Molecular medicine reports
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X‑linked inhibitor of apoptosis (XIAP), a key member of the inhibitors of apoptosis protein family, can inhibit apoptosis by directly binding to the initiator caspase‑9, ‑3 and ‑7, thereby promoting tumor cell survival during tumor progression. In the present study, XIAP basal expression levels were investigated and its contribution to the resistance to apoptosis was evaluated, in the RCC cell lines exposed to apoptosis‑inducing drugs. This was investigated by histological methods and western blot analysis. ⋯ Furthermore, a Caki‑1 cell line with no XIAP expression was used, and was demonstrated to be more sensitive to the apoptosis induced by the mitochondrial pathway. These results suggested that downregulation of XIAP expression could enhance the sensitivity of RCC cells to apoptosis, and the basal expression of XIAP during apoptosis is stable. This may provide novel insight for targeted gene therapy against XIAP, in the clinic.
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It has been previously demonstrated that sparstolonin B (SsnB) inhibits toll‑like receptor (TLR)‑2 and TLR‑4. The present study investigated the effect of SsnB on neuropathic pain (NP). A chronic constriction injury (CCI) model was constructed in rats and the protein expression of TLR‑2 and TLR‑4 was determined by western blot analysis. ⋯ The results also demonstrated that the mRNA and protein expression levels of NF‑κB, and the protein expression levels of TNF‑α and IL‑6, were increased in model group compared with the control group (P<0.001). Furthermore, these increases in expression were all reduced in the SsnB group compared with the model group. Therefore, the results indicate that SsnB may alleviate NP via suppression of TLR‑2 and TLR‑4, and may be a potential drug for the treatment of NP.
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The aim of the present study was to identify whether the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene modification is a potential treatment for diarrhea‑predominant irritable bowel syndrome (D‑IBS), via regulating the Na+ channel and the expression of nerve growth factor (NGF). The recombinant adenovirus vector of the SCN9A gene was established, and rat colon cells were isolated for SCN9A gene modification. All subjects were divided into four groups: i) The SCN9A‑modified (D‑IBS rat model implanted with SCN9A‑modified colon cells), ii) negative control (NC; D‑IBS rat model implanted with colon cells without SCN9A gene modification), iii) blank (D‑IBS rat model without any treatment) and iv) normal (normal rats without any treatment). ⋯ Compared with the normal group, the rats in the SCN9A, NC and blank groups had significantly elevated mRNA and protein expression levels of NGF, SCN9A, Nav1.8 and Nav1.9. The rats in the SCN9A group demonstrated significantly increased mRNA and protein expression levels of NGF, SCN9A, Nav1.8 and Nav1.9 compared with the NC group and the blank group (all P<0.05). SCN9A gene modification can promote the expression of Nav1.8 and Nav1.9 channels, in addition to NGF which may provide a novel therapeutic basis for treating of D‑IBS.
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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.