Erratum to: Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo (Mol Neurobiol, 10.1007/s12035-016-9836-z)

Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) concentration as a mechanical-stimuli in neurogenesis was investigated. Cell viability, membrane damage, and neural differentiation derived from endometrial stem cells encapsulated into self-assembling peptide nanofiber containing long motif of laminin were assessed. Then, two of their concentrations that had no significant difference of neural differentiation potential were selected for motor neuron investigation in SCI model of rat. MTT assay data showed that nanofibers at the concentrations of 0.125 and 0.25 % w/v induced higher and less cell viability than others, respectively, while cell viability derived from higher concentrations of 0.25 % w/v had ascending trend. Gene expression results showed that noggin along with laminin motif over-expressed TH gene and the absence of noggin or laminin motif did not in all concentrations. Bcl2 over-expression is concomitant with the decrease of nanofiber stiffness, NF+ cells increment, and astrogenesis inhibition and dark neuron decrement in SCI model. It seems that stiffness affects on Bcl2 gene expression and may through β-Catenin/Wnt signaling pathway and BMP-4 inhibition decreases astrogenesis and improves neurogenesis. However, stiffness had a significant effect on upregulation of GFAP+ cells and motor neuron recovery in in vivo. It might be concluded that eventually there is a critical definitive point concentration that at less or higher than of it changes cell behavior and neural differentiation through different molecular pathways

Silymarin-albumin nanoplex: preparation and its potential application as an antioxidant in nervous system in vitro and in vivo

In this study, we formulated silymarin-HSA nanoplex and assayed its ability to reduce LPSinduced toxicity in vitro and in vivo. Silymarin molecules were encapsulated into HSA nanoplex and the loading efficiency and characterization of fabricated nanoplex were performed by using HPLC, TEM, SEM, DLS, FTIR analysis, and theoretical studies. Afterwards, their protective effect against LPS (20 µg/ml) -induced toxicity in SH-SY5Y cells was investigated by MTT, ROS, and apoptosis assays. For in vivo experiments, rats were pre-treated with either silymarin or silymarin -HSA nanoplex (200 mg/kg) orally for 3 days and at third day received LPS by IP at a dose of 0.5 mg/kg, 150 min before scarification followed by SOD and CAT activity assay. The formulation of silymarin-HSA nanoplex showed a spherical shape with an average diameter between 50 nm to 150 nm, hydrodynamic radius of 188.3 nm, zeta potential of -26.6 mV, and a drug loading of 97.3%. In LPS-treated cells, pretreatments with silymarin-HSA noncomplex recovered the cell viability and decreased the ROS level and corresponding apoptosis more significantly than free silymarin. In rats, it was also depicted that, silymarin-HSA noncomplex can increase the SOD and CAT activity in brain tissue at LPS-triggered oxidative stress model more significantly than free counterpart. Nanoformulation of silymarin improved its capability to reduce LPS-induced oxidative stress by restoring cell viability and elevation of SOD and CAT activity in vitro and in vivo, respectively. Therefore, formulation of silymarin may hold a great promise in the field of antioxidant agent development

The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019

BACKGROUND: Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden

TRPV1 receptors augment basal synaptic transmission in CA1 and CA3 pyramidal neurons in epilepsy

Temporal lobe epilepsy in human and animals is attributed to alterations in brain function especially hippocampus formation. Changes in synaptic activity might be causally related to the alterations during epileptogenesis. Transient receptor potential vanilloid 1 (TRPV1) as one of the non-selective ion channels has been shown to be involved in synaptic transmission. However, the potential role of TRPV1 receptors in synaptic function in the epileptic brain needs to be elucidated. In the present study, we used quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry to assess hippocampal TRPV1 mRNA expression, protein content, and distribution. Moreover, the effects of pharmacologic activation and inhibition of TRPV1 receptors on the slope of evoked field excitatory postsynaptic potentials (fEPSPs) were analyzed in CA1 and CA3 pyramidal neurons, after 3. months of pilocarpine-induced status epilepticus (SE). SE induced an upregulation of TRPV1 mRNA and protein content in the whole hippocampal extract, as well as its distribution in both CA1 and CA3 regions. Activation and inhibition of TRPV1 receptors (via capsaicin 1. μM and capsazepine 10. μM, respectively) did not influence basal synaptic transmission in CA1 and CA3 regions of control slices, however, capsaicin increased and capsazepine decreased synaptic transmission in both regions in tissues from epileptic animals. Taken together, these findings suggest that a higher expression of TRPV1 in the epileptic condition is accompanied by alterations in basal synaptic transmission. © 2015 IBRO

Quality of life and its related factors in infertile couples

Background: Health related quality of life (QoL) has now been considered as a main tool for outcome measurement in infertility. The present study aimed to determine the association be-tween general and specified QoL with different psychological aspects of self-esteem, social sup-port, sexual satisfaction, and marital satisfaction in a sample of Iranian infertile couples. Method: This cross-sectional study was conducted on 385 infertile couples referred to the Fatemieh Hospital in Hamadan City, western Iran in 2012.To measure the self-esteem, the Iseng test was used. The social support scaling developed by Cassidy and Long was used for as-sessment of social support. The sexual satisfaction was also assessed by the Lindaberg ques-tionnaire. For assessing the general QoL state, the WHO-QoL-BREF and FertiQoL tools were employed. Results: Self-esteem scores were lower in the couples with longer infertility duration. The social support mean score was lower in low income couples. Those with higher educational level, shorter infertility duration, and higher income were more satisfied from their marital relationships. Besides, we revealed that the previous failed efforts for treatment of infertility were adversely associated with the lower social support and sexual satisfaction. The higher educational level, higher monthly income, living in urban area, shorter duration of marriage and infertility, and male gender were associated with better QoL status in the most components. Associations between QoL and self-esteem, social support, sexual satisfaction, and marital satisfaction were significant (P<0.05). Conclusion: The QoL status in infertile couples is directly associated with their self-esteem, social support, sexual satisfaction, and marital satisfaction

Erratum to: Mechano-Transduction Signals Derived from Self-Assembling Peptide Nanofibers Containing Long Motif of Laminin Influence Neurogenesis in In-Vitro and In-Vivo

Astroglial scaring and limited neurogenesis are two problematic issues in recovery of spinal cord injury (SCI). In the meantime, it seems that mechanical manipulations of scaffold to inhibit astroglial scarring and improve neurogenesis is worthy of value. In the present investigation, the effect of nanofiber (gel) concentration as a mechanical-stimuli in neurogenesis was investigated. Cell viability, membrane damage, and neural differentiation derived from endometrial stem cells encapsulated into self-assembling peptide nanofiber containing long motif of laminin were assessed. Then, two of their concentrations that had no significant difference of neural differentiation potential were selected for motor neuron investigation in SCI model of rat. MTT assay data showed that nanofibers at the concentrations of 0.125 and 0.25 w/v induced higher and less cell viability than others, respectively, while cell viability derived from higher concentrations of 0.25 w/v had ascending trend. Gene expression results showed that noggin along with laminin motif over-expressed TH gene and the absence of noggin or laminin motif did not in all concentrations. Bcl2 over-expression is concomitant with the decrease of nanofiber stiffness, NF+ cells increment, and astrogenesis inhibition and dark neuron decrement in SCI model. It seems that stiffness affects on Bcl2 gene expression and may through β-Catenin/Wnt signaling pathway and BMP-4 inhibition decreases astrogenesis and improves neurogenesis. However, stiffness had a significant effect on upregulation of GFAP+ cells and motor neuron recovery in in vivo. It might be concluded that eventually there is a critical definitive point concentration that at less or higher than of it changes cell behavior and neural differentiation through different molecular pathways. © 2016 Springer Science+Business Media New Yor

Alterations in ca1 pyramidal neuronal intrinsic excitability mediated by iH channel currents in a rat model of amyloid beta pathology

Amyloid beta (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Ab affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aβ (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aβ treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Ab-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aβ-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aβ-treated group as compared to control group. The enhancing effect of Aβ treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aβ treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD. © 2015 IBRO

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts