Notes

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The presence of quercetin in adipo-induced hBM-MSC culture inhibited the adipogenic differentiation depicted as suppressed lipid accumulation and expression of adipogenesis markers such as PPARγ, SREBP1c and C/EBPα. In conclusion, Q3G supplementation stimulated osteoblast differentiation and inhibited adipocyte differentiation in hBM-MSCs via Wnt/BMP and PPARγ pathways, respectively. This study provided useful information of the therapeutic potential of Q3G against osteoporosis mediated via regulation of MSC differentiation.The objective was to examine the association between maternal smoking during pregnancy (SDP) and (I) severity and (II) directionality of externalizing and internalizing symptoms in a sample of sibling pairs while rigorously controlling for familial confounds. The Missouri Mothers and Their Children Study is a family study (N = 173 families) with sibling pairs (aged 7 to 16 years) who are discordant for exposure to SDP. This sibling comparison study is designed to disentangle the effects of SDP from familial confounds. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount). Principal component analysis of externalizing and internalizing behavior, assessed with the Child Behavior Checklist and Teacher Report Form, was used to create symptom severity and directionality scores. The variance in severity and directionality scores was primarily a function of differences between siblings (71% and 85%, respectively) rather than differences across families (29% and 15%, respectively). The severity score that combines externalizing and internalizing symptom severity was not associated with SDP. However, a significant within-family effect of SDP on symptom directionality (b = 0.07, p = 0.04) was observed in the sibling comparison model. The positive directionality score indicates that SDP is associated with differentiation of symptoms towards externalizing rather than internalizing symptoms after controlling for familial confounds with a sibling comparison model. This supports a potentially causal relationship between SDP and externalizing behavior.Preventing the onset of dementia and Alzheimer's disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these diseases and different sociodemographic and clinical features. In EI1 , a case-control study was conducted in Spain in 2018-2019. The definition of a case was A person ≥ 65 years old with dementia and/or AD and a score of 5-7 on the Global Deterioration Scale (GDS). The sample consisted of 125 controls; among the cases, 96 had dementia and 74 had AD. The predictor variables were depression, dyslipidemia, type 2 diabetes mellitus, and hypertension. The results showed that depression, diabetes mellitus, and older age were associated with an increased likelihood of developing AD, with an Odds Ratio (OR) of 12.9 (95% confidence interval (CI) 4.3-39.9), 2.8 (95% CI 1.1-7.1) and 1.15 (95% CI 1.1-1.2), respectively. Those subjects with treated dyslipidemia were less likely to develop AD (OR 0.47, 95% CI 0.22-1.1). Therefore, depression and diabetes mellitus increase the risk of dementia, whereas treated dyslipidemia has been shown to reduce this risk.Thermosensitive chitosan/β-glycerophosphate (CS/BGP) systems have been developed as injectable hydrogels. However, the hydrogels exhibited poor mechanical properties due to their physically crosslinked networks. In this work, CS/BGP hydrogels were reinforced by covalent crosslinking using genipin (GE) and concomitantly semi-interpenetrating networks using pullulan (PL). Based on response surface methodology, the optimized formulation was composed of CS (1.05%, w/v), PL (1%, w/v), BGP (6%, w/v), and GE (70.79 mcg/mL). #link# The optimized hydrogels exhibited Young's modulus of 92.65 ± 4.13 kPa and a percentage of equilibrium swelling ratio of 3259.09% ± 58.90%. Scanning electron micrographs revealed a highly porous structure with nanofibrous networks in the CS/PL/BGP/GE hydrogels. The chemical interactions between the compositions were investigated by Fourier-transform infrared spectroscopy. Rheological measurements illustrated that the optimized hydrogels displayed sol-gel transition within one minute at 37 °C, a lower critical solution temperature of about 31 °C, and viscoelastic behavior with high storage modulus. Furthermore, the optimized hydrogels demonstrated higher resistance to in vitro enzymatic degradation, compared to the hydrogels without GE. Our findings could suggest that the thermosensitive CS/PL/BGP/GE hydrogels with enhanced mechanical properties and swelling capacity demonstrate the potential for use as scaffolds and carriers for cartilage tissue engineering and drug delivery applications.α-Synuclein amyloid aggregation is a defining molecular feature of Parkinson's disease, Lewy body dementia, and multiple system atrophy, but can also be found in other neurodegenerative disorders such as Alzheimer's disease. The process of α-synuclein aggregation can be initiated through alternative nucleation mechanisms and dominated by different secondary processes giving rise to multiple amyloid polymorphs and intermediate species. Some aggregated species have more inherent abilities to induce cellular stress and toxicity, while others seem to be more potent in propagating neurodegeneration. The preference for particular types of polymorphs depends on the solution conditions and the cellular microenvironment that the protein encounters, which is likely related to the distinct cellular locations of α-synuclein inclusions in different synucleinopathies, and the existence of disease-specific amyloid polymorphs. In this review, we discuss our current understanding on the nature and structure of the various types of α-synuclein aggregated species and their possible roles in pathology. Precisely defining these distinct α-synuclein species will contribute to understanding the molecular origins of these disorders, developing accurate diagnoses, and designing effective therapeutic interventions for these highly debilitating neurodegenerative diseases.
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