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Identification of potential biomarkers and candidate smallmolecule drugs for heart failure via comprehensive gene microarray analysis 通过综合基因微阵列分析鉴定心力衰竭的潜在生物标志物和候选小分子药物
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.7
Hailang Liu, Chunyang Yu, Zhongcheng Wei, Qing Zhang
Purpose: To identify potential novel biomarkers and to explore new small-molecule drugs for heart failure (HF). Methods: The Gene Expression Omnibus (GEO) microarray datasets were downloaded for analyzing the differentially expressed genes  (DEGs). Venn analysis was performed to calculate the overlapping genes which were then used for Gene Ontology (GO) analysis, and  Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using cluster Profiler in R package; a protein-protein interaction network (PPI) was constructed using STRING database. The hub genes were selected for small-molecule drug identification, while molecular  docking of small-molecule drugs and hub genes was performed using CBdock2. Results: Upregulated and downregulated DEGs were  obtained from GSE84796, GSE107569 and GSE116250 datasets, respectively. Eleven (11) overlapping genes, which were enriched in  collagen fiber tissue, collagen-containing extracellular matrix and collagen fiber-related pathways, were also enriched in AGE-RAGE and  relaxin signaling pathways. The PPI network of the DEGs was constructed, and five hub genes, with high connectivity, were significantly  upregulated in HF. The five hub genes were ranked as MFAP4, LTBP2, THBS4, COL3A1 and COL1A1. Two targets (COL1A1 and COL3A1) matched potential drugs, and fostamatinib shared by the two targets had the greatest therapeutic value for HF. Conclusion: Five novel  biomarkers and involved signaling pathways have been identified in HF via comprehensive microarray analyses. The results also show  that fostamatinib might be a promising drug candidate for HF treatment
目的:鉴定潜在的新型生物标志物,探索治疗心力衰竭(HF)的新小分子药物。方法:下载GEO微阵列数据集,分析差异表达基因(DEGs)。利用R包中的聚类分析器对重叠基因进行维恩分析和京都基因与基因组百科全书(KEGG)分析;利用STRING数据库构建蛋白质-蛋白质相互作用网络(PPI)。选择中心基因进行小分子药物鉴定,利用CBdock2. 结果:从GSE84796、GSE107569和GSE116250数据集中分别获得了上调和下调的deg。在胶原纤维组织、含胶原细胞外基质和胶原纤维相关通路中富集的11个重叠基因也在AGE-RAGE和relaxin信号通路中富集。构建了deg的PPI网络,其中5个具有高连通性的枢纽基因在HF中显著上调。5个中心基因依次为MFAP4、LTBP2、THBS4、COL3A1和COL1A1。两个靶点(COL1A1和COL3A1)匹配潜在药物,两个靶点共用的福司他替尼对HF的治疗价值最大。 结论:通过全面的微阵列分析,已经在HF中发现了五种新的生物标志物和相关的信号通路。结果还表明,福司他替尼可能是一种有希望的HF治疗候选药物
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引用次数: 0
Effectiveness of the combination of terbutaline and budesonide inhalation in treating acute bronchial asthma during pregnancy 特布他林联合布地奈德吸入治疗妊娠期急性支气管哮喘的疗效观察
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.26
Guozhi Zhang, Lina Zhou, Shanshan Guo, Mei Wang, Ling Han
Purpose: To investigate the therapeutic benefits of terbutaline sulfate aerosol inhalation combined with budesonide, and its influence on pulmonary function in pregnant women suffering from acute bronchial asthma attacks. Methods: A total of 100 pregnant patients diagnosed with acute bronchial asthma in PLA Strategic Support Force Characteristic Medical Center, Beijing, China were divided into control and study groups (n = 50 each). Control group received aerosol inhalation of normal saline along with standard treatments, viz, oxygen inhalation, sputum aspiration, anti-infection measures, and maintenance of water- electrolyte balance. Study group received combined terbutaline sulfate and budesonide aerosol inhalation in addition to standard treatment. Both groups underwent a 7-day treatment course, with inhalation therapy twice daily. Results: Study group showed significantly shorter relief times for cough, wheezing, and chest tightness compared to control group (p < 0.05). After treatment, 92.0 % of patients in study group exhibited improvement or relief from their symptoms, compared to 80.0 % in control group (p < 0.05). Pulmonary function indices, including first vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and FEV1/FVC, improved in both groups after treatment. Study group exhibited significantly lower laboratory indices, including immunoglobulin E (IgE), C-reactive protein (CRP), and eosinophils (EOS) compared to control group (p < 0.05). Conclusion: The combination of inhalation therapy of terbutaline sulfate with budesonide in pregnant women experiencing acute bronchial asthma demonstrates significant enhancements in clinical effectiveness, pulmonary function, and laboratory parameters. Clinical trials of this combined therapy should be carried out in other locations to ascertain the effect of population variation on treatment efficacy.
目的:探讨硫酸特布他林雾化吸入联合布地奈德对急性支气管哮喘发作孕妇肺功能的影响及疗效。方法:选取北京解放军战略支援部队特色医学中心诊断为急性支气管哮喘的孕妇100例,分为对照组和研究组各50例。对照组患者雾化吸入生理盐水,同时给予标准治疗,即吸氧、吸痰、抗感染、维持水电解质平衡。研究组在标准治疗的基础上给予硫酸特布他林联合布地奈德雾化吸入。两组均接受为期7天的疗程,吸入治疗每日2次。结果:与对照组相比,研究组咳嗽、喘息和胸闷的缓解时间明显缩短(p <0.05)。治疗后,研究组92.0%的患者症状改善或缓解,对照组为80.0% (p <0.05)。治疗后两组肺功能指标,包括第一肺活量(FVC)、每秒用力呼气量(FEV1)、呼气峰流量(PEF)、FEV1/FVC均有改善。与对照组相比,研究组的免疫球蛋白E (IgE)、c反应蛋白(CRP)和嗜酸性粒细胞(EOS)等实验室指标明显降低(p <0.05)强生# x0D;结论:硫酸特布他林联合布地奈德吸入治疗急性支气管哮喘孕妇在临床疗效、肺功能和实验室参数方面均有显著提高。这种联合治疗的临床试验应在其他地区进行,以确定人群差异对治疗效果的影响。
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引用次数: 0
Effect of 20-hydroxyecdysone and its metabolites in the absence or presence of IGF-1 on regulation of skeletal muscle cell growth IGF-1缺失或存在情况下,20-羟基蜕皮激素及其代谢物对骨骼肌细胞生长的调控作用
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.11
Kanokwan Suhatcho, Boon-ek Yingyongnarongkul, Saowanee Kumpun, Ratchakrit Srikuea
Purpose: To investigate the effect of 20-hydroxyecdysone (20E) and its metabolites and their synergistic effect with IGF-1 on regulation of skeletal muscle cell growth. Methods: Mouse skeletal muscle cell line (C2C12) was solely treated with 20E and its metabolites (14- deoxy- 20-hydroxyecdysone, poststerone, and 14-deoxypoststerone) at doses of 0.1, 1, and 10 µM or co-treated with IGF-1 (10 ng/ml). Cell viability and proliferative capacity were evaluated using MTT and BrdU incorporation assays, respectively. Myogenic differentiation proteins [embryonic myosin heavy chain (EbMHC) and MHC], androgen receptor (AR), and IGF-1 receptor (IGF-1R) protein expression were investigated using immunocytochemistry. Results: Treatments of 20E and its metabolites had no toxicity on skeletal muscle cells or induced AR/IGF-1R expression. In addition, solely treatment of 20E and its metabolites or co-treatment with IGF-1 had no significant effect on cell proliferation and myogenic differentiation capacity. In contrast, IGF-1 treatment alone significantly increased EbMHC expression (p<0.0001), MHC expression (p<0.05), and myotube number (p<0.05). Conclusion: These results indicate that 20E and its metabolites have no direct or synergistic effect with IGF-1 on skeletal muscle cell growth. Nevertheless, the pharmacological effects of 20E on skeletal muscle mass and strength in vivo that raises its therapeutic potential may associate with its indirect action.
目的:探讨20-羟基脱皮激素(20E)及其代谢产物对骨骼肌细胞生长的调控作用及其与IGF-1的协同作用。方法:小鼠骨骼肌细胞系(C2C12)分别以0.1、1和10 μ M剂量的20E及其代谢物(14-脱氧- 20-羟基脱皮酮、后睾酮和14-脱氧后睾酮)单独处理或与IGF-1 (10 ng/ml)共处理。分别用MTT和BrdU掺入法评价细胞活力和增殖能力。采用免疫细胞化学方法检测肌原分化蛋白[胚胎肌球蛋白重链(EbMHC)和MHC]、雄激素受体(AR)和IGF-1受体(IGF-1R)蛋白的表达。 结果:20E及其代谢物对骨骼肌细胞没有毒性作用,也没有诱导AR/IGF-1R的表达。此外,单独处理20E及其代谢物或与IGF-1共同处理对细胞增殖和成肌分化能力无显著影响。相比之下,单独使用IGF-1可显著增加EbMHC表达(p<0.0001)、MHC表达(p<0.05)和肌管数量(p<0.05)。结论:20E及其代谢物与IGF-1对骨骼肌细胞生长无直接或协同作用。然而,20E对体内骨骼肌质量和力量的药理作用,提高了其治疗潜力,可能与其间接作用有关。
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引用次数: 0
Ozone exposure induces cough hypersensitivity in mice 臭氧暴露引起小鼠咳嗽过敏
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.14
Tinglei Li, Shu Zhang, Xuemei Liu, Tianyuan Xin, Yu Chen, Zhe Chen
Purpose: To study the influence of O3 exposure on cough sensitivity, airway barrier function and airway inflammation in mice. Methods: Cough sensitivity was determined in healthy male C57/BL6 mice (aged 8 - 10 weeks) which were exposed to different concentrations of O3 (0.5 - 2 ppm) for 3 h daily for 9 days. Hematoxylin and eosin (H&E) staining of lung tissues, collection of BALF, and cell count were carried out. Inflammatory factor levels in pulmonary tissues were determined by enzyme-linked immunosorbent assay (ELISA), while Western blotting was used to assay TRPA1 and Claudin-1 protein expressions in lung tissues. Results: After 9 days of mice exposure to O3, cough sensitivity increased significantly, and TRPA1 protein was increased in pulmonary tissues, with exposure level of 1 ppm resulting in the highest level of TRPA1 protein expression. Claudin-1 expression in lung tissues of mice decreased after O3 exposure, especially in the groups exposed to O3 levels of 0.5 ppm and 2 ppm. The total cell count in alveolar lavage fluid of mice exposed to O3 was significantly increased (p < 0.05). In addition, O3 exposure increased IL-1α, IL-6 and TNF-α levels, with the most significant increase in the 0.5 ppm group (p < 0.05). Results from histology revealed that all mice had inflammatory reactions and destruction of lung tissues after O3 exposure. Conclusion: Exposure to O3 induces disruption of airway barrier function, infiltration of the airway by inflammatory cells, and increased secretion of inflammatory factors, thereby resulting in enhanced cough sensitivity.
目的:研究O3暴露对小鼠咳嗽敏感性、气道屏障功能及气道炎症的影响。 方法:对健康雄性C57/BL6小鼠(8 ~ 10周龄),每天暴露于不同浓度的O3 (0.5 ~ 2 ppm) 3 h,连续9 d,测定其咳嗽敏感性。肺组织苏木精和伊红(H&E)染色,BALF收集,细胞计数。采用酶联免疫吸附法(ELISA)检测肺组织中炎症因子水平,Western blotting检测肺组织中TRPA1、Claudin-1蛋白表达。 结果:小鼠暴露于O3 9天后,咳嗽敏感性显著升高,肺组织中TRPA1蛋白升高,暴露水平为1 ppm时,TRPA1蛋白表达水平最高。O3暴露后,小鼠肺组织中Claudin-1的表达下降,特别是在O3浓度为0.5 ppm和2 ppm的组中。暴露于O3的小鼠肺泡灌洗液中细胞总数显著增加(p <0.05)。此外,O3暴露使IL-1α、IL-6和TNF-α水平升高,其中以0.5 ppm组升高最为显著(p <0.05)。组织学结果显示,所有小鼠暴露于O3后均出现炎症反应和肺组织破坏。 结论:O3暴露可导致气道屏障功能破坏,炎症细胞浸润气道,炎性因子分泌增加,从而导致咳嗽敏感性增强。
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引用次数: 0
Efficacy of phentolamine combined with milrinone on severe pneumonia in children, and its effect on serum levels of MMP-9, TIMP-1 and sICAM-1 酚妥拉明联合米力酮治疗儿童重症肺炎的疗效及对血清MMP-9、TIMP-1、sICAM-1水平的影响
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.16
Jianbiao Chen, Hualong Lv, Zhimian Liang
Purpose: To investigate the effect of the co-administration of phentolamine and milrinone on severe pneumonia in children, as well as on serum MMP-9, TIMP-1 and sICAM-1 levels. Methods: From January 2021 to January 2022, 100 patients diagnosed with severe pneumonia were randomly divided into 2 groups; the control group received oxygen inhalation and other symptomatic treatment, while the study group received phentolamine concurrently with milrinone, Serum MMP-9, TIMP-1, sICAM-1 levels and clinical efficacy were determined in the two groups before and after treatment. Results: After treatment, there were significant differences in IL-6, IL-10, and TNF-α levels between the study group and the control group. Furthermore, IgA, IgG, and IgM levels in both groups were significantly higher after treatment than before treatment (p < 0.05). The study group exhibited significant differences in MMP-9, TIMP-1, and sICAM-1 levels after treatment compared to control group (p < 0.05). Healing and therapeutic effectiveness in the study group was 76 %, which was significantly greater than in the control group (48 %; p = 0.000). Additionally, total treatment effectiveness in the study group was 92 %, which was significantly higher than in the control group (80 %; p = 0.015). After treatment, the PEF, FRC, and TEF25 % in the study group were significantly higher than in the control group (p < 0.05). Conclusion: Co-administration of phentolamine and milrinone is highly effective for the treatment of severe pneumonia in children, and significantly reduces the levels of serum MMP-9, TIMP-1 and sICAM-1. However, multi-center clinical trials should be carried out prior to the adoption of this treatment mode in clinical practice.
目的:探讨酚妥拉明与米力酮合用治疗儿童重症肺炎的疗效及对血清MMP-9、TIMP-1、sICAM-1水平的影响。方法:于2021年1月~ 2022年1月将100例确诊为重症肺炎的患者随机分为2组;对照组给予吸氧等对症治疗,研究组给予酚妥拉明联合米力酮治疗,测定两组患者治疗前后血清MMP-9、TIMP-1、sICAM-1水平及临床疗效。 结果:治疗后,研究组患者IL-6、IL-10、TNF-α水平与对照组比较差异均有统计学意义。治疗后两组患者IgA、IgG、IgM水平均显著高于治疗前(p <0.05)。与对照组相比,研究组治疗后MMP-9、TIMP-1和sICAM-1水平有显著差异(p <0.05)。研究组的治愈率和治愈率为76%,显著高于对照组(48%;P = 0.000)。此外,研究组的总治疗有效性为92%,显著高于对照组(80%;P = 0.015)。治疗后,研究组PEF、FRC、tef25%均显著高于对照组(p <0.05)强生# x0D;结论:酚妥拉明与米力酮合用治疗儿童重症肺炎疗效显著,可显著降低血清MMP-9、TIMP-1、sICAM-1水平。但在临床应用该治疗模式前,需进行多中心临床试验。
{"title":"Efficacy of phentolamine combined with milrinone on severe pneumonia in children, and its effect on serum levels of MMP-9, TIMP-1 and sICAM-1","authors":"Jianbiao Chen, Hualong Lv, Zhimian Liang","doi":"10.4314/tjpr.v22i10.16","DOIUrl":"https://doi.org/10.4314/tjpr.v22i10.16","url":null,"abstract":"Purpose: To investigate the effect of the co-administration of phentolamine and milrinone on severe pneumonia in children, as well as on serum MMP-9, TIMP-1 and sICAM-1 levels.&#x0D; Methods: From January 2021 to January 2022, 100 patients diagnosed with severe pneumonia were randomly divided into 2 groups; the control group received oxygen inhalation and other symptomatic treatment, while the study group received phentolamine concurrently with milrinone, Serum MMP-9, TIMP-1, sICAM-1 levels and clinical efficacy were determined in the two groups before and after treatment.&#x0D; Results: After treatment, there were significant differences in IL-6, IL-10, and TNF-α levels between the study group and the control group. Furthermore, IgA, IgG, and IgM levels in both groups were significantly higher after treatment than before treatment (p < 0.05). The study group exhibited significant differences in MMP-9, TIMP-1, and sICAM-1 levels after treatment compared to control group (p < 0.05). Healing and therapeutic effectiveness in the study group was 76 %, which was significantly greater than in the control group (48 %; p = 0.000). Additionally, total treatment effectiveness in the study group was 92 %, which was significantly higher than in the control group (80 %; p = 0.015). After treatment, the PEF, FRC, and TEF25 % in the study group were significantly higher than in the control group (p < 0.05).&#x0D; Conclusion: Co-administration of phentolamine and milrinone is highly effective for the treatment of severe pneumonia in children, and significantly reduces the levels of serum MMP-9, TIMP-1 and sICAM-1. However, multi-center clinical trials should be carried out prior to the adoption of this treatment mode in clinical practice.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"91 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135685462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of the combination of minocycline and periodontal basic therapy in type 2 diabetes mellitus patients with chronic periodontitis 米诺环素联合牙周基础治疗2型糖尿病合并慢性牙周炎的疗效观察
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.17
Chuizhuang Chen, Shaodeng Li, Fuwen Xing
Purpose: To investigate the clinical efficacy of the combination of minocycline and periodontal basic treatment on type 2 diabetes mellitus (T2DM) patients with chronic periodontitis (CP) and its impact on inflammatory factors. Methods: A total of 90 T2DM patients with CP admitted to the Department of Stomatology in Hainan Medical College Second Affiliated Hospital, China from January 2020 to October 2022, were enrolled in this study and randomly assigned to two equal groups, viz, study and control group. Study group received minocycline in addition to routine hypoglycemic control and basic periodontal treatment, while control group received only routine hypoglycemic control and basic periodontal treatment. Treatment lasted for 8 weeks. Efficacy of the combination of minocycline and periodontal basic treatment of T2DM patients with CP in the two groups, as well as the periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (sulcus bleeding index, SBI), interleukin-36 (IL-36), interleukin-1β (IL1β), tumor necrosis factor-α (TNF-α), glycated hemoglobin (HbA1c) level, chewing function score, Oral Health Impact Profile-14 (OHIP-14) score, and incidence of adverse reactions before and after treatment were determined. Results: The effectiveness/efficacy of treatment in study group (91.11 %) was significantly higher than in control group (75.56 %, p < 0.05). After treatment, study group had reduced PD, PLI, and SBI scores than control group (p < 0.05). Study group also showed lower levels of IL-1β, IL-36, and TNF-α as well as reduced OHIP-14 score and a higher chewing function score than control group (p < 0.05). Conclusion: The combination of minocycline with periodontal basic treatment improves the efficacy in T2DM patients with CP, and reduces the level of inflammatory factors with a good margin of safety.
目的:探讨米诺环素联合牙周基础治疗治疗2型糖尿病(T2DM)合并慢性牙周炎(CP)的临床疗效及对炎症因子的影响。方法:选取2020年1月至2022年10月海南医学院第二附属医院口腔科收治的90例合并CP的T2DM患者,随机分为研究组和对照组。研究组在常规降糖和牙周基础治疗的基础上给予米诺环素治疗,对照组仅给予常规降糖和牙周基础治疗。治疗持续8周。米诺环素联合牙周基础治疗两组T2DM合并CP患者的疗效及牙周探诊深度(PD)、临床附著损失(CAL)、探诊出血(沟出血指数,SBI)、白细胞介素-36 (IL-36)、白细胞介素-1β (il -1β)、肿瘤坏死因子-α (TNF-α)、糖化血红蛋白(HbA1c)水平、咀嚼功能评分、口腔健康影响量表-14 (OHIP-14)评分、测定治疗前后不良反应发生率。 结果:研究组治疗有效率(91.11%)显著高于对照组(75.56%),p <0.05)。治疗后,研究组PD、PLI和SBI评分均低于对照组(p <0.05)。与对照组相比,研究组小鼠IL-1β、IL-36、TNF-α水平较低,OHIP-14评分较低,咀嚼功能评分较高(p <0.05)强生# x0D;结论:米诺环素联合牙周基础治疗可提高T2DM合并CP患者的疗效,降低炎症因子水平,且具有良好的安全边际。
{"title":"Efficacy of the combination of minocycline and periodontal basic therapy in type 2 diabetes mellitus patients with chronic periodontitis","authors":"Chuizhuang Chen, Shaodeng Li, Fuwen Xing","doi":"10.4314/tjpr.v22i10.17","DOIUrl":"https://doi.org/10.4314/tjpr.v22i10.17","url":null,"abstract":"Purpose: To investigate the clinical efficacy of the combination of minocycline and periodontal basic treatment on type 2 diabetes mellitus (T2DM) patients with chronic periodontitis (CP) and its impact on inflammatory factors.&#x0D; Methods: A total of 90 T2DM patients with CP admitted to the Department of Stomatology in Hainan Medical College Second Affiliated Hospital, China from January 2020 to October 2022, were enrolled in this study and randomly assigned to two equal groups, viz, study and control group. Study group received minocycline in addition to routine hypoglycemic control and basic periodontal treatment, while control group received only routine hypoglycemic control and basic periodontal treatment. Treatment lasted for 8 weeks. Efficacy of the combination of minocycline and periodontal basic treatment of T2DM patients with CP in the two groups, as well as the periodontal probing depth (PD), clinical attachment loss (CAL), bleeding on probing (sulcus bleeding index, SBI), interleukin-36 (IL-36), interleukin-1β (IL1β), tumor necrosis factor-α (TNF-α), glycated hemoglobin (HbA1c) level, chewing function score, Oral Health Impact Profile-14 (OHIP-14) score, and incidence of adverse reactions before and after treatment were determined.&#x0D; Results: The effectiveness/efficacy of treatment in study group (91.11 %) was significantly higher than in control group (75.56 %, p < 0.05). After treatment, study group had reduced PD, PLI, and SBI scores than control group (p < 0.05). Study group also showed lower levels of IL-1β, IL-36, and TNF-α as well as reduced OHIP-14 score and a higher chewing function score than control group (p < 0.05).&#x0D; Conclusion: The combination of minocycline with periodontal basic treatment improves the efficacy in T2DM patients with CP, and reduces the level of inflammatory factors with a good margin of safety.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"89 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135685385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxaliplatin regulates the autophagy of skin squamous cell carcinoma cell line through HMGB1 pathway 奥沙利铂通过HMGB1通路调节皮肤鳞状细胞癌细胞系的自噬
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.5
Lei Han, Jing Wang, Yu Xia, Jinping Maio, Juan Cao
Purpose: To determine the influence of oxaliplatin on skin squamous cell carcinoma cell line, and the involvement of autophagy- regulating pathway of high mobility group box 1 (HMGB1) in the process. Methods: A431 cells cultured in vitro were used. The cells were divided into groups A (treated with different concentrations of oxaliplatin) and B (treated with different concentrations of oxaliplatin combined with autophagy inhibitor 5 mmol/l3-ma). Changes in expression levels of autophagy marker molecules LC3-Ⅰ, LC3-Ⅱ, p62 and HMGB1 in A431 cells treated with different concentrations of oxaliplatin and different concentrations of HMGB1 were evaluated by Western blotting. Viability of A431 cells in both groups was assessed by CCK-8 assay. Results: With increase in oxaliplatin concentration, LC3-Ⅱ levels in A431 cells were up-regulated, p62 expression decreased, while autophagy level was increased significantly (p < 0.05). With increase in HMGB1 protein concentration, LC3-Ⅱ level in A431 cells was raised, while p62 level was reduced, while the level of autophagy was significantly increased (p < 0.05). Oxaliplatin treatment led to significantly higher expression level of HMGB1 in the experimental group than in the control group without oxaliplatin treatment. The viability of oxaliplatin-treated group was dose-dependently and significantly lower (p < 0.05) than that of the control group. Compared with the control group, the cell viability of the 3-mA + oxaliplatin group also showed a downward trend, and the decrease was greater than that of oxaliplatin-treated group (p < 0.05). Conclusion: Oxaliplatin upregulates autophagy by promoting HMGB1 protein expression, which may be a protective mechanism of tumor cells against oxaliplatin cytotoxicity thereby making HMGB1 protein a potential target in skin cancer therapy.
目的:探讨奥沙利铂对皮肤鳞状细胞癌细胞系的影响,以及自噬调节通路高迁移率组盒1 (HMGB1)在此过程中的参与情况。 方法:采用体外培养的A431细胞。将细胞分为A组(不同浓度奥沙利铂处理)和B组(不同浓度奥沙利铂联合自噬抑制剂5 mmol/l3-ma处理)。Western blotting检测不同浓度奥沙利铂和不同浓度HMGB1处理A431细胞后自噬标记分子LC3-Ⅰ、LC3-Ⅱ、p62和HMGB1表达水平的变化。CCK-8法检测两组A431细胞活力。 结果:随着奥沙利铂浓度的升高,A431细胞LC3-Ⅱ水平上调,p62表达降低,自噬水平显著升高(p <0.05)。随着HMGB1蛋白浓度的升高,A431细胞中LC3-Ⅱ水平升高,p62水平降低,自噬水平显著升高(p <0.05)。奥沙利铂治疗后,实验组HMGB1表达水平明显高于未治疗的对照组。奥沙利铂治疗组细胞活力呈剂量依赖性,且显著降低(p <0.05),显著高于对照组。与对照组相比,3-mA +奥沙利铂治疗组细胞活力也呈下降趋势,且下降幅度大于奥沙利铂治疗组(p <0.05)强生# x0D;结论:奥沙利铂通过促进HMGB1蛋白表达上调自噬,这可能是肿瘤细胞对抗奥沙利铂细胞毒性的保护机制,从而使HMGB1蛋白成为治疗皮肤癌的潜在靶点。
{"title":"Oxaliplatin regulates the autophagy of skin squamous cell carcinoma cell line through HMGB1 pathway","authors":"Lei Han, Jing Wang, Yu Xia, Jinping Maio, Juan Cao","doi":"10.4314/tjpr.v22i10.5","DOIUrl":"https://doi.org/10.4314/tjpr.v22i10.5","url":null,"abstract":"Purpose: To determine the influence of oxaliplatin on skin squamous cell carcinoma cell line, and the involvement of autophagy- regulating pathway of high mobility group box 1 (HMGB1) in the process.&#x0D; Methods: A431 cells cultured in vitro were used. The cells were divided into groups A (treated with different concentrations of oxaliplatin) and B (treated with different concentrations of oxaliplatin combined with autophagy inhibitor 5 mmol/l3-ma). Changes in expression levels of autophagy marker molecules LC3-Ⅰ, LC3-Ⅱ, p62 and HMGB1 in A431 cells treated with different concentrations of oxaliplatin and different concentrations of HMGB1 were evaluated by Western blotting. Viability of A431 cells in both groups was assessed by CCK-8 assay.&#x0D; Results: With increase in oxaliplatin concentration, LC3-Ⅱ levels in A431 cells were up-regulated, p62 expression decreased, while autophagy level was increased significantly (p < 0.05). With increase in HMGB1 protein concentration, LC3-Ⅱ level in A431 cells was raised, while p62 level was reduced, while the level of autophagy was significantly increased (p < 0.05). Oxaliplatin treatment led to significantly higher expression level of HMGB1 in the experimental group than in the control group without oxaliplatin treatment. The viability of oxaliplatin-treated group was dose-dependently and significantly lower (p < 0.05) than that of the control group. Compared with the control group, the cell viability of the 3-mA + oxaliplatin group also showed a downward trend, and the decrease was greater than that of oxaliplatin-treated group (p < 0.05).&#x0D; Conclusion: Oxaliplatin upregulates autophagy by promoting HMGB1 protein expression, which may be a protective mechanism of tumor cells against oxaliplatin cytotoxicity thereby making HMGB1 protein a potential target in skin cancer therapy.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"91 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135685458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of diquafosol sodium combined with M22 optimized pulsed light in the treatment of dry eye due to meibomian gland dysfunction 双喹fosol钠联合M22优化脉冲光治疗睑板腺功能障碍所致干眼症的疗效观察
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.18
Xiaodan Huang, Degui Wang, Dusheng Lin, Zhaotao Zhou
Purpose: To determine the efficacy and safety of 3 % diquafosol sodium combined with M22 optimized pulse light (OPT) in the treatment of dry eye due to meibomian gland dysfunction (MGD). Methods: Data from 97 dry eye patients admitted to Shantou Balder Eye Hospital with MGD-induced dry eye illness between August 2019 and June 2021 were retrospectively reviewed and analyzed. Patients meeting MGD diagnostic criteria in ophthalmology and exhibiting MGD-induced dry eye signs were split into two groups. The medication group (43 cases) received 3 % diquafosol sodium eye drops six times a day for three months, while the pulsed light group (44 cases) underwent three M22 OPT sessions at one-month intervals. Treatment efficacy of the two methods were compared by assessing changes in ocular surface, symptom severity, inflammatory factors (hs-CRP, IL-8, IL-1β), and quality of life before and three months after treatment commenced. Adverse reactions were also recorded. Results: Pulsed light group showed a slightly higher (but not significant) total effective rate (95.45 %) than the medication group (93.02 %; p > 0.05). Three months post-treatment, both groups exhibited significant improvements in various indicators such as FL, OSDI, symptom scores, tear biomarker levels, and overall eye health (p < 0.05). The incidence of adverse reactions was similar between the medication (4.65 %) and pulsed light (9.09 %) groups. Conclusion: Treatment with 3 % diquafosol sodium and M22 OPT for MGD-induced dry eye yields comparable efficacy and safety, improving symptoms, ocular surface function, reducing inflammation, and enhancing quality of life. However, 3 % diquafosol sodium shows better patient tolerance and fewer adverse reactions, but further research is needed due to the limited number of patients in this study.
目的:探讨3%双氟泊钠联合M22优化脉冲光(OPT)治疗睑板腺功能障碍(MGD)型干眼症的疗效和安全性。方法:回顾性分析2019年8月至2021年6月汕头市巴尔德眼科医院收治的97例mgd性干眼症患者的资料。符合MGD眼科诊断标准并表现出MGD干眼体征的患者分为两组。药物治疗组(43例)每天6次使用3%双氟索钠滴眼液,持续3个月,而脉冲光治疗组(44例)每隔一个月接受3次M22 OPT治疗。比较两种治疗方法治疗前和治疗后3个月的眼表变化、症状严重程度、炎症因子(hs-CRP、IL-8、IL-1β)和生活质量的变化。不良反应也有记录。 结果:脉冲光组总有效率(95.45%)略高于药物组(93.02%),但差异不显著;p比;0.05)。治疗3个月后,两组在各种指标上均有显著改善,如FL、OSDI、症状评分、泪液生物标志物水平和整体眼睛健康(p <0.05)。药物组不良反应发生率为4.65%,脉冲光组不良反应发生率为9.09%。 结论:3%双喹fosol钠联合M22 OPT治疗mgd性干眼症疗效和安全性相当,可改善症状和眼表功能,减轻炎症,提高生活质量。然而,3%双喹fosol钠表现出更好的患者耐受性和更少的不良反应,但由于本研究中患者数量有限,需要进一步研究。
{"title":"Efficacy of diquafosol sodium combined with M22 optimized pulsed light in the treatment of dry eye due to meibomian gland dysfunction","authors":"Xiaodan Huang, Degui Wang, Dusheng Lin, Zhaotao Zhou","doi":"10.4314/tjpr.v22i10.18","DOIUrl":"https://doi.org/10.4314/tjpr.v22i10.18","url":null,"abstract":"Purpose: To determine the efficacy and safety of 3 % diquafosol sodium combined with M22 optimized pulse light (OPT) in the treatment of dry eye due to meibomian gland dysfunction (MGD).&#x0D; Methods: Data from 97 dry eye patients admitted to Shantou Balder Eye Hospital with MGD-induced dry eye illness between August 2019 and June 2021 were retrospectively reviewed and analyzed. Patients meeting MGD diagnostic criteria in ophthalmology and exhibiting MGD-induced dry eye signs were split into two groups. The medication group (43 cases) received 3 % diquafosol sodium eye drops six times a day for three months, while the pulsed light group (44 cases) underwent three M22 OPT sessions at one-month intervals. Treatment efficacy of the two methods were compared by assessing changes in ocular surface, symptom severity, inflammatory factors (hs-CRP, IL-8, IL-1β), and quality of life before and three months after treatment commenced. Adverse reactions were also recorded.&#x0D; Results: Pulsed light group showed a slightly higher (but not significant) total effective rate (95.45 %) than the medication group (93.02 %; p > 0.05). Three months post-treatment, both groups exhibited significant improvements in various indicators such as FL, OSDI, symptom scores, tear biomarker levels, and overall eye health (p < 0.05). The incidence of adverse reactions was similar between the medication (4.65 %) and pulsed light (9.09 %) groups.&#x0D; Conclusion: Treatment with 3 % diquafosol sodium and M22 OPT for MGD-induced dry eye yields comparable efficacy and safety, improving symptoms, ocular surface function, reducing inflammation, and enhancing quality of life. However, 3 % diquafosol sodium shows better patient tolerance and fewer adverse reactions, but further research is needed due to the limited number of patients in this study.","PeriodicalId":23347,"journal":{"name":"Tropical Journal of Pharmaceutical Research","volume":"89 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135685382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of diclofenac emulgel prepared with sesame oil as a lipophilic carrier 以香油为亲脂载体制备双氯芬酸凝胶的研究
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.1
Zwanden Sule Yahaya, Latifat Oyiza Otaru, Boma Blessing Mohammed, Olutayo Ademola Adeleye, Na'anman Charles Dagogot, Idris Abdullahi
Purpose: To investigate the suitability of sesame oil as an oily phase for diclofenac emulgel formulation. Methods: Different batches of emulgel comprising different proportions of oils (sesame oil and/or Labrafac CC), surfactants (Tween-80 and/or cremophor EL-30), and gelling agents (xanthan gum or gelatin) were prepared. The formulations were evaluated for rheology, syneresis, Fourier transform infrared (FTIR) spectroscopy, spreadability, extrudability, and anti-inflammatory activity. Results: Product characteristics of batches A2, A4, and A6 were not consistent with those of emulgels. Because Batch A1 showed characteristics that were the most stable, such as no pH changes, nonstatistically significant changes (p = 1.000) in the viscosity results, and least spectrum changes following FTIR investigation, it was selected as the best batch. It showed similar anti-inflammatory activity when compared with commercially available diclofenac emulgel, giving a 50 % higher anti-inflammatory effect than aqueous diclofenac dispersion. Conclusion: Sesame oil is a potential lipophilic component in emulgel formulations for topical delivery of hydrophobic drugs.
目的:考察芝麻油作为双氯芬酸乳状剂油相的适宜性。方法:制备由不同比例的油(芝麻油和/或Labrafac CC)、表面活性剂(Tween-80和/或cremophor EL-30)和胶凝剂(黄原胶或明胶)组成的不同批次的凝胶。对配方进行了流变性、协同作用、傅里叶变换红外光谱(FTIR)、铺展性、挤压性和抗炎活性的评价。结果:A2、A4、A6批的产品特性与乳剂不一致。由于A1批次表现出最稳定的特性,如没有pH变化,粘度结果变化无统计学意义(p = 1.000), FTIR调查后光谱变化最小,因此被选为最佳批次。与市售双氯芬酸乳液相比,它显示出类似的抗炎活性,比双氯芬酸水分散液的抗炎效果高50%。& # x0D;结论:芝麻油是一种潜在的亲脂性成分,可用于局部递送疏水药物的凝胶制剂。
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引用次数: 0
Effect of dexmedetomidine on convalescence quality after general anesthesia and postoperative delirium, and on cognitive function in elderly patients undergoing lower limb surgery 右美托咪定对老年下肢手术患者全身麻醉后恢复期质量及术后谵妄的影响
4区 医学 Q4 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-06 DOI: 10.4314/tjpr.v22i10.22
Wenbo Wei, Lele Guo
Purpose: To investigate the effect of different doses of dexmedetomidine on the quality of postoperative recovery, incidence of postoperative delirium, and cognitive function in elderly patients undergoing lower limb surgery. Methods: A total of 112 patients who received treatment in the Department of Anesthesiology, Affiliated Hospital of Inner Mongolia Medical University, Hothot, China from January 2021 to January 2023 were divided into 3 groups, consisting of low-dose group (35 patients received 0.2 mg/kg), medium-dose group (39 patients received 0.4 mg/kg), and high-dose group (38 patients received 0.6 mg/kg). Parameters including, convalescence quality of general anesthesia, incidence of postoperative delirium, adverse reactions, Mini- mental State Examination (MMSE) scores, sedation effect (Ramsay), analgesia effect (visual analogue scale (VAS)), and stress indices, viz, norepinephrine (NE), epinephrine (E), and cortisol (COR) levels), were evaluated and compared. Results: There was no significant difference in tracheal extubation time, recovery time of spontaneous breathing, calling eye-opening time, or full awakening time among the three groups (p > 0.05). However, MMSE score was significantly higher in low-dose group on days 1 and 3 after surgery (p < 0.05) and VAS scores were significantly higher in low-dose group at 12 and 24 h after recovery compared to other groups (p < 0.05). Ramsay score was significantly higher in high-dose group (p < 0.05). Levels of NE, E, and COR were significantly lower in medium-dose group compared to other groups (p < 0.05). Incidence of adverse reactions were significantly lower in low and medium-dose groups compared to high- dose group (p < 0.05). Conclusion: Medium-dose dexmedetomidine demonstrates favorable sedative and analgesic effects with minimal impact on cognitive function and stress response in elderly patients undergoing lower limb surgery. Furthermore, it does not affect quality of postoperative recovery nor incidence of postoperative delirium. More large-scale, randomized controlled studies are needed to confirm these results.
目的:探讨不同剂量右美托咪定对老年下肢手术患者术后恢复质量、谵妄发生率及认知功能的影响。 方法:选取2021年1月~ 2023年1月内蒙古医科大学附属医院麻醉科收治的112例患者,分为低剂量组(35例,0.2 mg/kg)、中剂量组(39例,0.4 mg/kg)、高剂量组(38例,0.6 mg/kg)。对全麻恢复期质量、术后谵妄发生率、不良反应、精神状态检查(MMSE)评分、镇静效果(Ramsay)、镇痛效果(视觉模拟量表(VAS))、应激指标(去甲肾上腺素(NE)、肾上腺素(E)、皮质醇(COR)水平)进行评价和比较。 结果:三组患者气管拔管时间、自主呼吸恢复时间、睁眼时间、完全清醒时间差异均无统计学意义(p >0.05)。低剂量组术后第1、3天MMSE评分显著高于对照组(p <低剂量组在恢复后12、24 h的VAS评分显著高于其他组(p <0.05)。高剂量组Ramsay评分显著高于对照组(p <0.05)。中剂量组NE、E、COR水平明显低于其他组(p <0.05)。低、中剂量组不良反应发生率明显低于高剂量组(p <0.05)强生# x0D;结论:中剂量右美托咪定对老年下肢手术患者具有良好的镇静镇痛作用,对认知功能和应激反应的影响最小。此外,它不影响术后恢复质量,也不影响术后谵妄的发生率。需要更多大规模的随机对照研究来证实这些结果。
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引用次数: 0
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Tropical Journal of Pharmaceutical Research
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