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This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.
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Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.
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Objective:To explore the mechanism of Herba Centipedae in the treatment of asthma by screening out the active ingredients and targets, so as to construct a target-pathway network.Methods:Based on TCMSP and Drugbank database to screen out active ingredients and corresponding targets of Herba Centipedae by using Cytoscape software to construct the interactive network among targets and the crosslink analysis to screen out the potential ingredients and targets of Herba Centipedae in the treatment of asthma . Finally, the information of signaling pathway was obtained after the GO enrichment analysis and KEGG pathway analysis were performed based on DAVID database, and then the ingredient-target-pathway network model was established.Results:Expect to get 15 active ingredients, and 75 targets. And futher predict that the mechanism may relate to chemokine activity signaling pathway, extracellular space signaling pathway and TNF signaling pathway. Among the pathways, IL6, TNF, MAPK1, TP53, JUN genes may play a crucial role.Conclusions:Based on the network of pharmacology, this study focuses on the characteristics of the multi-component, multi-target, and multi-pathway of Herba Centipedae in the treatment of asthma.
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Objective@#To explore the mechanism of Herba Centipedae in the treatment of asthma by screening out the active ingredients and targets, so as to construct a target-pathway network.@*Methods@#Based on TCMSP and Drugbank database to screen out active ingredients and corresponding targets of Herba Centipedae by using Cytoscape software to construct the interactive network among targets and the crosslink analysis to screen out the potential ingredients and targets of Herba Centipedae in the treatment of asthma . Finally, the information of signaling pathway was obtained after the GO enrichment analysis and KEGG pathway analysis were performed based on DAVID database, and then the ingredient-target-pathway network model was established.@*Results@#Expect to get 15 active ingredients, and 75 targets. And futher predict that the mechanism may relate to chemokine activity signaling pathway, extracellular space signaling pathway and TNF signaling pathway. Among the pathways, IL6, TNF, MAPK1, TP53, JUN genes may play a crucial role.@*Conclusions@#Based on the network of pharmacology, this study focuses on the characteristics of the multi-component, multi-target, and multi-pathway of Herba Centipedae in the treatment of asthma.
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Diabetes mellitus is a metabolic disease characterized by hyperglycemia,resulting in chronic damage and dysfunction of many organs,such as the eyes,kidneys,heart,blood vessels,nerves,etc.,which increase the difficulty of treatment for diabetes.In recent years,gene therapy for diabetes mellitus has become a hot topic.Ultrasound targeted microbubble destruction (UTMD) has the advantage of safety,good repeatability and tissue targeting,and has become a potential strategy for gene delivery.The related study progresses of UTMD in gene therapy of diabetes mellitus were reviewed in this article.
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Objective To assess the efficacy of different internal fixations of palatal fracture.Methods Seventy-four patients with palatal fracture admitted between October 2007 and October 2013 were reviewed retrospectively.Through out-patient follow-up,postoperative occlusion and palatal complications were examined and fracture healing was evaluated using CT scan.Results Palatal type Ⅰ-Vfractures involved in 8 patients (11％),14 patients (19％),26 (35％),12 patients (16％),6 patients (8％),and 8 patients (11％) respectively.Forty-three patients were available to follow-up,including 31 patients with good or acceptable occlusion.All wounds healed without palate associated infections,plate exposure or oronasal fistula.Of the 27 patients classified as type Ⅱ,Ⅲ and V sagittal palatal fractures,both nasomaxillary and zygomatico-maxillary struts fixation (n =17) and isolated zygomatico-maxillary struts fixation (n =10) had insignificant differences in success rate as to occlusion assessment (82％ vs 80％,P ＞0.05).Whereas compared with isolated vertical buttress fixation (n =15),additional immobilization of horizontal alveolar buttresses (n =12) had significantly higher success rate (100％ vs 67％,P ＜ 0.05).Conclusion Complete rigid fixation at early stage,including vertical buttress fixation,in particular the zygomatico-maxillary struts,and horizontal alveolar buttress fixation can achieve satisfactory outcome.
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Objective To study the effect of pelvic autonomic nerve preservation(PANP)on urination and sexual function in total mesorectal excision(TME). Methods Two hundred and forty cases of male rectal cancer patients,divided into the PANP who accept the pelvic autonomic nerve preservation in TME,and the control group of 120 patients who do not.The urination and sexual function were observed and compared.3-year-survival rate,local recurrence rates of the two groups were recorded. Results The urinary disorder rates,erective disorder rates and ejaculation disorder rates of PANP group were 30.8%,28.3%and 34.2%,while values of control group were 55.0%、60.0%and 62.5%.The difference between them had statistical significance(P<0.05).The 3-year-survival rate and local recurrence rate of PANP group were 9.4%and 75.0%.The 3-year-survival rate and local recurrence rate of control group were 9.0%and 65.0%.There was no significant difference between them(P>0.05). Conclusion The PANP technique in TME could improve the urinary and sexual function of male patients without affect the prognosis.
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Objective To investigate the effect of aminoguanidine and tienam on bacterial translocation in mice with acute necrotizing pancreatitis (ANP) and the preventive and curative effect on pancreatic infection. Methods 50 SD mice were randomly divided into 5 groups, including group A: normal control (n=10), group B: ANP group (n=10), group C: aminoguanidine treatment group (n=10), group D: tienam treatment group (n=10), and group E: aminoguanidine plus tienam treatment group (n=10). ANP was induced by intrapancreatic injection of 5% sodium tanrocholate (2.5 ml/kg). Aminoguanidine (100 mg/kg) was injected intraperitioneally 30 minutes after ANP induction, tienam (60 mg/kg) was injected intraperitioneally 6 hours after ANP induction. The mice were killed at 48 hours, and serum amylase, serum D- lactate, pancreatic MPO were measured. Pathological alterations in the pancreas were examed. The pancreas, liver, blood, mesenteric lymph node and ascites were collected for microbiological study. Results In group C and E, the levels of serum amylase were 91173.30±199.73) U/L and (1075.00±200.40) U/L; the serum D-lactate were (7.165±1.2533) μg/ml and (6.980±1.060)μg./ml; the pancreatic MPO were (0.8035±0.0711) U/g wet film and (0.7765±0.0843 ) U/g wet film; the average bacterial positive rates were 20% and 16%. In group B, the serum amylase was (2234.60±692.06 )U/L;the serum D-lactate was (12.408±1.779)μg,/ml, the pancreatic MPO was (1.5942±0.1965) U/g wet film; the average bacterial positive rate were 60%. The differences between group C, E and group B were statistically significant (P＜ 0.05). In group D, the pancreatic MPO was (0.8002±0.0603 ) U/g wet film and the the average bacterial positive rate was 18%, and they were statistically different when compared with those of group B (P±0.05). While in group D, the serum amylase and D-lactate was not statistically different when compared with those of group B (P＞0.05). There were lamellar necrosis in the parenchyma, hyperaemia and leukocytic infiltrate in the pancreatic mesenchyma in the ANP group, while no leukocytic infiltrating in group C, D, E was found. Conclusions The aminoguanidine and tienam might decrease gut bacterial translocation and prevent pancreatic infection in ANP.