Osteocytes autophagy mediated by mTORC2 activation controls osteoblasts differentiation and osteoclasts activities under mechanical loading.

Autophagy is an important mechanosensitive response for cellular homeostasis and survival in osteocytes. However, the mechanism and its effect on bone metabolism have not yet clarified. The objective of this study was to evaluate how compressive cyclic force (CCF) induced autophagic response in osteocytes and to determine the effect of mechanically induced-autophagy on bone cells including osteocytes, osteoblasts, and osteoclasts. Autophagic puncta observed in MLO-Y4 cells increased after exposure to CCF. The upregulated levels of the LC3-II isoform and the degradation of p62 further confirmed the increased autophagic flux. Additionally, ATP synthesis and release, osteocalcin (OCN) expression, and cell survival increased in osteocytes as well. The Murine osteoblasts MC3T3-E1 cells and RAW 264.7 macrophage cells were cultured in conditioned medium collected from MLO-Y4 cells subjected to CCF. The concentration of FGF23 increased and the concentrations of SOST and M-CSF and RANKL/OPG ratio decreased significantly in the conditioned medium. Moreover, the promotion of osteogenic differentiation in MC3T3-E1 cells and inhibition of osteoclastogenesis and function in RAW 264.7 cells were significantly attenuated when osteocytes autophagy was inhibited by siAtg7. Our findings suggested that CCF induced protective autophagy in osteocytes and subsequently enhanced osteocytes survival and osteoblasts differentiation and downregulated osteoclasts activities. Further study revealed that CCF induced autophagic response in osteocytes through mechanistic target of rapamycin complex 2 (mTORC2) activation. In conclusion, CCF-induced osteocytes autophagy upon mTORC2 activation promoted osteocytes survival and osteogenic response and decreased osteoclastic function. Thus, osteocytes autophagy will provide a promising target for better understanding of bone physiology and treatment of bone diseases.

Immobilized triatomic CuB2 clusters on 2D carbon nitride: highly selective conversion of CO to ethanol at low potentials.

A promising pathway for carbon usage and energy storage is electrocatalytic reduction of CO to form high-value multi-carbon products. Herein, the d-p coupled triatomic catalyst CuB2@g-C3N4 with significant activity and selectivity for ethanol is presented for the first time. Density functional theory calculations elucidate that these spatially confined triatomic centers are capable of immobilizing multiple CO molecules, providing an exclusive reaction channel for direct C-C coupling. The CuB2@g-C3N4 catalyst can effectively reduce the energy barrier of CO dimerization to 0.46 eV. The limiting potential is only -0.19 V, which is much smaller than that of other Cu-based catalysts. Additionally, the CuB2@g-C3N4 catalyst can effectively inhibit the generation of competing C1 products and hydrogen evolution reactions. Excitingly, CuB2 loading makes g-C3N4 more optically active in visible and even infrared light. This work provides important ideas for the atomically precise design of novel d-p coupled catalysts for the direct conversion of CO2/CO into energetic fuels and high-value chemicals.

Depression among Korean American immigrants living in rural Alabama: use of social determinants of health framework.

OBJECTIVES: Depression among Korean American (KA) immigrants in rural Alabama is understudied. This study aims to utilize the social determinants of health (SDOH) framework to explore factors associated with depressive symptoms among KA immigrants living in rural communities of Alabama. DESIGN: Data were collected from two sites in rural Alabama from September 2019 to February 2020. Convenience sampling was conducted to recruit study participants from the KA community. A total number of 261 KA immigrants aged 23-75 were included in the study. All measures originally in English were translated into Korean using back-translation to assure comparability and equivalence in the meaning of measures. Multiple linear regression modeling was used to explore the predictors of depression. RESULTS: Perceived race discrimination was significantly associated with greater depressive symptoms (ß = .180, SE = .534, p < .01). Three SDOH were identified to have significant relationship with depressive symptoms. Participants who could not see a doctor because of cost (ß = .247, SE = 1.118, p < .001), had lower level of health literacy (ß = -.121, SE = .280, p < .05), and had higher social isolation scores (ß = .157, SE = .226, p < .05) tended to have higher scores of depressive symptoms. CONCLUSION: Rural-living KA immigrants' depression can be significantly affected by race discrimination and SDOH factors, emphasizing the need for culturally competent interventions and services. Policymakers, federal and local governments, non-governmental organizations, and social workers can make joint efforts to address racial discrimination and improve the mental health services among immigrant populations, especially those living in rural areas.

Disparities in depression among Chinese older adults with neurodegenerative diseases.

OBJECTIVES: Neurodegenerative diseases (NDs), such as Parkinson's disease and Alzheimer's disease and related dementias, are a leading cause of death and disability in China. Although studies have demonstrated that depression is associated with NDs, little is known about the factors impacting this relationship. This study aimed to explore and identify the risk and protective factors of depression among Chinese older adults with NDs. METHODS: Data selection was based on the behavioral model of late-life depression. Data from the latest wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 1998-2014) in 2014 were analyzed. Among the sample, 334 older adults aged 65 and older with NDs were included in the analysis. A logistic regression analysis was conducted by SPSS 24.0. RESULTS: Participants who lived in urban areas (O.R.= 2.494, p< .05) or needed more support for Activity of Daily Living (O.R.= 1.136, p< .05) were more likely to have depression. Participants who lived with household members (O.R.= .380, p< .05), self-reported their health status as fair (O.R.= .250, p< .01), or believed their health status remained the same (O.R.= .331, p< .01) were less likely to have depression. CONCLUSION: Our findings suggest that policymakers and healthcare professionals should pay specific attention to the regional disparities of healthcare services and the cultural background to understand the relationship between NDs and depression and improve the well-being of ND patients.

Cytotoxic Sesquiterpenoids from Atractylodes chinensis (DC.) Koidz.

Four new sesquiterpenoids named atrchiterpenes A-D (1-4), a new natural product (5), and twelve known compounds (6-17) were isolated from Atractylodes chinensis (DC.) Koidz. Compound 1 was a rare N-containing eudesmane-type sesquiterpenoid. Structure elucidation was performed by spectroscopic techniques, including 1D, 2D NMR spectra, and HR-ESI-MS. Compounds 6-11, 14, and 17 were reported from Atractylodes for the first time. All the isolated compounds were evaluated for cytotoxicity activity. Compound 16 showed moderate cytotoxicity against HepG2 cells with an IC50 value of 5.81±0.47.

Durability of infiltrated resin application on white spot lesions after different challenges: An ex vivo study.

STATEMENT OF PROBLEM: Infiltrated resin has been widely used as a minimally invasive approach to masking white spot lesions and reinforcing demineralized enamel. Recent evidence confirms its satisfactory effect in the short term, but studies focusing on its long-term performance are lacking. PURPOSE: The purpose of this ex vivo study was to evaluate the durability of infiltrated resin on white spot lesions after pH cycling and long-term thermocycling, staining, and toothbrushing. MATERIAL AND METHODS: Four axial surfaces of 25 extracted human molars were sectioned and fabricated as specimens. The enamel surface of each specimen was prepared in 3 areas: sound enamel, demineralized enamel (white spot lesions), and demineralized enamel treated by infiltrated resin. Then, 4 specimens of each molar were allocated to different challenges simulating a 10-year follow-up: pH cycling, thermocycling, staining, and toothbrushing. The surface roughness, microhardness, and CIELab color values were measured before and after different treatments. A scanning electron microscope (SEM) was used to observe representative specimens. Linear mixed models were used to evaluate the effect of different treatments on microhardness, roughness, and color differences (ΔE) (α=.05). RESULTS: Resin infiltration reduced the surface roughness and increased the microhardness of demineralized lesions, (P<.001) but the values of sound enamel at baseline were not reached. The pH cycling led to the greatest roughness values (515.6 ±56.9 nm) on resin-infiltrated lesions, followed by thermocycling (450.7 ±64.7 nm), toothbrushing (291.2 ±43.5 nm), and staining (183.6 ±49.3 nm) (all P<.001). Only pH cycling significantly decreased the microhardness of resin-infiltrated lesions (81.6 ±14.8 HV 0.2) after progressive demineralization (P<.001). No clinically identified differences were found between resin-infiltrated white spot lesions and sound enamel (ΔE=3.4 ±2.0) at baseline. However, resin-infiltrated lesions demonstrated significantly greater discoloration after pH cycling (ΔE=8.0 ±4.5, P<.001), thermocycling (ΔE=5.4 ±2.0, P=.014), and staining treatments (ΔE=10.4 ±3.2, P<.001) than sound enamel. CONCLUSIONS: Infiltrated resin application reduced surface roughness, improved microhardness, and masked white spot lesions immediately. However, it could not reestablish the characteristics of sound enamel completely and resist chemical and mechanical challenges over time.

Effect of surface treatments on bond durability of zirconia-reinforced lithium silicate ceramics: An in vitro study.

STATEMENT OF PROBLEM: The influence of surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramics (ZLS) is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effect of different surface treatments on the bond durability of zirconia-reinforced lithium silicate ceramic after long-term thermocycling. MATERIAL AND METHODS: Five computer-aided design and computer-aided manufacturing (CAD-CAM) dental ceramic blocks, including 2 zirconia-reinforced lithium silicate ceramic materials (Vita Suprinity/VS and Cetra Duo/CD), 2 commonly used glass-ceramic materials (e.max CAD/EM and Empress CAD/EP), and 1 yttria-stabilized zirconia (Y-TZP, Zenostar/ZS) were tested. Rectangular ceramic blocks were divided into 6 groups and subjected to different surface treatments: group Control (no treatment), group Uni (universal adhesive), group HF (hydrofluoric acid), group CoJet, group HF+Uni (HF and universal adhesive), and group CoJet+Uni (CoJet and universal adhesive). Subsequently, the specimens were cemented to composite resin blocks, sectioned into rectangular microbars of approximately 2×2×12 mm in size, and assigned to 2 groups with and without 100 000 thermal cycles (n=15 per group). The microtensile bond strength (µTBS) test was performed using a universal testing machine. Failure modes were observed with a stereomicroscope and scanning electron microscope (SEM). Three-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons was performed to evaluate the effects of surface treatments, ceramics, and thermocycling on µTBS (α=.05). RESULTS: The µTBS (MPa) was affected by the surface treatment (P<.001), ceramic type (P<.001), and thermocycling (P<.001). The bond strength after HF etching and universal adhesive treatment was highest in glass-ceramic groups (VS, CD, EP, and EM), while CoJet combined with universal adhesive indicated the highest bond strength in the ZS group before (34.3 ±4.2 MPa) and after thermocycling (16.0 ±2.9 MPa). No significant differences for µTBS were found among ZLS (VS and CD), lithium disilicate ceramic group (EM), and leucite-based ceramic group (EP, P>.05), but they demonstrated better bond strength than zirconia (ZS group, P<.01) after thermocycling. Adhesive failure increased in all groups, and the cohesive failure of glass-ceramic decreased after thermocycling. CONCLUSIONS: ZLS showed similar µTBS with traditional glass-ceramics, including lithium disilicate ceramic and leucite-based ceramic, and more durable bonding than zirconia to resist thermocycling. Moreover, the combination of HF and universal adhesive treatments was the most effective method for ZLS among all the different surface treatments in this study.

Chatbots to Support People With Dementia and Their Caregivers: Systematic Review of Functions and Quality.

BACKGROUND: Over the past decade, there has been an increase in the use of information technologies to educate and support people with dementia and their family caregivers. At the same time, chatbot technologies have become increasingly popular for use by the public and have been identified as having benefits for health care delivery. However, little is known about how chatbot technologies may benefit people with dementia and their caregivers. OBJECTIVE: This study aims to identify the types of current commercially available chatbots that are designed for use by people with dementia and their caregivers and to assess their quality in terms of features and content. METHODS: Chatbots were identified through a systematic search on Google Play Store, Apple App Store, Alexa Skills, and the internet. An evidence-based assessment tool was used to evaluate the features and content of the identified apps. The assessment was conducted through interrater agreement among 4 separate reviewers. RESULTS: Of the 505 initial chatbots identified, 6 were included in the review. The chatbots assessed varied significantly in terms of content and scope. Although the chatbots were generally found to be easy to use, some limitations were noted regarding their performance and programmed content for dialog. CONCLUSIONS: Although chatbot technologies are well established and commonly used by the public, their development for people with dementia and their caregivers is in its infancy. Given the successful use of chatbots in other health care settings and for other applications, there are opportunities to integrate this technology into dementia care. However, more evidence-based chatbots that have undergone end user evaluation are needed to evaluate their potential to adequately educate and support these populations.

Artificial Intelligence in Health Care: Bibliometric Analysis.

BACKGROUND: As a critical driving power to promote health care, the health care-related artificial intelligence (AI) literature is growing rapidly. OBJECTIVE: The purpose of this analysis is to provide a dynamic and longitudinal bibliometric analysis of health care-related AI publications. METHODS: The Web of Science (Clarivate PLC) was searched to retrieve all existing and highly cited AI-related health care research papers published in English up to December 2019. Based on bibliometric indicators, a search strategy was developed to screen the title for eligibility, using the abstract and full text where needed. The growth rate of publications, characteristics of research activities, publication patterns, and research hotspot tendencies were computed using the HistCite software. RESULTS: The search identified 5235 hits, of which 1473 publications were included in the analyses. Publication output increased an average of 17.02% per year since 1995, but the growth rate of research papers significantly increased to 45.15% from 2014 to 2019. The major health problems studied in AI research are cancer, depression, Alzheimer disease, heart failure, and diabetes. Artificial neural networks, support vector machines, and convolutional neural networks have the highest impact on health care. Nucleosides, convolutional neural networks, and tumor markers have remained research hotspots through 2019. CONCLUSIONS: This analysis provides a comprehensive overview of the AI-related research conducted in the field of health care, which helps researchers, policy makers, and practitioners better understand the development of health care-related AI research and possible practice implications. Future AI research should be dedicated to filling in the gaps between AI health care research and clinical applications.

Family-centeredness in dementia care: what is the evidence?

Over the last decade, person-centered practices in care for adults with Alzheimer's disease and related dementias (AD/RD) has received significant attention from the health care and social service literature, though less attention has been paid to family-centered care (FCC). Initially conceptualized for application in pediatric care, FCC is an approach where clinicians develop partnerships with care recipients' family members and views family members as having expertise to contribute to the clinical team. More recently, FCC has been extended to the literature on AD/RD care, though little is known about the extent to which family-centered interventions have been developed for use in AD/RD clinical practice, or the effectiveness of family-centered care for this population. To contribute to gaps in scholarship, this systematic review identified and evaluated intervention studies examining FCC in AD/RD clinical care. Implications for research and practice are discussed.

Influence of low-temperature degradation on the wear characteristics of zirconia against polymer-infiltrated ceramic-network material.

STATEMENT OF PROBLEM: Low-temperature degradation may affect zirconia restorations during their clinical service. Concerns have been raised about the effect of low-temperature degradation on the wear behavior of zirconia. Moreover, the wear resistance of this novel polymer-infiltrated ceramic-network material needs to be better evaluated. PURPOSE: The purpose of this in vitro study was to investigate the influence of aging on the wear resistance of zirconia opposing polymer-infiltrated ceramic-network material. MATERIAL AND METHODS: Twelve specimens for 2 newly developed polymer-based materials (a polymer-infiltrated ceramic-network material VITA ENAMIC and a resin nanocomposite material Lava Ultimate), 2 commonly used glass-ceramic materials (IPS e.max CAD and VITABLOCS Mark II), and 2 conventional composite resin materials (VITA CAD-Temp and PMMA Disk) were tested; human enamel was used as a control group. The wear simulator used was a ball-on-disk type with zirconia balls, with and without autoclaving (134°C, 200 kPa, 20 hours) as antagonists. The vertical loss and volume loss of specimens and the roughness average of zirconia antagonists were measured with a 3-dimensional optical profilometer. Vickers hardness values were determined using a micro-Vickers hardness tester. Data were statistically analyzed with a mixed-model ANOVA for wear loss (vertical loss [µm] and volume loss [mm3]) and roughness average (µm) of zirconia antagonists and with the Kruskal-Wallis test for Vickers hardness values (α=.05). The Spearman correlation coefficient was used to determine the relationship between wear loss and hardness. RESULTS: Results showed that specimens opposing the non-aged zirconia balls demonstrated significantly higher wear than those opposing the aged ones (P<.001). The polymer-infiltrated ceramic-network material VITA ENAMIC group (vertical loss=27.44-33.53 µm, volume loss=0.0198-0.315 mm3) and the resin nanocomposite material Lava Ultimate group (vertical loss=24.42-27.83 µm, volume loss=0.0159-0.0233 mm3) showed lower vertical loss and volume loss than the conventional composite resin groups (vertical loss=43.95-61.87 µm, volume loss=0.0395-0.0593 mm3) but higher wear than the glass-ceramic groups (IPS e.max CAD and VITABLOCS Mark II; vertical loss=8.95-11.47 µm, volume loss=0.0072-0.0094 mm3) and human enamel (vertical loss=9.95-12.32 µm; volume loss=0.0089-0.0103 mm3). The aged zirconia antagonists indicated greater roughness average values than the aged zirconia balls after the wear test (P<.001). Distinct abrasion-induced tracks were observed on the contact surfaces of the aged zirconia antagonists. CONCLUSIONS: Even though zirconia ceramic subjected to low-temperature degradation exhibited increased roughness after the wear test, it was still nonabrasive toward opposing materials. The polymer-infiltrated ceramic-network material showed intermediate wear resistance compared with glass-ceramic and conventional composite resin.

Fully human monoclonal antibodies to TRAIL-R1 enhance TRAIL-induced apoptosis via activation of caspase-8 pathway.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic antibodies targeting TRAIL-receptors (TRAIL-Rs) can selectively induce apoptosis in cancer cells. However, they have limited antitumor efficacy in clinical trials. We previously generated ten fully human monoclonal Abs to TRAIL-receptor type 1 (TR1-mAbs) using immunospot array assay on a chip (ISAAC technology). We found that the TR1-mAbs exhibited different effects on TRAIL-induced apoptosis (enhanced or blocked apoptosis). Here, we further demonstrated that some mAbs competed with TRAIL for binding to TRAIL-R1 expressed on tumor cells that blocked TRAIL-induced apoptosis (B-TR1-Ab), whereas others did not compete with TRAIL that enhanced TRAIL-induced apoptosis (E-TR1-Ab). Combination of E-TR1-Ab (TR1-419) with TRAIL leads to enhanced antitumor activity in various tumor cells in vitro. E-TR1-419 and TRAIL could cooperate to upregulate the mRNA expression and protein levels of TRAIL-R1 and to promote caspase-8 cleavage and increased JNK phosphorylation. Our results suggest that combining E-TR1 Ab with TRAIL could provide a new therapeutic strategy for tumor immunotherapies.

Concomitant activation of the PI3K/Akt and ERK1/2 signalling is involved in cyclic compressive force-induced IL-6 secretion in MLO-Y4 cells.

IL-6 has a dual role in bone remodelling. The ERK1/2 pathway partially upregulated IL-6 secretion in osteocyte-like MLO-Y4 cells exposed to CCF. We have now investigated the possible role of phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway in the CCF-induced IL-6 expression. MLO-Y4 cells were treated with CCF 2,000 µstrain, 2 Hz, or 10, 30 min, 1, 3 and 6 h. IL-6 expression, Akt and ERK1/2 and PI3K/Akt phosphorylation were determined by RT-PCR, ELISA and Western blotting. Inhibition of PI3K/Akt with LY294002 or ERK1/2 with PD98059 significantly attenuated IL-6 upregulation, and IL-6 expression was abolished by inhibiting both pathways. Inhibition of one pathway downregulated the other's phosphorylation level. In conclusion, concomitant activation of PI3K/Akt and ERK1/2 pathways mediated IL-6 expression in MLO-Y4 cells under CCF.

Characterization of a low shrinkage dental composite containing bismethylene spiroorthocarbonate expanding monomer.

In this study, a novel dental composite based on the unsaturated bismethylene spiroorthocarbonate expanding monomer 3,9-dimethylene-1,3,5,7-tetraoxa-spiro[5,5]undecane (BMSOC) and bisphenol-S-bis(3-meth acrylate-2-hydroxypropyl)ether (BisS-GMA) was prepared. CQ (camphorquinone) of 1 wt % and DMAEMA (2-(dimethylamino)ethyl methacrylate) of 2 wt % were used in a photoinitiation system to initiate the copolymerization of the matrix resins. Distilled water contact angle measurements were performed for the wettability measurement. Degree of conversion, volumetric shrinkage, contraction stress and compressive strength were measured using Fourier Transformation Infrared-FTIR spectroscopy, the AccuVol and a universal testing machine, respectively. Within the limitations of this study, it can be concluded that the resin composites modified by bismethylene spiroorthocarbonate and BisS-GMA showed a low volumetric shrinkage at 1.25% and a higher contact angle. The lower contraction stress, higher degree of conversion and compressive strength of the novel dental composites were also observed.

Wear behavior of seven artificial resin teeth assessed with three-dimensional measurements.

STATEMENT OF PROBLEM: Artificial resin teeth are widely used for removable dental prostheses because of their excellent properties. An evaluation of their wear behavior is important for predicting good clinical performance. PURPOSE: The purpose of the study was to examine the wear behavior of 7 different artificial resin teeth with 3-dimensional measurements. MATERIAL AND METHODS: The artificial denture teeth tested were 2 composite resin teeth (Yamahachi PX, Huge Kaijing), 3 cross-linked acrylic resin teeth (Cosmo HXL, Premium 8, Vita Lingoform), and 2 conventional acrylic resin teeth (Yamahachi FX, Shengjian). The specimens were subjected to an abrasive tester for masticatory simulation. The wear loss (vertical loss and volume loss) was determined with a confocal laser scanning microscope. Data were analyzed with 1-way ANOVA followed by the Games-Howell post hoc test (α=.05). RESULTS: The mean vertical loss and volume loss for all cross-linked acrylic resin teeth (0.987-1.03 µm, 0.858-0.939 mm(3) × 10(-3)) were higher than for all composite resin teeth (0.636-0.698 µm, 0.507-0.650 mm(3) × 10(-3), P<.001) but lower than those for conventional acrylic resin teeth Yamahachi FX and Shengjian (1.39 µm, 1.24 mm(3) × 10(-3); 12.1 µm, 16.4 mm(3) × 10(-3); P<.001). No significant differences for wear loss were found between the Vita Lingoform group and the other cross-linked acrylic resin teeth (P>.05). CONCLUSION: The wear behavior of the artificial teeth examined differed with regard to their compositions. The composite resin teeth and high cross-linked acrylic resin teeth found superior wear resistance over the conventional acrylic resin teeth.

Influence of repeated insertion-removal cycles on the force and magnetic flux leakage of magnetic attachments: an in vitro study.

STATEMENT OF PROBLEM: Magnetic attachments are widely used in overdentures and maxillofacial prostheses. Because the patient will routinely have to insert and remove a removable prosthesis, the retentive force and magnetic flux leakage of the magnetic attachments after repeated insertion and removal must be evaluated to assess their clinical performance. PURPOSE: The purpose of this in vitro study was to investigate the retentive force and flux leakage of magnetic attachments after repeated insertion and removal. MATERIAL AND METHODS: Magfit EX600W magnet-keeper combinations (n=5) were used in this study. After 5000, 10,000, and 20,000 insertion-removal cycles, the retentive force of the magnetic attachments was measured 5 times at a crosshead speed of 5 mm/min with a universal testing machine. Magnetic flux leakage at 3 positions (P1, the upper surface of the magnet; P2, the lower surface of the keeper; and P3, the lateral side of the magnetic attachment set) was evaluated with a gaussmeter. Data were statistically analyzed by 1-way ANOVA (α=.05). The morphology of the abraded surfaces for both the magnet and the keeper was observed with an optical microscope (5×). RESULTS: The mean retentive force decreased significantly after 5000, 10,000, and 20,000 insertion-removal movements (P<.05). Significant differences of flux leakage were also observed at P1 after 5000 cycles and 10,000 cycles, at P2 after 5000 cycles, and at P3 after 5000, 10,000, and 20,000 insertion-removal cycles (P < .05). However, no significant differences in flux leakage were evident after 20,000 cycles at P1 and 10,000 cycles and 20,000 cycles at P2. CONCLUSIONS: Repeated insertion and removal influenced the retentive force and magnetic flux leakage of the magnetic attachments. Retentive force decreased significantly after repeated insertion-removal cycles, whereas the variation of magnetic flux leakage depended on refitting cycles and positions of the magnetic attachments.

[Nitric oxide and prostaglandin E2 secretion in osteocytes induced by intermittent cyclic compressive force].

This paper is aimed to investigate the effect of rest-inserted loading on the mechanosensitivity of osteocytes. In the investigation, cultured MLO-Y4 osteocyte-like cells were strained on cyclic compressive force (CCF) by the self-made compressive loading device. Then we observed the effect of different rest periods-inserted loading (5 s, 15 s, 30 s, respectively) on the mechanosensitivity of osteocytes. We then determined the levels of secreted nitric oxide (NO) and prostaglandin E2 (PGE2) by Griess method and enzyme linked immunosorbent assay (ELISA), respectively. We then stained the cytoskeleton F-actin using immunofluorescence. We found that the expressions of NO and PGE2 in rest-inserted strained groups (> 15 s) were significantly increased compared to those in the continuous strained group. And rest-inserted loading promoted the parallel alignment of stress fibers. It indicates that rest-inserted loading could promote the mechanosensitivity of osteocytes, and this might be related to the parallel alignment of stress fibers.

Euchronin A-F isolated from the Arnebia euchroma (Royle) Johnst. and their anti-proliferative activities in vitro.

Six new naphthoquinones, euchronin A-F (1-6) and nine known naphthoquinones (7-15), were isolated from the roots of Arnebia euchroma (Royle) Johnst. The structures of the new compounds were confirmed by extensive spectroscopic analyses, including UV, IR, HR-ESI-MS, 1D and 2D NMR. In the present study, we estimated the anti-proliferative activities of these compounds with HaCaT cells. The results indicated that compounds 2 and 4 showed strong anti-proliferative activities at 25 µM, with relative viability at 38.83% and 68.44%, respectively.

Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

Syringa reticulata potently inhibits the activity of SARS-CoV-2 3CL protease.

The ongoing coronavirus infectious disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still urgently requires effective treatments. The 3C-like (3CL) protease of SARS-CoV-2 is a highly conserved cysteine protease that plays an important role in the viral life cycle and host inflammation, providing an ideal target for developing broad-spectrum antiviral drugs. Herein, we describe the discovery of a large number of herbs mainly produced in Heilongjiang Province, China, that exhibited different inhibitory activities against SARS-CoV-2 3CL protease. We confirmed that Syringa reticulata, which is used for clinical treatment of chronic bronchitis and asthma, is a specific and potent inhibitor of 3CL protease. A 70 % ethanol extract of S. reticulata dose-dependently inhibited the cleavage activity of 3CL protease in a fluorescence resonance energy transfer assay with an IC50 value of 0.0018 mg/mL, but had minimal effect in pseudovirus-based cell entry and luciferase-based RNA-dependent RNA polymerase assays. These results suggest that S. reticulata will be a potential leading candidate for COVID-19 treatment.