Metabolic and pharmacological profiling of Penicillium claviforme by a combination of experimental and bioinformatic approaches

BackgroundPenicillium produces a wide range of structurally diverse metabolites with significant pharmacological impacts in medicine and agriculture. For the first time, a complete metabolome of Penicillium claviforme (P. claviforme) (FBP-DNA-1205) was studied alongside pharmacological research in this study.MethodsThe metabolic profile of P. claviforme fermented on Potato Dextrose Broth (PDB) was investigated in this work. The complete metabolomics studies of fungus were performed using GC-MS and LC-MS-QTOF techniques. An in vitro model was utilised to study the cytotoxic and antioxidant activities, while an in vivo model was employed to investigate the antinociceptive and acute toxicity activities. Molecular Operating Environment (MOE) software was used for molecular docking analysis.ResultsGC-MS study showed the presence of alkanes, fatty acids, esters, azo and alcoholic compounds. Maculosin, obtain, phalluside, quinoline, 4,4’-diaminostilbene, funaltrexamine, amobarbital, and fraxetin were among the secondary metabolites identified using the LC-MS-QTOF technique. The n-hexane fraction of P. claviforme displayed significant cytotoxic activity in vitro, with an LD50 value of 92.22 µgml⁻¹. The antinociceptive effects in vivo were dose-dependent significantly (p < .001). Interestingly, during the 72 h of investigation, no acute toxicity was demonstrated. In addition, a docking study of tentatively identified metabolites against the inflammatory enzyme (COX-2) supported the antinociceptive effect in an in silico model.ConclusionMetabolic profile of P. claviforme shows the presence of biologically relevant compounds in ethyl acetate extract. In addition, P. claviforme exhibits substantial antioxidant and cytotoxic activities in an in vitro model as well as antinociceptive activity in an in vivo model. The antinociceptive action is also supported by a molecular docking study. This research has opened up new possibilities in the disciplines of mycology, agriculture, and pharmaceutics.

Key messages

• The first time explored complete metabolome through GC-MS and LC-MS-QTOF.
• Both in vivo & in vitro pharmacological investigation of P. claviforme.
• In silico molecular docking of LC-MS-QTOF metabolites.

     

三叉神经痛的分子发病机制的研究进展

三叉神经痛(trigeminal neuralgia,TN)是指三叉神经的一支或几支分布区的反复性、阵发性剧痛,对病人的生活质量影响较大的一种较难完全治愈的疾病,临床一般分为原发性和继发性TN。关于原发性TN的病因和发病机制目前尚不明确。现在,随着分子生物学研究的进展,已经发现多种神经类物质和TN有着密切的联系。该文从分子方面对TN的发病机制研究进展情况作一综述,旨在为TN的治疗提供理论依据。     

依诺肝素和那屈肝素联合阿司匹林、氯吡格雷治疗高危急性冠脉综合征

目的比较依诺肝素和那屈肝素在高危急性冠脉综合征(ACS)患者中的安全性和有效性。方法84例高危ACS患者随机分为依诺肝素组(n=44)和那屈肝素组(n=40),均予负荷剂量阿司匹林(300mg)和氯吡格雷(300mg)口服后,继以口服维持(阿司匹林300mg/d,氯吡格雷75mg/d),皮下注射依诺肝素1mg/kg或那屈肝素0.1ml/10kg,每12小时1次,共7d。每日测定抗Xa因子活性,使用低分子肝素(LMWH)后48h行经皮冠状动脉介入治疗(PCI)。最后一次注射LMWH后8h内进入导管室,术中不追加LMWH或普通肝素(UFH)。结果第三次给药后4h两组抗Xa因子活性均>0.5IU/ml,48h后基本达到较稳定水平。30d随访中,临床主要心脏事件(MACE)、出血发生率、每日所测定的抗Xa因子活性两组均无显著性差异(P>0.05)。结论两种LMWH对高危ACS患者均安全有效。     

Discal cyst: a rare cause of low back pain and sciatica

We report a case of a 54-year-old man suffering from sciatalgia unresponsive to medical treatment. Imaging revealed a discal cyst the level L3-L4, a rare cause of low back pain, which has characteristic imaging features. In particular, on Magnetic Resonance Imaging it appears as a cystic formation with fluid content, which usually arises from the posterior contour of the intervertebral disc and it frequently has air bubbles within it. The patient underwent surgical treatment with resolution of symptoms.     

2005-2020年我国职业健康风险评估文献计量学分析

职业健康风险评估(以下简称风险评估)是指通过全面、系统地识别和分析工作场所风险因素及防护措施,定性或定量地测评职业健康风险水平,从而采取相应控制措施的过程[1].随着我国职业卫生理论研究的深入,越来越多风险评估方法应用到不同行业领域或不同职业病危害因素中,相关文献层出不穷.本文拟通过对2005-2020年国内期刊公开发...     

能谱CT多参数成像评估胆结石成分的应用价值

目的 探究能谱CT多参数成像评估胆固醇结石和非胆固醇结石的应用价值.方法 收集125枚胆结石置入猪肝模型中行CT能谱模式扫描,并重建普通螺旋CT图像,测量所有胆结石单能量40 keV、100 keV时的CT值(HU40 keV、HU100 keV)、有效原子序数(Eff-Z)和普通螺旋CT值(HU120 kVp lik...     

Headache-related circuits and high frequencies evaluated by EEG,MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review

BackgroundThe diagnosis of migraine is mainly clinical and self-reported, which makes additional examinations unnecessary in most cases. Migraine can be subtyped into chronic (CM) and episodic (EM). Despite the very high prevalence of migraine, there are no evidence-based guidelines for differentiating between these subtypes other than the number of days of migraine headache per month. Thus, we consider it timely to perform a systematic review to search for physiological evidence from functional activity (as opposed to anatomical structure) for the differentiation between CM and EM, as well as potential functional biomarkers. For this purpose, Web of Science (WoS), Scopus, and PubMed databases were screened.FindingsAmong the 24 studies included in this review, most of them (22) reported statistically significant differences between the groups of CM and EM. This finding is consistent regardless of brain activity acquisition modality, ictal stage, and recording condition for a wide variety of analyses. That speaks for a supramodal and domain-general differences between CM and EM that goes beyond a differentiation based on the days of migraine per month. Together, the reviewed studies demonstrates that electro- and magneto-physiological brain activity (M/EEG), as well as neurovascular and metabolic recordings from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), show characteristic patterns that allow to differentiate between CM and EM groups.ConclusionsAlthough a clear brain activity-based biomarker has not yet been identified to distinguish these subtypes of migraine, research is approaching headache specialists to a migraine diagnosis based not only on symptoms and signs reported by patients. Future studies based on M/EEG should pay special attention to the brain activity in medium and fast frequency bands, mainly the beta band. On the other hand, fMRI and PET studies should focus on neural circuits and regions related to pain and emotional processing.     

红外热成像对蚕沙外熨辅助治疗糖尿病胃轻瘫的疗效评价研究

目的 研究采用蚕沙外熨腹部的方法辅助治疗糖尿病胃轻瘫的有效性,探讨治疗过程中红外热成像对临床疗效评价的作用.方法 将110例糖尿病胃轻瘫患者随机分为治疗组55例、对照组55例.其中治疗组脱落3例,完成病例观察52例,脱落率为5.45％;对照组脱落5例,完成病例观察50例,脱落率为9.09％.2组均予基础治疗,治疗组在基...     

应用心肌速度梯度评价胸部放疗患者左室功能的研究

目的探讨定量组织速度成像心肌速度梯度技术在评价胸部放疗患者左室功能方面的临床价值。方法应用定量组织速度成像(QTVI)技术离线分析40例胸部肿瘤放疗患者和20例正常人(对照组)左心室各心肌节段长轴方向和短轴方向上的速度曲线,并将40例胸部肿瘤放疗患者按照放疗进程分为2组:A组治疗2.7～3.3周,照射剂量30～40 Gy;B组治疗4.1～5.5周,照射剂量50～60 Gy。测量2组收缩期峰值速度(Vs)及舒张早期峰值速度(Ve)、舒张晚期峰值速度(Va),并分别计算左心室长轴方向收缩期和舒张早期、晚期心肌速度梯度MVG1、MVG2参数及短轴方向上收缩期和舒张早期、晚期心肌速度梯度MVGs、MVGE和MVGA参数。结果 A组、B组左室二尖瓣口血流速率(E/A)比值较对照组减低(P均<0.05);B组的E/A比值较A组减低(P<0.05)。A组、B组前壁、前间隔、后壁各节段MVG1、MVG2及MVG等参数均较对照组明显减低(P均<0.05);B组前壁、前间隔、后壁各节段MVG1、MVG2及MVG等参数较A组减低(P均<0.05);A组、B组侧壁、后间隔、下壁各节段MVG1、MVG2及MVG等参数在3组之间比较均无显著性差异(P>0.05)。结论胸部放疗患者左心室长轴和短轴方向局部心肌收缩及舒张功能均存在一定程度的降低,心肌速度梯度可作为一种新方法对其评价。