Investigation of lignin obtained by processing of Betula pendula with ionic liquids

Imidazolium-based ionic liquids bearing chloride, acetate, mesylate, and tosylate as anion were investigated for the treatment of birch (Betula pendula) bark to extract lignin. Although birch bark was previously extracted with methanol to remove low molecular weight organic compounds, various fatty acids and ferulic acid esters were analyzed in the lignin fraction using UPLC/ESI(?)-QTOFMS. GPC analysis shows differences in the molecular weight of the lignin samples obtained by treating bark with 1-butyl-3-methylimidazolium acetate and 1-ethyl-3-methylimidazolium tosylate. The use of 1-butyl-3-methylimidazolium chloride or 1-ethyl-3-methylimidazolium mesylate for the extraction of bark resulted in aromatic oligomers that are not fully soluble in the eluent used for GPC analysis. Therefore, the molecular weight as determined by GPC is only representative for the soluble part of these samples and not for the entire sample. Results obtained by investigation of the lignin samples extracted from bark using GPC and UPLC/ESI(?)-QTOFMS let us conclude that 1-butyl-3-methylimidazolium acetate is the most efficient ionic liquid among the solvents investigated for the extraction of lignin from bark. The high efficiency may be attributed to a high catalytic function of this ionic liquid in bound cleavage on the one hand and an active contribution of the acetate ion to trans-esterifications on the other hand.     

室温离子液体1-丁基-3-甲基咪唑四氟硼酸盐的制备及其在有机合成中的应用

目的采用无溶剂微波法制备室温离子液体1丁基3甲基咪唑四氟硼酸盐,并以其作反应溶剂和催化剂合成乙酸苄酯。方法在家用微波炉中间歇式加热。结果与结论在家用微波炉中采用无溶剂、间歇加热方式制备得到1丁基3甲基咪唑四氟硼酸盐,该法反应时间短、收率高;通过引入室温离子液体作为溶剂和催化剂,实现了由醋酸钠与氯苄在相对温和条件下及较短的反应时间内微波法合成了乙酸苄酯,并获得较高收率。     

皮试阴性的头孢曲松不良反应文献分析

目的:分析皮试阴后使用头孢曲松而发生不良反应的特点,为临床安全合理用药提供参考。方法:对1998―2015年检索中国生物医学文献数据库、中国期刊全文数据库及万方医学网中报道的头孢曲松皮试阴性的不良反应病例进行统计分析。结果:共收集到45例不良反应报告,大部分发生在开始用药后5~10 min以及连续用药后>24h,以呼吸系统(31.54%)、皮肤及附件(19.46%)和心血管系统(18.79%)损害表现为主。结论:头孢曲松的使用和皮试需进一步规范;即使皮试结果为阴性,在使用时仍应做到严密监护,以保证用药安全。     

钙拮抗剂对小鼠迟发型变态反应性肝损伤的影响

目的研究２,４,６ 三硝基氯苯（ｐｉｃｒｙｌｃｈｌｏｒｉｄｅ,ＰＣｌ）致迟发型变态（ＤＴＨ）反应ＰＣｌ ＤＴＨ诱导肝损伤过程中Ｃａ２＋的参与机制及钙拮抗剂的影响。方法将ＰＣｌ导致的ＤＴＨ反应导入肝脏诱发肝损伤,原子吸收分光光度法测定损伤后不同时间肝组织Ｃａ２＋含量,攻击前１ｈ及后８ｈ２次口服给予５０ｍｇ·ｋｇ－１钙拮抗剂硝苯吡啶或维拉帕米,观察血清谷丙转氨酶（ＡＬＴ）水平及肝组织Ｃａ２＋含量与对照组的差异。结果ＰＣｌ肝穿刺攻击后６ｈ肝组织Ｃａ２＋含量开始上升,１８ｈ达峰值,３６ｈ恢复正常;钙拮抗剂在保护肝损伤的同时降低了血清ＡＬＴ水平,且两者呈线性相关。结论Ｃａ２＋参与了该肝损伤过程,钙拮抗剂的降钙作用与其对该肝损伤的保护作用相关。     

1-丁基-3-甲基咪唑-L-樟脑磺酸盐催化合成monastrol

目的探索环境友好、操作简便的monastrol合成方法。方法以间羟基苯甲醛、乙酰乙酸乙酯和硫脲为起始原料,在无溶剂微波加热条件下,用绿色室温离子液体1-丁基-3-甲基咪唑-L-樟脑磺酸盐催化Biginelli反应合成monastrol。结果 1-丁基-3-甲基咪唑-L-樟脑磺酸盐在无溶剂微波加热条件下可催化Biginelli反应合成monastrol,操作简单、耗时缩短、环境友好。结论以新型绿色室温离子液体1-丁基-3-甲基咪唑-L-樟脑磺酸盐为催化剂,经微波促进无溶剂Biginelli反应合成monastrol是一种操作简便、反应温和的绿色合成方法。     

帕博利珠单抗致严重免疫相关皮肤不良反应的文献分析

目的: 探讨帕博利珠单抗致Stevens-Johnson综合征(SJS)、中毒性表皮坏死松懈症(TEN)严重皮肤反应的临床特点,旨在为临床合理使用帕博利珠单抗提供参考。方法: 检索中国知网、维普、万方、PubMed、Web of Science 和Medline 等数据库,收集整理自数据库建库至2022年2月关于帕博利珠单抗致SJS/TEN的个案报道,分析该药致SJS/TEN的临床特点。结果: 共收集25例病例,其中帕博利珠单抗致SJS病例13例,TEN7例,SJS/TEN重叠征5例。3种类型SJS/TEN反应中TEN发生最早,中位发生时间为16(3,39)d;其次为SJS/TEN重叠征,发生时间为30(22.5,115)d;SJS反应最晚为55(7,106.5)d。25例中有22例(88.0%)伴随着黏膜受累,17例(68.0%)在黏膜受累或皮肤脱落之前出现前驱性皮疹。25例患者24例(96.0%)接受了全身性糖皮质激素治疗,9例(36.0%)接受静脉注射免疫球蛋白,4例(16.0%)接受免疫抑制剂。最终,25例患者中17例(68.0%)好转或痊愈,5例(20.0%)死亡,3例(12.0%)预后未知。结论: 帕博利珠单抗可诱发SJS/TEN,应注意黏膜损伤,异常皮疹等可能为SJS/TEN发生信号,除了全身性糖皮质激素治疗以外,静脉注射免疫球蛋白和环孢素治疗证实是有益补充。     

Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage

The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box–Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2?±?6.0?nm, 0.245?±?0.069 and ?44.8?±?5.24?mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.     

DIDS对SIN-1诱导大鼠海马神经元凋亡及PARP-1/AIF表达的影响

目的观察氯通道阻断剂4,4'-二异硫氰基芪-2,2'-二磺酸(DIDS)对NO诱导的大鼠离体海马神经元凋亡的保护作用。方法离体培养12 d的SD大鼠海马神经元,随机分为正常对照组、3-吗啡斯德酮亚胺(3-morpholinosyndnomine,SIN-1)处理组、SIN-1+DIDS组。对各组神经元分别在相应的时间点用MTT法测定细胞生存率、Hoechst 33258测定凋亡百分数、免疫化学荧光分析检测凋亡信号蛋白PARP-1/AIF的变化、Western blot分析凋亡蛋白Caspase-3的变化。结果 DIDS呈剂量依赖性地抑制SIN-1诱导的神经元损伤,减少凋亡发生数目,并能抑制损伤所引起的Caspase-3的激活、削弱PARP-1/AIF的表达。结论氯通道可能参与了NO诱导的海马神经元损伤,氯通道阻断剂DIDS的保护作用可能与削弱PARP-1/AIF的表达有关。     

Effects of MPEP on locomotion, sensitization and conditioned reward induced by cocaine or morphine

Exposure to environmental cues is considered a major cause of relapse in detoxified addicts. Recent findings showed an involvement of glutamate in cue-induced relapse and suggest that subtype 5 of metabotropic glutamate receptors (mGluR5) is involved in conditioned drug-reward. The present study applied the conditioned place preference (CPP) paradigm to examine the involvement of mGluR5 in cocaine- and morphine-induced behaviours. Results of previous mice-studies were extended into rats by using the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP). As a result, the evaluated behavioural parameters were dose-relatedly affected by MPEP. Low-dosed MPEP (10 mg/kg, i.p.) did not affect spontaneous locomotion, reduced cocaine-induced hyperlocomotion and produced sensitized locomotion, while showing no effect on sensitized locomotion induced by repeated cocaine or morphine. Low-dosed MPEP did not genuinely block development of cocaine- and morphine-CPP, but rendered CPP expression state-dependent. The medium MPEP-dose (30 mg/kg) was most effective in reducing spontaneous locomotion. The high MPEP-dose (50 mg/kg) was most effective in reducing both body-weight and morphine-CPP expression. Cocaine-CPP expression was not affected by any MPEP-dose. In conclusion, mGluR5 are involved in modulation of spontaneous and cocaine-induced locomotion, in state-dependent learning and in expression of morphine-CPP. Thus, MPEP may be beneficial for relapse prevention in morphine-addicts.     

3-氧葡萄糖醛酮体外生成AGEs模型的建立

目的:建立可用于药物筛选的体外蛋白质非酶糖基化模型.方法:37℃孵育l周后用流动注射法于波长(λEx/Em);370/440 am处测定糖基化终产物(AGEs). 结果:反应l周后,反应体系内3-脱氧葡萄糖醛酮(3-DG)浓度与AGEs的吸收度值呈线性关系,y=22.946x 22.846;r=0.998 5. 结论:随着各反应体系中底物3-DG浓度的增加及反应时间的延长.蛋白质非酶糖基化反应增强3-DG为底物与牛血清白蛋白组成反应系统,能较可靠地反映AGEs的生成变化,有望成为体外蛋白质非酶糖基化的1种新模型.     

三氧化二砷对人胃癌细胞株癌相关基因表达

目的：研究三氧化二砷（As2O3）对人胃癌细胞株癌相关基因的影响，探讨：以As2O3作用于体外培养的人胃癌细胞株，通过免疫组化技术对P53、Cyclin-D,PCNA基因编码蛋白的表达进行检测。结果：经As2O3作用的人胃癌细胞P53、Cyclin-D,PCNA基因编码蛋白表达减少，结论：初步证实As2O3具有下调P53、Cyclin-D,PCNA基因编码蛋白表达，抑制肿瘤的增殖和转移，从而具有抗肿瘤作用。     

Impairment of wound healing by reactive skin decontamination lotion (RSDL®) in a Göttingen minipig® model

Abstract

Reactive Skin Decontamination Lotion (RSDL^®) is an FDA-approved skin decontamination kit carried by service members for removal and neutralisation of vesicants and nerve agents. The RSDL kit, comprised of a lotion-impregnated sponge, was shown to be the superior medical decontamination device for chemical warfare agent (CWA) exposure on intact skin. In the event of a chemical exposure situation (i.e. terrorism, battlefield) physical injuries are probable, and preservation of life will outweigh the risk associated with application of RSDL to compromised skin. The purpose of this study was to quantify the rate and quality of wound healing in epidermal skin wounds treated with RSDL in a porcine model. Degree of wound healing was assessed using bioengineering methods to include ballistometry, colorimetry, evaporimetry, and high-frequency ultrasonography. Clinical observation, histopathology and immunohistochemistry were also utilised. All pigs received four bilateral superficial abdominal wounds via a pneumatic dermatome on their ventral abdomen, then were treated with the following dressings over a seven-day period: RSDL sponge, petroleum based Xeroform^® gauze, 3?M? Tegaderm? Film, and 3?M? Tegaderm? Foam. Two additional non-wounded sites on the flank were used as controls. Two groups of pigs were then evaluated for a 21- or 56-day time period, representing short- and long-term wound-healing progression. Our findings indicated RSDL had a negative impact on wound-healing progression at both 21 and 56?days post-injury. Wounds receiving RSDL demonstrated a decreased skin elasticity, significant transepidermal water loss, and altered skin colouration and thickness. In addition, the rate of wound healing was delayed, and return to a functional skin barrier was altered when compared to non-RSDL-treated wounds. In conclusion, wound management care and clinical therapeutic intervention plans should be established to account for a prolonged duration of healing in patients with RSDL-contaminated wounds.     

替米沙坦对AGEs诱导人内皮细胞表达VCAM-1及MCP-1的作用和机制

目的 通过观察替米沙坦对晚期糖基化终末产物（AGEs）诱导的人脐静脉内皮细胞表达血管细胞黏附因子-1（VCAM-1）和单核细胞趋化蛋白-1（MCP-1）的影响,研究替米沙坦对AGEs所致动脉粥样硬化（AS）的干预作用和机制。方法 采用胶原酶消化法获取人脐静脉内皮细胞,分为4组：空白对照组,牛血清白蛋白（BSA）对照组,AGEs诱导组（10^-4~10^-1mg/mL）,AGEs+替米沙坦组（1、10、100 nmol/L）。活性氧检测试剂盒检测及倒置荧光显微镜观察细胞内活性氧含量,RT-PCR检测VCAM-1、MCP-1及晚期糖基化终末产物受体（RAGE）的mRNA。结果 AGEs组人内皮细胞内活性氧荧光强度增强,替米沙坦干预后降低;AGEs呈浓度依赖性地增强人内皮细胞对VCAM-1和MCP-1基因的转录,与空白对照组相比,AGEs（10^-4mg/mL）组VCAM-1和MCP-1 mRNA表达水平显著增高（0.24±0.01 vs 0.07±0.02;0.25±0.01 vs 0.18±0.03,P<0.05）;替米沙坦呈浓度依赖性地抑制人内皮细胞对VCAM-1和MCP-1基因的转录,与AGEs诱导组相比,替米沙坦（10 nmol/L）组人内皮细胞的VCAM-1和MCP-1基因转录水平显著降低（0.23±0.01 vs 0.85±0.11;0.62±0.10 vs 1.05±0.04,P<0.05）;与AGEs诱导组相比,替米沙坦（1 nmol/L）组人内皮细胞RAGE基因表达水平显著降低（0.64±0.03 vs 1.18±0.10,P<0.05）。结论 AGEs增强人内皮细胞表达VCAM-1和MCP-1;替米沙坦可能通过抑制RAGE表达来抑制AGEs诱导的人内皮炎性损伤。     

Evaluation of DNA damage induced by norcantharidin in human cultured lymphocytes

Norcantharidin (NCTD) is currently used in the treatment of several cancers such as leukemia, melanoma and hepatoma. The mechanism of action of NCTD is suggested to involve induction of apoptosis of cancer cells via production of reactive oxygen species. In this study, the genotoxic effect of different concentrations of NCTD (1, 10 and 20?μm) in human lymphocytes was investigated using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays. The results revealed that NCTD significantly increased the rate of SCEs (p?<?0.05) in a dose-dependent manner. In addition, NCTD significantly increased the number of high-frequency cells (SCEs?≥?8, p?<?0.05). However, NCTD did not have any significant effect on the rate of CAs (p?>?0.05). In addition, no significant differences were detected in the mitotic index or proliferative index at examined doses (up to 20?μm). In conclusion, NCTD is genotoxic to human cultured lymphocytes as measured by SCE assay.     

Protective effect of metoclopramide against organophosphate‐induced apoptosis in the murine skin fibroblast L929

This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)‐ and malathion (MLT)‐induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm ) or 1.0 μm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate‐stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin‐V/propidium iodide, processing and activation of the executioner caspase‐3, cleavage of the poly‐ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 μm ) did not induce apoptosis or activation of caspase‐3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose‐dependent manner reaching ~70–80% protection when they were preincubated at 1 and 5 μm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor‐α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti‐apoptotic effect of the drug is specific to organophosphates. The strong and specific anti‐apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.     

The interplay between ASMase signaling pathway and NLRP3 in the epithelial to mesenchymal transition of HBE cells induced by silica

Epithelial–mesenchymal transition (EMT) is an important part of pulmonary fibrosis. Our earlier study illustrated that the acid sphingomyelinase (ASMase) pathway plays significant role in silica (SiO₂)-induced transformation of lung fibroblasts into myofibroblasts. The metabolite of ASMase, ceramide (Cer), activates the inflammatory response by activating Nod-like receptor protein 3 (NLRP3) in macrophages, and NLRP3 is also involved in the EMT process. However, whether ASMase and NLRP3 are involved in regulating SiO₂-induced EMT has not been confirmed. In this study, an in vitro model of EMT in human bronchial epithelial (HBE) cells was established by SiO₂ dust staining to investigate the role of ASMase and NLRP3 in EMT and to provide new clues for the molecular mechanism of silicosis. HBE cells were stained with 100 μg/ml SiO₂ dust for 72 h to establish the EMT model. The ASMase inhibitor desipramine decreased the level of S1P and the expression of α-smooth muscle actin (α-SMA) and NLRP3 in SiO₂ dust-stained HBE cells, whereas the expression of E-cadherin (E-cad) increased. The NLRP3 inhibitor MCC950 inhibited the secretion of interleukin-1β (IL-1β) and decreased the expression of NLRP3, Caspase-1, and α-SMA in SiO₂ dust-stained HBE cells, whereas E-cad expression increased and ASMase activity and S1P levels decreased. It was concluded that SiO₂ dust increases the release of the inflammatory factor and induces EMT in HBE cells. Inhibition of ASMase activity or NLRP3 expression reduced the SiO₂ dust-induced cell inflammatory response and slowed the occurrence of EMT in HBE cells. Therefore, NLRP3 and ASMase may interact in SiO₂ dust-induced EMT in HBE cells.     

枸橼酸西地那非对复合因素诱导大鼠慢性阻塞性肺疾病和肺动脉高压治疗作用的评估

目的：探讨西地那非对COPD大鼠肺组织损伤和肺血管重构的治疗作用。方法：应用香烟烟雾复合克雷伯杆菌滴鼻制作大鼠COPD模型,肺功能显著降低后,给予西地那非治疗。通过肺功能检测、平均肺泡数和平均内衬间隔检测及肺组织形态观察,评估药物对肺气肿、肺病理损伤的影响;通过肺动脉压、右心肥大指数及肺小动脉血管分型检测,评估药物对肺动脉高压、肺血管重构和右心室肥大的影响。结果：香烟烟雾复合克雷伯杆菌攻击大鼠8周、停止攻击4周后,动物肺功能显著降低（P<0.05或0.01）,提示COPD模型建立、停止攻击后至少维持4周。停止攻击后,给予西地那非治疗,与模型组比较,肺功能未见显著性改善（P>0.05）;西地那非显著降低肺动脉压和减少右心室肥大指数（P<0.05或0.01）,显示出剂量依赖性。与模型组比较,西地那非减轻肺间质、支气管和血管周围的炎症细胞浸润;但与正常组比较,炎症细胞浸润仍较严重,提示西地那非抑制但不能消除肺组织的炎症反应。西地那非显著减少肌化肺血管的百分率（P<0.01）、显著增加平均肺泡数量（P<0.01）,抑制肺血管重构和肺气肿。结论：西地那非对大鼠COPD及PH具有治疗作用。     

Mixed function oxygenation of the lower fatty acyl residues--I. Hydroxylation of the acetic, propionic, butyric, and valeric residues by rabbit liver microsomes.

Rates of hydroxylation of C-atoms in various positions [ω-, (ω-1)-, (ω-2)-] of an increasing chain length have been measured with the 4-chloroanilides of acetic, propionic, butyric, and valeric acid as substrates. The hydroxylation products were separated by t.l.c, quantified by u.v. spectroscopy and further characterized by n.m.r. and o.r.d. spectroscopy. The hydroxylation products in which an asymmetric centre had been introduced by oxygenation, were shown to be optically active, the sign of the optical rotation indicating an excess of the S-over the R-isomer. From the alteration of the hydroxylation pattern caused by previous treatment of rabbits with either phenobarbital or 3-methylcholanthrene it can be deduced that the ω, (ω-1), and (ω-2)-hydroxylation of the lower fatty acyl residues is not only catalysed by PB- and 3-MCh-inducible forms of cytochrome P-450 but also by the forms not inducible by either PB or 3-MCh.