Given the increasing prevalence of drug-resistant tuberculosis (TB), there is an urgent demand in developing novel anti-TB medications with highly effective, safe, and utilize innovative mechanisms of action. Blocking the mycolic acid synthesis pathway is well-established to be a significant strategy in developing anti-TB drugs, and Pks13 was identified as a crucial enzyme in this process. Importantly, the modes of action of recognized Pks13 inhibitors differ from traditional anti-TB medications, highlighting Pks13 as a potential and promising target in drug development within TB treatment. In this study, we discovered a compound named BMVC-8C3O that effectively inhibited the activity of Pks13 with a 6.94 μM IC50 value. The binding between BMVC-8C3O and Pks13 was validated through surface plasmon resonance (SPR) assay as well as molecular docking analysis. Moreover, the SPR assay showed that the mutation of Asn1640 and Ser1533 resulted in decreased affinity of BMVC-8C3O to Pks13. Additionally, BMVC-8C3O not only exhibited activity against Mycobacterium tuberculosis (MTB), but also displayed potential intracellular anti-TB activity in macrophages. In summary, our findings indicate that BMVC-8C3O holds great potential as a lead compound against TB.

Abstract Background Bedaquiline (BDQ), a first-in-class diarylquinoline compound, was approved for therapy of multidrug-resistant tuberculosis (MDR-TB) by the FDA in 2012. Previous studies have shown that the addition of BDQ to the preferred regimen resulted in faster sputum-culture conversion, but more deaths compared with the placebo group. Since the mechanism of BDQ is related to ATP synthase, and ATP synthase is closely linked to aging-related diseases, we hypothesized that BDQ may cause mitochondrial dysfunction, leading to cellular apoptosis and senescence. Methods The Cell Counting Kit-8 (CCK-8) assay is used to assess the viability of cells in the presence or absence of bedaquiline treatment. We used flow cytometry to detect Annexin V-PI and ROS levels in different groups of cells. TMRM staining is performed to examine the changes in mitochondrial membrane potential of the cells. Western blot is used to measure the expression levels of proteins associated with aging and apoptosis. The β-Galactosidase kit is used for staining to examine the proportion of senescent cells in different groups. Results In the current study, we evaluated the apoptosis and senescence induction effects of BDQ in human embryonic lung fibroblasts MRC-5 cells and rat cardiomyocytes H9C2 cells and explored the potential molecular mechanisms. The results demonstrated that BDQ reduced the cell viability in a dose- and time-dependent manner. In addition, BDQ induced cellular apoptosis and senescence, and increased Reactive Oxygen Species (ROS) level. Conclusions Our results revealed that BDQ can cause cellular apoptosis and senescence for the first time, with the aim of optimizing anti-TB drug regimens in anticipation of better outcomes.

AIM: To investigate the effect of 0.01% atropine sulphate eye gel on myopia progression and axial elongation in a 6-month treatment in children. METHODS: Totally 185 children aged 6-12y with binocular myopia of 3.0 D or less in both eyes were enrolled in this prospective cohort study. The atropine group (n=125) received one drop of 0.01% atropine sulphate eye gel in each eye before bedtime daily. The control group included 60 matched children without drug intervention during the same period. The spherical equivalent and axial length was recorded at baseline and the sixth month of treatment. The efficacy was evaluated by the change of the spherical equivalent and axial length. Adverse events were also recorded. RESULTS: The average spherical equivalent and axial length at baseline were not statistically significant between the atropine group (-1.64±0.80 D, 24.13±0.76 mm) and the control group (-1.59±0.94 D, 24.06±0.77 mm, P>0.05). After 6mo, there was significantly difference in the spherical equivalent progression between the atropine and the control group (-0.27±0.33 vs -0.60±0.35 D, P<0.001), with a relative reduction of 55.0% in myopia progression. The increase in axial elongation in the atropine group was significantly less than control group (0.19±0.14 vs 0.26±0.14 mm, P<0.001), with a relative reduction of 26.9% in axial length. The 84.4% and 38.4% of the eyes progressed by less than 0.50 D and remained stable in the atropine group, compared with 51.7% and 4.2% in the control group. No adverse events were observed. CONCLUSION: Atropine sulphate eye gel 0.01% can slow down myopia progression and axial elongation in children with a 6-month treatment.

目的:探讨积雪草苷对阿霉素诱导的足细胞中α-actinin-4、synaptopodin蛋白及ERK/JNK通路的影响.方法:1)MTT法检测积雪草苷对足细胞及阿霉素诱导的足细胞活力的影响.2)选用1μmol/L阿霉素制造足细胞损伤模型,蛋白印迹法(Western blotting)检测足细胞α-actinin-4、synaptopodin蛋白表达.3)免疫荧光检测足细胞骨架及Western blotting检测ERK/JNK信号通路的磷酸化水平.结果:1)低浓度积雪草苷(10～80μg/mL)对足细胞活力无明显影响,而高浓度积雪草苷(>80μg/mL)可降低足细胞活力;2)阿霉素体外可损伤足细胞,降低足细胞活力;积雪草苷浓度依赖性地减轻阿霉素对足细胞的损伤,增加足细胞活力;阿霉素体外可增加足细胞骨架蛋白α-actinin-4的表达,减少足细胞骨架蛋白synaptopodin的表达,而积雪草苷可下调阿霉素诱导的足细胞α-actinin-4蛋白表达,上调阿霉素抑制的足细胞synaptopodin的表达;3)阿霉素(1μmol/L)能升高ERK、JNK的磷酸化水平,与空白对照组比较差异有统计学意义(P<0.05);积雪草苷预处理细胞后,能够有效遏制阿霉素诱导的ERK活化,与模型对照组比较差异有统计学意义(P<0.05),但却不能抑制阿霉素诱导的JNK信号通路中JNK的活化.结论:积雪草苷预处理细胞后可能通过遏制阿霉素诱导的ERK信号通路的活化,减少阿霉素对足细胞骨架的损伤作用,从而改变了α-actinin-4、synaptopodin蛋白表达.

Dexmedetomidine (DEX) exerts cardioprotection against ischemia/reperfusion injury. However, the precise mechanisms underlying this cardioprotective effect in diabetic rats are still not fully understood. The aim of the present study was to investigate the cardioprotective mechanism of DEX pretreatment on myocardial ischemia/reperfusion (I/R) injury in diabetic rats. A total of 25 streptozotocin-induced diabetic rats were equally randomized into five groups: i) Sham, ii) DEX (100 μg/kg); iii) myocardial I/R; iv) myocardial I/R+DEX (10 μg/kg); and v) myocardial I/R+DEX (100 μg/kg) groups. Primary cardiomyocytes were cultured in DEX for 1 h, and then oxygen and glucose deprivation (OGD)/R for 36 h. These results showed that pretreatment with DEX significantly decreased the I/R-induced size of the myocardial infarction, structural damage, morphological changes and apoptosis in myocardial cells, as well as levels of creatinine kinase, malondialdehyde and cardiac troponin I, and increased the I/R-induced superoxide dismutase activity in vivo and in vitro. Furthermore, immunohistochemical staining and western blot analysis revealed that DEX pretreatment significantly increased the I/R-induced expression levels of B-cell lymphoma 2 (Bcl-2), phosphorylated phosphoinositide 3-kinase (pPI3K) and pAkt, and significantly decreased those of pBcl-2 associated agonist of cell death, Bcl-2-associated X protein and cleaved caspase 3 in vivo and in vitro. In addition, all of these cardioprotective effects of DEX were reversed by yohimbine and LY294002 pretreatment. These results suggested that DEX pretreatment may activate the PI3K/Akt signaling pathway in an α2 adrenoceptor-dependent manner. DEX pretreatment may exert cardioprotective effects against myocardial ischemia/reperfusion injury in diabetic rats through the I/R-induced inhibition of cell apoptosis by activating the PI3K/Akt signaling pathway.

Aldosterone regulates the initiation and development of atherosclerosis which is identified as a chronic inflammatory disease by promoting the generation of C-reactive protein in vascular smooth muscle cells. Curcumin is the most active ingredient of turmeric with anti-inflammation and antioxidation effects. Here, the effect of curcumin on aldosterone-induced C-reactive protein generation in vascular smooth muscle and the molecular mechanisms involved were explored. Primary rat vascular smooth muscle cells and hyperaldosteronism model rats were used in this study. The amount of C-reactive protein, reactive oxygen species, and the signaling pathway-related molecules generated were estimated. We found that curcumin inhibited aldosterone-induced C-reactive protein generation in vascular smooth muscle cells by interfering with the reactive oxygen species-ERK1/2 signal pathway. The results provide new evidence for the potential anti-inflammatory and cardiovascular protective effects of curcumin.

Quercetin is a flavonoid abundant in the plant kingdom. Various types of bioactivities of quercetin have been demonstratedin vitro. Although quercetin has been proposed to exhibit numerous pharmacological benefits, it suffers from low bioavailability on account of its obviously poor solubility in water. Cocrystals have generated interest recently as a way of enhancing the dissolutionin vitroand creating relative bioavailability of insoluble medicine. In this study, quercetin-nicotinamide cocrystals were obtainedviaa solvent evaporation technique. Furthermore, quercetin-nicotinamide cocrystals were characterizedviaFourier transform infrared (FI-IR) spectroscopy, X-ray powder diffraction (PXRD), and differential scanning calorimetry (DSC) techniques. Quercetin-nicotinamide cocrystals are a new phase material, and the established intermolecular forces such as hydrogen bonds between quercetin and nicotinamide existed in the quercetin-nicotinamide cocrystals, as confirmed from the solid-state analysis. The dissolution of quercetin-nicotinamide cocrystals was found to be significantly higher than that of quercetin crystals. The pharmacokinetic data from thein vivoexperiments suggested that quercetin-nicotinamide cocrystals could significantly increase the oral absorption of quercetin by nearly 4-fold. These results demonstrate that the developed quercetin-nicotinamide cocrystals are a promising oral formulation toward improvement in the dissolution and bioavailability of quercetin.

Atherosclerosis is a chronic inflammatory disease of the arterial wall. Inflammation causes endothelial injury and dysfunction, which is an initial step of atherosclerosis. Fibrinopeptide A (FPA) is a biomarker of the activation of the coagulation system, and a high concentration of FPA in the blood occurs in patients with ischemic cardiocerebrovascular diseases. The present research observed that FPA stimulated the generation of C-reactive protein (CRP), IL-1β, and IL-6 in human umbilical vascular endothelial cells (HUVECs); and anti-IL-1 β and anti-IL-6 neutralizing antibodies did not alter FPA-induced CRP expression in HUVECs. The subchronic administration of FPA into rats increased the plasma FPA and CRP levels. Further studies showed that FPA stimulated superoxide anion generation, activated ERK1/2 and p38, promoted nuclear factor κB (NF-κB) nuclear translocation, and raised the NF-κB level in the nuclei of HUVECs. Antioxidant N-acetylcysteine (NAC), complex II inhibitor thenoyltrifluoroacetone (TTFA), and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited FPA-stimulated generation of superoxide anion, and NAC reduced FPA-induced expressions of the phosphorylated ERK1/2 and p38. NAC, TTFA, DPI, inhibitors of ERK1/2, p38, and NF-κB all downregulated FPA-induced CRP expression. These results indicate that FPA induces CRP expression in HUVECs via the ROS-ERK1/2/p38-NF-κB signal pathway. Moreover, this is the first report that FPA produces a proinflammatory effect on the vascular endothelial cells.

LncRNA plays a vital role in many diseases, and abnormal expression of LncRNA has been reported in many types of tumors. In this study, we analyzed the available public TCGA and GEO databases, and found that the expression of SNHG3 was increased in clear cell renal cell carcinoma (ccRCC), which was positively correlated with many clinicopathological parameters, and the higher expression of SNHG3 predicted worse clinical prognosis. Functional experiments indicated that knockdown of SNHG3 could significantly inhibit the proliferation and metastasis of ccRCC in vitro and in vivo. Subsequently, through luciferase reporter assays, qPCR and rescue experiments, it was found that SNHG3 could bind to miR-139-5p, thereby up-regulating the expression of its target gene TOP2A, and play a role in promoting tumor progression in ccRCC. The correlation analysis showed that there was a significant positive correlation between the expression of SNHG3 and TOP2A, and both of them were significantly negative correlated with the expression of miR-139-5p. Our work suggested that the SNHG3/miR-139-5p/TOP2A axis plays an important role in the proliferation and metastasis of ccRCC, and was expected to be a new biomarker for diagnosis, prognosis and a target for treatment of ccRCC.

AIMS:Apigenin-7-O-β-d-(-6″-p-coumaroyl)-glucopyranoside (APG) was considered as the major active compound derived from Clematis tangutica. Though we have demonstrated that APG exerts cardioprotective effects, the mechanism of APG-mediated cardioprotection remains largely unknown. Numerous studies indicate that endoplasmic reticulum stress (ERS) is a vital injury factor in myocardial ischemia reperfusion (MI/R). In this study, we mainly investigated whether modulation of the ERS and AMPK were involved in the cardioprotective action of APG during MI/R injury.MAIN METHODS:The perfused isolated rat heart or primary neonatal rat cardiomyocytes which exposed to APG with or else without the AMPK inhibitor Compound C was then subject to MI/R. After reperfusion, the degree of myocardial injury was assessed by using lactate dehydrogenase (LDH) release, creatine kinase (CK) release, histological examination, and TTC staining. The protein expressions of p-AMPK, AMPK, p-PERK, PERK, p-eIF2α, eIF2α, CHOP, Bax, Bcl2 and Cleaved Caspase 3 were analyzed by western blot. The cell viability was assessed by CCK-8 kit while apoptosis assessed by using TUNEL assay.KEY FINDINGS:Pretreatment of APG significantly improved cardiac function and suppressed ERS through activating the AMPK signaling pathway, which could simultaneously improve cardiac function, alleviate myocardial injury, increase the cell viability and decrease apoptosis.SIGNIFICANCE:To conclude, APG ameliorates MI/R injury by activating the AMPK signaling pathway and relieving endoplasmic reticulum stress. APG may be a natural product with pharmacological preconditioning activity, which could do us a favor to develop more novel therapy methods to against MI/R injury in the future.

Sepsis-induced brain injury is frequently encountered in critically ill patients with severe systemic infection. Butein (3,4,2',4'-tetrahydroxychalcone) has been demonstrated as the neuro-protective agent via reducing inflammation and oxidative stress on neurons. Moreover, activation of silent information regulator 1 (SIRT1) inhibits apoptosis, oxidation and inflammation thus alleviating sepsis-induced multiorgan injuries. In present study, we show that butein administrated intraperitoneally (10 mg/kg) saved mice from sepsis-induced lethality by increasing 7-day survival rate after cecal ligation and puncture (CLP) surgery. Additionally, butein treatment enhanced SIRT1 signaling thus decreasing the Ac-NF-κB, Ac-FOXO1 and Ac-p53 levels, thus attenuating the brain injury of mice after CLP surgery by decreasing cerebral edema, maintaining the blood-brain barrier integrity, inhibiting neuronal apoptosis, and decreasing pro-inflammatory cytokines production (IL-6, TNF-α and IL-1β) and oxidative stress (downregulation of MDA, and upregulation of SOD and CAT) in both serum and cerebral cortex tissues. Moreover, butein treatment attenuated LPS induced neurological function loss. However, all above mentioned neuro-protective actions of butein were partially inhibited by EX527 co-treatment, one standard SIRT1 inhibitor. Collectively, butein attenuates sepsis-induced brain injury through alleviation of cerebral inflammation, oxidative stress and apoptosis by SIRT1 signaling activation.

Excessive ethanol (EtOH) intake affects cognitive function and leads to permanent learning and memory deficits. EtOH-induced neuroinflammation plays an important role in EtOH neurotoxicity. Studies have shown that EtOH activates microglia and induces an inflammatory response. Resveratrol (Rsv) is a natural polyphenol found in a wide variety of plants and fruits, and produces the neuroprotective and anti-inflammatory effects in the central nervous system. However, effect of Rsv on EtOH-induced neuroinflammation is still unknown. We investigated the anti-inflammatory effect of Rsv in the context of EtOH-induced neurotoxicity and the molecular mechanisms potentially involved in the effect. The results showed that treatment of rats with Rsv prevented the deficits of spatial reference memory induced by EtOH and mitigated EtOH-induced neuroinflammation by inhibiting microglial activation and decreasing the levels of inflammatory cytokines including interleukin-1β, interleukin-6 and tumor necrosis factor α. The further studies indicated that Rsv reduced TLR2 expression in vivo and in vitro, and downregulated expression of myeloid differentiation primary response 88 (MyD88) and phosphorylation of nuclear factor κB (NF-κB). These data demonstrate that Rsv alleviates the ethanol-induced neuroinflammation via inhibition of TLR2-MyD88-NF-κB signal pathway.

目的 分析美托洛尔的药理特性及不良反应.方法 先择2010年1月-2017年1月该院使用美托洛尔后发生不良反应患者54例为研究对象,开展不良反应调查,并分析药物药理特性.结果 54例美托洛尔不良反应患者中男41例,女13例.不良反应发生集中在41～70岁;主要累及消化、呼吸、神经、皮肤、心血管等系统,其中心血管系统受损最为严重.所有患者均以口服方式服药,其中单一用药22例,联合用药32例.不良反应出现在用药后0.5～24 h比例最高.结论 美托洛尔不良反应的发生与β-受体被阻断有关,医师用药时应全面掌握禁忌证,在真正意义上做到合理用药,全面提升用药安全性,降低不良反应发生率.

AIMS:C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 are involved in the inflammation of atherosclerosis lesions. Genistein (Gen) has been demonstrated to exert beneficial effect on the cardiovascular system. However, it remains unclear whether Gen produces anti-inflammatory effect in vascular smooth muscle cells (VSMCs). Therefore, we investigated the effects of Gen on CRP and MMP-9 expressions induced by angiotensin (Ang) II in VSMCs and the related molecular mechanism.MAIN METHODS:Rat VSMCs were cultured, and Ang II was used as a stimulant for CRP and MMP-9 expressions. CRP level was measured by ELISA. The mRNA and protein expressions of related indexes were identified by reverse transcription-polymerase chain reaction and western blot, respectively.KEY FINDINGS:Gen inhibited Ang II-stimulated CRP and MMP-9 mRNA and protein expressions in concentration- and time-dependent manners. Additionally, Gen ameliorated Ang II-induced p-ERK1/2, p-p38 and NF-κB expressions, antagonized Ang II-downregulated peroxisome proliferation-activated receptor (PPAR) γ and estrogen receptor (ER) β expressions. After treating the VSMCs with GW9662 or ICI182780 in Gen treated groups, inhibitory effect of Gen on CRP and MMP-9 expressions were antagonized in Ang II-stimulated VSMCs. The treatment of VSMCs with ICI182780 abolished downregulations of p-p38/p-ERK1/2, and antagonized upregulation of PPARγ by Gen in Ang II-stimulated VSMCs. Moreover, the inhibitory effect of Gen on Ang II-stimulated NF-κB expression was abolished after preincubation of VSMCs with GW9662 in Gen treated groups.SIGNIFICANCE:Gen exerts anti-inflammatory property via the ER-p38/ERK1/2-PPARγ-NF-κB-CRP/MMP-9 signal pathway in Ang II-stimulated VSMCs.

Background/Aims: Atherosclerosis is a chronic inflammatory disease in the artery walls. Fibrinopeptide A (FPA) is a biomarker of the activation of coagulation system, and a high concentration of FPA in blood occurs in patients with ischemic heart disease etc. However, there exist few studies on the pathological effects of FPA in cardiovascular system. Therefore, the present study examined the effect of FPA on CRP expression in VSMCs and the molecular mechanisms. Methods: mRNA and protein expression was identified by quantitative real-time PCR and Western blot, respectively. Reactive oxygen species (ROS) and the immunofluorescence staining were observed by a fluorescence microscope. Plasma FPA and CRP level was determined by ELISA. Results: FPA induced the expressions of CRP, IL-1β and IL-6 in VSMCs, and anti-IL-1β and anti-IL-6 neutralizing antibodies partially reduced FPA-induced CRP expression in VSMCs. The subchronic administration of FPA to rats increased FPA level in plasma and CRP expression in the aortic artery walls. The further studies showed that FPA promoted superoxide anion generation in VSMCs. Antioxidant NAC antagonized FPA-stimulated superoxide anion generation and inhibited FPA-induced CRP expression in VSMCs. FPA activated ERK1/2 and p38 phosphorylation, and PD98059 and SB203580 reduced FPA-induced CRP expression. Moreover, NAC inhibited the activation of ERK1/2 and p38. In addition, FPA enhanced NF-κB level in the nuclei of VSMCs, and PDTC reduced FPA-induced expression of CRP. Conclusions: FPA induces CRP expression in VSMCs via ROS-ERK1/2/p38-NF-κB signal pathway. This finding for the first time provides an experimental evidence for pro-inflammatory effect of FPA.

Atherosclerosis is a chronic inflammatory disease in the vessel wall. As a representative inflammatory cytokine, C-reactive protein (CRP) participates in the formation and development of atherosclerosis. It is demonstrated that aldosterone induces CRP generation in vascular smooth muscle cells (VSMCs). This study explored the inhibitory effect of eplerenone on aldosterone-induced CRP expression in VSMCs and mechanism. In the in vitro experiments, rat VSMCs were cultured and aldosterone (10 nM) was used as a stimulant for CRP generation. VSMCs were pretreated with eplerenone for 1 h prior to the stimulation. Messenger RNA (mRNA) and protein expression were identified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot, respectively. The production of reactive oxygen species (ROS) was observed by a fluorescence microscope. In the in vivo experiment, a model of hyperaldosteronism was established by the subcutaneous administration of aldosterone to rats with the osmotic minipumps for 4 weeks. Serum aldosterone and CRP levels were determined with a radioimmunoassay and ELISA (enzyme-linked immunosorbent assay), respectively. The results showed that eplerenone inhibited aldosterone-induced mRNA and protein expression of CRP in VSMCs in vitro and in vivo, and decreased the circulating CRP level of hyperaldosteronism rats. Meanwhile, eplerenone reduced aldosterone-stimulated ROS generation and aldosterone-activated ERK1/2 phosphorylation in VSMCs. In summary, eplerenone inhibits aldosterone-induced CRP generation in VSMCs by regulating the MR-ROS-ERK1/2 signal pathway. These results provide new evidence for the potential anti-inflammatory effect of eplerenone.

Inflammation plays a key role in many chronic diseases such as cardiovascular diseases and liver diseases. As a representative inflammatory molecule, C-reactive protein (CRP) is mainly produced in the liver. Hepatic CRP plays a direct role in the inflammatory hepatic diseases and in development of atherosclerosis when entering into the blood circulation. In the present study, we observed the effect of epigallocatechin-3-gallate (EGCG) on Ang II-induced CRP generation in hepatocytes and the molecular mechanism. Rats were delivered with the subcutaneous infusion of Ang II and/or intragastric administration of EGCG for 7 days. Hepatocytes were pretreated with EGCG before stimulation with Ang II in vitro. CRP level in the serum and liver was determined with ELISA and the immunohistochemical staining. RNA and protein expressions were determined using RT-PCR and Western blot. The in vivo experiment confirmed that EGCG reduced not only CRP generation in the liver of Ang II-infused rats but also serum CRP level. The in vitro results showed that pretreatment of hepatocytes with EGCG inhibited Ang II-induced mRNA and protein expression of CRP in a concentration-dependent manner. Further study exhibited that EGCG downregulated AT1 expression, attenuated Ang II-activated phosphorylation of ERK1/2, and upregulated Ang II-inhibited peroxisome proliferator-activated receptor gamma (PPARγ) expression in vitro and in vivo. In addition, EGCG decreased Ang II-stimulated reactive oxygen species (ROS) generation in hepatocytes. These demonstrate that EGCG is able to inhibit Ang II-induced CRP generation by interfering with AT1-ROS-ERK1/2 signal pathway in hepatocytes, which provides the new evidence and mechanism for the anti-inflammatory effect of EGCG.

Inflammation plays a pivotal role throughout the formation and progression of atherosclerosis. As the most representative inflammatory marker, C-reactive protein (CRP) directly participates in the initiation and development of atherosclerosis. The elevated homocysteine (Hcy) level in plasma is an independent risk factor for atherosclerosis. We previously reported that Hcy produces a pro-inflammatory effect by stimulating CRP expression in vascular smooth muscle cells (VSMCs). The present study observed the effect of simvastatin on Hcy-induced CRP expression in VSMCs and the molecular mechanisms. The in vitro experiments revealed that pretreatment of VSMCs with simvastatin decreased Hcy-induced mRNA and protein expression of CRP in a concentration-dependent fashion. The in vivo results showed that simvastatin not only inhibited CRP expression in the vessel walls in mRNA and protein levels, but also reduced the circulating CRP level in hyperhomocysteinemic rats. Further experiments displayed that simvastatin reduced Hcy-induced reactive oxygen species (ROS) generation, ameliorated Hcy-activated phosphorylations of ERK1/2 and p38, and antagonized Hcy-downregulated peroxisome proliferator-activated receptor gamma expression in VSMCs. These data demonstrate that simvastatin is able to inhibit Hcy-induced CRP generation in VSMCs so to relieve the vascular inflammatory response via interfering with the ROS-MAPK signal pathway. The present results provide new evidence for understanding of the potential anti-inflammatory and anti-atherosclerotic effects of simvastatin. As the high level of Hcy in plasma is related to atherosclerosis formation and mediates cardiovascular risk, our findings emphasize the importance and necessity of therapy with statins for hyperhomocysteinemia in atherosclerosis.

目的:探讨前列地尔注射液的不良反应发生情况.方法:采用回顾性研究方法,2015年7月-2016年4月选择我院使用前列地尔注射液治疗的患者1800例作为研究对象,对前列地尔注射液的不良反应情况进行记录与统计,对患者的一般资料、原患疾病、不良反应表现、处理和结果等方面进行统计分析.结果:经过调查,在1800例患者中,出现不良反应150例,发生率为8.3%;其中皮肤反应37例,循环系统反应77例,神经系统反应18例,其他反应18例;有56例在使用后第1d发生,84例在使用后第2d发生;119例未加处理患者仍可耐受.结论:前列地尔注射液的不良反应比较常见,多造成循环系统反应、皮肤反应、神经系统反应等,需要临床上合理使用.

Inflammation is a commonly pathological change in liver diseases, and promotes the development of acute and chronic liver diseases by excessive production of inflammatory cytokines. C-reactive protein (CRP) is primarily synthesized in the liver and participates in many chronic diseases. Our previous study confirmed that Ang II stimulates CRP generation in hepatocytes. This study investigated the effect of rosiglitazone (RSG) on Ang II-stimulated CRP expression and the molecular mechanism in hepatocytes. The results showed that the subcutaneous infusion of Ang II to rats for 7days through the osmotic minipumps increased CRP expression in the liver and serum CRP level. The simultaneous treatment of rats with RSG reduced CRP generation in the liver and CRP concentration in serum. Further study showed that RSG down-regulated Ang II-induced mRNA and protein expression of CRP and AT1 as well as phosphorylation of ERK1/2 and JNK, enhanced mRNA and protein expression of PPARγ in hepatocytes in vivo and in vitro. In addition, RSG increased superoxide dismutase activity in the liver of Ang II-infused rats in vivo, and decreased Ang II-stimulated reactive oxygen species (ROS) production in hepatocytes in vitro. In conclusion, the present study demonstrates that RSG is able to inhibit Ang II-induced CRP generation by interfering with AT1-ROS-ERK1/2/JNK signal pathway and up-regulating PPARγ expression in hepatocytes, which provides the new evidence and mechanisms for the beneficial effect of RSG to relieve hepatic inflammation and suggests the possibility that RSG is used for the inflammatory hepatic diseases.