A randomized,triple‐blind,placebo‐controlled clinical trial,evaluating the sesamin supplement effects on proteolytic enzymes,inflammatory markers,and clinical indices in women with rheumatoid arthritis

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple‐blind, placebo‐controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200‐mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases‐3) and inflammatory biomarkers (hs‐CRP, IL‐1β, IL‐6, TNF‐α, and cyclooxygenase‐2) were measured with enzyme‐linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases‐3 decreased significantly in sesamin group. Also, serum levels of hs‐CRP, TNF‐α, and cyclooxygenase‐2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.     

Cellular responses to protein accumulation involve autophagy and lysosomal enzyme activation

Protein oligomerization and aggregation are key events in age-related neurodegenerative disorders, causing neuronal disturbances including microtubule destabilization, transport failure and loss of synaptic integrity that precede cell death. The abnormal buildup of proteins can overload digestive systems and this, in turn, activates lysosomes in different disease states and stimulates the inducible class of lysosomal protein degradation, macroautophagy. These responses were studied in a hippocampal slice model well known for amyloidogenic species, tau aggregates, and ubiquitinated proteins in response to chloroquine-mediated disruption of degradative processes. Chloroquine was found to cause a pronounced appearance of prelysosomal autophagic vacuoles in pyramidal neurons. The vacuoles and dense bodies were concentrated in the basal pole of neurons and in dystrophic neurites. In hippocampal slice cultures treated with Abeta(142), ultrastructural changes were also induced. Autophagic responses may be an attempt to compensate for protein accumulation, however, they were not sufficient to prevent axonopathy indicated by swellings, transport deficits, and reduced expression of synaptic components. Additional chloroquine effects included activation of cathepsin D and other lysosomal hydrolases. Abeta(142) produced similar lysosomal activation, and the effects of Abeta(142) and chloroquine were not additive, suggesting a common mechanism. Activated levels of cathepsin D were enhanced with the lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK). PADK-mediated lysosomal enhancement corresponded with the restoration of synaptic markers, in association with stabilization of microtubules and transport capability. To show that PADK can modulate the lysosomal system in vivo, IP injections were administered over a 5-day period, resulting in a dose-dependent increase in lysosomal hydrolases. The findings indicate that degradative responses can be modulated to promote synaptic maintenance.     

Efficacy and tolerability of pharmacotherapies for attention-deficit hyperactivity disorder in adults

This review examines the evidence regarding the efficacy and tolerability of long- and short-acting stimulant medications, as well as the non-stimulant medications atomoxetine and bupropion in the treatment of adult attention-deficit hyperactivity disorder (ADHD). Effect sizes in adults appear to be of almost the same magnitude as in school-age children when robust doses are used. There are adequate data demonstrating short-term efficacy and safety of medication in ADHD during adulthood but long-term studies are lacking, particularly in view of concerns regarding cardiovascular adverse events. There is some evidence that stimulant medication can improve driving performance in adults with ADHD. The extent to which medication may improve academic, occupational and social functioning in adults with ADHD is unclear, and future research should investigate these outcomes. Medication treatment of adults with ADHD in sports is controversial. Both stimulant and non-stimulant medications seem to be well tolerated. Monitoring of pulse and blood pressure is recommended with these drugs because of their cardiovascular effects. There have been extremely rare case reports of sudden death in adults and children treated with stimulants and atomoxetine, but it is difficult to clearly establish causality. In view of reports of treatment-related suicide-related behaviour with atomoxetine, it is recommended that adults should be observed for agitation, irritability, suicidal thinking, self-harming or unusual behaviour, particularly in the first months of treatment, or after a change of dose. ADHD in adults continues to remain an under-recognized disorder in many parts of the world and there is a lack of specialist clinics for assessment and treatment of adult ADHD. Studies to date have failed to show efficacy of medications in the treatment of ADHD in the substance misuse population. There is little evidence so far to suggest an increased misuse of stimulants or diversion amongst substance misusers; however, data are insufficient to draw firm conclusions. Further work is necessary to evaluate effective treatments in subgroups such as the substance misuse population, those with multiple co-morbidities and different ADHD subtypes.     

OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer

OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT-4 has been introduced as a molecular marker for germ cell tumors, little is known about its expression in somatic cancers. Here, we have investigated the potential expression of OCT-4 in bladder cancer. We used semiquantitative RT-PCR to examine the expression of OCT-4 in 32 tumors, 13 apparently nontumor tissues taken from the margin of tumors and 9 normal urothelial tissues. The expression of OCT-4 at protein level was further determined by Western blotting and immunohistochemical (IHC) analysis. OCT-4 expression was detected in almost all examined tumors (31/32), but at much lower level (p<0.001) in some nonneoplastic samples (6/22). A significantly strong correlation of 0.6 has been observed between OCT-4 expression and the presence of tumors (p<0.001). Western blot analysis further confirmed the expression of OCT-4 in tumor biopsies. According to IHC results, OCT-4 is primarily localized in the nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Our study demonstrated, for the first time, the expression of OCT-4 in bladder cancer and a further clue to the involvement of embryonic genes in carcinogenesis.     

Association of RAD51 and XRCC2 Gene Polymorphisms with Cervical Cancer Risk in the Bangladeshi Women

Objective: Alterations in common DNA repair genes (RAD51 and XRCC2) may lead to cervical cancer (CC) development. In the present study, we analyzed the association between RAD51 rs1801320 and XRCC2 rs3218536 polymorphisms and CC. Methods: Variants were selected based on their associations with some cancers in several ethnicities and the risk allele frequency (>0.05) in different populations. The variants were detected using the PCR-RFLP method. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined by logistic regression models. Result: Significantly increased risk (p <0.05) were detected for both SNPs with CC (rs1801320- GC vs. GG: aOR=2.21, 95% CI=1.43-3.42; CC vs. GG: aOR=4.48, 95% CI=1.76-11.42; dominant model: aOR=2.49, 95% CI=1.65-3.76; recessive model: aOR=3.52, 95% CI=1.40-8.88; allele model: OR=2.30, 95% CI=1.63-3.26, and rs3218536- GA vs. GG: aOR=2.77, 95% CI=1.85-4.17; AA vs. GG: aOR=5.86, 95% CI=2.08-16.50; dominant model: aOR=2.97, 95% CI=1.99-4.42; recessive model: aOR=3.56, 95% CI=1.30-9.73; and allele model: aOR=2.21, 95% CI=1.62-3.00). Besides, older patients (>60 years) with rs1801320 showed significantly reduced risk (OR=0.53, 95% CI=0.29-0.96, p=0.04) but with rs3218536 depicted significantly increased risk (aOR=2.44, 95% CI=1.20-4.96, p=0.01) for CC. Conclusion: This study indicates an association of rs1801320 and rs3218536 polymorphisms with CC and confirms that patients older than 60 years are more likely to develop CC for rs3218536 polymorphism.     

Selegiline induces neuronal phenotype and neurotrophins expression in embryonic stem cells

The antiaging effect of selegiline was reported by several investigators; therefore, there is a growing interest in the potential use of stem cell therapy in aging. In this investigation, selegiline was used to induce neuronal differentiation in undifferentiated pluripotent embryonic stem cells (ESCs). The results show that selegiline can induce neuronal phenotype associated with neurotrophic factor expression. Morphologic and immunohistochemical techniques were used to evaluate the differentiation of the CCE cells, Cresyl violet for the morphologic study, anti-synaptophysin and antityrosine hydroxylase antibodies for characterizing the neuronal phenotype of ESCs, and RT-PCR to study the neurotrophins. The results showed that selegiline can induce dose-dependent ESC differentiation into neurons. Moreover, selegiline can induce neurotrophin expression. This study suggests the potential use of combined selegiline and stem cell therapy to improve deficits in neurodegenerative diseases in aging.