Pub Date : 2024-05-08eCollection Date: 2024-04-01DOI: 10.1177/15593258241251594
Zheng Yang, Tiantian Hao, Junbing Ma, Dan Yang, Min Qiu, Rui Wang
Background: Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo.
Objective: This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation.
Methods: We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the "drug or disease-target" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1β in the lungs through many pathways and targets.
Conclusion: This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.
背景：急性肺损伤（ALI）是一种严重的疾病，可供选择的治疗方法很少。刺蒺藜甙是从中国刺蒺藜植物中提取的一种天然类黄酮，可有效解决头痛、头晕、瘙痒和白癜风等多种健康问题：本研究旨在通过网络药理学和实验验证相结合的方法，探索刺蒺藜苷治疗 ALI 的作用机制：方法：我们从PubChem数据库中获得了曲布洛苷的二维结构和SMILES编号。我们使用SwissTargetPrediction数据库识别药理学靶点。通过检查 GeneCards 数据库，我们发现了 1215 个与 ALI 相关的靶点。我们使用 String 数据库和 Cytoscape 软件创建了 "药物或疾病-靶点 "网络以及蛋白质-蛋白质相互作用 (PPI)。通过评估相关的生物过程和通路富集度，我们确定了关键靶点。维尼图显示三拗苷与 ALI 之间有 49 个交叉点。使用 AutoDockTools 进行分子对接发现，Tribuloside 与 IL6、BCL2、TNF、STAT3、IL1B 和 MAPK3 有很高的亲和力，而这 6 个目标是 PPI 网络中 Degree 值最高的目标。为了测试三拗苷对 ALI 的疗效，研究人员使用脂多糖构建了小鼠急性肺损伤模型。结果显示，三拗皂苷通过多种途径和靶点减少了炎症细胞浸润，降低了纤维化面积，修复了受损肺泡，抑制了肺部炎症因子IL-6、TNF-α和IL-1β：本研究揭示，根据网络药理学预测和实验证实，三拗皂苷可通过靶向多种途径和靶点治疗 ALI。
{"title":"Tribuloside: Mechanisms and Efficacy in Treating Acute Lung Injury Revealed by Network Pharmacology and Experimental Validation.","authors":"Zheng Yang, Tiantian Hao, Junbing Ma, Dan Yang, Min Qiu, Rui Wang","doi":"10.1177/15593258241251594","DOIUrl":"10.1177/15593258241251594","url":null,"abstract":"<p><strong>Background: </strong>Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo.</p><p><strong>Objective: </strong>This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation.</p><p><strong>Methods: </strong>We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the \"drug or disease-target\" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1β in the lungs through many pathways and targets.</p><p><strong>Conclusion: </strong>This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint.
Methods: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells.
Results: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner.
Conclusion: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.
{"title":"Collaborative Study of Thresholds for Mutagens: Adaptive Responses in the Micronucleus Test and Gene Induction by Mutagenic Treatments.","authors":"Shizuyo Sutou, Akiko Koeda, Kana Komatsu, Toshiyuki Shiragiku, Hiroshi Seki, Toshiyuki Kudo","doi":"10.1177/15593258241252040","DOIUrl":"10.1177/15593258241252040","url":null,"abstract":"<p><strong>Background: </strong>We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint.</p><p><strong>Methods: </strong>The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells.</p><p><strong>Results: </strong>When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H<sub>2</sub>O<sub>2</sub> using TK6 cells, two genes, <i>GADD45 A</i> and <i>P21</i>, were induced in a dose- and time-dependent manner.</p><p><strong>Conclusion: </strong>Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1177/15593258241248931
Haojing Xiong, Hechen Xu, Yang Yang, Bailong Hu, Ke Jiang, Xiaohua Zou
ObjectiveCiprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED50) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil.MethodsWe studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1 μg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4 mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T0-T7).ResultsIn the group A, when combined with 0.1 μg/kg sufentanil, the ED50 of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23 mg/kg, and the 95% CI was 0.09∼0.30 mg/kg; in the group B, the ED50 was 0.18 mg/kg, and the 95% CI was 0.13∼0.22 mg/kg.ConclusionThe ED50 of ciprofol in combination with sufentanil (0.1 μg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23 mg/kg in group A and 0.18 mg/kg in group B.
{"title":"Median Effective Dose of Ciprofol Combined With Sufentanil for Inhibiting the Upper Gastrointestinal Endoscopic Placement Reaction in Elderly Patients","authors":"Haojing Xiong, Hechen Xu, Yang Yang, Bailong Hu, Ke Jiang, Xiaohua Zou","doi":"10.1177/15593258241248931","DOIUrl":"https://doi.org/10.1177/15593258241248931","url":null,"abstract":"ObjectiveCiprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED<jats:sub>50</jats:sub>) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil.MethodsWe studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1 μg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4 mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T<jats:sub>0</jats:sub>-T<jats:sub>7</jats:sub>).ResultsIn the group A, when combined with 0.1 μg/kg sufentanil, the ED<jats:sub>50</jats:sub> of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23 mg/kg, and the 95% CI was 0.09∼0.30 mg/kg; in the group B, the ED<jats:sub>50</jats:sub> was 0.18 mg/kg, and the 95% CI was 0.13∼0.22 mg/kg.ConclusionThe ED<jats:sub>50</jats:sub> of ciprofol in combination with sufentanil (0.1 μg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23 mg/kg in group A and 0.18 mg/kg in group B.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140799514","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}
The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 μg·kg−1·h−1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 μg·kg−1·h−1 (95% CI: .29–.35) and .48 μg·kg−1·h−1 (95% CI: .44–.56), respectively. Probit(p) = −2.84 + 9.28 × ln (Dose), (χ2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.
{"title":"The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial","authors":"BaiYun Wei, CuiYu Yu, JinBo Xiao, Huang Xu, Ping Zheng, WeiBing Wang","doi":"10.1177/15593258241248919","DOIUrl":"https://doi.org/10.1177/15593258241248919","url":null,"abstract":"The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 μg·kg<jats:sup>−1</jats:sup>·h<jats:sup>−1</jats:sup>. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 μg·kg<jats:sup>−1</jats:sup>·h<jats:sup>−1</jats:sup> (95% CI: .29–.35) and .48 μg·kg<jats:sup>−1</jats:sup>·h<jats:sup>−1</jats:sup> (95% CI: .44–.56), respectively. Probit(p) = −2.84 + 9.28 × ln (Dose), (χ<jats:sup>2</jats:sup> = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624650","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}
Pub Date : 2024-04-18DOI: 10.1177/15593258241247980
Ahlam M. Alhusaini, Hanan K. Alghibiwi, Wedad S. Sarawi, Juman S. Alsaab, Samiyah M. Alshehri, Qamraa H. Alqahtani, Aliah R. Alshanwani, Ebtesam A. Aljassas, Ebtesam N. Alsultan, Iman H. Hasan
Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50 mg/kg, s.c.) twice a week for 2 weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20 mg/kg/day, p.o.) along with ISO for 2 weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14 days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis.
异丙肾上腺素（ISO）是一种化学合成的儿茶酚胺，属于β肾上腺素受体激动剂，用于治疗心动过缓。β肾上腺素能激动剂是心肌新陈代谢和收缩力的重要调节剂；然而，过量接触 ISO 会引发氧化应激和炎症。本研究旨在探讨 ISO 诱导心脏重塑的分子机制、白藜芦醇（RSVR）及其脂质体制剂（L-RSVR）对这种心脏变化的保护作用。将 Wistar 白化大鼠平均分为 4 组。对照组、ISO 组（每周两次，每次 50 毫克/千克，静脉注射）、RSVR 和 L-RSVR 处理组（RSVR 或 L-RSVR（20 毫克/千克/天，口服）与 ISO 同时服用，为期 2 周）。与对照组相比，ISO 导致心脏组织中 BAX 和 MEF2 mRNA、S100A1 和细胞色素 C 蛋白的表达水平以及 DNA 断裂水平明显升高。使用 RSVR 或 L-RSVR 治疗 14 天后，ISO 诱导的损伤明显改善，这体现在所有测量参数的改善上。本研究表明，L-RSVR 对 ISO 诱导的大鼠心脏损伤具有更好的心脏保护作用，这很可能是通过调节心脏 S100A1 蛋白的表达以及抑制炎症和细胞凋亡实现的。
{"title":"Resveratrol-Based Liposomes Improve Cardiac Remodeling Induced by Isoproterenol Partially by Modulating MEF2, Cytochrome C and S100A1 Expression","authors":"Ahlam M. Alhusaini, Hanan K. Alghibiwi, Wedad S. Sarawi, Juman S. Alsaab, Samiyah M. Alshehri, Qamraa H. Alqahtani, Aliah R. Alshanwani, Ebtesam A. Aljassas, Ebtesam N. Alsultan, Iman H. Hasan","doi":"10.1177/15593258241247980","DOIUrl":"https://doi.org/10.1177/15593258241247980","url":null,"abstract":"Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50 mg/kg, s.c.) twice a week for 2 weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20 mg/kg/day, p.o.) along with ISO for 2 weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14 days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140629375","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}
Pub Date : 2024-04-13DOI: 10.1177/15593258241247185
Ijaz Hussain, Manoj Kumar, Amin Ali, Fizzah Naz, Wasif Ahmed Khan, Muhammad Sohail Salat, Shahzad Rauf, Gul Ambreen, Kashif Hussain
BackgroundCaffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses’ effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5 mg/kg/day as the standard regimen.MethodThis retrospective cohort study included neonates of ≤36 weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15–28 and 29–42 days of life (DOL). Based on daily CC-dose, formed group-I=(5 mg/kg/day), group-II=(>5–7 mg/kg/day), and group-III=(>7 mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard.ResultsThe study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88 g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88 g/kg/d vs 16.7 ± .71, P < .001). During 29–42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d, P = .003) and comparable with group-II. During 15–28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29–42 DOL was significant only in group-III.ConclusionExposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.
背景枸橼酸咖啡因（CC）引起的能量消耗过多、利尿、利尿和其他CC相关潜在副作用（CC-APSEs）导致早产新生儿日增重（WG）降低。本研究以 5 毫克/千克/天作为标准方案，旨在评估更高的 CC 剂量对平均日增重（MD-WG）和 CC-APSE 发展的影响。在出生后的两个阶段对相同的参与者进行了数据分析：出生后 15-28 天和 29-42 天 (DOL)。根据每天的CC剂量，第一组=（5毫克/千克/天），第二组=（5-7毫克/千克/天），第三组=（7毫克/千克/天）。以第一组为标准，分别分析第二组和第三组的数据。在第一阶段，第一组的 MD-WG 明显高于第二组（19.9 ± .88 g/kg/d vs 17.5 ± .49，P = .031）和第三组（19.9 ± .88 g/kg/d vs 16.7 ± .71，P <.001）。在 29-42 DOL 期间，I 组的 MD-WG 仅显著高于 III 组（21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d，P = .003），与 II 组相当。在 15-28 DOL 期间，CC-APSEs 在 II 组和 III 组显著较高，但在 29-42 DOL 期间，只有 III 组显著较高。
{"title":"Dose–Response Study of Caffeine on Postnatal Weight Gain in Premature Neonates—A Retrospective Cohort Study","authors":"Ijaz Hussain, Manoj Kumar, Amin Ali, Fizzah Naz, Wasif Ahmed Khan, Muhammad Sohail Salat, Shahzad Rauf, Gul Ambreen, Kashif Hussain","doi":"10.1177/15593258241247185","DOIUrl":"https://doi.org/10.1177/15593258241247185","url":null,"abstract":"BackgroundCaffeine citrate (CC)-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side effects (CC-APSEs) result in lower daily weight gain (WG) in premature neonates. This study aimed to assess higher CC-doses’ effect on the mean daily-WG (MD-WG) and CC-APSE development, considering 5 mg/kg/day as the standard regimen.MethodThis retrospective cohort study included neonates of ≤36 weeks gestational age and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15–28 and 29–42 days of life (DOL). Based on daily CC-dose, formed group-I=(5 mg/kg/day), group-II=(>5–7 mg/kg/day), and group-III=(>7 mg/kg/day). Data was analyzed separately for group-II and group-III using group-I as the standard.ResultsThe study included 284 neonates. During phase-I, the MD-WG was significantly higher in group-I than group-II (19.9 ± .88 g/kg/d vs 17.5 ± .49, P = .031) and group-III (19.9 ± .88 g/kg/d vs 16.7 ± .71, P < .001). During 29–42 DOL, the MD-WG of group-I was only significantly higher than group-III (21.5 ± .42 g/kg/d vs 18.1 ± .39 g/kg/d, P = .003) and comparable with group-II. During 15–28 DOL, CC-APSEs were significantly higher in group-II and group-III but during 29–42 DOL was significant only in group-III.ConclusionExposure to higher caffeine doses in this study cohort is associated with lower postnatal WG in preterm neonates than standard daily doses may be due to its catabolic effects and CC-APSEs.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599175","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}
Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.
{"title":"Enhancement of the Tumor Suppression Effect of High-dose Radiation by Low-dose Pre-radiation Through Inhibition of DNA Damage Repair and Increased Pyroptosis","authors":"Xinfeng Wei, Junxuan Yi, Citong Zhang, Mingwei Wang, Rui Wang, Weiqiang Xu, Mingqi Zhao, Mengdie Zhao, Teng Yang, Wei Wei, Shunzi Jin, Hui Gao","doi":"10.1177/15593258241245804","DOIUrl":"https://doi.org/10.1177/15593258241245804","url":null,"abstract":"Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598887","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}
In this work, we study the effect of 6 MeV electron beam irradiation on the physicochemical properties of lyophilized Human Haemoglobin A (HbA). Electron beams generated from Race Track Microtron accelerator with energy 6 MeV were used to irradiate HbA at fluences of 5 × 1014 e−/cm2 and 10 × 1014 e−/cm2. Pristine and electron beam irradiated HbA were characterized using UV-visible and Fourier transform infrared spectroscopy (FTIR) spectroscopy. The interfacial tension of the aqueous solutions of HbA are also analysed by pendant drop method. Absorbance intensity, % transmittance and interfacial tension decrease with fluence. The peak position of the Soret band (λsoret = 404 nm) remains unaffected by the fluences. FTIR spectroscopy confirms the changes in the secondary structure of the haemoglobin. In the amide band I, the percentage of α-helix reduced from 8% to 1%, and an increase in β-sheet (19% to 29%) and β helix (6.3% to 15%) is observed. Interfacial tension decreases from 46.0 mN/m and 44.0 mN/m with increase in irradiation dose. These finding provides realistic guideline for biological cells exposure to electron beam radiation doses.
{"title":"Probing Effect of 6 MeV Electron Beam Irradiation on Haemoglobin Protein Using Spectroscopic Techniques","authors":"Sarika Hinge, Sanjay Dhole, Arun Banpurkar, Gauri Kulkarni","doi":"10.1177/15593258241240233","DOIUrl":"https://doi.org/10.1177/15593258241240233","url":null,"abstract":"In this work, we study the effect of 6 MeV electron beam irradiation on the physicochemical properties of lyophilized Human Haemoglobin A (HbA). Electron beams generated from Race Track Microtron accelerator with energy 6 MeV were used to irradiate HbA at fluences of 5 × 10<jats:sup>14</jats:sup> e<jats:sup>−</jats:sup>/cm<jats:sup>2</jats:sup> and 10 × 10<jats:sup>14</jats:sup> e<jats:sup>−</jats:sup>/cm<jats:sup>2</jats:sup>. Pristine and electron beam irradiated HbA were characterized using UV-visible and Fourier transform infrared spectroscopy (FTIR) spectroscopy. The interfacial tension of the aqueous solutions of HbA are also analysed by pendant drop method. Absorbance intensity, % transmittance and interfacial tension decrease with fluence. The peak position of the Soret band (λ<jats:sub>soret</jats:sub> = 404 nm) remains unaffected by the fluences. FTIR spectroscopy confirms the changes in the secondary structure of the haemoglobin. In the amide band I, the percentage of α-helix reduced from 8% to 1%, and an increase in β-sheet (19% to 29%) and β helix (6.3% to 15%) is observed. Interfacial tension decreases from 46.0 mN/m and 44.0 mN/m with increase in irradiation dose. These finding provides realistic guideline for biological cells exposure to electron beam radiation doses.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140599077","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}
Pub Date : 2024-04-01DOI: 10.1177/15593258241248775
Lu Cai
This is an editorial from the new editor-in-chief, EIC, who starts his role in March 2024. Due to the remarkable advance of various research fields in terms of its concepts and technology, the emerging concepts of “Exposome” and associated “Exposomics” have been introduced into the toxicology research. Therefore, the mission of “Dose-Response” will remain adhered to the original goals but will incorporate with these new concepts as the next chapter’s principle and strategies. Accordingly, although it remains with special interest in the biological response to low-dose (level) ranges of stresses. The types and contents of interested manuscripts will be extended with more diverse, newer concepts from a wide range of disciplines. We wish this journal can open a door for various discipline scientists and researchers to share their state-of-the-art discoveries to shed new insight to understand the impact of environmental and toxicological medicine and develop more specific and effective intervention strategies.
{"title":"Perspective of Dose-Response: New Chapter With New “Exposome” and “-omics”","authors":"Lu Cai","doi":"10.1177/15593258241248775","DOIUrl":"https://doi.org/10.1177/15593258241248775","url":null,"abstract":"This is an editorial from the new editor-in-chief, EIC, who starts his role in March 2024. Due to the remarkable advance of various research fields in terms of its concepts and technology, the emerging concepts of “Exposome” and associated “Exposomics” have been introduced into the toxicology research. Therefore, the mission of “Dose-Response” will remain adhered to the original goals but will incorporate with these new concepts as the next chapter’s principle and strategies. Accordingly, although it remains with special interest in the biological response to low-dose (level) ranges of stresses. The types and contents of interested manuscripts will be extended with more diverse, newer concepts from a wide range of disciplines. We wish this journal can open a door for various discipline scientists and researchers to share their state-of-the-art discoveries to shed new insight to understand the impact of environmental and toxicological medicine and develop more specific and effective intervention strategies.","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780534","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}
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