Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer–Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.     

MiR-29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1

MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR-29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP-treated mice or MPP⁺-intoxicated SH-SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR-29c was employed to examine its biological function on PD progress. We found that miR-29c was down-expressed but SP1 was high-expressed in substantia nigra pars compacta (SNpc) of MPTP-induced PD mice. Overexpression of miR-29c attenuated dopaminergic neuron loss and α-synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and TUNEL-positive apoptotic cells in MPTP-treated mice were ameliorated by miR-29c. Similarly, in SH-SY5Y cell models of PD, we also found that miR-29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro-apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR-29c. Luciferase reporter assay confirmed that SP1 was complementary with miR-29c. Knockdown of SP1 with siRNA restored α-synuclein accumulation, inflammation and apoptosis in MPP⁺-induced SH-SY5Y cells. Collectively, this current work presents that miR-29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.     

雌激素及雌激素受体信号转导途径在严重创伤中的作用及机制

随着社会的不断发展和进步,交通事故、建筑工伤、自然灾害频繁发生,创伤仍然是全球一项重大的卫生与社会问题。严重创伤的高病死率和致残率给社会及个人带来巨大的经济和精神负担。近年来研究表明雌激素可能在严重创伤进程中扮演重要角色,一系列临床调查研究表明女性严重创伤患者病死率、并发症发生率显著低于男性;基于严重创伤动物模型的实验研究也为性别相关的结果差异提供了初步证据,但结果并不完全一致。然而严重创伤病理生理学机制涉及多个方面和环节,至今尚未完全清楚。笔者就雌激素及雌激素受体(estrogen receptor,ER)信号转导途径在严重创伤中的作用及机制综述如下。     

黄藤素分散片联合替硝唑治疗慢性盆腔炎的临床研究

目的探讨黄藤素分散片联合替硝唑治疗慢性盆腔炎的临床疗效。方法选取2015年10月—2016年10月三门峡市中心医院进行治疗的慢性盆腔炎患者92例,根据治疗方案分为对照组(46例)和治疗组(46例)。对照组静脉滴注替硝唑氯化钠注射液,1支/次,2次/d。治疗组在对照组的基础上口服黄藤素分散片,4片/次,3次/d。两组均连续治疗2周。治疗后,观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、血清细胞因子水平及不良反应情况。结果治疗后,对照组和治疗组的总有效率分别为80.43%、97.82%,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和可溶性细胞黏附因子-1(s ICAM-1)水平均较治疗前明显降低,IL-4水平明显增高,同组比较差异有统计学意义(P0.05);且治疗组上述血清细胞因子水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者临床症状评分均较治疗前明显降低,同组比较差异具有统计学意义(P0.05);且治疗组临床症状评分低于对照组,两组比较差异具有统计学意义(P0.05)。两组均无明显不良反应发生。结论黄藤素分散片联合替硝唑治疗慢性盆腔炎效果显著,可明显改善患者临床症状和细胞因子水平,具有一定的临床推广应用价值。     

妇可靖胶囊联合奥硝唑分散片治疗慢性盆腔炎的临床研究

目的探讨妇可靖胶囊联合奥硝唑分散片治疗慢性盆腔炎的临床疗效。方法以2015年9月—2016年9月在商丘市妇幼保健院进行治疗的86例慢性盆腔炎患者为研究对象,根据治疗方案的差别分为对照组和治疗组,每组各43例。对照组口服奥硝唑分散片,1片/次,2次/d。治疗组在对照组治疗的基础上口服妇可靖胶囊,3粒/次,3次/d。两组患者均连续治疗3周。观察两组临床疗效,比较两组治疗前后血清学指标、临床症状评分的变化。结果治疗后,对照组、治疗组总有效率分别为79.07%、97.67%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组血清白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、转化生长因子β1(TGF-β1)、血管内皮生长因子(VEGF)水平均较同组治疗前明显改善(P0.05);且治疗组改善得更明显(P0.05)。治疗后,两组患者临床症状评分均较治疗前明显降低(P0.05);且治疗组降低得更明显(P0.05)。两组不良反应发生率的比较没有明显差别。结论妇可靖胶囊联合奥硝唑分散片治疗慢性盆腔炎的临床效果显著,可明显改善患者临床症状,减轻机体炎症反应,值得临床推广应用。     

[10]-姜酚对缺氧/复氧诱导的乳鼠心肌细胞损伤的保护作用及机制研究

目的：研究[10]-姜酚对缺氧/复氧诱导原代乳鼠心肌细胞损伤的保护作用及其机制。方法：提取原代乳大鼠心肌细胞,分为空白对照组、模型组、[10]-姜酚不同剂量组（1、3、10 μmol?L-1）。细胞缺氧4 h,复氧2h制备缺氧/复氧损伤模型;CCK-8法测定心肌细胞存活率;测定细胞上清液中生化指标,如乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）;测定上清液中炎症因子,如肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、白介素-1β（IL-1β）含量;Western blot 测定心肌细胞RhoA、ROCK1、p-NF-κB蛋白表达。结果：与模型组相比,[10]-姜酚增加乳鼠心肌细胞存活率,显著降低细胞上清液中LDH、CK-MB、TNF-α、IL-6、IL-1β含量。[10]-姜酚能降低心肌细胞中RhoA、ROCK1、p-NF-κB蛋白表达。结论：[10]-姜酚对乳鼠原代心肌细胞缺氧/复氧损伤具有保护作用,其机制可能与其抑制RhoA/ROCK1/NF-κB信号通路、减轻炎症反应相关。     

Designing small molecule CXCR3 antagonists

Introduction: By virtue of its specificity for chemokines induced in Th1-associated pathologies, CXCR3 has attracted considerable attention as a target for therapeutic intervention. Several pharmacologically distinct small molecules with in vitro and in vivo potency have been described in the literature, although to date, none have shown efficacy in clinical trials.

Areas covered: In this article, the author outlines the rationale for targeting CXCR3 and discusses the potential pitfalls in targeting receptors in poorly understood areas of chemokine biology. Furthermore, they cover emerging therapeutic areas outside of the ‘traditional’ Th1 arena in which CXCR3 antagonists may ultimately bear fruit. Finally, they discuss the design of recently discovered small molecules targeting CXCR3.

Expert opinion: CXCR3 and its ligands appear to play roles in a multitude of diverse diseases in humans. In vitro studies suggest that CXCR3 is inherently ‘druggable’ and that potent, efficacious small molecules targeting CXCR3 antagonists will find a clinical niche. However, the well-trodden path to failure of small molecule chemokine receptor antagonists in clinical trials suggests that a cautious approach should be undertaken. Ideally, unequivocal evidence elucidating the precise role of CXCR3 should be obtained before targeting the receptor in a particular disease cohort.