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1.
Pharm Stat ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671481

RESUMO

The win ratio has been studied methodologically and applied in data analysis and in designing clinical trials. Researchers have pointed out that the results depend on follow-up time and censoring time, which are sometimes used interchangeably. In this article, we distinguish between follow-up time and censoring time, show theoretically the impact of censoring on the win ratio, and illustrate the impact of follow-up time. We then point out that, if the treatment has long-term benefit from a more important but less frequent endpoint (eg, death), the win ratio can show that benefit by following patients longer, avoiding masking by more frequent but less important outcomes, which occurs in conventional time-to-first-event analyses. For the situation of nonproportional hazards, we demonstrate that the win ratio can be a good alternative to methods such as landmark survival rate, restricted mean survival time, and weighted log-rank tests.

2.
Cell Mol Immunol ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649305

RESUMO

Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1ß, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1ß, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments.

3.
J Autoimmun ; : 102336, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31601476

RESUMO

Excessive inflammatory cytokines play crucial roles in the pathogenesis of rheumatoid arthritis (RA), however, the underlying mechanism remains unclear. In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1ß and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyroptosis in RA-serum pre-incubated monocytes by coordinately enhancing NLRP3 inflammasome over-activation and inducing GSDMD cleavage, cell swelling with large bubbles, caspase-1-dependent cell death and inflammatory cytokine release including IL-6. On the other hand, IL-6 promoted PTX3 plus C1q-induced pyroptosis in both normal and RA serum pre-incubated monocytes. These findings collectively implicated an important role of IL-6 in driving PTX3 plus C1q-mediated pyroptosis in RA and shed lights on a potential new treatment strategy targeting pyroptosis-mediated persistent inflammatory cytokine release.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31596568

RESUMO

Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.

5.
Biomater Sci ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31626246

RESUMO

Xerogels usually possess a stable structure and have a low swelling rate due to their inferior dynamics. Herein, a xerogel was synthesized by "imitative" click chemistry based on lipoic acid for picking up bacteria from wound sites, and thus accelerating tissue repair. The cross-linking structure of disulfide and thioether inside the xerogel not only exhibited good ductility and intrinsic self-healing performance, but also showed superior biocompatibility. The xerogel captured more than 60% of the bacteria Staphylococcus aureus via strong electrostatic adsorption in the colonies with a bacteria count of 106. In addition, this xerogel can stick to the skin in the form of patches in the wounds during therapy for wound healing and can be easily stripped from the skin after treatment, which makes it appropriate for the portable therapy of bacteria-infected wounds in emergency circumstances.

6.
Arch Virol ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31598844

RESUMO

In this study, we report a novel double-stranded RNA (dsRNA) virus, Beauveria bassiana partitivirus 3 (BbPV-3), derived from the entomogenous fungus Beauveria bassiana isolate RCEF5853 from China. The genome of BbPV-3, whose sequence was determined by metagenomic sequencing, RT-PCR, and RACE cloning, comprises two dsRNA genome segments that are 1,856 and 1,719 bp long. The first segment contains a single ORF (ORF-1) encoding a 584-amino-acid-long protein (66.05 kDa) with a conserved RNA-dependent RNA polymerase (RdRp) motif. The second segment also has a single ORF (ORF-2) encoding a 500-amino-acid-long coat protein (CP) (55.9 kDa). The CP and RdRp sequences showed highest identity of 43.4% and 60.2%, respectively, to those of Colletotrichum eremochloae partitivirus 1. Phylogenetic analysis of the RdRp domain of the polyprotein revealed that BbPV-3 grouped together with the members of the genus Epsilonpartitivirus. Hence, we proposed that Beauveria bassiana partitivirus 3 is a novel member of the proposed genus Epsilonpartitivirus.

7.
J Environ Manage ; 252: 109635, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610446

RESUMO

Regional inequality has caused large social and economic problems in China. Numerous researchers have sought to understand the status of economic inequality in the past decades. However, studies are lacking on other aspects of regional inequality, particularly when multiple facets must be considered. In this study, we have innovatively proposed a Pareto law-based method that can help assess multiple dimensions of regional inequality simultaneously. With this approach, we can rank multiple aspects of inequality and provide robust, reasonable goals for different groups of administrative districts. The proposed approach was successfully implemented by using Chinese data for 2015 and 2016, a period during which China was experiencing both severe PM2.5 pollution and economic regional inequality. The results indicate that (1) Shanghai and Shenzhen represent the optimal condition of economic development; (2) different from the spatial distribution of economic inequality alone, inequality was higher in central China for both economic development and PM2.5 air quality; (3) in the context of severe economic inequality in China, the tradeoff between economic development and air quality will result in a relatively equitable condition. In addition, the proposed method is open-ended and can be extended to incorporate more aspects of regional inequality. This approach appears to possess substantial potential for integration into decision-making regarding regional inequality.

8.
Chembiochem ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560820

RESUMO

Protein S-glutathionylation is one of the important cysteine oxidation events that regulate various redox-mediated biological processes. Despite several existing methods, there are few proteomic approaches to identify and quantify specific cysteine residues susceptible to S-glutathionylation. We previously developed a clickable glutathione approach that labels intracellular glutathione with azido-Ala by using a mutant form of glutathione synthetase. In this study, we developed a quantification strategy with clickable glutathione by using isotopically labeled heavy and light derivatives of azido-Ala, which provides the relative quantification of glutathionylated peptides in mass spectrometry-based proteomic analysis. We applied isotopically labeled clickable glutathione to HL-1 cardiomyocytes, quantifying relative levels of 1398 glutathionylated peptides upon addition of hydrogen peroxide. Importantly, we highlight elevated levels of glutathionylation on sarcomere-associated muscle proteins while validating glutathionylation of two structural proteins, α-actinin and desmin. Our report provides a chemical proteomic strategy to quantify specific glutathionylated cysteines.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31506979

RESUMO

OBJECTIVES: To evaluate the peri-implant trabecular bone volume and architecture changes with 6-month follow-up after local application of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) using high-resolution micro-CT. MATERIAL AND METHODS: Seventy-two dental implants were placed into healed mandibular sites of 9 beagle dogs. Implants were randomly divided into 4 groups following a split-mouth design: control I; control II; PPP; and PRP. Primary and secondary stabilities were assessed using resonance frequency analyses. At 1, 3, and 6 months after implant loading, trabecular structural parameters were evaluated at 0.5, 1, and 1.5 mm away from implants using micro-CT (voxel = 20 µm). RESULTS: Primary and secondary stabilities were equivalent in all conditions. PPP and PRP groups showed higher bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) but lower trabecular separation (Tb.Sp) and total porosity percentage (Po (tot)) at all 3 time points. A significant decrease in BV/TV and Tb.Th was found for the control groups after 3 months of healing, while this was not observed in both the PPP and PRP groups. However, no distinct difference was found between the PRP and PPP groups over time. Moreover, as the investigated distance from the implant surface increased, BV/TV and Po (tot) within the same group and time point stayed the same, yet Tb.Th and Tb.Sp continued to increase. CONCLUSIONS: Platelet-rich plasma and PPP with conventional implant placement lead to similar primary and secondary implant stability, but improved peri-implant bone volume and structural integration. The present research does not seem to suggest a different bone remodeling pattern when using PRP or PPP.

10.
Soft Robot ; 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31553262

RESUMO

Existing robots capable of hopping or running mostly rely on rigid actuators, but soft hopping or running robots based on muscle-like actuators have not yet been achieved. In this article, we report a tethered soft robot capable of hopping-running on smooth and rough surfaces with high speed. The hopping-running robot is composed of two soft joints that simulate the foreleg and hind leg driven by dielectric elastomer. The mass, length, width, and height of the robot are 6.5 g, 8.5 cm, 4.8 cm, and 50 cm, respectively. The robot can run at a speed of 51.83 cm/s (6.10 body lengths/s), which is much faster than previously reported locomotion robots driven by soft responsive materials. The robot also shows good adaptability to different terrains, such as marble, wood, rubber, sandpaper, and slopes. The robot can carry a load equal to its weight, can maintain a high locomotion speed, and demonstrates the potential ability to carry its power supply and control circuitry.

11.
Cell Death Dis ; 10(10): 705, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31543513

RESUMO

Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C-X-C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3'-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31552201

RESUMO

Malaria, a mosquito-borne infectious disease, is a severe health problem worldwide. As reported, some anti-malarial drugs with anti-parasitic properties also block mast cells (MCs) activities. It is hypothesized that MCs activity may be correlated with the pathogenesis of malaria. Thus, the role of MCs on malarial pathogenesis and the involved physiological action and pathways need to be further investigated. This study aimed to investigate the effect of MCs activation on malaria disease severity using KunMing mice with Plasmodium berghei ANKA (PbANKA) infection treated with MCs degranulator (compound 48/80, C48/80) or MCs stabilizer (disodium cromoglycate, DSCG). PbANKA infection caused a dramatic increase in MCs density and level of MCs degranulation in cervical lymph node (CLN) and skin. Compared with infected control, C48/80 treatment had shortened survival time, increased parasitemia, exacerbated liver inflammation and CLN hyperplasia, accompanied with increase in vascular leakage and leukocyte number. The infected mice with C48/80 treatment also elevated the release of CCL2, CXCL1, and MMP-9 from MCs in CLN and skin, and TNF-α, IFN-γ, CCR2, and CXCR2 mRNA expression in CLN and liver. In contrast, the infected mice treated with DSCG showed longer survival time, lower parasitemia, improved liver inflammation and CLN hyperplasia, followed by a decline of vascular leakage and leukocyte number. Decreased MCs-derived CCL2, CXCL1, and MMP-9 from CLN and skin, mRNA expression in CLN and liver (TNF-α, IFN-γ, CCR2, and CXCR2) were also observed in infected mice with DSCG treatment. Our data indicated that MCs activation may facilitate the pathogenesis of PbANKA infection.

13.
Environ Sci Technol ; 53(20): 11960-11968, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31532631

RESUMO

Urban growth comes with significant warming impacts and related increases in air pollution concentrations, so many cities have implemented growth management to minimize "sprawl" and its environmental consequences. However, controlling the amount of growth is costly. Therefore, in this Article, we focus on urban warming and investigate whether climate-conscious urban growth planning (CUGP), that is, urban growth with the same magnitude but optimized spatial arrangements, brings significant mitigation effects. First, the classical spatial multiobjective land-use optimization (SMOLA) model is improved by integrating the spatially, diurnally, and compositionally varying associations between land-use and their warming impacts. We then solve the improved model using the nondominated genetic algorithm (NSGA-II) to generate urban growth plans with minimal warming impacts and minimal cost of change without reducing the amount of urban growth. Results show that climate-conscious urban growth brings 33.3 ± 4.6% less warming impacts as compared to unplanned urban growth in Shenzhen, China, and suggest a compact and spatially equalized development pattern. This study provides evidence that spatial planning tools such as the CUGP can help mitigate human impacts on the environment. Meanwhile, the improved SMOLA model could be applied to balance urban development and other environmental consequences such as air pollution.

14.
Immunity ; 51(3): 522-534.e7, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31471107

RESUMO

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

15.
J Appl Genet ; 60(3-4): 335-346, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372832

RESUMO

MicroRNAs (miRNAs) are key regulators that play important biological roles in carcinogenesis and are promising biomarkers for cancer diagnosis and therapy. hsa-miR-375-3p (miR-375) has been suggested to serve as a tumor suppressor or oncogene in various tumor types; however, its specific expression and potential regulatory role in malignant breast cancer remain unclear. In this study, the results from noncoding RNA microarray analysis indicated that the miR-375 expression level is significantly decreased in malignant basal-like breast cancer compared with luminal-like breast cancer. A total of 1895 co-downregulated and 1645 co-upregulated genes were identified in miR-375 mimic-transfected basal-like breast cancer cell lines. Predicted miR-375 targets were obtained from the online databases TargetScan and DIANA-microT-CDS. Combined KEGG enrichment analysis for coregulated genes and predicted miR-375 targets provided information and revealed differences in potential dynamic signaling pathways regulated by miR-375 and also indicated specific regulatory pathways, such as RNA transport and processing, in basal-like breast cancer. Additionally, gene expression microarray analysis accompanied by UALCAN analysis was performed to screen upregulated genes in the basal-like subtype. Four potential key genes, including LDHB, CPNE8, QKI, and EIF5A2, were identified as candidate target genes of miR-375. Therefore, the present study demonstrated that miR-375 may be a potential key regulator and provide a promising direction for diagnostic and therapeutic developments for malignant breast cancer.

16.
ACS Synth Biol ; 8(9): 2092-2105, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31465214

RESUMO

As an important post-transcriptional regulatory machinery mediated by ∼21nt short-interfering double-stranded RNA (siRNA), RNA interference (RNAi) is a powerful tool to delineate gene functions and develop therapeutics. However, effective RNAi-mediated silencing requires multiple siRNAs for given genes, a time-consuming process to accomplish. Here, we developed a user-friendly system for single-vector-based multiplex siRNA expression by exploiting the unique feature of restriction endonuclease BstXI. Specifically, we engineered a BstXI-based shotgun cloning (BSG) system, which consists of three entry vectors with siRNA expression units (SiEUs) flanked with distinct BstXI sites, and a retroviral destination vector for shotgun SiEU assembly. For proof-of-principle studies, we constructed multiplex siRNA vectors silencing ß-catenin and/or Smad4 and assessed their functionalities in mesenchymal stem cells (MSCs). Pooled siRNA cassettes were effectively inserted into respective entry vectors in one-step, and shotgun seamless assembly of pooled BstXI-digested SiEU fragments into a retroviral destination vector followed. We found these multiplex siRNAs effectively silenced ß-catenin and/or Smad4, and inhibited Wnt3A- or BMP9-specific reporters and downstream target expression in MSCs. Furthermore, multiplex silencing of ß-catenin and/or Smad4 diminished Wnt3A and/or BMP9-induced osteogenic differentiation. Collectively, the BSG system is a user-friendly technology for single-vector-based multiplex siRNA expression to study gene functions and develop experimental therapeutics.

17.
Oncogene ; 38(44): 6970-6984, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31409901

RESUMO

Clinical applications of antiangiogenic agents profoundly affect tumor cell behaviors via the resultant hypoxia. To date, how the hypoxia regulates tumor cells remains unclear. Here, we show that hypoxia promotes the growth of human breast tumorigenic cells that repopulate tumors [tumor-repopulating cells (TRCs)] in vitro and in vivo. This stimulating effect is ascribed to hypoxia-induced reactive oxygen species (ROS) that activates Akt and NF-κB, dependent on the attenuated tricarboxylic acid (TCA) cycle. We find that fumarate is accumulated in the TCA cycle of hypoxic TRCs, leading to glutathione succination, NADPH/NADP+ decrease, and an increase in ROS levels. Mechanistically, hypoxia-increased HIF-1α transcriptionally downregulates the expression of mitochondrial phosphoenolpyruvate carboxykinase (PCK2), leading to TCA cycle attenuation and fumarate accumulation. These findings reveal that hypoxia-reprogrammed TCA cycle promotes human breast TRCs growth via a HIF-1α-downregulated PCK2 pathway, implying a need for a combination of an antiangiogenic therapy with an antioxidant modulator.

18.
Sci Rep ; 9(1): 11390, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388026

RESUMO

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been recognized as a therapeutic target for EML4-ALK fusion-positive nonsmall cell lung cancer (NSCLC) treatment using type I kinase inhibitors such as crizotinib to take over the ATP binding site. According to Shaw's measurements, ALK carrying G1202R mutation shows reduced response to crizotinib (IC50 = 382 nM vs. IC50 = 20 nM for wild-type), whereas L1198F mutant is more responsive (IC50 = 0.4 nM). Interestingly, the double mutant L1198F/G1202R maintains a similar response (IC50 = 31 nM) to the wild-type. Herein we conducted molecular modeling simulations to elucidate the varied crizotinib sensitivities in three mutants carrying L1198F and/or G1202R. Both L1198 and G1202 are near the ATP pocket. Mutation G1202R causes steric hindrance that blocks crizotinib accessibility, which greatly reduces efficacy, whereas mutation L1198F enlarges the binding pocket entrance and hydrophobically interacts with crizotinib to enhance sensitivity. With respect to the double mutant L1198F/G1202R, F1198 indirectly pulls R1202 away from the binding entrance and consequently alleviates the steric obstacle introduced by R1202. These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and MET G1163R mutations that are also resistant to crizotinib treatment in NSCLC.

19.
Med Sci Monit ; 25: 5961-5968, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400110

RESUMO

BACKGROUND The aim of this study was to determine the effects of myeloma cells exposed to fluid shear stress on osteocytes and osteoclasts, and clarify the potential underlying mechanisms. MATERIAL AND METHODS A flow and a non-flow model were established using a flow fluid chamber. The myeloma cell line U266 and murine osteocytic MLO-Y4 cells were cultured in vitro. The osteocytes and osteoclasts were examined under a microscope. Osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) activity. RANKL and osteoprotegerin (OPG) gene expression were detected using reverse transcription-quantitative polymerase chain reaction. RESULTS Compared with the controls, Y4 cells cultured with U266 culture supernatant showed altered morphology, fewer osteocytes, increased RANKL gene expression, a higher RANKL/OPG gene ratio, and a greater number of TRAP-positive osteoclasts (P<0.05 for all). Compared to the no-flow model, the flow model showed a higher number of Y4 cells, increased OPG gene expression, decreased RANKL gene expression, a lower RANKL/OPG gene ratio, and fewer TRAP-positive osteoclasts (P<0.05 for all). CONCLUSIONS Our study revealed that fluid shear stress ameliorated the inhibitory effects of myeloma cells on osteocyte growth and inhibited osteoclast proliferation by means of decreasing RANKL/OPG gene expression. This may have clinical implications in patients with multiple myeloma in that mechanical loading with low-intensity vibration or mild exercise may prevent the progression of myeloma bone disease.

20.
Nat Commun ; 10(1): 3741, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431616

RESUMO

Clinical experience suggests increased incidences of neonatal jaundice when air quality worsens, yet no studies have quantified this relationship. Here we reports investigations in 25,782 newborns showing an increase in newborn's bilirubin levels, the indicator of neonatal jaundice risk, by 0.076 (95% CI: 0.027-0.125), 0.029 (0.014-0.044) and 0.009 (95% CI: 0.002-0.016) mg/dL per µg/m3 for PM2.5 exposure in the concentration ranges of 10-35, 35-75 and 75-200 µg/m3, respectively. The response is 0.094 (0.077-0.111) and 0.161 (0.07-0.252) mg/dL per µg/m3 for SO2 exposure at 10-15 and above 15 µg/m3, respectively, and 0.351 (0.314-0.388) mg/dL per mg/m3 for CO exposure. Bilirubin levels increase linearly with exposure time between 0 and 48 h. Positive relationship between maternal exposure and newborn bilirubin level is also quantitated. The jaundice-pollution relationship is not affected by top-of-atmosphere incident solar irradiance and atmospheric visibility. Improving air quality may therefore be key to lowering the neonatal jaundice risk.

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