Circ-Bptf Ameliorates Learning and Memory Impairments via the miR-138-5p/p62 Axis in APP/PS1 Mice.

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy.

Fibrocyte: A missing piece in the pathogenesis of fibrous epulis.

OBJECTIVES: To explore the role of fibrocytes in the recurrence and calcification of fibrous epulides. METHODS: Different subtypes of fibrous epulides and normal gingival tissue specimens were first collected for histological and immunofluorescence analyses to see if fibrocytes were present and whether they differentiated into myofibroblasts and osteoblasts upon stimulated by transforming growth factor-ß1 (TGF-ß1). Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human peripheral blood mononuclear cells (PBMCs) were subsequently isolated from in vitro models to mimic the microenvironment in fibrous epulides to identify whether TGF-ß1 as well as the calcium and phosphorus ion concentration in the extracellular matrix (ECM) of a fibrous epulis trigger fibrocyte differentiation. RESULTS: Fibrous epulides contain fibrocytes that accumulate in the local inflammatory environment and have the ability to differentiate into myofibroblasts or osteoblasts. TGF-ß1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner, while TGF-ß1 stimulates the fibrocytes to differentiate into osteoblasts when combined with a high calcium and phosphorus environment. CONCLUSIONS: Our study revealed fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the inhibition of recurrence of fibrous epulides.

Research progress on the molecular mechanism of electroacupuncture at "Zusanli" (ST36) for regulating gastrointestinal dysfunction. / 电针"足三里"è°ƒèŠ‚èƒƒè‚ åŠŸèƒ½å¼‚å¸¸çš„åˆ†å­æœºåˆ¶ç ”ç©¶è¿›å±•.

Gastrointestinal dysfunction is manifested as digestive symptoms. Clinically, Zusanli (ST36) is crucial in the acupoint prescriptions of acupuncture no matter which type of the disease is differentiated in traditional Chinese medicine, but the underlying mechanism remains to be explored. Aiming to summarize the current status of the researches in terms of ameliorating gastrointestinal mucosal damage and regulating gastrointestinal motility disorders, we systematically reviewed the basic researches on the intervention with electroacupuncture (EA) at "ST36" in treatment of the diseases related to gastrointestinal dysfunction in the past 5 years, after searching the articles from Chinese and English databases. The results suggest that EA at ST36 may regulate the local gastrointestinal inflammation, oxidative stress and immune microenvironment to relieve gastrointestinal mucosal damage and adjust gastrointestinal motility disorders by means of modulating the central and peripheral nerve signaling as well as the function of mast cells and Cajal interstitial cells.

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES.

BACKGROUND: Although tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown. METHODS: Data were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association. RESULTS: The association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (ß=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food. CONCLUSIONS: The association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.

The immunomodulatory effects of RNA-based biomaterials on bone regeneration.

The use of RNA as therapeutic agents is a visionary idea in contemporary medicine. Some forms of RNA can modulate the immune response of the host to enhance tissue regeneration events such as osteogenesis. Herein, RNA molecules commercially available for immunomodulatory applications (imRNA) were used to prepare biomaterials for bone regeneration. The polyanionic imRNA stabilized calcium phosphate ionic clusters to produce imRNA-ACP that had the capacity to mineralize the intrafibrillar compartments of collagen fibrils. For the first time, it was shown that incorporating imRNA-ACP into collagen scaffolds resulted in rapid new bone formation in cranial defects of mice. Both in vivo and in vitro results demonstrated that macrophage polarization was highly-sensitive to the imRNA-ACP containing collagen scaffolds. Macrophages were polarized into the anti-inflammatory M2 phenotype that produced anti-inflammation cytokines and growth factors. The favorable osteoimmunological microenvironment created by the scaffolds prevented their immunorejection and facilitated osteogenesis. The potential of RNA in creating immunomodulatory biomaterials has been underestimated in the past. The overall aim of this study was to explore the potential application of imRNA-based biomaterials in bone tissue engineering, with the competitive edge of facile synthesis and excellent biocompatibility. STATEMENT OF SIGNIFICANCE: In this work, commercially available RNA extracted from bovine spleens for immunomodulatory applications (imRNA) were used to stabilize amorphous calcium phosphate (ACP) and induce mineralization within collagen fibrils. Incorporation of imRNA-ACP into collagen scaffolds regenerated new bone in-situ. Because of its immunomodulatory effects, the imRNA-ACP that was incorporated into collagen scaffolds modulated the local immune environment of murine cranial defects by altering the macrophage phenotype through JAK2/STAT3 signaling pathway. The novelty of this work existed in the discovery of RNA's potential in creating immunomodulatory biomaterials. With the competitive edge of facile synthesis and excellent biocompatibility, the imRNA-based biomaterials are potentially useful for future bone tissue engineering applications.

A seminal perspective on the role of chondroitin sulfate in biomineralization.

Chondroitin sulfate (CS) is an important extracellular matrix component of mineralized tissues. It participates in biomineralization, osteoblast differentiation and promotes bone tissue repair in vitro. However, the mechanism in which CS functions is unclear. Accordingly, an in-depth investigation of how CS participates in mineralization was conducted in the present study. Chondroitin sulfate was found to directly induce intrafibrillar mineralization of the collagen matrix. The mineralization outcome was dependent on whether CS remained free in the extracellular matrix or bound to core proteins; mineralization only occurred when CS existed in a free state. The efficacy of mineralization appeared to increase with ascending CS concentration. This discovery spurred the authors to identify the cause of heterotopic ossification in the Achilles tendon. Chondroitin sulfate appeared to be a therapeutic target for the management of diseases associated with heterotopic calcification. A broader perspective was presented on the applications of CS in tissue engineering.

[Accumulation Characteristics and Sources of PAEs in Agricultural Soils in Gansu Province].

In order to understand the composition and accumulation characteristics of phthalates esters (PAEs) in agricultural soils in Gansu province, a total of 41 soil samples from four agricultural soils in Gansu province were collected, and the content of six PAEs compounds was analyzed using a gas chromatography-single quadrupole mass spectrometer (GC-MS). The results showed that the average value of PAEs compounds in agricultural soils in Gansu province was 432.4 µg·kg-1. The detection rates of DMP, DEP, DnBP, DEHP, and DNOP in the soil were 100%, and BBP was not detected. The order of the average value of PAEs content in the four agricultural soils in Gansu province was:greenhouse>farmland (open field)>forest>grassland. The exceeding rates of dibutyl phthalate (DnBP), dimethyl phthalate (DMP), and dimethyl phthalate (DEP) were 94%, 28%, and 27%, and the remaining three did not exceed the standard. The composition of PAEs in different agricultural soils was different due to their different sources. DEHP and DnBP components in the six different PAEs monomers accounted for a higher proportion and were the main pollutants of PAEs in agricultural soils in Gansu province. In this study, the contents of soil PAEs and DEHP were significantly positively correlated with the residual amount of mulch film in the farmland (P<0.05). In general, the content of soil PAEs in the Hexi area of Gansu province was significantly higher than that in the Longdong area.

Regulation of biomineralization by proteoglycans: From mechanisms to application.

Proteoglycans consist of core proteins and one or more covalently-linked glycosaminoglycan chains. They are structurally complex and heterogeneous. Proteoglycans bind to cell surface receptors, cytokines, growth factors and have strong affinity for collagen fibrils. Together with their complex spatial structures and different charge densities, proteoglycans are directly or indirectly involved in biomineralization. The present review focused on the potential mechanisms of proteoglycans-mediated biomineralization. Topics covered include the ability of proteoglycans to influence the proliferation and differentiation of odontoblasts and osteoblasts through complex signaling pathways, as well as regulate the aggregation of collagen fibrils and mineral deposition. The functions of proteoglycans in mineralization regulation and biomimetic properties render them important components in bone tissue engineering. Hence, the integrated impact of proteoglycans on bone formation was also succinctly deliberated. The potential of proteoglycans to function therapeutic targets for relieving the symptoms of ectopic mineralization and mineralization defects was also comprehensively addressed.

Multifunctional Nanomachinery for Enhancement of Bone Healing.

The visionary idea that RNA adopts nonbiological roles in today's nanomaterial world has been nothing short of phenomenal. These RNA molecules have ample chemical functionality and self-assemble to form distinct nanostructures in response to external stimuli. They may be combined with inorganic materials to produce nanomachines that carry cargo to a target site in a controlled manner and respond dynamically to environmental changes. Comparable to biological cells, programmed RNA nanomachines have the potential to replicate bone healing in vitro. Here, an RNA-biomineral nanomachine is developed, which accomplishes intrafibrillar and extrafibrillar mineralization of collagen scaffolds to mimic bone formation in vitro. Molecular dynamics simulation indicates that noncovalent hydrogen bonding provides the energy source that initiates self-assembly of these nanomachines. Incorporation of the RNA-biomineral nanomachines into collagen scaffolds in vivo creates an osteoinductive microenvironment within a bone defect that is conducive to rapid biomineralization and osteogenesis. Addition of RNA-degrading enzymes into RNA-biomineral nanomachines further creates a stop signal that inhibits unwarranted bone formation in tissues. The potential of RNA in building functional nanostructures has been underestimated in the past. The concept of RNA-biomineral nanomachines participating in physiological processes may transform the nanoscopic world of life science.

Efficacy of cathodal transcranial direct current stimulation on electroencephalographic functional networks in patients with focal epilepsy: Preliminary findings.

BACKGROUND: Neuromodulation is a promising therapeutic alternative for epilepsy. We aimed to explore the efficacy and safety of cathodal transcranial current direct stimulation (ctDCS) on electroencephalographic functional networks in focal epilepsy. METHODS: A sham-controlled, double-blinded, randomized study was conducted on 25 participants with focal epilepsy who underwent a 5-day, -1.0 mA, 20 min ctDCS, which targeted at the most active interictal epileptiform discharge (IED) region. We examined the electroencephalograms (EEGs) at baseline, immediately and at 4 weeks following ctDCS. The graph theory-based brain networks were established through time-variant partial directed coherence (TVPDC), and were calculated between each pair of EEG signals. The functional networks were characterized using average clustering coefficient, characteristic path length, and small-worldness index. The seizure frequencies, IEDs, graph-theory metrics and cognitive tests were compared. RESULTS: Preliminary findings indicated an IED reduction of 30.2% at the end of 5-day active ctDCS compared to baseline (p < 0.10) and a significant IED reduction of 33.4% 4 weeks later (p < 0.05). In terms of the EEG functional network, the small-worldness index significantly reduced by 3.5% (p < 0.05) and the characteristic path length increased by 1.8% (p < 0.10) at the end of the session compared to the baseline. No obvious change was found in the seizure frequency during follow-up (p > 0.05). The Mini-Mental State Examination (MMSE) showed no difference between the active and sham groups (p > 0.05). No severe adverse reactions were observed. CONCLUSIONS: In focal epilepsy, the 5-day consecutive ctDCS may potentially decrease the IEDs and ameliorate the EEG functional network, proposing a novel personalized therapeutic scenario for epilepsy.