The effects of Rhizoma Curculiginis and Rhizoma Drynariae extracts on bones

Background  

Rhizoma Curculiginis (Xianmao) and Rhizoma Drynariae (Gusuibu) are 'Yang-tonifying' traditional Chinese herbal medicines used to strengthen bones. This investigation aims to assess the systemic effect of extracts of Rhizoma Curculiginis and Rhizoma Drynariae on bone histomorphology and formation, and their local effect on bone healing.     

Early introduction of allergenic foods for the prevention of food allergy from an Asian perspective—An Asia Pacific Association of Pediatric Allergy,Respirology & Immunology (APAPARI) consensus statement

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the USA and Europe recommending early peanut introduction for high‐risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries—such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high‐risk infants in Asia.     

Brain responses to stimuli mimicking dental treatment among non‐phobic individuals: A meta‐analysis

Numerous neuroimaging studies have attempted to identify how the brain responds to stimuli mimicking dental treatment in normal non‐phobic individuals. However, results were sometimes inconsistent due to small sample sizes and methodological variations. This meta‐analysis employs standardized procedures to summarize data from previous studies to identify brain regions that were consistently activated across studies, elicited by stimuli such as pictures, sounds, or audiovisual footage mimicking those encountered during dental treatments. A systematic literature search was carried out using PubMed and Scopus. The meta‐analysis analyzed data from 120 healthy subjects from seven neuroimaging studies. We assessed the risk of bias among the included studies with the Risk of Bias Assessment Tool for Nonrandomized Studies. One study appeared to have a high risk of selection bias, whereas the others were considered to have a low risk of bias. Results revealed three clusters of activation with cluster sizes ranging from 768 mm³ to 1,424 mm³. Stimuli mimicking dental treatment consistently activated the bilateral anterior insula; right dorsal anterior cingulate, putamen, and medial prefrontal cortex; and left claustrum. This study confirmed that audio and/or visual stimuli mimicking dental treatment consistently activated the fear‐related brain regions among healthy subjects, mostly consistent with activations from general anxiety but without the involvement of the amygdala.     

Developmental enamel defects in the primary dentition: aetiology and clinical management

Developmental enamel defects, presenting as enamel hypoplasia or opacities are caused by damage or disruption to the developing enamel organ as a result of inherited and acquired systemic conditions. The high prevalence of these defects in the primary dentition demonstrates the vulnerability of the teeth to changes in the pre‐ and postnatal environment. The presence of enamel hypoplasia increases the risk of primary teeth to early childhood caries and tooth wear as the defective enamel is thinner, more plaque retentive and less resistant to dissolution in acid compared to normal enamel. The purpose of this paper was to critically review the aetiology and clinical complications of developmental enamel defects in the primary dentition and propose recommendations for the clinical management of affected teeth.     

Regulatory mechanisms of tau protein fibrillation under the conditions of liquid–liquid phase separation

One of the hallmarks of Alzheimer’s disease and several other neurodegenerative disorders is the aggregation of tau protein into fibrillar structures. Building on recent reports that tau readily undergoes liquid–liquid phase separation (LLPS), here we explored the relationship between disease-related mutations, LLPS, and tau fibrillation. Our data demonstrate that, in contrast to previous suggestions, pathogenic mutations within the pseudorepeat region do not affect tau441’s propensity to form liquid droplets. LLPS does, however, greatly accelerate formation of fibrillar aggregates, and this effect is especially dramatic for tau441 variants with disease-related mutations. Most important, this study also reveals a previously unrecognized mechanism by which LLPS can regulate the rate of fibrillation in mixtures containing tau isoforms with different aggregation propensities. This regulation results from unique properties of proteins under LLPS conditions, where total concentration of all tau variants in the condensed phase is constant. Therefore, the presence of increasing proportions of the slowly aggregating tau isoform gradually lowers the concentration of the isoform with high aggregation propensity, reducing the rate of its fibrillation. This regulatory mechanism may be of direct relevance to phenotypic variability of tauopathies, as the ratios of fast and slowly aggregating tau isoforms in brain varies substantially in different diseases.

Tau is a major neuronal protein that plays a key role in Alzheimer’s disease (AD) and a number of other neurodegenerative disorders that are collectively classified as tauopathies. The latter include frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), progressive supranuclear palsy, Pick’s disease, corticobasal degeneration, and chronic traumatic encephalopathy (1–5). Under normal physiological conditions, tau is localized to axons where it is involved in the assembly of microtubules (1–6). In tauopathies, the protein self-associates into different forms of filaments that contain largely hyperphosphorylated tau and have properties of amyloid fibrils (1–5).Alternative splicing of the MAPT gene that encodes tau results in six major isoforms in the human central nervous system. These isoforms differ with respect to the number of N-terminal inserts as well as the number of 31 to 32 residue pseudorepeat sequences in the C-terminal part of the protein (1–5). Structurally, tau is largely an intrinsically disordered protein, with local secondary structures existing only within the pseudorepeat region (1, 7). A large number of mutations have been identified in the latter region that correlate with inherited cases of FTDP-17 (8, 9). These mutations not only diminish the ability of tau to promote microtubule assembly, but many also promote self-association of tau into amyloid fibrils (10–12). This strongly suggests that tau misfolding and aggregation is one of the key events in disease pathogenesis.A number of recent reports indicate that purified full-length tau (tau441) has a high propensity to undergo liquid–liquid phase separation (LLPS) in vitro in the presence of crowding agents that emulate the high concentration of macromolecules in the cell. This was observed both for the phosphorylated (13) and nonphosphorylated protein (14–16), and it was determined that tau LLPS is driven largely by attractive electrostatic intermolecular interactions between the negatively charged N-terminal and positively charged middle/C-terminal regions of the protein (15). Tau condensation into droplets (complex coacervation) was also observed in the presence of polyanions such as RNA or heparin (17, 18). These observations in vitro are partially supported by studies in cells (13, 19–24), especially within the context of tau interaction with microtubules (21). However, it remains unclear whether tau could undergo LLPS in cells on its own or, rather, its recruitment to membraneless organelles such as stress granules is largely driven by interactions with other proteins and/or RNA. These limitations notwithstanding, the observations that tau has a propensity for LLPS have potentially important implications for the pathogenic process in tauopathies, as studies with other proteins involved in neurodegenerative diseases (e.g., TDP-43, FUS) indicate that the environment of liquid droplets is conducive to the pathological aggregation of these proteins (25–32). In line with these findings, it was recently suggested that LLPS can initiate tau aggregation. However, the evidence for this was very limited and largely based on optical microscopy observations (13).In the present study, we explored the relationship between pathogenic mutations of tau, protein LLPS, and aggregation into amyloid fibrils. Our data show that, in contrast to previous suggestions (13), pathogenic mutations within the pseudorepeat region do not affect the propensity of tau to undergo LLPS. These mutations, however, do dramatically accelerate the liquid-to-solid phase transition within the droplets, leading to rapid formation of fibrillar aggregates. Most important, this study also reveals a previously unrecognized mechanism by which LLPS can regulate the rate of amyloid formation in mixtures containing tau isoforms with different aggregation propensities. These findings strongly suggest that LLPS may play a major regulatory role in the formation of pathological tau aggregates in neurodegenerative diseases.     

Macrophage-activating cytokines in human immununodeficiency virus type 1-infected and -uninfected patients with pulmonary tuberculosis

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected patients globally and occurs throughout the course of HIV-1 disease. Here the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMC) of HIV-1-infected versus -uninfected patients with newly diagnosed pulmonary TB (PTB) was compared. Findings were correlated with cytokine profiles, clinical presentation, and expression of inducible nitric oxide (iNOS). Most HIV-1/PTB patients with a CD4 cell count of 200-500 cells/microL had high IFN-gamma production and radiographic evidence of atypical PTB. Low IFN-gamma production and radiographic evidence of reactivated PTB characterized both HIV-1/PTB patients with a CD4 cell count >or=500 cells/microL and HIV-1-uninfected patients. TNF-alpha levels were similar in all HIV-1/PTB patients, regardless of CD4 cell count. Induction of iNOS in PBMC was low and was associated with low IFN-gamma production. These data underscore the potential pathogenic role of macrophage-activating cytokines in TB in HIV-1-infected patients.     

儿童哮喘非侵入性气道炎症监测的研究进展

尽管目前对哮喘的发病机制已有较深入的了解,但是许多研究显示,在世界的许多地方,哮喘并未能得到理想控制[1].虽然气道炎症是哮喘发病的最重要原因之一,哮喘治疗的根本是抗炎,但常规的临床评估并未涉及准确的气道炎症评价.气道炎症的严重度与特应性和气道高反应性(AHR)密切相关.