Molecular medicine reports
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Intervertebral disc degeneration (IVDD) is the most common pathogeny of lumbago. It is the pathological basis for a series of spinal degenerative diseases. For a long time, the diagnosis and treatment of lumbago have rendered difficult, since the pathogeny has not been identified. ⋯ Treatment with Sparstolonin B significantly suppressed toll‑like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor (NF)‑κB protein expression, inhibited NAPDH oxidase 2 protein expression and induced phosphoinositide 3‑kinase and phosphorylated protein kinase B protein expression in the IVDD rat model. These results demonstrated that Sparstolonin B prevents lumbar IVDD‑induced inflammation, oxidative stress and apoptosis through TLR4/MyD88/NF‑κB, NADPH oxidase activation and the phosphoinositide 3‑kinase/protein kinase B signaling pathway. These results implicate Sparstolonin B for use as a therapeutic agent for IVDD in clinical applications.
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The present study aimed to determine the effects of Tianxiangdan Granule on nuclear factor (NF)-κB p65 and p38 mitogen‑activated protein kinase (MAPK) inflammatory signaling pathways, and explored the possible mechanism underlying the effects of Tianxiangdan Granule on prevention and treatment of atherosclerosis. A total of 48 apolipoprotein E‑/‑ mice (age, 8 weeks) were selected and divided into two groups: The normal control group (n=12) and the modeling group (n=36). In the modeling group, mice were fed a high‑fat diet and were maintained in an artificial climate box, in order to stimulate the climate and eating habit characteristics of Xinjiang. ⋯ The results indicated that the concentrations of IL‑1β and TNF‑α were significantly higher in mice in the model group compared with in the normal control group (P<0.01), whereas the concentrations of IL‑1β and TNF‑α were lower in the Tianxiangdan and atorvastatin groups compared with in the model group (P<0.01). Furthermore, the protein expression levels of phosphorylated (p)‑NF‑κB p65 and p‑p38 MAPK protein were higher in aortic tissues from the model group compared with in the normal control group (P<0.01), p‑NF‑κB p65 and p‑p38 MAPK protein expression was reduced in the atorvastatin and Tianxiangdan groups compared with in the model group. The present study indicated that the mechanism underlying the effects of Tianxiangdan Granule on the prevention and treatment of atherosclerosis may be as follows: Tianxiangdan Granule may decrease the expression of the inflammatory cytokines IL‑1β and TNF‑α, and suppress activation of the NF‑κB p65 and p38 MAPK signaling pathways.
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The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. ⋯ The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential biomarkers for this disease.
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Leptin is a cytokine‑like hormone secreted by adipocytes, which serves to control energy expenditure and metabolism. In addition, leptin may modulate the innate and adaptive immune responses. The innate immune cell sensor nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome is mainly expressed in myeloid immune cells, including macrophages. ⋯ The results of the present study demonstrated that leptin enhanced the mRNA and protein expression levels of IL‑18 in RAW 264.7 cells via activation of the NLRP3 inflammasome. This is achieved partly by enhancing the production of reactive oxygen species and K+ efflux. Therefore, leptin may be considered a novel activator and modulator of the NLRP3 inflammasome.
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Betaine has previously been demonstrated to protect the liver against alcohol‑induced fat accumulation. However, the mechanism through which betaine affects alcohol‑induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. ⋯ The downregulation of hepatic AdipoR1 which resulted from alcohol exposure was partially attenuated by betaine. No significant differences in liver function, TNF‑α, phospholipid and AdipoR2 levels were observed among the control, ethanol and ethanol + betaine groups. Overall, these results indicated that betaine attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of DGAT1, DGAT2, SREBP‑1c, FAS, SREBP‑2 and HMG‑CoA reductase and upregulation of PGC‑1α.