Rheumatoid arthritis molecular targets and their importance to flavonoid-based therapy.

Rheumatoid arthritis (RA) is a progressive, chronic, autoimmune, inflammatory, and systemic condition that primarily affects the synovial joints and adjacent tissues, including bone, muscle, and tendons. The World Health Organization recognizes RA as one of the most prevalent chronic inflammatory diseases. In the last decade, there was an expansion on the available RA therapeutic options which aimed to improve patient's quality of life. Despite the extensive research and the emergence of new therapeutic approaches and drugs, there are still significant unwanted side effects associated to these drugs and still a vast number of patients that do not respond positively to the existing therapeutic strategies. Over the years, several references to the use of flavonoids in the quest for new treatments for RA have emerged. This review aimed to summarize the existing literature about the flavonoids' effects on the major pathogenic/molecular targets of RA and their potential use as lead compounds for the development of new effective molecules for RA treatment. It is demonstrated that flavonoids can modulate various players in synovial inflammation, regulate immune cell function, decrease synoviocytes proliferation and balance the apoptotic process, decrease angiogenesis, and stop/prevent bone and cartilage degradation, which are all dominant features of RA. Although further investigation is necessary to determine the effectiveness of flavonoids in humans, the available data from in vitro and in vivo models suggest their potential as new disease-modifying anti-rheumatic drugs. This review highlights the use of flavonoids as a promising avenue for future research in the treatment of RA.

Cerebellar damage affects the inference of human motion.

The present study aims at the cerebellum's role in prediction mechanisms triggered by action observation. Five cerebellar patients and six age-paired control subjects were asked to estimate the occluded end point position of the shoulder's trajectories in Sit-to-Stand (STS) or Back-to-Sit (BTS) conditions, following or not biological rules. Contrarily to the control group, the prediction accuracy of the end point position in cerebellar patients did not depend on biological rules. Interestingly, both groups presented similar results when estimating the vanishing position of the target. Taken together, these results suggest that cerebellar damage affectsthe capacity of predicting upcoming actions by observation.

Coating independent cytotoxicity of citrate- and PEG-coated silver nanoparticles on a human hepatoma cell line.

The antibacterial potential of silver nanoparticles (AgNPs) resulted in their increasing incorporation into consumer, industrial and biomedical products. Therefore, human and environmental exposure to AgNPs (either as an engineered product or a contaminant) supports the emergent research on the features conferring them different toxicity profiles. In this study, 30nm AgNPs coated with citrate or poly(ethylene glycol) (PEG) were used to assess the influence of coating on the effects produced on a human hepatoma cell line (HepG2), namely in terms of viability, apoptosis, apoptotic related genes, cell cycle and cyclins gene expression. Both types of coated AgNPs decreased cell proliferation and viability with a similar toxicity profile. At the concentrations used (11 and 5µg/mL corresponding to IC50 and ~IC10 levels, respectively) the amount of cells undergoing apoptosis was not significant and the apoptotic related genes BCL2 (anti-apoptotic gene) and BAX (pro-apoptotic gene) were both downregulated. Moreover, both AgNPs affected HepG2 cell cycle progression at the higher concentration (11µg/mL) by increasing the percentage of cells in S (synthesis phase) and G2 (Gap 2 phase) phases. Considering the cell-cycle related genes, the expression of cyclin B1 and cyclin E1 genes were decreased. Thus, this work has shown that citrate- and PEG-coated AgNPs impact on HepG2 apoptotic gene expression, cell cycle dynamics and cyclin regulation in a similar way. More research is needed to determine the properties that confer AgNPs at lower toxicity, since their use has proved helpful in several industrial and biomedical contexts.

The use of comet assay in plant toxicology: recent advances.

The systematic study of genotoxicity in plants induced by contaminants and other stress agents has been hindered to date by the lack of reliable and robust biomarkers. The comet assay is a versatile and sensitive method for the evaluation of DNA damages and DNA repair capacity at single-cell level. Due to its simplicity and sensitivity, and the small number of cells required to obtain robust results, the use of plant comet assay has drastically increased in the last decade. For years its use was restricted to a few model species, e.g., Allium cepa, Nicotiana tabacum, Vicia faba, or Arabidopsis thaliana but this number largely increased in the last years. Plant comet assay has been used to study the genotoxic impact of radiation, chemicals including pesticides, phytocompounds, heavy metals, nanoparticles or contaminated complex matrices. Here we will review the most recent data on the use of this technique as a standard approach for studying the genotoxic effects of different stress conditions on plants. Also, we will discuss the integration of information provided by the comet assay with other DNA-damage indicators, and with cellular responses including oxidative stress, cell division or cell death. Finally, we will focus on putative relations between transcripts related with DNA damage pathways, DNA replication and repair, oxidative stress and cell cycle progression that have been identified in plant cells with comet assays demonstrating DNA damage.

Balance Impairments after Brachial Plexus Injury as Assessed through Clinical and Posturographic Evaluation.

OBJECTIVE: To investigate whether a sensorimotor deficit of the upper limb following a brachial plexus injury (BPI) affects the upright balance. DESIGN: Eleven patients with a unilateral BPI and 11 healthy subjects were recruited. The balance assessment included the Berg Balance Scale (BBS), the number of feet touches on the ground while performing a 60 s single-leg stance and posturographic assessment (eyes open and feet placed hip-width apart during a single 60 s trial). The body weight distribution (BWD) between the legs was estimated from the center of pressure (COP) lateral position. The COP variability was quantified in the anterior-posterior and lateral directions. RESULTS: BPI patients presented lower BBS scores (p = 0.048) and a higher frequency of feet touches during the single-leg stance (p = 0.042) compared with those of the healthy subjects. An asymmetric BWD toward the side opposite the affected arm was shown by 73% of BPI patients. Finally, higher COP variability was observed in BPI patients compared with healthy subjects for anterior-posterior (p = 0.020), but not for lateral direction (p = 0.818). CONCLUSIONS: This study demonstrates that upper limb sensorimotor deficits following BPI affect body balance, serving as a warning for the clinical community about the need to prevent and treat the secondary outcomes of this condition.

Management of diabetic nephropathy in older patients: a need for flexible guidelines.

As the population ages and diabetes mellitus increases in prevalence, the incidence of diabetic nephropathy (DN) is becoming a disease of older people (aged ≥ 75 years). As the epidemiology of diabetes mellitus and DN shifts toward this patient population, the pathogenesis of DN in old age is changing: the pathologic findings suggest ischemia and hypertension, and the classic Kimmelstiel-Wilson lesions may be absent. The demographic shift in the epidemiology and the associated changes in pathology because of aging and atherosclerosis will have a significant impact on various aspects related to the disease in old age. This article reviews the authors' current understanding of DN and its implications on clinical management relevant to current guidelines.

Electrophysiological correlates of biological motion permanence in humans.

Spatiotemporal discontinuity of visual input is a common occurrence in daily life. For example, when a walking person disappears temporarily behind a wall, observers have a clear sense of his physical presence despite the absence of any visual information (movement permanence). To investigate the neural substrates of biological motion permanence, we recorded scalp EEG activity of sixteen subjects while they passively observed either biological or scrambled motion disappearing behind an occluder and reappearing. The moment of the occluder's appearance was either fixed or randomized. The statistical comparison between the biological and scrambled motion ERP waveforms revealed a modulation of activity in centro-parietal and right occipito-temporal regions during the occlusion phase when the biological motion disappearance was time-locked, possibly reflecting the recall of sensorimotor representations. These representations might allow the prediction of moving organisms in occlusion conditions. When the appearance of the occluder was unpredictable there was no difference between biological and scrambled motion either before or during occlusion, indicating that temporal prediction is relevant to the processing of biological motion permanence.