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Glucocerebrosidase 1 (GBA1) mutations are the most important genetic risk factors for Parkinson's disease (PD). Clinically, mild (e.g., p.N370S) and severe (e.g., p.L444P and p.D409H) GBA1 mutations have different PD phenotypes, with differences in age at disease onset, progression, and the severity of motor and non-motor symptoms. We hypothesize that GBA1 mutations cause the accumulation of α-synuclein by affecting the cross-talk between cellular protein degradation mechanisms, leading to neurodegeneration. Accordingly, we tested whether mild and severe GBA1 mutations differentially affect the degradation of α-synuclein via the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy and differentially cause accumulation and/or release of α-synuclein. Our results demonstrate that endoplasmic reticulum (ER) stress and total ubiquitination rates were significantly increased in cells with severe GBA1 mutations. CMA was found to be defective in induced pluripotent stem cell (iPSC)-derived dopaminergic neurons with mild GBA1 mutations, but not in those with severe GBA1 mutations. When examining macroautophagy, we observed reduced formation of autophagosomes in cells with the N370S and D409H GBA1 mutations and impairments in autophagosome-lysosome fusion in cells with the L444P GBA1 mutation. Accordingly, severe GBA1 mutations were found to trigger the accumulation and release of oligomeric α-synuclein in iPSC-derived dopaminergic neurons, primarily as a result of increased ER stress and defective macroautophagy, while mild GBA1 mutations affected CMA, which is mainly responsible for the degradation of the monomeric form of α-synuclein. Overall, our findings provide new insight into the molecular basis of the clinical variability in PD associated with different GBA1 mutations., (© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Introduction: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD)., Methods: An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted., Results: A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS., Conclusion: Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs., Competing Interests: The authors declared no conflict of interest, (Copyright© 2023 Iranian Neuroscience Society.)

Nature has a vast array of biomineralization mechanisms. The commonly shared mechanism by many living organisms to form hardened tissues is the nucleation of mineral structures via proteins. Living materials, thanks to synthetic biology, are providing many opportunities to program cells for many functionalities. Here we have demonstrated a living material system for biosilicification. Silaffins are utilized to synthesize silicified cell walls by one of the most abundant organism groups called diatoms. The R5 peptide motif of the silaffins is known for its ability to precipitate silica in ambient conditions. Therefore, various studies have been conducted to implement the silicification activity of R5 in different application areas, such as regenerative medicine and tissue engineering. However, laborious protein purification steps are required prior to silica nanoparticle production in recombinant approaches. In this study, we aimed to engineer an alternative bacterial platform to achieve silicification using released and bacteria-intact forms of R5-attached fluorescent proteins (FP). Hence, we displayed R5-FP hybrids on the cell surface of E. coli via antigen 43 (Ag43) autotransporter system and managed to demonstrate heat-controllable release from the surface. We also showed that the bacteria cells displaying R5-FP can be used in silicification reactions. Lastly, considering the stimulating effect of silica on osteogenic differentiation, we treated human dental pulp stem cells (hDPSCs) with the silica aggregates formed via R5-FP hybrids. Earlier calcium crystal deposition around the hDPSCs was observed. We envision that our platform can serve as a faster and more economical alternative for biosilicification applications, including endodontics., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Urartu Ozgur Safak Seker reports financial support was provided by Scientific and Technological Research Council of Turkey. None., (© 2022 Published by Elsevier Ltd.)

Introduction: Vitamin D3 plays an important role in the mineralization mechanism and is often deficient in diabetic patients. The objective of this study was to investigate the odonto/osteogenic differentiation potential of the combination of mineral trioxide aggregate (MTA)/1α,25-dihydroxyvitamin D3 (VD3) on dental pulp stem cells (DPSCs) of patients with type 1 diabetes mellitus (T1DM)., Methods: DPSCs isolated from donors (control and T1DM) were cultured and characterized. Cell proliferation and wound healing assays were performed. DPSCs were exposed to 4 different media: growth medium (Dulbecco's modified Eagle's medium, 10% fetal bovine serum, antibiotic, and antimycotic), differentiation medium (DM) (growth medium plus ß-glycerophosphate and ascorbic acid), DM + MTA (DM plus 0.02 mg/mL MTA), and DM + MTA + VD3 (DM + MTA and 10 nmol/L vitamin D3). Odonto/osteogenic differentiation of DPSCs was evaluated by the alizarin red test, relative real-time polymerase chain reaction (dentin sialophosphoprotein, dentin matrix protein 1, collagen type 1 alpha 1, and osteocalcin), immunocytochemistry (antibone sialoprotein II, anti-dentin matrix protein 1, and anti-collagen type 1 alpha 1), and Western blot (dentin matrix protein 1 and osteocalcin) methods., Results: The proliferation rates of DPSCs isolated from controls were significantly higher than DPSCs isolated from T1DM in a time-dependent manner (P < .05). Alizarin red staining and the expression of odonto/osteogenic markers showed that odonto/osteogenic differentiation was more pronounced in controls (P < .05) compared with T1DM patients. Although DM + MTA caused the odonto/osteogenic differentiation in DPSCs derived from controls, DM + MTA + VD3 resulted in the odonto/osteogenic differentiation in DPSCs of T1DM patients (P < .05)., Conclusions: Odonto/osteogenic differentiation was affected by both supplements used for differentiation and the systemic disease, diabetes mellitus. The differentiation potential of T1DM-derived DPSCs was clearly increased with the VD3 supplement, although it was not as efficient as in the controls. The VD3 supplement showed a positive effect on the differentiation of T1DM DPSCs compared with MTA alone., (Copyright © 2022 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Chanarin-Dorfman syndrome (CDS) is a very rare autosomal recessive inherited neutral lipid metabolism disorder associated with congenital ichthyosis and multi-system involvement. Observation of lipid vacuoles in neutrophils (Jordan's anomaly) in peripheral blood smears in patients with ichthyosiform erythroderma is diagnostic. Herein we present 2 siblings with CDS that were referred to Dokuz Eylul University School of Medicine Department of Pediatrics due to ichthyosis. They had hepatomegaly, cataract, growth retardation, and sensorineural hearing loss. Some lipid vacuoles in neutrophils were noted in peripheral blood smear evaluation. Genetic analysis showed homozygous N209X mutation in both patients. They were put on a low-fat high-carbohydrate diet supplemented with medium-chain fatty acids. During 6 months of follow-up, no improvement was observed in both patients. In conclusion, although CDS is a rare lipid storage disease, it should always be a consideration in patients with congenital ichthyosis, especially those with extracutaneous symptoms or signs. The diagnosis of CDS is made based on a very simple test-peripheral blood smear., Conflict of Interest: None declared.

A 30-year-old man presented with numerous papules, nodules and inflamed cysts. The lesions were located all over the body, including the scalp, except the palms and soles. His mother and one sister had had similar but less extensive lesions. Histopathology of the biopsy specimens obtained from the anterior chest wall, axillae and the back region was consistent with steatocystoma multiplex (SM). A diagnosis of steatocystoma multiplex suppurativum was made. The inflamed lesions were treated with oral isotretinoin (1 mg/kg per daily) for 6 months. At the same time, cryotherapy was used for non-suppurating lesions smaller than 2 cm. When the patient was evaluated 6 months later, cosmetic results were good. No new lesions have appeared in the subsequent 12-month follow up.

It is accepted that studies evaluating histamine-induced wheal and flare reactions in the skin represent a simple and reliable method for demonstrating pharmacodynamic activity and pharmacokinetics of the H1-receptor antagonists. In this study, the effects of single oral doses of acrivastine (8 mg), loratadine (10 mg) and cetirizine (10 mg) on the histamine-induced wheal and flare reactions were compared in 60 healthy volunteers. The wheal and flare responses were produced by prick test using 1% histamine solution. Measurements were performed before the ingestion of antihistamines (baseline values) and afterwards at 15, 30, 90, 240, 360 min and 24 h. The values obtained for each antihistamine were compared with each other and with baseline values. Cetirizine was found to be superior to acrivastine and loratadine for the suppression of wheal and flare responses at 240, 360 min and 24 h (P < 0.05) and acrivastine was superior to the other two antihistamines for the suppression of flare response at 30 min (P < 0.05). Our results indicate that a single dose of cetirizine provides a more effective and long acting suppression on wheal and flare reactions in urticaria when compared to acrivastine and loratadine.