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Promotion of hepatic stellate cell activation and liver fibrosis by microRNA-33a-5p through targeting the Dickkopf-1-mediated wingless-related integration site/beta-catenin pathway. 微小RNA-33a-5p通过靶向Dickkopf-1介导的无翼相关整合位点/β-连环蛋白途径促进肝星状细胞活化和肝纤维化。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.07
H Liu, S Zhang, Z Li, Z Zheng, W Shi, M Hu, F Liu

Liver fibrosis occurs in response to chronic liver injury and is characterized by the production of excess extracellular matrix (ECM) proteins, largely by activated hepatic stellate cells (HSCs). Numerous studies have implicated micro-ribonucleic acids (miRNAs) in liver fibrosis, but the mechanisms remain unclear. Herein, HSC activation by miR-33a-5p during hepatic fibrosis was investigated. The miR-33a-5p was increased in the fibrotic mice and activated HSCs. AntagomiR-33a-5p inhibited HSC activation, proliferation, and migration in vitro, while simultaneously inducing apoptosis. The luciferase reporter assays indicated that the miR-33a-5p bound to the three prime untranslated region (3'UTR) of Dickkopf-1 (DKK1). Further investigation revealed that the miR-33a-5p targeted DKK1-modulated wingless-related integration site (Wnt)/β-catenin signaling directly to control hepatic fibrosis. Notably, the mice treated with antgomiR-33a-5p exhibited increased expression of DKK1 and reduced expression of fibrosis markers, along with reduced fibrosis. The RNA was isolated from activated and quiescent LX-2 cells and subsequently sequenced. Transcriptomic and bioinformatic analyses indicated strong downregulation of DKK1 during LX-2 cell activation. This paper presents the first demonstration of the miR-33a-5p-mediated modulation of liver fibrosis, with miR-33a-5p found to interact with DKK1, leading to regulation of Wnt/β-catenin signaling. The transcriptomic changes occurring during HSC activation were also defined. Overall, the findings suggest that both miR-33a-5p and DKK1 may be useful targets for treating liver fibrosis.

肝纤维化是对慢性肝损伤的反应,其特征是产生过量的细胞外基质(ECM)蛋白,主要由活化的肝星状细胞(HSC)产生。许多研究表明,微小核糖核酸(miRNA)与肝纤维化有关,但其机制尚不清楚。本文研究了肝纤维化过程中miR-33a-5p对HSC的激活。miR-33a-5p在纤维化小鼠中增加并激活HSC。AntagomiR-33a-5p在体外抑制HSC的活化、增殖和迁移,同时诱导细胞凋亡。萤光素酶报告基因分析表明,miR-33a-5p与Dickkopf-1(DKK1)的三个主要非翻译区(3’UTR)结合。进一步的研究表明,miR-33a-5p靶向DKK1直接调节无翼相关整合位点(Wnt)/β-catenin信号传导以控制肝纤维化。值得注意的是,用antgomiR-33a-5p处理的小鼠表现出DKK1的表达增加和纤维化标志物的表达减少,同时纤维化减少。从活化和静止的LX-2细胞中分离RNA,随后测序。转录组学和生物信息学分析表明,在LX-2细胞活化过程中,DKK1强烈下调。本文首次证明了miR-33a-5p介导的肝纤维化调节,发现miR-33a-5 p与DKK1相互作用,导致Wnt/β-catenin信号的调节。还定义了HSC激活过程中发生的转录组学变化。总之,这些发现表明miR-33a-5p和DKK1可能是治疗肝纤维化的有用靶点。
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引用次数: 0
Effect of emodin combined with cisplatin on the invasion and migration of HepG2 hepatoma cells. 大黄素联合顺铂对HepG2肝癌细胞侵袭迁移的影响。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.04
M Yang, Z Xiong, H Deng, X Chen, Q Lai, H Wang, Y Leng

Cisplatin is the leading chemotherapy agent for advanced liver cancer. However, the resistance to cisplatin in liver cancer reduces its efficacy. A potential strategy to increase its effectiveness and reduce toxicity is to combine cisplatin with 1,3,8-trihydroxy-6-methylanthraquinone (emodin). In this study, we examined the effects of emodin combined with cisplatin on the invasion and migration of HepG2 cells and analyzed the role of emodin. The effects of cisplatin, emodin and their combination were assessed in HepG2 cells. Proliferation, invasion and migration of HepG2 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), scar and Transwell assays. The gelatinase spectrum and an ELISA detected the expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). The expression of E-cadherin and vimentin was detected by immunofluorescence and Western blots. Emodin inhibited cell invasion and migration in HepG2 hepatoma cells, increased E-cadherin expression, decreased vimentin, MMP-2, and MMP-9 expression. The combination of emodin and cisplatin-induced a more significant effect in a dose-dependent manner. In this study, we found that emodin inhibited hepatocellular carcinoma (HCC) metastasis. Compared with either cisplatin or emodin alone, the combination of both showed a more significant synergistic effect. Emodin can enhance the sensitivity of HepG2 HCC cells to cisplatin by inhibiting epithelial-mesenchymal transition, and thus, play a role in preventing recurrence and metastasis in HCC.

顺铂是治疗晚期癌症的主要化疗药物。然而,癌症对顺铂的耐药性降低了其疗效。一种提高其有效性和降低毒性的潜在策略是将顺铂与1,3,8-三羟基-6-甲基蒽醌(大黄素)联合使用。在本研究中,我们检测了大黄素与顺铂联合对HepG2细胞侵袭和迁移的影响,并分析了大黄素的作用。在HepG2细胞中评估顺铂、大黄素及其组合的作用。用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴化盐(MTT)、scar和Transwell法检测HepG2细胞的增殖、侵袭和迁移。明胶酶谱和ELISA检测基质金属肽酶2(MMP-2)和基质金属肽蛋白酶9(MMP-9)的表达。免疫荧光和蛋白质印迹检测E-钙粘蛋白和波形蛋白的表达。大黄素抑制HepG2肝癌细胞的侵袭和迁移,增加E-钙粘蛋白的表达,降低波形蛋白、MMP-2和MMP-9的表达。大黄素和顺铂的组合以剂量依赖的方式诱导了更显著的效果。在这项研究中,我们发现大黄素抑制肝细胞癌(HCC)的转移。与单独的顺铂或大黄素相比,两者的组合显示出更显著的协同作用。大黄素可以通过抑制上皮-间质转化来增强HepG2肝癌细胞对顺铂的敏感性,从而在预防肝癌复发和转移中发挥作用。
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引用次数: 0
Histopatological parameters of the spinal cord in different phases of experimental autoimmune encephalomyelitis. A mouse model of multiple sclerosis examined by classical stainings combined with immunohistochemistry. 实验性自身免疫性脑脊髓炎不同阶段脊髓的组织病理学参数。通过经典染色结合免疫组织化学检测多发性硬化症小鼠模型。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.09
G Pyka-Fosciak, M Fosciak, B Wojcik, G J Lis, J A Litwin

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are characterized by three main histopathological parameters: inflammation, demyelination and axonal damage. In this study, these parameters were assessed in spinal cords of mice in the successive phases of EAE by quantitative histology and immunohistochemistry. The number of inflammatory lesions, the intensity of inflammation and expression of CD45 corresponded with the severity of clinical symptoms: they increased from the onset phase to the peak phase of the disease and subsided in the chronic phase. Demyelination increased in the peak phase and did not change in the chronic phase of EAE, although axonal damage gradually increased from the onset phase to the chronic phase, suggesting compensatory hypermyelination in that phase. The markers of myelin and axonal injury: myelin basic protein (MBP) and beta amyloid precursor protein (β-APP) showed changes (decrease and increase, respectively) of expression parallel to changes in demyelination and axonal damage. Results of this study indicate that although inflammation intensity subsides in the chronic phase of EAE, the neurodestructive processes: demyelination and axonal damage continue in that phase.

多发性硬化症(MS)及其动物模型实验性自身免疫性脑脊髓炎(EAE)具有三个主要的组织病理学参数:炎症、脱髓鞘和轴突损伤。在本研究中,通过定量组织学和免疫组织化学在EAE连续阶段的小鼠脊髓中评估这些参数。炎症病变的数量、炎症的强度和CD45的表达与临床症状的严重程度相对应:从发病期到发病高峰期增加,在慢性期消退。脱髓鞘在EAE的高峰期增加,在慢性期没有改变,尽管轴突损伤从发作期到慢性期逐渐增加,表明该期存在代偿性髓鞘形成过度。髓鞘和轴突损伤的标志物:髓鞘碱性蛋白(MBP)和β-淀粉样蛋白前体蛋白(β-AP)的表达变化(分别减少和增加)与脱髓鞘和轴突损害的变化平行。这项研究的结果表明,尽管炎症强度在EAE的慢性期消退,但神经破坏过程:脱髓鞘和轴突损伤仍在该期继续。
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引用次数: 0
The formation of complexes with albumin increases the stability of the protoporphyrin IX spectra. 与白蛋白形成复合物增加了原卟啉IX光谱的稳定性。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.10
L Sulkowski, A Matyja, C Osuch, M Matyja

Photodynamic therapy is a high-target, low-invasive treatment utilized to manage a variety of malignant diseases and precancerous lesions. Protoporphyrin IX (PpIX) is one of the most important photosensitizers used in photodynamic therapy, carried to the cancer tissue by serum albumin. Its delivery by transport protein is one of the major factors in determining the efficacy of photodynamic therapy. The distribution of the albumin-PpIX complexes to the target tissue enables the accomplishment of an optimal PDT effect. This study aimed to assess in vitro the stability of spectrofluorimetric spectra of albumin-PpIX complexes. The experiment used three chemicals: PpIX, human serum albumin (HSA), and bovine serum albumin (BSA). Spectral data was recorded using a Kontron SFM-25 Instrument AG, at two excitation wavelengths λex=280 nm and 295 nm. A concentration of 1x10-5M of PpIX, in combination with 1.25x10-6M of HSA and 4x10-7M of BSA, have been recorded repetitively for ten days and compared to the initial spectrum. The maximum of PpIX fluorescence changed significantly on the first day following sample preparation. The maximum of PpIX - serum albumin complex was stable 10 and 4 days for HSA and 5 and 2 days for BSA for λex=280 nm and 295 nm, respectively. The formation of a complex between PpIX and serum albumin was seen to extend the stability of the spectrofluorimetric spectrum. However, a less significant effect was observed in the case of BSA, which could most plausibly be attributed to the variations in primary structure between HSA and BSA, leading to discernible variations in spectroscopic measurements.

光动力疗法是一种高靶点、低侵袭性的治疗方法,用于治疗各种恶性疾病和癌前病变。原卟啉IX(PpIX)是光动力治疗中最重要的光敏剂之一,通过血清白蛋白携带到癌症组织。其通过转运蛋白的递送是决定光动力疗法疗效的主要因素之一。白蛋白-PpIX复合物向靶组织的分布能够实现最佳PDT效果。本研究旨在评估白蛋白-PpIX复合物的荧光光谱的体外稳定性。实验使用了三种化学物质:PpIX、人血清白蛋白(HSA)和牛血清白蛋白(BSA)。使用Kontron SFM-25 Instrument AG在两个激发波长λex=280nm和295nm下记录光谱数据。1x10-5M的PpIX浓度,与1.25x10-6M的HSA和4x10-7M的BSA组合,已经重复记录了十天,并与初始光谱进行了比较。PpIX荧光的最大值在样品制备后的第一天发生了显著变化。当λex=280nm和295nm时,PpIX-血清白蛋白复合物的最大稳定时间分别为HSA 10天和4天,BSA 5天和2天。PpIX和血清白蛋白之间的复合物的形成被认为扩展了荧光光谱的稳定性。然而,在BSA的情况下观察到不太显著的影响,这可能最有可能归因于HSA和BSA之间一级结构的变化,导致光谱测量的明显变化。
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引用次数: 0
Regulatory effects of baicalin, a flavonoid compound, on adipocyte metabolism. 黄酮类化合物黄芩苷对脂肪细胞代谢的调节作用。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.05
T Szkudelski, K Konieczna, K Szkudelska

Baicalin is a plant-derived, biologically active compound exerting numerous advantageous effects. Adipocytes store and release energy in the process of lipogenesis and lipolysis. Rodent studies have shown that baicalin treatment positively affects fat tissue, however, data on the direct influence of this compound on adipocyte metabolism is lacking. In the present research, the short-term effects of 25, 50, and 100 μM baicalin on glucose transport, conversion to lipids, and oxidation, and also on lipolysis in primary rat adipocytes were explored. Lipolysis was measured as glycerol release from adipocytes. It was shown that 100 μM baicalin reduced glucose oxidation but at any concentration did not affect glucose transport and lipogenesis. Baicalin significantly increased the adipocyte response to physiological and pharmacological lipolytic stimuli (such as epinephrine - adrenergic agonist, DPCPX - adenosine A1 receptor antagonist, and amrinone - cAMP phosphodiesterase inhibitor). The stimulatory effects of baicalin on epinephrine-induced lipolysis were markedly diminished by insulin (activator of cAMP phosphodiesterases) and H-89 (PKA inhibitor). It was also demonstrated that baicalin evoked a similar rise in epinephrine-induced lipolysis in the presence of glucose and alanine. Our results provided evidence that baicalin may reduce glucose oxidation and is capable of enhancing lipolysis in primary rat adipocytes. The action on lipolysis is glucose-independent and covers both the adrenergic and adenosine A1 receptor pathways. The rise in cAMP content is proposed to be responsible for the observed potentiation of the lipolytic process.

黄芩苷是一种植物来源的具有生物活性的化合物,具有许多有益的作用。脂肪细胞在脂肪生成和分解的过程中储存和释放能量。啮齿动物研究表明,黄芩苷治疗对脂肪组织有积极影响,但缺乏该化合物对脂肪细胞代谢直接影响的数据。在本研究中,探讨了25、50和100μM黄芩苷对原代大鼠脂肪细胞葡萄糖转运、转化为脂质和氧化以及脂肪分解的短期影响。脂解是通过脂肪细胞释放甘油来测量的。结果表明,100μM黄芩苷能降低葡萄糖氧化,但在任何浓度下都不会影响葡萄糖转运和脂肪生成。黄芩苷显著增加脂肪细胞对生理和药理学脂解刺激(如肾上腺素-肾上腺素能激动剂、DPCPX-腺苷A1受体拮抗剂和氨里酮-cAMP磷酸二酯酶抑制剂)的反应。胰岛素(cAMP磷酸二酯酶的激活剂)和H-89(PKA抑制剂)显著降低了黄芩苷对肾上腺素诱导的脂解的刺激作用。研究还表明,在葡萄糖和丙氨酸存在的情况下,黄芩苷引起肾上腺素诱导的脂解类似增加。我们的研究结果提供了证据,证明黄芩苷可以减少葡萄糖氧化,并能够增强原代大鼠脂肪细胞的脂解作用。对脂解的作用是不依赖于葡萄糖的,并且涵盖肾上腺素能和腺苷A1受体途径。cAMP含量的增加被认为是观察到的脂肪分解过程增强的原因。
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引用次数: 0
Acute daily exposure to ambient air pollution impairs endothelium-dependent vasodilator responses in young, healthy individuals. 每天急性暴露于环境空气污染会损害年轻健康个体的内皮依赖性血管舒张反应。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.03
B Jasiewicz-Honkisz, G Osmenda, G Wilk, K Urbanski, K Luc, B Guzik, T P Mikołajczyk, T J Guzik

Exposure to ambient air pollution influences cardiovascular (CV) morbidity and mortality. The differential effects of changing particulate or gaseous air pollution on endothelial function in young healthy individuals remain unclear. The aim of this study was to evaluate the relationships between exposures to different pollutants and vascular function in a group of 39 young (33±11 years old) subjects with low CV risk. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were performed, when air pollution reached highest levels (heating period) and repeated in a subgroup of 18 participants a few months later (just before the heating period starts). Daily mean concentrations of PM2.5 and PM10 were inversely correlated with FMD, and this relationship remained significant after adjusting for factors known to affect vascular dysfunction. Endothelial function did not differ between the two time points studied. However, we observed a strong inverse association between the change in the concentration of particulate matter (deltaPM2.5 and deltaPM10) and the change in FMD (deltaFMD) between the two visits (R= -0.65, p= 0.02; R= -0.64, p= 0.02, respectively). In summary, we provide evidence that the concentration of PM2.5 and PM10, but not SO2, NO, NO2, CO, or O3 is associated with impaired endothelial function in young, healthy individuals.

暴露于环境空气污染会影响心血管(CV)发病率和死亡率。颗粒物或气体空气污染变化对年轻健康个体内皮功能的不同影响尚不清楚。本研究的目的是评估39名低CV风险的年轻(33±11岁)受试者暴露于不同污染物与血管功能之间的关系。当空气污染达到最高水平(加热期)时,进行流介导的扩张(FMD)和硝酸甘油介导的舒张(NMD),并在几个月后(加热期开始前)在18名参与者的亚组中重复。PM2.5和PM10的日均浓度与FMD呈负相关,在调整了已知影响血管功能障碍的因素后,这种关系仍然显著。内皮功能在研究的两个时间点之间没有差异。然而,我们观察到颗粒物浓度的变化(deltaPM2.5和deltaPM10)与两次就诊之间的FMD变化(delta FMD)之间存在强烈的负相关(分别为R=-0.65,p=0.02;R=-0.64,p=0.02)。总之,我们提供的证据表明,PM2.5和PM10的浓度,而不是SO2、NO、NO2、CO或O3的浓度,与年轻健康个体的内皮功能受损有关。
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引用次数: 0
Advances in non-pharmacological management of Parkinson's disease complicated with blood pressure abnormalities. 帕金森病合并血压异常的非药物治疗进展。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.01
Q Xing, X Zhao, L Xie, X Chen, Y Wang, Y Xie

Parkinson's disease (PD) often presents with autonomic dysregulation, leading to blood pressure irregularities such as neurogenic orthostatic hypotension (nOH), neurogenic supine hypertension (nSH), and postprandial hypotension (PPH). Unfortunately, these conditions remain prevalent and receive insufficient attention in scientific discourse. They not only cause complications like syncope, falls, and fractures but also result in long-term damage to vital organs, diminishing patients' quality of life. Early implementation of appropriate non-pharmacologic management is crucial to prevent severe adverse events later on. This review focuses on the types, clinical characteristics, mechanisms, and common non-pharmacologic management measures for PD complicated by abnormal blood pressure. By promoting early diagnosis, recognizing symptoms of abnormal blood pressure, and employing non-pharmacologic interventions such as health education, dietary adjustments, exercise, and Chinese medicine techniques, we aim to improve patients' symptoms and quality of life while providing practical guidance for managing PD-related blood pressure abnormalities.

帕金森病(PD)通常表现为自主神经失调,导致血压不规则,如神经源性直立性低血压(nOH)、神经源性仰卧位高血压(nSH)和餐后低血压(PPH)。不幸的是,这些情况仍然普遍存在,在科学讨论中没有得到足够的重视。它们不仅会导致晕厥、跌倒和骨折等并发症,还会对重要器官造成长期损害,降低患者的生活质量。早期实施适当的非药物管理对于预防以后的严重不良事件至关重要。本文综述了PD并发血压异常的类型、临床特征、机制和常见的非药物治疗措施。通过促进早期诊断,识别血压异常症状,并采用非药物干预措施,如健康教育、饮食调整、锻炼和中医技术,我们旨在改善患者的症状和生活质量,同时为管理PD相关的血压异常提供实际指导。
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引用次数: 0
Healing effect of warfarin in the course of cerulein-induced acute pancreatitis in rats. 华法林在天蓝素诱导的大鼠急性胰腺炎过程中的愈合作用。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.08
K Konarska-Bajda, P Ceranowicz, J Cieszkowski, G Ginter, A Chmura, A Stempniewicz, K Galazka, B Kusmierz-Cabala, P Dumnicka, J Bonior, M Sporek, T Brzozowski, Z Warzecha

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 μg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1β, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 μg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

急性胰腺炎(AP)是最常见的胃肠道疾病,可导致住院和意外死亡。AP的发展导致胰腺微循环受损,随后发生一系列事件,导致凝血障碍等。先前的研究表明,抗凝血剂可能是重要的治疗剂。肝素和acencoumarol可以减轻AP的进程,并加速胰腺的愈合和炎症后再生。本研究的目的是确定华法林(一种比阿苯库酚效果更稳定的药物)是否会影响天蓝素诱导的AP中胰腺的愈合和再生。大鼠腹腔注射天蓝素诱发AP。第一剂华法林(45、90或180μg/kg)在第一剂天蓝素后24小时给药,随后10天每天重复一次华法林剂量。AP的严重程度在最后一次给药后立即评估,以及在AP诱导后的第1、2、3、5和10天评估。华法林治疗剂量依赖性地增加了国际标准化比值(INR),并在组织学检查中减轻了胰腺炎的严重程度,加速了胰腺的恢复。这些作用伴随着AP引起的血清淀粉酶和脂肪酶活性、促炎性白细胞介素-1β的血清浓度和血浆D-二聚体水平增加的更快降低。此外,华法林治疗降低了AP大鼠的胰腺重量(胰腺水肿指数)并改善了胰腺血流量。90μg/kg剂量的华法林给药后,治疗效果尤其明显。我们的结论是,华法林治疗可加速蓝精灵诱导的轻度水肿型急性胰腺炎的胰腺再生和恢复。
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引用次数: 0
Melatonin attenuates inflammation and cardiac dysfunction in myocardial infarction by regulating the miRNA-200b-3p/high mobility group box chromosomal protein 1 axis. 褪黑素通过调节miRNA-200b-3p/高迁移率组盒染色体蛋白1轴来减轻心肌梗死中的炎症和心脏功能障碍。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.02
Z H Liu, F Wu, K Ren, J L Huo

Melatonin confers protection against myocardial injury by reducing inflammation and inhibiting apoptosis. In the present study, we investigated whether melatonin regulates cardiomyocyte proliferation and improves cardiac function in rats with myocardial infarction (MI). Two MI models were established in vitro (H9c2 cells were cultured under hypoxia) and in vivo (the left anterior descending coronary artery of rats was surgically ligated). miR-200b-3p and high mobility group box 1 (HMGB1) levels were detected. Cell proliferation and apoptosis were analyzed in vitro, and cardiac function, inflammatory cytokines, and myocardial injury markers in vivo were tested. The experimental results reported that melatonin promoted proliferation and impaired apoptosis of H9c2 cells cultured in hypoxia. In vivo, melatonin improved cardiac function and inhibited the inflammation and myocardial injury of rats with MI. miR-200b-3p was downregulated and HMGB1 was upregulated in MI, while melatonin could upregulate miR-200b-3p and downregulate HMGB1. The HMGB1 was targeted by miR-200b-3p. Upregulating miR-200b-3p or downregulating HMGB1 could further promote the therapeutic effect of melatonin, and downregulating miR-200b-3p or upregulating HMGB1 could abolish the therapeutic effect of melatonin. In conclusion, melatonin alleviates inflammation and cardiac dysfunction after MI by regulating the miR-200b-3p/HMGB1 axis, offering a new therapeutic strategy for MI.

褪黑素通过减少炎症和抑制细胞凋亡来保护心肌免受损伤。在本研究中,我们研究了褪黑素是否调节心肌梗死(MI)大鼠的心肌细胞增殖和改善心功能。在体外(H9c2细胞在缺氧条件下培养)和体内(大鼠左冠状动脉前降支手术结扎)建立两种MI模型。miR-200b-3p和高迁移率组盒1(HMGB1)水平。体外分析细胞增殖和凋亡,体内检测心功能、炎性细胞因子和心肌损伤标志物。实验结果表明,褪黑素能促进缺氧培养的H9c2细胞的增殖,抑制细胞凋亡。在体内,褪黑激素改善了MI大鼠的心脏功能,抑制了炎症和心肌损伤。MI中miR-200b-3p下调,HMGB1上调,而褪黑激素可以上调miR-200b-2p并下调HMGB1。HMGB1被miR-200b-3p靶向。上调miR-200b-3p或下调HMGB1可进一步促进褪黑素的治疗作用,下调miR-200b-2p或上调HMGB1则可消除褪黑素的治疗效果。总之,褪黑素通过调节miR-200b-3p/HMGB1轴来减轻MI后的炎症和心功能障碍,为MI提供了一种新的治疗策略。
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引用次数: 0
Ostarine does not enhance the metabolic effect of exercise in obese rats. Ostarine不能增强肥胖大鼠运动的代谢作用。
IF 2.2 4区 医学 Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-08-01 Epub Date: 2023-10-16 DOI: 10.26402/jpp.2023.4.06
N Leciejewska, E Pruszynska-Oszmalek, M Sassek, M Głowacki, T Lehmenn, A Rekas-Dudziak, L Nogowski, K W Nowak, P A Kolodziejski

Overweight and obesity are associated with severe metabolic disorders and an increased risk of cardiovascular diseases. It is a known fact that physical activity has a positive effect on metabolic parameters, and also reduces the risk of diseases such as diabetes. Some products can enhance the rate of lipolysis and help in improving fat loss. One of these are selective androgen receptor modulators (SARMs) which act as anabolic agents and are also believed to aid in fat-burning. In this study, we investigated whether 30 days of ostarine administration could potentially improve metabolic parameters using the rat model of obesity combined with exercise. We assessed the levels of biochemical and hormonal parameters in serum samples as well as insulin sensitivity indices of tissues. There were significant changes in the metabolic parameters with exercise. However, we did not find any additive effects of ostarine and exercise on most of the parameters tested. Similar results were obtained from the analysis of gene expression and the concentration of leptin and adiponectin. Our results indicated that ostarine had a lowering effect on cholesterol concentration in the serum (P<0.05). Moreover, when combining ostarine and exercise, additive changes were only observed in the levels of total and HDL cholesterol. No significant change was observed in the metabolic parameters of obese rats with the use of ostarine at the dose of 0.4 mg/kg body weight. Since ostarine is known to enhance performance, further research on its effects is needed.

超重和肥胖与严重的代谢紊乱和心血管疾病风险增加有关。众所周知,体育活动对代谢参数有积极影响,还可以降低患糖尿病等疾病的风险。有些产品可以提高脂肪分解率,有助于改善脂肪损失。其中之一是选择性雄激素受体调节剂(SARMs),它作为合成代谢剂,也被认为有助于脂肪燃烧。在这项研究中,我们使用肥胖大鼠模型结合运动,研究了30天的ostarine给药是否有可能改善代谢参数。我们评估了血清样本中的生化和激素参数水平以及组织的胰岛素敏感性指数。代谢参数随运动而发生显著变化。然而,我们没有发现ostarine和运动对大多数测试参数的任何相加效应。从基因表达和瘦素和脂联素浓度的分析中也获得了类似的结果。结果表明,ostarine对血清胆固醇浓度有降低作用(P
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引用次数: 0
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Journal of Physiology and Pharmacology
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