Melatonin hormone as a therapeutic weapon against neurodegenerative diseases

Brain disorders such as Alzheimer’s and Parkinson’s disease (PD) are irreversible conditions with several cognitive problems, including learning disabilities, memory loss, movement abnormalities, and speech problems. These disorders are caused by a variety of factors, mainly due to the toxic pollutants-induced biochemical changes in protein production, uncontrolled neuronal electrical activity, and altered neurotransmitter levels. Oxidative stress and toxicity associated with the increased glutamate levels decreased acetylcholine levels, and brain inflammation is the main contributing factor. Melatonin hormone is considered one of the potent treatment approaches for neurodegenerative disorders. Melatonin is released from the pineal gland and has a critical role in brain function regulation. Membrane receptors, binding sites, and chemical interaction mediate hormonal actions having multiple phenotypic expressions. It acts as a neurodegenerative agent against some neurological disorders such as Alzheimer’s disease (AD), PD, depression, and migraines. Melatonin inhibits neurotoxic pollutants-induced Tau protein hyperphosphorylation, especially in AD. Other pivotal features of melatonin are its anti-inflammatory properties, which decrease pro-inflammatory cytokines expression and factors such as IL-8, IL-6, and TNF. Melatonin also reduces NO (an inflammation factor). In this review, we have highlighted the protective effects of melatonin, mainly spotlighting its neuroprotective mechanisms that will be beneficial to assess their effects in environmental pollution-induced neurodegenerative pathology.

The Physiometrics of Inflammatory Proteins and Implications for Medical and Psychiatric Research: Investigation of Empirically-informed Inflammatory Composites

Much inflammation research examines individual proteins; however, some studies have used summed score composites of all available inflammatory markers without first investigating dimensionality. Using three different samples (MIDUS-2: N = 1,255 adults, MIDUS-R: N =863 adults, and ACE: N = 315 adolescents), this study investigates the dimensionality of eight inflammatory proteins (C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-a; (TNF-a;), fibrinogen, E-selectin, and intercellular adhesion molecule (ICAM)-1) and compares the resulting factor structure to a) an a priori factor structure in which all inflammatory proteins equally load onto a single dimension (a technique that has been used previously) and b) proteins modeled individually (i.e., no latent variable) in terms of model fit, replicability, reliability, temporal stability, and their associations with medical history and depression symptoms. A hierarchical factor structure with two first-order factors (Factor 1A: CRP, IL-6, fibrinogen; Factor 2A: TNFa;, IL-8, IL-10, ICAM-1, IL-6) and a second-order general inflammation factor was identified in MIDUS-2 and replicated in MIDUS-R and partially replicated in ACE (which unfortunately only had CRP, IL-6, IL-8, IL-10, and TNFa; but, unlike the other two, has longitudinal data). Both the empirically-identified structure and modeling proteins individually fit the data better compared to the one-dimensional a priori structure. Results did not clearly indicate whether the empirically-identified factor structure or the individual proteins modeled without a latent variable had superior model fit. Modeling the empirically-identified factors and individual proteins (without a latent factor) as outcomes of medical diagnoses resulted in comparable conclusions, but modeling empirically-identified factors resulted in fewer results lost to correction for multiple comparisons. Importantly, when the factor scores were recreated in a longitudinal dataset, none of the individual proteins, the a priori factor, or the empirically-identified general inflammation factor significantly predicted concurrent depression symptoms in multilevel models. However, both empirically-identified first-order factors were significantly associated with depression, in opposite directions. Measurement properties are reported for the different aggregates and individual proteins as appropriate, which can be used in the design and interpretation of future studies. These results indicate that modeling inflammation as a unidimensional construct equally associated with all available proteins does not fit the data well. Instead, empirically-supported aggregates of inflammation, or individual inflammatory markers, should be used in accordance with theory. Further, the aggregation of shared variance achieved by constructing empirically-supported aggregates might increase predictive validity compared to other modeling choices, maximizing statistical power.

Depression as a risk factor for dementia in older people with type 2 diabetes and the mediating effect of inflammation

Aims/hypothesis We aimed to determine the association of depression with dementia risk in people with type 2 diabetes, and to explore the possible mediating role of inflammation in this relationship. Methods The Edinburgh Type 2 Diabetes Study is a prospective cohort of 1066 men and women with type 2 diabetes aged 60–75 years. Cox proportional hazards regression analysis was used to investigate the association between depression, assessed at baseline, and subsequent risk of dementia over 10 years. Depression was defined using the Hospital Anxiety and Depression Scale, while incident dementia was defined using medical records, prescription data and death certificates. The potential mediating effect of systemic inflammation was assessed by adjusting models for a generalised inflammation factor, derived from four inflammatory markers measured at baseline (C-reactive protein, IL-6, TNF-α and fibrinogen), and carrying out an exploratory mediation analysis. Results Dementia developed in 105 participants over a median follow-up of 10.6 years. After adjusting for age and sex, depression was associated with over a 2.5-fold increase in risk of dementia (HR 2.59 [95% CI 1.62, 4.15]). Additional adjustment for the generalised inflammation factor and other covariates did not attenuate the size of association between depression and incident dementia and mediation analysis showed that it was not a mediator. Adjusted logistic regression models showed cross-sectional associations of C-reactive protein and IL-6 with depression. Conclusions/interpretation Depression is an important risk factor for dementia in people with type 2 diabetes. Some inflammatory markers were associated with depression, but systemic inflammation does not appear to mediate the relationship between depression and dementia.

Hypericin ameliorates maternal separation-induced cognitive deficits and hippocampal inflammation in rats

Objective: Maternal separation as an epigenetic agent provokes a severe change in the brain such as inflammation response, which is a key risk factor for the progression of autism spectrum disorders (ASD). Methods: This study evaluated the preventive effect of hypericin on maternal separation-induced cognitive deficits and hippocampal inflammation. Here, we reported that pups are subjected to maternal separations for 1 h per day from postnatal days (PND) 1–9 displayed apparent memory impairment in young rats (postnatal day 34) compared to controls group. Furthermore, the maternal separation significantly increased inflammation factors in hippocampus area. Anti-inflammation constituent shed light on treating ASD. Results: In this study, we found that, treatment with hypericin (10 and 50 mg/kg) significantly suppresses expression of hippocampal interleukin-6 (IL-6) and tumor necrosis factor α (TNF- α) in maternal separation rat model. Also, we found that hypericin prevented the decrease of hippocampal dopamine level in offspring of maternal separation rats. Conclusion: The data indicated that hypericin may play a neuroprotective role in hippocampal cell and ameliorates dysfunctions in memory and level of inflammation factor in this autism model. Thus, hypericin could be used as an intervention for treating ASD.

TRIM27 promotes IL-6-induced proliferation and inflammation factor production by activating STAT3 signaling in HaCaT cells

The IL-6/STAT3 signaling pathway is required for the development of psoriatic lesions, and tripartite motif-containing 27 (TRIM27) is a protein inhibitor of activated STAT3 (PIAS3)-interacting protein that could modulate IL-6-induced STAT3 activation. However, whether TRIM27 is associated with the IL-6/STAT3 signaling pathway in psoriasis remains enigmatic. TRIM27 expression and gene set enrichment analysis in patients with psoriasis were determined using bioinformatics. Human keratinocyte HaCaT cells treated with recombinant protein IL-6 (rh-IL-6) were transduced with lentivirus silencing TRIM27 and/or PIAS3 or, otherwise, transduced with lentivirus expressing TRIM27 and/or lentivirus silencing STAT3, or MG132, a proteasome-specific protease inhibitor. Cell proliferation and inflammation factor production were measured using Cell Counting Kit-8 and ELISA, respectively. TRIM27, proliferation marker protein Ki-67 (Ki67), phospho-STAT3 (p-STAT3), STAT3, and PIAS3 expressions were determined using real-time quantitative PCR, immunofluorescence staining, or Western blot analysis. Coimmunoprecipitation combined with ubiquitination analysis was performed to explore the interaction between TRIM27 and PIAS3. In the present study, TRIM27 expression was increased in psoriatic lesions, associated with the IL-6 signaling pathway, and induced by rh-IL-6 in a time-dependent manner. The increased cell proliferation, inflammation factor production, and expression of Ki67 and of p-STAT3 relative to STAT3 induced by rh-IL-6 and TRIM27 overexpression were significantly inhibited by TRIM27 silencing and STAT3 silencing, respectively. More importantly, TRIM27 interacted with PIAS3, and its overexpression promoted PIAS3 ubiquitination in HaCaT cells. PIAS3 silencing also significantly promoted TRIM27-dependent and IL6-induced STAT3 activation, cell proliferation, and inflammation factor production. In conclusion, our results highlight that TRIM27 expression is significantly increased by IL-6 and suggest a TRIM27/STAT3-dependent mechanism for regulation of inflammation and proliferation-associated development of psoriasis.

Application of the Nutrition Tools under a Study in Order to Develop a Menu to Maintain a Healthy Lifestyle

: Eating is the basis for life and a permanent acting factor that determines metabolic process development and the food is the source and controller for the exchange process. Food is achieved by daily consumption of varying amounts of aliments or food products. A diet (menu) is a set of dishes which are obtained by grouping in a certain order the food consumed at one meal or one day. Planning diet is a scientific tool to make an “intelligent” diet addressed to various healthy or unhealthy people. The daily menu provides the necessary food for 24 hours, by categories of consumers, according to the body's physiological requirements. This study’s main aim was to detect improper eating habits or nutritional problems of individuals in order to planned (designing) and develop a menu to ensure a balanced and healthy diet. Initially we assessed the volunteers’ health by questionnaire, medical test and anthropometric data. Then with the help of nutritional programs we have developed for each volunteer a planned menu, ensuring the requirements for variety, seasonality and the strength of satiation, including scientific parameters (as GI, and inflammation factor). This study was conducted for one month, during which each volunteer was req