCT which had been published as an abstract, three non-RCTs, and four ongoing studies. We also identified 551 records (PubMed 446, Google Scholar 68, and Scopus 37) for preclinical studies and performed a meta-analysis. Finally, we found three papers that matched our inclusion criteria for preclinical studies. Results indicated the effectiveness of the application of Tregs in the treatment of ALS. Our meta-analysis on preclinical studies revealed that Tregs significantly prolonged survival in mice models of ALS. Overall, our analysis testified that exertion of Tregs in the treatment of ALS is a promising approach, that notwithstanding, requires further evaluations.     

Principal Component Analysis of Time-Related Changes of Some Essential Mineral Contents of Canned Silver Carp (Hypophthalmichthys molitrix) in Different Filling Media

Biological Trace Element Research - The kinetic reaction for changes in some essential mineral contents (iron, zinc, calcium, sodium, and copper) of silver carp canned in sunflower oil, soybean...     

A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation

Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called “GLUR6”) that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU_K6 protein, which is supported by electrophysiological data. This finding provides the first proof that GLU_K6 is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.     

Interaction of methylxanthines and gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa: role of phosphodiesterase inhibition

Previous studies showed that methylxanthines increased the antimicrobial activity of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. In this study, the effect of non-selective phosphodiesterase (PDE) inhibitors (methylxanthines: aminophylline and caffeine) and partially selective PDE inhibitors, dipyridamole and sildenafil, was evaluated on the antimicrobial activity of gentamicin using checkerboard method. Aminophylline at concentrations of 0.5 and 1 mg/ml reduced the minimal inhibitory concentration (MIC) of gentamicin (2 μg/ml) 2 and 4 times against S. aureus, and at concentrations of 0.5 and 2 mg/ml reduced the MIC of gentamicin (4 μg/ml) 2 and 4 times, respectively, against P. aeruginosa. Caffeine at concentrations of 1 and 2 mg/ml reduced the MIC of gentamicin (2 μg/ml) 4 and 32 times against S. aureus, and at concentrations of 0.12 and 2 mg/ml reduced the MIC of gentamicin (4 μg/ml) 2 and 4 times, respectively, against P. aeruginosa. However, dipyridamole and sildenafil (32 μg/ml) did not show any effect on MIC of gentamicin against S. aureus and P. aeruginosa. These results suggest that methylxanthines could increase gentamicin effects against S. aureus and P. aeruginosa but this effect is not mediated by inhibition of PDE 5, 6, 8, 10 and 11.     

Anaplastic large cell lymphoma in a human immunodeficiency virus-positive patient with cytologic findings in bladder wash: a case report

BACKGROUND: Anaplastic large cell lymphoma (ALCL) (Ki-1/CD-30 positive) is an uncommon lymphoproliferative disorder that may be of T cell or null cell type. ALCL has been reported in fine needle aspirations of lymph nodes and pleural or peritoneal fluid cytology. In human immunodeficiency virus (HIV)-positive patients, ALCL appears to be more common and run a more aggressive course. CASE: A 39-year-old black man, seropositive for HIV, presented with acute renal failure secondary to bilateral ureteral obstruction by a pelvic mass involving the urinary bladder. Bladder wash cytology and subsequent biopsy of the mass were diagnostic of ALCL. The ALCL was CD30+ and null cell type, with negative CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD45, CD79a, ALK-1, granzyme B, cytokeratin (AE1/AE3), placental alkaline phosphatase (PLAP) and S-100. The patient expired 9 months after the diagnosis, despite aggressive therapy. CONCLUSION: This is a rare occurrence of ALCL (CD 30 positive, null cell type) in the urinary bladder in an HIV+ patient. Presumptive diagnosis was made by bladder wash cytology and subsequently confirmed by biopsy. Urinary cytologic examination is a useful diagnostic tool. In HIV+/immunosuppressed patients with urinary symptoms and an obstructive mass, ALCL should be considered in the differential diagnosis.     

Plasmodium falciparum: sequence analysis of the gene encoding the C-terminus region of the merozoite surface protein-1, a potential malaria vaccine antigen, in Iranian clinical isolates

C-terminal region of merozoite surface protein-1 of Plasmodium falciparum (PfMSP-1) isolated from different parts of the world revealed sequence variability, however no data exist on sequence heterogeneity of this region from Iran. To address this question, DNA encoding the carboxyl (C)-terminal region of PfMSP-1 was amplified in 144 Iranian P. falciparum clinical isolates, using allele type-specific primers. In this study both MAD20 (88.2%) and K1 (7.6%) types were detected. Sequence analysis of 33 and 92 fragments corresponding to pfmsp-1(42) and pfmsp-1(19) revealed eight (15MAD1-15MAD7 and 15KCH) and five [A1 (E/TSR/L), A2 (Q/KNG/F), A3 (E/KNG/F), A4 (E/TSG/L), and A5 (Q/KNG/L)] distinct haplotypes, respectively. E/TSG/L variant type was the predominant haplotype, and reported only from Thailand and India, but E/KNG/L is widespread in Africa, Asia, and Latin America; but not found among Iranian isolates. In summary, result of this study indicates limited antigenic diversity, and thus support the potential utility of the C-terminal region of PfMSP-1 in designing polyvalent vaccine constructs.     

Bioproduction of phenylethanoid glycosides by plant cell culture of Scrophularia striata Boiss.: from shake-flasks to bioreactor

Phenylethanoid glycosides (PeG) are a class of polyphenols found in some plants that have pharmaceutical effects as anti-inflammatories and anti-oxidants. The presence of PeG (acteoside) in the aerial parts of Scrophularia striata Boiss. has been demonstrated. Considerable progress has been made using plant cell cultures to stimulate formation and accumulation of secondary metabolites. The present study optimized phenylethanoid production from shake flasks to bioreactor using a cell culture of S. striata. The optimal conditions for production of cell biomass by scale-up to a bioreactor were determined to be a pH of 4.8, air flow rate of 0.5–1.5 l min⁻¹, and mixing speed of 110–170 rpm at 25 ± 1 °C in darkness. Growth parameters and PeG production were measured and compared with the results from the shake flasks. The results showed that cell biomass was high in the bioreactor (15.64 g l⁻¹ DW) and in the shake flasks (14.16 g l⁻¹ DW). The acteoside content in the bioreactor was 1404.20 μg g⁻¹ DW, which is threefold higher than in the shake flasks (459.71 μg g⁻¹ DW). The echinacoside concentration in the bioreactor was 1449.39 μg g⁻¹, 1.36-fold lower than in the shake flasks (1973.03 μg g⁻¹ DW). This study established an efficient way for production of acteoside, the major PeG, in a bioreactor.

     

Zinc Oxide Nanoparticles Inhibition of Initial Adhesion and ALS1 and ALS3 Gene Expression in Candida albicans Strains from Urinary Tract Infections

Mycopathologia - The aim of this study was to evaluate effects of zinc oxide nanoparticles (ZnO-np) on initiation adhesion and agglutinin-like sequence (ALS) 1 and ALS3 gene expression, which is...     

Correlation between the papanicolaou stain and the Wright-Giemsa stain in body fluids: a quality assurance study

OBJECTIVE: To compare the use of Papanicolaou and Wright-Giemsa stains for the evaluation of body fluids in cytology and hematology laboratories and determine whether other factors account for discrepancies in diagnosis. STUDY DESIGN: We retrospectively reviewed cytopathology reports of peritoneal, pleural, and cerebrospinal fluids received by hematology and cytology laboratories for 1 year. Cases were divided into 3 categories-benign, atypical, and malignant--and slides of discrepant diagnoses were reviewed. RESULTS: During this period, 198 of 3212 (0.61%) cases received by the hematology laboratory and 252 of 4402 (0.57%) cases received by the cytology laboratory were diagnosed as malignant or atypical. Of 3212 cases simultaneously received by the cytology and hematology laboratories, 17 diagnosed as malignant by hematology were diagnosed benign by cytology (sensitivity 96%). Sixteen cases diagnosed as malignant by cytology were diagnosed as benign by hematology (sensitivity 97%). No benign cases were diagnosed as malignant (specificity 100%). Review of the glass slides of the discrepant cases revealed 8 cases undercalled by hematology and 7 cases undercalled by cytology. CONCLUSION: Papanicolaou stain is superior for carcinoma and Wright-Giemsa stain for hematopoietic disorders, but used together they may reduce false negative results. Delays in processing, staining technique, and interobserver variability contribute to discrepancy.     

Unraveling salinity stress responses in ancestral and neglected wheat species at early growth stage: A baseline for utilization in future wheat improvement programs

In this study, we analyzed the behavior of several neglected, ancestral, and domesticated wheat genotypes, including Ae. triuncialis, Ae. neglecta, Ae. caudata, Ae. umbellulata, Ae. tauschii, Ae. speltoides, T. boeoticum, T. urartu, T. durum, and T. aestivum under control and salinity stress to assess the mechanisms involved in salinity tolerance. Physiological and biochemical traits including root/shoot biomasses, root/shoot ion concentrations, activity of antioxidant enzymes APX, SOD, and GXP, and the relative expression of TaHKT1;5, TaSOS1, APX, GXP, and MnSOD genes were measured. Analysis of variance (ANOVA) revealed significant effects of the salinity treatments and genotypes for all evaluated traits. Salinity stress (350 mM NaCl) significantly decreased root/shoot biomasses, K+ concentration in root/shoot, and root/shoot K+/Na+ ratios. In contrast, salinity stress significantly increased Na+ concentration in root and shoot, activity of antioxidant enzymes (APX, SOD, and GPX) and relative expression of salt tolerance-related genes (TaHKT1;5, TaSOS1, APX, GPX, and MnSOD). Based on heat map and principal component analysis, the relationships among physiological traits and relative expression of salt-responsive genes were investigated. Remarkably, we observed a significant association between the relative expression of TaHKT1;5 with root K+ concentration and K+/Na+ ratio and with TaSOS1. Taken together, our study revealed that two neglected (Ae. triuncialis) and ancestral (Ae. tauschii) wheat genotypes responded better to salinity stress than other genotypes. Further molecular tasks are therefore essential to specify the pathways linked with salinity tolerance in these genotypes.