Spinal cord injury (SCI) results in inflammation, and TLR4, which is an inflammatory factor, has an important role in the pathological injury that occurs following SCI. Recently, bone marrow stromal cells (BMSCs) have been demonstrated to be a novel treatment in SCI. However, the underlying mechanism of neuroprotection in SCI by BMSCs remains unclear. The present study was designed to investigate the therapeutic mechanism of BMSCs in SCI by analysis of Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) expression. The present results demonstrated that BMSC transplantation promoted functional recovery and tissue repair in SCI rats. Interestingly, it also reduced the expression of TLR4 and NF-κB after SCI. Furthermore, it was demonstrated that BMSCs downregulated the expression of apoptosis factor caspase-12 in the SCI rat model. The present results demonstrated that BMSCs may have incorporated into the spinal cord to improve locomotor function after SCI, partly via the TLR4/NF-κB signaling pathway. To the best of our knowledge, this is the first study to determine that BMSCs prevented secondary injury and enhanced functional recovery in SCI via inhibition of TLR4/NF-κB-mediated inflammation.
Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG.Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored.A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up.Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.
Abstract Neoagaro-oligosaccharides derived from agarose have been demonstrated to possess a variety of biological activities, such as anti-bacteria and anti-oxidative activities. In this study, we mainly explored the inhibitory effects and the mechanisms of neoagaro-oligosaccharide monomers against LPS-induced inflammatory responses in mouse macrophage RAW264.7 cells. The results indicated that neoagaro-oligosaccharide monomers especially neoagarotetraose could significantly reduce the production and release of NO in LPS-induced macrophages. Neoagarotetraose significantly suppressed the expression and secretion of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines such as TNF-α and IL-6. The inhibition mechanisms may be associated with the inhibition of the activation of p38MAPK, Ras/MEK/ERK and NF-κB signaling pathways. Thus, neoagarotetraose may attenuate the inflammatory responses through downregulating the MAPK and NF-κB signaling pathways in LPS-stimulated macrophages. In summary, the marine-derived neoagaro-oligosaccharide monomers merit further investigation as novel anti-inflammation agents in the future.
Previous studies have implicated 5-HT1A receptor gene (HTR1A) polymorphisms in the therapeutic response to antidepressants, especially selective serotonin reuptake inhibitors. A functional HTR1A C-1019G polymorphism (rs6295) in the promoter region was found to be associated with antidepressant pharmacogenetics in different populations. However, inconsistent and inconclusive results have been obtained. In this study, we tested whether rs6295 genetic variants are related to antidepressant effects using a meta-analysis method. The relevant literature was acquired through deliberate searching and selection based on the established inclusion criteria for publications. A total of 10 articles were identified, all of which evaluated the HTR1A C-1019G polymorphism and antidepressant response. Dominant and recessive models were tested in the analyses, and the results revealed no association between the HTR1A C-1019G polymorphism and antidepressant response.
Genetic factors can influence specific human coping styles. Polymorphisms in the Src family tyrosine kinase FYN gene have been associated with several personality traits, but no studies have examined the possible relationship between FYN alleles and coping styles. To this end, we examined the association between three single nucleotide polymorphisms of FYN (rs706895, rs3730353, and rs6916861) and coping styles as measured by the Simplified Coping Style Questionnaire in 488 healthy Chinese-Han individuals. In the total sample population, there were no significant differences in the scores for active coping and passive coping among the genotypes of these three polymorphisms. In sex-specific analyses, however, both rs3730353 and rs6916861 polymorphisms showed a significant relationship with passive coping scores in female participants (rs3730353: χ(2)=8.08, P=0.018; rs6916861: χ(2)=7.78, P=0.020). Our results provided suggestive evidence that the FYN gene contributes toward the variance in human coping styles.
Platelet mitophagy is a major pathway involved in the clearance of injured mitochondria during hemostasis and thrombosis. Prohibitin 2 (PHB2) has recently emerged as an inner mitochondrial membrane receptor involved in mitophagy. However, the mechanisms underlying PHB2‑mediated platelet mitophagy and activation are not completely understood. PHB2 is a highly conserved inner mitochondrial membrane protein that regulates mitochondrial assembly and function due to its unique localization on the mitochondrial membrane. The present study aimed to investigate the role and mechanism underlying PHB2 in platelet mitophagy and activation. Phorbol‑12‑myristate‑13‑acetate (PMA) was used to induce MEG‑01 cells maturation and differentiate into platelets following PHB2 knockdown. Cell Counting Kit‑8 assays were performed to examine platelet viability. Flow cytometry was performed to assess platelet mitochondrial membrane potential. RT‑qPCR and western blotting were conducted to measure mRNA and protein expression levels, respectively. Subsequently, platelets were exposed to CCCP and the role of PHB2 was assessed. The results of the present study identified a crucial role for PHB2 in platelet mitophagy and activation, suggesting that PHB2‑mediated regulation of mitophagy may serve as a novel strategy for downregulating the expression of platelet activation genes. Although further research into mitophagy is required, the present study suggested that PHB2 may serve as a novel therapeutic target for thrombosis‑related diseases due to its unique localization on the mitochondrial membrane.
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