The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together ...with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment. Further, the reduced bone formation in GIO mice could not only be prevented by osteoblasts-specific Ckip-1 ablation, but also be attenuated after osteoblasts-specific Smad1 overexpression. Moreover, osteoblasts-targeting CKIP-1 siRNA treatment also attenuated the bone formation reduction in GIO mice. These study suggest that the highly expressed CKIP-1 in osteoblasts could suppress the Smad-dependent BMP signaling and contribute to the bone formation reduction in GIO. Targeting osteoblastic CKIP-1 would be a novel bone anabolic strategy for GIO patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription ...unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3'-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.
Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational ...follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 95% CI, 0.18 to 0.71; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 95% CI, 0.46 to 0.89; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we investigated the ...role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA.
The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies.
PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model.
These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
Background: Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Here, we ...investigated the role of osteoblastic pleckstrin homology domain-containing family O member 1 (PLEKHO1), a negative regulator of osteogenic lineage activity, in regulating joint inflammation in RA. Methods: The level of osteoblastic PLEKHO1 in RA patients and collagen-induced arthritis (CIA) mice was examined. The role of osteoblastic PLEKHO1 in joint inflammation was evaluated by a CIA model and a K/BxN serum-transfer arthritis (STA) model which were induced in osteoblast-specific Plekho1 conditional knockout mice and mice expressing high Plekho1 exclusively in osteoblasts, respectively. The effect of osteoblastic PLEKHO1 inhibition was explored in a CIA mice model and a non-human primate arthritis model. The mechanism of osteoblastic PLEKHO1 in regulating joint inflammation were performed by a series of in vitro studies. Results: PLEKHO1 was highly expressed in osteoblasts from RA patients and CIA mice. Osteoblastic Plekho1 deletion ameliorated joint inflammation, whereas overexpressing Plekho1 only within osteoblasts exacerbated local inflammation in CIA mice and STA mice. PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-κB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition diminished joint inflammation and promoted bone formation in CIA mice and non-human primate arthritis model. Conclusions: These data strongly suggest that the highly expressed PLEKHO1 in osteoblasts contributes to joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA. Keywords: Osteoblast, PLEKHO1, Rheumatoid arthritis, Inflammation, Bone formation
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
AIM To compare the effect of University of Wisconsin(UW) solution with or without metformin, an AMP-activated protein kinase(AMPK) activator, for preserving standard and marginal liver grafts of ...young and aged rats ex vivo by hypothermic machine perfusion(HMP).METHODS Eighteen young(4 mo old) and 18 aged(17 mo old)healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group(UWP), and UW solution with metformin perfusion group(MUWP). Aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), interleukin-18(IL-18), and tumor necrosis factor-alpha(TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase(e NOS) in liver sinusoidal endothelial cells were also examined.Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done. RESULTS AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively,significantly lower in the MUWP group than in the UWP group(P < 0.05), but no significant differences were found between the young and aged MUWP groups.Metformin increased the expression of AMPK and e NOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-e NOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.CONCLUSION The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.
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•Wedelolactone, a natural compound, shows outstanding effects of anti-inflammation and anti-oxidative stress.•The alleviation to doxorubicin(DOX)-driven podocyte injury may contribute ...to the attenuation of renal damage.•Wedelolactone can regulate the IκK/IκB/NF-κB signaling pathway to alleviate levels of oxidative stress and inflammation.
The acute kidney injury(AKI) caused by nephrotoxic drugs contributes to inflammation and oxidative injury in podocytes. Wedelolactone (WED), a natural compound, is found with activities as anti-inflammation, anti-oxidative, anti-free radical,and etc. In this present study, MPC-5 cells were exposed to the nephrotoxic drugs doxorubicin (DOX). The results showed that WED significantly increased the SOD activity, CAT and GSH-Px levels, while significantly decreased the MDA content and ROS levels in DOX-induced MPC-5 cells. WED could also significantly decrease the levels of cytokines IL-6, MCP-1, TNF-α, and TGF-β1. Additionally, the activation and phosphorylation of IκKα, IκBα and NF-κB p65 was inhibited by WED. The co-treatment of PDTC (NF-κB inhibitor) and WED significantly reduced NF-κB p65 phosphorylation. These findings suggested that WED alleviated inflammation and oxidative stress of doxorubicin-induced MPC-5 cells through IκK/IκB/NF-κB signaling pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This letter focuses on joint user activity and data detection in the uplink grant-free non-orthogonal multiple access systems based on approximate message passing (AMP) and expectation maximization ...(EM) algorithms. The proposed Joint-EM-AMP detection algorithm consists of three steps in each iteration. First, AMP decouples the superimposed received signal into uncoupled scalar problems. Then, at the denoising step, AMP computes the posterior means and variances of the transmitted symbols with the extended modulation constellation. The third step is to estimate user activity parameters using EM based on the frame-wise joint sparsity of user activity. In contrast to existing state-of-the-art algorithms, the proposed Joint-EM-AMP algorithm demonstrates significant performance gain in terms of bit error rate, which will be verified in simulation results.
To investigate the epizootic of swine influenza virus (SIV), 60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City, Shandong Province of China in April 2017. SIV was isolated ...by inoculating into 10-day-old Special Pathogen Free embryonated eggs and the whole genome was sequenced. An H1N1 subtype SIV was isolated and designated as A/swine/Shandong/TA04/2017(H1N1). Phylogenetic analysis showed that apart from the polymerase A (PA) fragment belonging to the 2009 pandemic H1N1 branch, seven genome segments belonged to avian-like H1N1 influenza virus lineage. The cleavage site sequence of the hemagglutinin (HA) protein was PSIQSR↓G, which is a typical molecular biological characteristic. Five potential N-glycosylation sites (N14, N26, N277, N484 and N543) were found in the HA gene. To further investigate the epidemiology of SIV in this farm, the 995 serum samples were assessed with EAH1N1 2009 pandemic H1N1 and H3N2 antigens. The results showed that the total positive rate was 65.43%. The positive rates of single virus infection detected by EAH1N1, 2009pdmH1N1 and H3N2 for serum HI (Hemagglutination inhibition) were 48.35, 30.85 and 7.47%, respectively. The results showed that SIV in Shandong Province has been reassorted in some segments and the SIV-positive rate was high on the SIV outbreak farm. These data provide evidence of an epizootic of SIV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
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