Pub Date : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.03
K Bontor, B Gabryel
The lipid peroxidation product 4-hydroxynonenal (HNE) may be involved in vascular endothelial cell damage by induction of oxidative stress, apoptosis, and loss of redox homeostasis. There is evidence that stimulation of endothelial cells with 4-HNE induces the activation of the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) pathway. Sestrin2 protein (SESN2) is one of the key regulators of Nrf2 and is involved in the cellular response to oxidative stress. However, the function of SESN2 in HNE-induced endothelial injury is not yet understood. Sulodexide (SDX) is a mixture of glycosaminoglycans used in clinical practice in the treatment of chronic venous and arterial diseases. While SDX has well-documented endothelial protective properties, little is known about its antioxidant effects. The aim of this study was to elucidate the molecular mechanisms activated by SDX in human umbilical endothelial cells (HUVECs) under HNE-induced oxidative stress. In this experimental model, we decided to evaluate the anti-apoptotic and antioxidant potential of SDX and its effect on the SESN2/Nrf2/GSH pathway. HUVECs were treated with 25 _M HNE or HNE combined with 0.5 LRU/mL SDX for 4 hours. Cell viability, apoptosis and intracellular reactive oxygen species (ROS) production were assessed by MTT assay and fluorescence microscopy. The expressions of Bax, cleaved caspase-3, Keap-1 and Nrf2 were determined by Western blot analysis. The intracellular concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) were measured by colorimetric assay. SESN2, glutamate-cysteine ligase catalytic subunit (GCLc) and glutathione synthase (GSS) were assessed using ELISA. RT-qPCR was performed to detect Nrf2, GCLc and GSS mRNA levels. Transient Nrf2 silencing was obtained by short interfering RNA (siRNA). We have demonstrated that SDX can reduce the negative impact of HNE on HUVECs. SDX significantly protected HNE-treated HUVECs from apoptosis (p<0.001) and oxidative stress (p<0.001). SDX treatment significantly reduced Bax (p<0.05) and cleaved caspase-3 (p<0.01) expression. Co-administration of HNE and SDX increased GSH content (p<0.001) and GSH:GSSG ratio (p<0.001) as well as decreased SESN2 concentration (p<0.001) and Nrf2 (p<0.01), GCLc (p<0.05) and GSS (p<0.01) gene expression compared with the HNE group. Moreover, we revealed a negative correlation between SESN2 levels and GSH concentrations (p<0.001). Nrf2 silencing significantly decreased the effect of HNE and SDX on the induction of GCLc and GSS genes. SDX also significantly ameliorated the increase of nuclear Nrf2 in response to HNE (p<0.05). The results confirmed that SDX may protect against HNE-induced endothelial damage through its antioxidant effect and modulation of the SESN2/Nrf2/GSH signaling pathway.
{"title":"Sulodexide protects endothelial cells against 4-hydroxynonenal-induced oxidative stress and glutathione-dependent redox imbalance by modulation of sestrin2/nuclear factor erythroid 2-related factor 2 pathway.","authors":"K Bontor, B Gabryel","doi":"10.26402/jpp.2024.4.03","DOIUrl":"10.26402/jpp.2024.4.03","url":null,"abstract":"<p><p>The lipid peroxidation product 4-hydroxynonenal (HNE) may be involved in vascular endothelial cell damage by induction of oxidative stress, apoptosis, and loss of redox homeostasis. There is evidence that stimulation of endothelial cells with 4-HNE induces the activation of the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap-1) pathway. Sestrin2 protein (SESN2) is one of the key regulators of Nrf2 and is involved in the cellular response to oxidative stress. However, the function of SESN2 in HNE-induced endothelial injury is not yet understood. Sulodexide (SDX) is a mixture of glycosaminoglycans used in clinical practice in the treatment of chronic venous and arterial diseases. While SDX has well-documented endothelial protective properties, little is known about its antioxidant effects. The aim of this study was to elucidate the molecular mechanisms activated by SDX in human umbilical endothelial cells (HUVECs) under HNE-induced oxidative stress. In this experimental model, we decided to evaluate the anti-apoptotic and antioxidant potential of SDX and its effect on the SESN2/Nrf2/GSH pathway. HUVECs were treated with 25 _M HNE or HNE combined with 0.5 LRU/mL SDX for 4 hours. Cell viability, apoptosis and intracellular reactive oxygen species (ROS) production were assessed by MTT assay and fluorescence microscopy. The expressions of Bax, cleaved caspase-3, Keap-1 and Nrf2 were determined by Western blot analysis. The intracellular concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG) were measured by colorimetric assay. SESN2, glutamate-cysteine ligase catalytic subunit (GCLc) and glutathione synthase (GSS) were assessed using ELISA. RT-qPCR was performed to detect Nrf2, GCLc and GSS mRNA levels. Transient Nrf2 silencing was obtained by short interfering RNA (siRNA). We have demonstrated that SDX can reduce the negative impact of HNE on HUVECs. SDX significantly protected HNE-treated HUVECs from apoptosis (p<0.001) and oxidative stress (p<0.001). SDX treatment significantly reduced Bax (p<0.05) and cleaved caspase-3 (p<0.01) expression. Co-administration of HNE and SDX increased GSH content (p<0.001) and GSH:GSSG ratio (p<0.001) as well as decreased SESN2 concentration (p<0.001) and Nrf2 (p<0.01), GCLc (p<0.05) and GSS (p<0.01) gene expression compared with the HNE group. Moreover, we revealed a negative correlation between SESN2 levels and GSH concentrations (p<0.001). Nrf2 silencing significantly decreased the effect of HNE and SDX on the induction of GCLc and GSS genes. SDX also significantly ameliorated the increase of nuclear Nrf2 in response to HNE (p<0.05). The results confirmed that SDX may protect against HNE-induced endothelial damage through its antioxidant effect and modulation of the SESN2/Nrf2/GSH signaling pathway.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479371","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.01
M Kuczeriszka, L Dobrowolski
Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.
{"title":"Myriad of factors involved in blood pressure control. Salt intake connects them all.","authors":"M Kuczeriszka, L Dobrowolski","doi":"10.26402/jpp.2024.4.01","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.01","url":null,"abstract":"<p><p>Long-lasting elevated blood pressure (BP), i.e. hypertension, is a major contributor to morbidity and mortality worldwide. As a multifactorial and systemic disease that involves multiple systems, hypertension remains a challenging disease to study. Models of hypertension are a basic source of knowledge to drive and support the discovery of the specific genetic, cellular, and molecular mechanisms underlying essential hypertension, as well as to discover and introduce new possible treatments to lower BP. Animal models of hypertension deliver a huge amount of information but it is important to choose the proper one for our scientific hypothesis. In this review, we discuss the physiological, and biochemical background of rodent models of hypertension through a systems approach and a myriad of mechanisms and pathways involved in blood pressure control. We also pay attention to how target organs and systems including the kidneys, vasculature, the sympathetic nervous system (SNS), and immunological system, interfere with each other, and their activity is differentially controlled by sodium delivery, which still remains a pivotal troublemaker.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479369","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.02
M Kopanska, D Ochojska, J Trojniak, I Sarzynska, J Szczygielski
Electroencephalography (EEG) is a non-invasive diagnostic tool, enabling us to assess the electrical activity of the brain and its disturbance in a great number of psychiatric conditions. This paper provides a narrative overview of the most recent advantages of EEG use in various psychiatric disorders that are associated. This article analyses selected psychiatric disorders. We discussed anxiety disorders characterized by chronic fear, dementia leading to cognitive decline, schizophrenia disrupting logical thinking, bipolar affective disorder with alternating episodes of mania and depression, and depression manifested by gradual loss of vital energy. We have shown that EEG testing, by monitoring the electrical activity of the brain, is a helpful tool in identifying specific brain wave patterns associated with these disorders. In the study of mental illness the EEG variant called quantitative EEG (QEEG) is of particular avail as to the spatial discrimination. QEEG is based on digital coding and transformation according to Fourier algorithm. Recently, even more complex methods of EEG data analysis have been implemented, including artificial intelligence (AI), deep learning (DL) and its branch: machine learning (ML). The use of sophisticated EEG postprocessing adds important information about the pathophysiology of mental disorders. More so, EEG/QEEG recording (in particular spectral analysis), if repeated over time may help to follow up the treatment results and to establish a prognosis as to the course of the given condition. Reliability, safety and availability of EEG makes it to be an indispensable tool in modern psychiatry. Use of EEG, QEEG may lead to faster and more precise differential diagnostic workup. Use of EEG/QEEG changes as an objective outcome measure in clinical trials may support the development of personalized pharmacotherapy or psychotherapy.
{"title":"The role of quantitative electroencephalography in diagnostic workup of mental disorders.","authors":"M Kopanska, D Ochojska, J Trojniak, I Sarzynska, J Szczygielski","doi":"10.26402/jpp.2024.4.02","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.02","url":null,"abstract":"<p><p>Electroencephalography (EEG) is a non-invasive diagnostic tool, enabling us to assess the electrical activity of the brain and its disturbance in a great number of psychiatric conditions. This paper provides a narrative overview of the most recent advantages of EEG use in various psychiatric disorders that are associated. This article analyses selected psychiatric disorders. We discussed anxiety disorders characterized by chronic fear, dementia leading to cognitive decline, schizophrenia disrupting logical thinking, bipolar affective disorder with alternating episodes of mania and depression, and depression manifested by gradual loss of vital energy. We have shown that EEG testing, by monitoring the electrical activity of the brain, is a helpful tool in identifying specific brain wave patterns associated with these disorders. In the study of mental illness the EEG variant called quantitative EEG (QEEG) is of particular avail as to the spatial discrimination. QEEG is based on digital coding and transformation according to Fourier algorithm. Recently, even more complex methods of EEG data analysis have been implemented, including artificial intelligence (AI), deep learning (DL) and its branch: machine learning (ML). The use of sophisticated EEG postprocessing adds important information about the pathophysiology of mental disorders. More so, EEG/QEEG recording (in particular spectral analysis), if repeated over time may help to follow up the treatment results and to establish a prognosis as to the course of the given condition. Reliability, safety and availability of EEG makes it to be an indispensable tool in modern psychiatry. Use of EEG, QEEG may lead to faster and more precise differential diagnostic workup. Use of EEG/QEEG changes as an objective outcome measure in clinical trials may support the development of personalized pharmacotherapy or psychotherapy.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479386","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.07
L M Hardt, P C Konturek, H J Herrmann, D Reljic, L Kugler, J Meyer, M F Neurath, Y Zopf
Oral nutritional supplements (ONS) play a key role in the therapy of cancer-cachexia, but adherence to ONS-intake remains challenging. To improve adherence, a wide variety of ONS is crucial. We compared the acceptance and adherence of a commercial liquid ONS (LS) with a newly developed, energy- and protein-rich, semisolid, fruit-gum based product (FG) in oncological patients. Forty cancer patients with indication for artificial nutritional therapy were randomly assigned to LS and FG in crossover design for 4 weeks with a 1-week washout phase in-between. Adherence to ONS was recorded with MARS-D questionnaire. Sensory properties were evaluated and safety monitoring was performed. Energy and nutrient intake, nutrition and performance status and quality of life remained stable in both groups throughout the study (all p-values for the comparison between baseline and after 9 weeks were >0.05). Taste (p=0.004), smell (p=0.025) and enjoyment (p=0.027) of the LS were rated significantly better compared to FG and a higher adherence (p=0.005) for the LS was found. Nevertheless, patients were very interested about the new alternative of ONS, so that 16 of the study participants would buy it or strive for a medical prescription. The balanced, protein-rich ONS based on fruit gum is an innovative formulation that stabilizes nutritional status and might therefore extend the options for nutritional support in cancer patients in the future. However, the sensory properties must first be further improved to increase acceptance and adherence.
口服营养补充剂(ONS)在治疗癌症腹痛症中发挥着关键作用,但坚持服用ONS仍是一项挑战。为了提高依从性,口服营养补充剂的多样性至关重要。我们比较了肿瘤患者对商用液体 ONS(LS)和新开发的富含能量和蛋白质的半固体果胶产品(FG)的接受度和依从性。40 名有人工营养疗法适应症的癌症患者被随机分配到液态营养补充剂和果胶营养补充剂中,交叉使用 4 周,中间有 1 周的清洗期。通过 MARS-D 问卷记录患者对 ONS 的依从性。对感官特性进行了评估,并进行了安全监测。在整个研究过程中,两组的能量和营养素摄入量、营养状况、表现状态和生活质量均保持稳定(基线与 9 周后的所有对比 p 值均大于 0.05)。与 FG 相比,LS 的口感(p=0.004)、气味(p=0.025)和享受(p=0.027)明显更好,LS 的依从性更高(p=0.005)。尽管如此,患者对新的替代性 ONS 非常感兴趣,因此研究参与者中有 16 人愿意购买或争取医生处方。以果胶为基础的均衡、富含蛋白质的 ONS 是一种创新配方,可稳定营养状况,因此未来可能会扩大癌症患者营养支持的选择范围。不过,首先必须进一步改进其感官特性,以提高接受度和依从性。
{"title":"Adherence and acceptance of a new oral nutritional supplement in cancer patients - a pilot study in crossover design.","authors":"L M Hardt, P C Konturek, H J Herrmann, D Reljic, L Kugler, J Meyer, M F Neurath, Y Zopf","doi":"10.26402/jpp.2024.4.07","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.07","url":null,"abstract":"<p><p>Oral nutritional supplements (ONS) play a key role in the therapy of cancer-cachexia, but adherence to ONS-intake remains challenging. To improve adherence, a wide variety of ONS is crucial. We compared the acceptance and adherence of a commercial liquid ONS (LS) with a newly developed, energy- and protein-rich, semisolid, fruit-gum based product (FG) in oncological patients. Forty cancer patients with indication for artificial nutritional therapy were randomly assigned to LS and FG in crossover design for 4 weeks with a 1-week washout phase in-between. Adherence to ONS was recorded with MARS-D questionnaire. Sensory properties were evaluated and safety monitoring was performed. Energy and nutrient intake, nutrition and performance status and quality of life remained stable in both groups throughout the study (all p-values for the comparison between baseline and after 9 weeks were >0.05). Taste (p=0.004), smell (p=0.025) and enjoyment (p=0.027) of the LS were rated significantly better compared to FG and a higher adherence (p=0.005) for the LS was found. Nevertheless, patients were very interested about the new alternative of ONS, so that 16 of the study participants would buy it or strive for a medical prescription. The balanced, protein-rich ONS based on fruit gum is an innovative formulation that stabilizes nutritional status and might therefore extend the options for nutritional support in cancer patients in the future. However, the sensory properties must first be further improved to increase acceptance and adherence.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479364","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.08
F F Wang, Y Li, M M Liu, Y M Han, Z W Sun, C Wang, L L Wang, M Guo, P L Li
The demographic of women of advanced maternal age (AMA), defined as those over 35 years, is expanding in response to the liberalization of China's three-child policy. A significant proportion of these women are electing to undergo noninvasive prenatal testing (NIPT). Nonetheless, next-generation sequencing (NGS) is the recommended method for prenatal screening among women of AMA in the world. Consequently, the decision between opting for NIPT or NGS has emerged as topic of considerable debate and interest within the medical community. The objective was to explore which prenatal screening and diagnosis is suitable for women of AMA with different comorbidities. In this retrospective study, 326 pregnant women with AMA were divided into 9 groups to investigate clinically significant copy number variation (CNV) in different amniocentesis indications by amniocentesis and NGS. Clinically significant chromosomal abnormalities were identified in 84 cases (25.8%). Among the 119 detected segmental imbalances, 16 cases (13.4%) exhibited pathogenic or likely pathogenic microdeletions or micro-duplications. The incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with soft ultrasound markers group compared to the general AMA group (11.5% vs. 1.1%; P=0.016). Additionally, the incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with NIPT group compared to the general AMA group (48.7% vs. 1.1%; P<0.001). The incorporation of soft ultrasound markers and NIPT significantly enhanced the detection rate of clinically significant CNVs in women of AMA by 10.4% and 47.6%, respectively. Furthermore, the detection rate of clinically significant CNVs increased by 37% in women of AMA who underwent NIPT, when soft ultrasound markers were present. The positive predictive value of NIPT in detecting sex chromosome aneuploidy notably improved from 57.9% to 80% with the inclusion of soft ultrasound markers. Therefore, the combination of NIPT and soft ultrasound markers in women of AMA should be strongly considered and recommended for prenatal diagnosis.
随着中国三胎政策的放开,高龄产妇(AMA)(指 35 岁以上的妇女)的人数正在不断增加。这些妇女中有很大一部分选择接受无创产前检测(NIPT)。尽管如此,下一代测序(NGS)仍是世界上AMA妇女产前筛查的推荐方法。因此,选择 NIPT 还是 NGS 已成为医学界颇受争议和关注的话题。本研究旨在探讨哪种产前筛查和诊断方法适合患有不同合并症的 AMA 妇女。在这项回顾性研究中,326 名患有 AMA 的孕妇被分为 9 组,通过羊膜腔穿刺术和 NGS 研究不同羊膜腔穿刺适应症中具有临床意义的拷贝数变异(CNV)。结果发现 84 例(25.8%)有临床意义的染色体异常。在 119 例检测到的节段不平衡中,16 例(13.4%)表现为致病性或可能致病性微缺失或微重复。与普通 AMA 组相比,带有软超声标记物的 AMA 组致病性或可能致病性 CNV 的发生率明显更高(11.5% 对 1.1%;P=0.016)。此外,与普通 AMA 组相比,使用 NIPT 的 AMA 组致病性或可能致病性 CNV 的发生率明显更高(48.7% vs. 1.1%;P=0.016)。
{"title":"Chromosomal analysis in pregnant women of advanced maternal age: indications for prenatal diagnosis.","authors":"F F Wang, Y Li, M M Liu, Y M Han, Z W Sun, C Wang, L L Wang, M Guo, P L Li","doi":"10.26402/jpp.2024.4.08","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.08","url":null,"abstract":"<p><p>The demographic of women of advanced maternal age (AMA), defined as those over 35 years, is expanding in response to the liberalization of China's three-child policy. A significant proportion of these women are electing to undergo noninvasive prenatal testing (NIPT). Nonetheless, next-generation sequencing (NGS) is the recommended method for prenatal screening among women of AMA in the world. Consequently, the decision between opting for NIPT or NGS has emerged as topic of considerable debate and interest within the medical community. The objective was to explore which prenatal screening and diagnosis is suitable for women of AMA with different comorbidities. In this retrospective study, 326 pregnant women with AMA were divided into 9 groups to investigate clinically significant copy number variation (CNV) in different amniocentesis indications by amniocentesis and NGS. Clinically significant chromosomal abnormalities were identified in 84 cases (25.8%). Among the 119 detected segmental imbalances, 16 cases (13.4%) exhibited pathogenic or likely pathogenic microdeletions or micro-duplications. The incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with soft ultrasound markers group compared to the general AMA group (11.5% vs. 1.1%; P=0.016). Additionally, the incidence of pathogenic or likely pathogenic CNVs was significantly higher in the AMA with NIPT group compared to the general AMA group (48.7% vs. 1.1%; P<0.001). The incorporation of soft ultrasound markers and NIPT significantly enhanced the detection rate of clinically significant CNVs in women of AMA by 10.4% and 47.6%, respectively. Furthermore, the detection rate of clinically significant CNVs increased by 37% in women of AMA who underwent NIPT, when soft ultrasound markers were present. The positive predictive value of NIPT in detecting sex chromosome aneuploidy notably improved from 57.9% to 80% with the inclusion of soft ultrasound markers. Therefore, the combination of NIPT and soft ultrasound markers in women of AMA should be strongly considered and recommended for prenatal diagnosis.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479365","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.05
T Sun, Q-L Sun, Y Liu, Y-Y Zhang, P Sheng, N Cui, N Zhang, S-H Wang, D Su
In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.
{"title":"The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study.","authors":"T Sun, Q-L Sun, Y Liu, Y-Y Zhang, P Sheng, N Cui, N Zhang, S-H Wang, D Su","doi":"10.26402/jpp.2024.4.05","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.05","url":null,"abstract":"<p><p>In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479372","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.06
N Fabisiak, A Tarasiuk-Zawadzka, A Fabisiak, M Wlodarczyk, J Fichna
Patients with inflammatory bowel diseases (IBD) frequently experience malnutrition and develop nutrients deficiencies such as vitamin D or iron. Collectively, 39 patients were recruited to the study - 32 with IBD and 7 patients constituting the control group (CG). Quantitative real-time polymerase chain reaction was used to assess the expression of vitamin D receptor (VDR), hepcidin (HAMP) and cathelicidin antimicrobial peptide (CAMP) in colon mucosa. The mean expression of VDR and CAMP was higher in patients with ulcerative colitis than other groups (VDR vs. CG, p<0.05). However, the mean HAMP expression reached higher values in CG than in groups with IBD. Further research to understand the relationship between the VDR, HAMP and CAMP may constitute the way for development of future diagnostic and therapeutic options in patients with IBD.
炎症性肠病(IBD)患者经常会出现营养不良和维生素 D 或铁等营养素缺乏症。本研究共招募了 39 名患者--32 名 IBD 患者和 7 名对照组(CG)患者。研究采用定量实时聚合酶链反应评估结肠粘膜中维生素 D 受体(VDR)、肝素(HAMP)和柔毛素抗菌肽(CAMP)的表达。溃疡性结肠炎患者 VDR 和 CAMP 的平均表达量高于其他组别(VDR 与 CG 相比,p
{"title":"Determining the expression of vitamin D receptor, regulator of iron metabolism hepcidin and cathelicidin antimicrobial peptide genes for development of future diagnostic and therapeutic options in patients with inflammatory bowel disease.","authors":"N Fabisiak, A Tarasiuk-Zawadzka, A Fabisiak, M Wlodarczyk, J Fichna","doi":"10.26402/jpp.2024.4.06","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.06","url":null,"abstract":"<p><p>Patients with inflammatory bowel diseases (IBD) frequently experience malnutrition and develop nutrients deficiencies such as vitamin D or iron. Collectively, 39 patients were recruited to the study - 32 with IBD and 7 patients constituting the control group (CG). Quantitative real-time polymerase chain reaction was used to assess the expression of vitamin D receptor (VDR), hepcidin (HAMP) and cathelicidin antimicrobial peptide (CAMP) in colon mucosa. The mean expression of VDR and CAMP was higher in patients with ulcerative colitis than other groups (VDR vs. CG, p<0.05). However, the mean HAMP expression reached higher values in CG than in groups with IBD. Further research to understand the relationship between the VDR, HAMP and CAMP may constitute the way for development of future diagnostic and therapeutic options in patients with IBD.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479366","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.09
N N Wang, L Li, Z Q Gu
The tooth movement is a fundamental requirement during any orthodontic treatment. This study aimed to investigate the action and mechanism of strontium ranelate (SR) in orthodontic tooth movement (OTM). Rats were given SR by gavage daily, along with lentiviral vectors interfering with circBACH1 or miR-155-5p. Three weeks later, an OTM rat model was established. RANKL and osteoprotegerin (OpG) in serum were measured. The gap between the first and second molar and root resorption were examined. Osteoclast test was used; and root condition was examined. Detection of miR-155-5p, circBACH1, CLC7 and cathepsin K was performed. The binding of circBACH1 to miR-155-5p was verified. In OTM rats, circBACH1 was elevated (p<0.05) and miR-155-5p was silenced (p<0.05). SR reduced osteoclast activity (p<0.05) and improved root resorption (p<0.05) in OTM rats, which was enhanced by silenced circBACH1 (p<0.05) or elevated miR-155-5p (p<0.05). circBACH1 inhibited miR-155-5p expression (p<0.05). Silenced miR-155-5p reversed the ameliorative effect of circBACH1 on tooth root resorption in OTM rats (all p<0.05). SR modulates circBACH1/miR-155-5p to ameliorate root resorption and tooth fixation during OTM.
{"title":"Strontium ranelate modulates circular RNA BACH1/microRNA-155-5p to ameliorate root resorption and tooth anchoring during orthodontic tooth movement.","authors":"N N Wang, L Li, Z Q Gu","doi":"10.26402/jpp.2024.4.09","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.09","url":null,"abstract":"<p><p>The tooth movement is a fundamental requirement during any orthodontic treatment. This study aimed to investigate the action and mechanism of strontium ranelate (SR) in orthodontic tooth movement (OTM). Rats were given SR by gavage daily, along with lentiviral vectors interfering with circBACH1 or miR-155-5p. Three weeks later, an OTM rat model was established. RANKL and osteoprotegerin (OpG) in serum were measured. The gap between the first and second molar and root resorption were examined. Osteoclast test was used; and root condition was examined. Detection of miR-155-5p, circBACH1, CLC7 and cathepsin K was performed. The binding of circBACH1 to miR-155-5p was verified. In OTM rats, circBACH1 was elevated (p<0.05) and miR-155-5p was silenced (p<0.05). SR reduced osteoclast activity (p<0.05) and improved root resorption (p<0.05) in OTM rats, which was enhanced by silenced circBACH1 (p<0.05) or elevated miR-155-5p (p<0.05). circBACH1 inhibited miR-155-5p expression (p<0.05). Silenced miR-155-5p reversed the ameliorative effect of circBACH1 on tooth root resorption in OTM rats (all p<0.05). SR modulates circBACH1/miR-155-5p to ameliorate root resorption and tooth fixation during OTM.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479370","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.10
J-Y Dai, S-Q Li, X Jia, M-Y Wu, B Song, J-Y Li, Y Guo, R Gao
In this study, we established an experimental rat model to simulate orthodontic tooth movement relapse and a human periodontal ligament stem cell (PDLScs) model. Our aim was to explore the relationship between microRNA-146a (miR-146a) expression in periodontal tissue, the inflammatory factor interleukin-6 (IL-6), and orthodontic relapse subsequent to mechanical intervention. In the animal experiment, a total of 30 healthy male Wistar rats were randomly allocated to either the control group (n=6) or the model group (n=24). In the model group, the orthodontic appliance was removed 14 days after force application. Gingival crevicular fluid (GcF) and periodontal tissue samples were collected at intervals of days 0, 7, 14, and 21 following removal of the orthodontic appliance to assess alterations in miR-146a and IL-6 expressions. In the in vitro cell culture study, human premolar tooth tissue was isolated 24 hours following the addition of the transfection reagent to harvest PDLScs. Reverse transcription quantitative polymerase chain reaction was employed to evaluate the expression levels of the miRNA-146a gene, while Western blot analysis was utilized to assess the production of the IL-6 protein. As a result in comparison to the control group, the protein expression of IL-6 notably escalated to its peak value in the model-day 7 group (p<0.05). Subsequently, although experiencing a slight decline, the IL-6 expression in the model-day 14 group remained significantly elevated compared to control group (p<0.05). In the model-day 21 group, the protein expression of IL-6 approached that of the control group, with no significant difference observed (p>0.05). conversely, in relation to the control group, the gene expression of miR-146a drastically decreased to its lowest point in the model-day 7 group (p<0.05). While exhibiting a slight increase, the miR-146a expression in the model-day 14 group remained significantly diminished compared to control group (p<0.05). Following the identification of human periodontal ligament cells (hPDLcs) through immunofluorescence in the in vitro study, a subsequent experiment was conducted to specifically inhibit miR-146a expression. In comparison to the control group, the protein expression of IL-6 demonstrated a significant increase in the anti-miRNA oligodeoxyribonucleotide (AMO) group, where miR-146a expression was effectively suppressed (p<0.05). Throughout the process of orthodontic tooth movement relapse in rats, there was a notable reduction in the gene expression of miR-146a, accompanied by a significant increase in the expression of IL-6.
{"title":"Expression patterns of interleukin-6 and microRNA-146A during orthodontic relapse in a rat model.","authors":"J-Y Dai, S-Q Li, X Jia, M-Y Wu, B Song, J-Y Li, Y Guo, R Gao","doi":"10.26402/jpp.2024.4.10","DOIUrl":"https://doi.org/10.26402/jpp.2024.4.10","url":null,"abstract":"<p><p>In this study, we established an experimental rat model to simulate orthodontic tooth movement relapse and a human periodontal ligament stem cell (PDLScs) model. Our aim was to explore the relationship between microRNA-146a (miR-146a) expression in periodontal tissue, the inflammatory factor interleukin-6 (IL-6), and orthodontic relapse subsequent to mechanical intervention. In the animal experiment, a total of 30 healthy male Wistar rats were randomly allocated to either the control group (n=6) or the model group (n=24). In the model group, the orthodontic appliance was removed 14 days after force application. Gingival crevicular fluid (GcF) and periodontal tissue samples were collected at intervals of days 0, 7, 14, and 21 following removal of the orthodontic appliance to assess alterations in miR-146a and IL-6 expressions. In the in vitro cell culture study, human premolar tooth tissue was isolated 24 hours following the addition of the transfection reagent to harvest PDLScs. Reverse transcription quantitative polymerase chain reaction was employed to evaluate the expression levels of the miRNA-146a gene, while Western blot analysis was utilized to assess the production of the IL-6 protein. As a result in comparison to the control group, the protein expression of IL-6 notably escalated to its peak value in the model-day 7 group (p<0.05). Subsequently, although experiencing a slight decline, the IL-6 expression in the model-day 14 group remained significantly elevated compared to control group (p<0.05). In the model-day 21 group, the protein expression of IL-6 approached that of the control group, with no significant difference observed (p>0.05). conversely, in relation to the control group, the gene expression of miR-146a drastically decreased to its lowest point in the model-day 7 group (p<0.05). While exhibiting a slight increase, the miR-146a expression in the model-day 14 group remained significantly diminished compared to control group (p<0.05). Following the identification of human periodontal ligament cells (hPDLcs) through immunofluorescence in the in vitro study, a subsequent experiment was conducted to specifically inhibit miR-146a expression. In comparison to the control group, the protein expression of IL-6 demonstrated a significant increase in the anti-miRNA oligodeoxyribonucleotide (AMO) group, where miR-146a expression was effectively suppressed (p<0.05). Throughout the process of orthodontic tooth movement relapse in rats, there was a notable reduction in the gene expression of miR-146a, accompanied by a significant increase in the expression of IL-6.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479367","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 : 2024-08-01Epub Date: 2024-10-10DOI: 10.26402/jpp.2024.4.04
L Q Lin, F K Mao, J Lin, L Guo, W R Yuan, B Y Wang
It is significant to note that 50% of patients with sepsis show cardiac insufficiency. Ginsenoside-Rg1 (G-Rg1) has been shown to have a cardiovascular protective effect. However, whether G-Rg1 is involved in the mechanism of action of sepsis-induced myocardial damage (SIMD) is unclear. This study aimed to investigate the protective effect of G-Rg1 on SIMD and to further investigate its mechanism and mechanisms of regulation of downstream pathways. An in vivo model of sepsis was established in mice by cecal ligation and puncture (CLP), and mice was administered intraperitoneally 35 or 70 mg/kg G-Rg1 after surgery. The damage to cardiac tissue was detected by hematoxylin and eosin (HE) staining. Forkhead transcription factor O subfamily member 3a (FOXO3A) in SIMD mice was detected by immunohistochemistry. Apoptosis in mouse myocardial tissue was determined by TUNEL staining. The effect of G-Rg1 on SIMD cardiomyocytes was evaluated by incubating the cells with lipopolysaccharide to induce inflammation as an in vitro model of SIMD. Cardiomyocyte viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and Fe2+ markers of heart damage were detected by the kit. The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) in heart tissue and H9c2 cells were determined by ELISA. The factors related to the focal adhesion kinase (FAK)/protein kinase B (AKT)-FOXO3A signaling pathway were determined by RT-qPCR and Western blot. High-dose G-Rg1 had a significant inhibitory effect on SIMD mouse model and lipopolysaccharide (LPS)-induced H9c2 cardiomyocytes, reducing serum levels of LDH, CK-MB, and cTnI concentrations, which effectively alleviated SIMD. G-Rg1 restored the abnormally elevated levels of TNF-α, IL-1β, and iron ions and promoted the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression, inhibiting apoptosis and inflammatory responses. In addition, G-Rg1 reversed the inhibitory effect of G-Rg1 on LPS-induced H9c2 cardiomyocyte injury through activation of the FAK/AKT signaling pathway and up-regulation of FOXO3A. G-Rg1 promoted the activation of the FAK/AKT signalling pathway and up-regulation of the protein expression levels of pathway-associated proteins, p-FAK and p-AKT. Therefore, G-Rg1 mediated the FAK/AKT-FOXO3A signaling pathway and played a role in the treatment of SIMD. We conclude that G-Rg1 inhibited apoptosis and inflammation of cardiomyocytes induced by sepsis and reduced iron ion levels by regulating FAK/AKT-FOXO3A signaling pathway.
{"title":"Ginsenoside Rg1 induces ferroptosis by regulating the focal adhesion kinase/protein kinase B-forkhead box O3A signaling pathway and alleviates sepsis-induced myocardial damage.","authors":"L Q Lin, F K Mao, J Lin, L Guo, W R Yuan, B Y Wang","doi":"10.26402/jpp.2024.4.04","DOIUrl":"10.26402/jpp.2024.4.04","url":null,"abstract":"<p><p>It is significant to note that 50% of patients with sepsis show cardiac insufficiency. Ginsenoside-Rg1 (G-Rg1) has been shown to have a cardiovascular protective effect. However, whether G-Rg1 is involved in the mechanism of action of sepsis-induced myocardial damage (SIMD) is unclear. This study aimed to investigate the protective effect of G-Rg1 on SIMD and to further investigate its mechanism and mechanisms of regulation of downstream pathways. An in vivo model of sepsis was established in mice by cecal ligation and puncture (CLP), and mice was administered intraperitoneally 35 or 70 mg/kg G-Rg1 after surgery. The damage to cardiac tissue was detected by hematoxylin and eosin (HE) staining. Forkhead transcription factor O subfamily member 3a (FOXO3A) in SIMD mice was detected by immunohistochemistry. Apoptosis in mouse myocardial tissue was determined by TUNEL staining. The effect of G-Rg1 on SIMD cardiomyocytes was evaluated by incubating the cells with lipopolysaccharide to induce inflammation as an in vitro model of SIMD. Cardiomyocyte viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry. Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and Fe<sup>2+</sup> markers of heart damage were detected by the kit. The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) in heart tissue and H9c2 cells were determined by ELISA. The factors related to the focal adhesion kinase (FAK)/protein kinase B (AKT)-FOXO3A signaling pathway were determined by RT-qPCR and Western blot. High-dose G-Rg1 had a significant inhibitory effect on SIMD mouse model and lipopolysaccharide (LPS)-induced H9c2 cardiomyocytes, reducing serum levels of LDH, CK-MB, and cTnI concentrations, which effectively alleviated SIMD. G-Rg1 restored the abnormally elevated levels of TNF-α, IL-1β, and iron ions and promoted the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) expression, inhibiting apoptosis and inflammatory responses. In addition, G-Rg1 reversed the inhibitory effect of G-Rg1 on LPS-induced H9c2 cardiomyocyte injury through activation of the FAK/AKT signaling pathway and up-regulation of FOXO3A. G-Rg1 promoted the activation of the FAK/AKT signalling pathway and up-regulation of the protein expression levels of pathway-associated proteins, p-FAK and p-AKT. Therefore, G-Rg1 mediated the FAK/AKT-FOXO3A signaling pathway and played a role in the treatment of SIMD. We conclude that G-Rg1 inhibited apoptosis and inflammation of cardiomyocytes induced by sepsis and reduced iron ion levels by regulating FAK/AKT-FOXO3A signaling pathway.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479368","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}