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- Gao, TL, et al.
(author)
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Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain
- 2021
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In: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 11, s. 523769-
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Journal article (peer-reviewed)abstract
- The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.
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- He, YQ, et al.
(author)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Journal article (peer-reviewed)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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- Liang, N, et al.
(author)
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Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1684-
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Journal article (peer-reviewed)abstract
- Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.
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- Ogura, Y, et al.
(author)
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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4730-
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Journal article (peer-reviewed)abstract
- Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
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- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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