Molecular medicine reports
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Chronic inflammation and the calcification of aortic valve interstitial cells (AVICs) are the primary etiologies of calcific aortic valve disease (CAVD). However, the underlying mechanism remains to be elucidated. The present study investigated the importance of high mobility group box 1 (HMGB1) via toll‑like receptor 4 (TLR4) for the regulation of inflammation and calcification in AVICs. ⋯ In addition, calcification was inhibited by TLR4-specific antibodies in primary AVICs. HMGB1 induced the activation of p38 and nuclear factor-κB (NF-κB) in TLR4‑/‑ primary AVICs, and inhibited p38 and NF‑κB in wild‑type AVICs treated with TLR4‑specific antibodies. The present study demonstrated that TLR4 may function as an essential mediator of HMGB1‑induced calcification and in the activation of p38 and NF-κB.
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The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase‑2 (MMP‑2) and tissue inhibitor of metalloproteinase‑1 (TIMP‑1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague‑Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. ⋯ Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP‑9 and the altered dynamic equilibrium between MMP‑9 and TIMP‑1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP‑9 is a predictive marker of HO.
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The aim of the present study was to determine whether amyloid-β (Aβ) protein could be detected in the serum and cerebrospinal fluid (CSF) of rats with traumatic spinal cord injury (SCI) and whether Aβ protein levels in serum and CSF correlated with the injury severity. A total of 140 adult female Sprague‑Dawley rats were randomly divided into four groups: Sham, mild injury, moderate injury and severe injury. Serum and CSF samples were collected at 12 h, 1, 3, 7, 14, 21 and 28 days post‑injury. ⋯ A significant correlation between Aβ protein level in serum and CSF and neurological deficits (BBB score) was also observed (P<0.01). The protein level of Aβ in serum and CSF was severity and time‑dependent during the acute phase in rats with traumatic SCI. Monitoring the level of Aβ protein in serum may improve the evaluation of SCI severity and the neuron functional status following SCI.
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Joubert syndrome (JS) is an autosomal recessive disorder, which is characterized by hypotonia, ataxia, psychomotor delay, and variable occurrences of oculomotor apraxia and neonatal breathing abnormalities. JS is clinically and genetically heterogeneous. The present study investigated a typical JS family. ⋯ Further investigation indicated that the proband's father was the c.2581G>A carrier, whereas the mother was the c.2848C>T carrier. These results indicated that JS in the proband was caused by novel compound heterozygous mutations in CC2D2A, which were inherited from both parents. These findings may be used to establish prenatal molecular diagnostic criteria, which may be beneficial in future pregnancies.
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It is known that inhaled anesthetics induce neuroinflammation and facilitate postoperative cognitive dysfunction (POCD) in aged individuals; however, the mechanisms by which they mediate these effects remain elusive. Inhalation of the isoflurane anesthetic leads to opening of the mitochondrial permeability transition pore and loss of mitochondrial membrane potential. Therefore, mitochondrial retrograde signaling, which is an adaptive mechanism that facilitates the transmission of signals from dysfunctional mitochondria to the nucleus to activate target gene expression, may be activated during isoflurane inhalation. ⋯ In addition, CaN and NF‑κB inhibition attenuated isoflurane-induced neuroinflammation and subsequent cognitive impairment. In conclusion, the results of the present study demonstrate the role of mitochondrial retrograde signaling and associated protein factors in inhaled anesthetic-induced neuroinflammation and cognitive impairment. These protein factors may therefore present promising therapeutic targets for the prevention of POCD.