Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Intravenous parecoxib for early postoperative cognitive dysfunction in elderly patients: evidence from a meta-analysis.

BACKGROUND: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor parecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the efficacy and safety of parecoxib on early POCD in geriatric patients. OBJECTIVE: This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients. METHODS: Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane's Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to conduct meta-analysis. RESULTS: Eight RCTs comprising a total of 1106 subjects prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved Mini-Mental State Examination (MMSE) score. Parecoxib could significantly reduce the concentrations of interleukin-6, but results regarding the changes in tumor necrosis factor-alpha, C-reactive protein, and S100ß levels remained inconsistent. CONCLUSION: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving the MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in the Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

Human nail stem cells are retained but hypofunctional during aging.

The nail is a continuous skin appendage. Cells located around the nails, which display coordinated homeostatic dynamics and release a flow of stem cells in response to regeneration, have been identified in mice. However, very few studies regarding human nail stem cells exist in the literature. Using specimens isolated from humans, we detected an unreported population of cells within the basal layer of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail root. These cells were multi-expressing and expressed stem cell markers, such as keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very similar to mouse nail stem cells in terms of cell marker expression and their location within the nail. We also found that the putative nail stem cells maintained their abundance with advancing age, but cell proliferation and nail growth rate were decreased on comparison of young and aged specimens. To summarize, we found a putative population of stem cells in postnatal human nails located at NPFs and the nail matrix. These cells may have potential for cell differentiation and be capable of responding to injury, and were retained, but may be hypofunctional during aging.

Efficacy and Safety of Postoperative Pain Relief by Parecoxib Injection after Laparoscopic Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This study aims to evaluate the efficacy and safety of parecoxib injection in pain relief after laparoscopic surgeries. METHODS: A comprehensive literature search based on 4 online databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane Collaboration's tool was applied to evaluate the methodological quality of included studies. A standardized data collection sheet was designed to extract data from included studies. RevMan version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis. RESULTS: A total of 1,060 participants who were scheduled for gynecological laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12 selected RCTs. The methodological qualities of the studies were evaluated as moderate to high. The combined data showed that perioperative parecoxib injection could significantly reduce the proportion of patients who required adjuvant pain relieve after laparoscopic surgeries. Significantly lower pain scores in the parecoxib groups were observed, which proved that preoperative or intraoperative injection of 40 mg parecoxib was more effective than placebo for immediate pain relief after LC. But preoperative injection of 40 mg parecoxib showed no improvement compared with placebo in the management of immediate pain following gynecological laparoscopic surgery. The occurrence of adverse events showed no differences between perioperative parecoxib administration and placebo control. CONCLUSION: Perioperative parecoxib administration was effective in reducing the proportion of patients who required adjuvant pain relief after laparoscopic surgeries without significant adverse events compared with placebo. The effect of parecoxib injection on immediate pain relief remains in question. Future RCTs with larger sample sizes are encouraged.

Protective action of liraglutide in beta cells under lipotoxic stress via PI3K/Akt/FoxO1 pathway.

Liraglutide, a modified form of glucagon-like peptide-1 (GLP-1), has been found to improve beta cell function in type 2 diabetes (T2DM). However, the effect of liraglutide on beta cell function under lipotoxic stress and the underlying molecular mechanisms remain unclear. In the present study, we investigated the role of PI3K/Akt/FoxO1 signaling in liraglutide-involved beta cell protection in high free fatty acids (FFAs) condition. The apoptosis, proliferation, and insulin secretion capability of MIN6 cells and islets from C57BL/6J mice were evaluated when exposed to FFAs with/without liraglutide. The expression of effectors involved in PI3K/Akt/FoxO1signalling pathway was detected by real-time PCR and western blotting in MIN6 cells and islets from C57BL/6J mice. Liraglutide substantially inhibited the lipoapoptosis and improved the proliferation and insulin secretion of beta cells in high FFAs condition. Western blot revealed that the phosphorylation of Akt and FoxO1 was markedly decreased under lipid stress but was elevated when treated with liraglutide. Moreover, FFAs could up-regulate the expression levels of p27, Bax, Cidea but down-regulate the expression levels of Pdx-1, MafA, and NeuroD in beta cells, which was canceled by the addition of liraglutide. Moreover, LY294002, a PI3K inhibitor, could significantly abrogate all the protective actions of liraglutide against lipotoxicity. We concluded that liraglutide markedly improved beta cell function under lipid stress and that the protective action of liraglutide was mediated by activation of PI3K/Akt, which resulted in inactivation of FoxO1 along with the down-regulation of p27, Bax, Cidea and up-regulation of Pdx-1, MafA, and NeuroD expressions.

Treatment of scaphoid nonunion: pedicled vascularized bone graft vs. traditional bone graft.

The clinical results of the application of pedicled vascularized bone graft (VBG) from Lister's tubercle vs. traditional bone graft (TBG) were evaluated and compared. Thirteen cases of symptomatic scaphoid nonunion were treated between January 2011 and December 2012, including 7 cases subject to VBG and the rest 6 cases to TBG, respectively. Outcomes were assessed by modified Mayo wrist score system. All cases were followed up for an average period of 3.5 months after operation. The results showed that total scores in VBG group were 86.4±9.4 after operation with excellent result in 4 cases, good in 2 and acceptable in one, and those in TBG group were 71.7±9.3 after operation with good result in 2 cases, acceptable in 3 and disappointing in one. Total score of wrist function was significantly improved in VBG group as compared with TBG group (P<0.05). Our study suggests that VBG method is more effective for treating scaphoid nonunion than TBG method.

Constituent ratio of motor fibers from the C5-C7 spinal nerves in the radial nerve is greater in pup rats than in adult rats.

Clinically, injuries of C5-C7 of the brachial plexus cause falling of the wrist and fingers in infants but not in adults unless 4 consecutive spinal nerves are injured. The purpose of this study was to compare the constituent difference of spinal nerves in the radial nerve between pup and adult rats.A group of 16 pup rats and a group of 16 adult rats were each divided into 2 groups of 8 (P1 and A1 groups, C5-C6 were divided; P2 and A2 groups, C5-C7 were divided]). A nerve conduction study and histological examination were performed to evaluate radial nerve innervation to the extensor digitorum communis muscle after dividing the spinal nerves. Retrograde tracing with 5% cholera toxin B for anterior horn motoneurons of the spinal cord innervating the radial nerve was performed in 8 pup rats and 8 adult rats. Results showed that the division of C5-C7 caused more significant damage to radial nerve innervation to the extensor digitorum communis in pups than in adults, although the division of C5-C6 did not. In pups, the percentages (median with interquartile) of anterior horn motoneurons of the spinal cord innervating the radial nerve were 36.4 (28.3-38.5) in C5-C6, 28.1 (24.5-32.5) in C7, and 37.5 (36.5-39.3) in C8-T1. In adults, they were 24.2 (23.6-27.8) in C5-C6, 21.8 (19.5-26.3) in C7, and 50.7 (48.7-55.5) C8-T1.This study implies that C7 innervation in the radial nerve in humans may be more critical to the function of this nerve in infants than in adults.