Molecular medicine reports
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Cardiac arrest (CA) is a leading cause of mortality worldwide. The majority of the associated mortalities are caused by post‑CA syndrome, which includes symptoms, such as neurologic damage, myocardial dysfunction and systemic inflammation. Following CA, return of spontaneous circulation (ROSC) leads to a brain reperfusion injury, which subsequently causes adverse neurologic outcomes or mortality. ⋯ In addition, the study identified the beneficial role of spontaneous hypothermia in ameliorating the ROSC‑induced inflammation and neurologic deficit in CA rat models, including the downregulation of inflammasome components and attenuating neuronal apoptosis. The present study contributes to the understanding of underlying mechanisms in CA‑evoked inflammation and the subsequent neurologic damage following ROSC. A novel potential therapeutic strategy that may increase survival times and the quality of life for patients suffering from post‑CA syndrome is proposed in the present study.
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To investigate the effects of catalpol on corneal neovascularization (CNV) and associated inflammation, eye drops (5 mM catalpol or PBS) were administered four times daily to alkali‑burn rat models of CNV and inflammation. Clinical evaluations of CNV and the degree of inflammation were performed on days 0, 4, 7, 10 and 14 under slit lamp microscopy. Eyes were collected on day 14 and prepared for hematoxylin and eosin, and immunofluorescence staining; corneal cell apoptosis was investigated via terminal deoxynucleotidyl transferase‑mediated nick end labeling (TUNEL) staining. ⋯ Western blot analysis revealed reduced protein expression levels of VEGF and TNF‑α; however, PEDF and phosphorylated‑NF‑κB p65 were increased due to catalpol administration. The present study demonstrated the inhibitory effects exerted by catalpol on CNV and inflammation within alkali‑burned rat models. Topical application of catalpol in vivo was associated with reduced CNV and inflammation; therefore, catalpol may be considered an anti‑inflammatory agent for the clinical treatment of CNV.
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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.