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Traumatic brain injury (TBI) is a major reason for temporary or permanent dyskinesia and cognitive impairment of the organism. Generally, TBI induces subsequent neuroinflammation to assist cell debris removal and tissue repair and regeneration after injury. However, overactivation or long-term activation of immune cells will exacerbate nerve damage or death, cause cognitive dysfunction, and ultimately lead to neurodegenerative diseases. Therefore, secondary damage caused by persistent inflammation is a key component of TBI pathological process. As the main metabolite of anaerobic glycolysis, lactate is increased after TBI and participates in brain inflammation as an important immune regulatory molecule rather than a metabolic waste. Importantly, histone lysine lactylation as a novel type of histone post-translational modifications (HPTM) derived from lactate allows lactate to participate in the regulation of complex immunopathophysiological processes of the central nervous system after TBI. Further study on the process of histone lactylation and its immune regulation mechanism during TBI may provide new insights for early intervention and improvement of TBI prognosis. Thus, the authors reviewed the role of histone lactylation in the immune regulation of TBI, so as to further elucidate the mechanism of TBI and the explore new warning and prevention measures from the perspective of HPTM.
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Click chemistry has been proven to be very useful in drug delivery. Due to the availability of a large number of click reactions with a various characteristics, selection of appropriate chemistry for a given application is often not a trivial task. This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts. For this, the review gives an overview of available click reactions organized by application types. Further, the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications. For this, we highlight the need to analyze the relationship among reaction kinetics, concentration effects, and reaction time scales, knowing that lack of such analysis could easily lead to failures. Further, possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs. Recent examples and extensive references are also provided to aid in-depth understanding of technical details. We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.
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Objective:To investigate the changes of cognitive function in non-fatal drowning rats after blast-induced traumatic brain injury (bTBI).Methods:Eighty SD rats were divided into normal group, bTBI group, drowning group and bTBI plus drowning group according to the random number table, with 20 rats per group. Rats in normal group were not injured. In bTBI group, bTBI was established in a BST-I biological shock tube with a pressure of 4.0 MPa in the driving section. In drowning group, rats were subjected to non-fatal drowning by falling into the water with temperature of 18 ℃ and depth of 30 cm from the height of 1 m and were taken out quickly after swimming to exhaustion. After being injured in a biological shock tube, rats in bTBI plus drowning group were immediately forced to drowning using the same method. On day 3 post-injury, the neurocognitive function was evaluated by elevated plus maze and Morris water maze tests. Morphological changes of neurons in CA1 and CA3 regions of hippocampus were observed by Nissl staining, and the number of surviving neurons were counted. The concentrations of hippocampal neurotransmitters glutamate, γ-aminobutyric acid (GABA), glycine and endoplasmic reticulum stress (ERS) related glucose-regulated protein 78 (GRP78) and caspase-12 were examined by ELISA analysis. Levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein (Bax) and caspase-3 were detected by Western blotting. The ratio of Bcl-2 to Bax was calculated as well.Results:In elevated plus maze test, the percentage of open arm entry and number of head-dipping behaviour were decreased in bTBI plus drowning group compared with normal and bTBI groups at 3 days after injury ( P<0.05 or 0.01), with no statistical difference from those in drowning group ( P>0.05). The number of head-dipping behaviour in drowning group was lower than that in bTBI group ( P<0.05). In Morris water maze test, bTBI plus drowning group showed increased target latency on the third and fourth days of spatial acquisition training and decreased number of crossing the target area and percentage of swimming time in the target quadrant during probe trials as compared with normal group ( P<0.05 or 0.01), but there was no statistical difference among bTBI, drowning and normal groups (all P>0.05). Nissl staining showed that the neurons in the CA1 and CA3 regions of hippocampus in normal group were arranged neatly with clear Nissl bodies at 3 days after injury, while the other groups showed different degrees of injury. In contrast with normal group, the neurons in the CA1 and CA3 regions of hippocampus in all other groups were decreased with the lowest number in bTBI plus drowning groups ( P<0.05 or 0.01). In ELISA analysis, the level of hippocampal glutamate in bTBI plus drowning group was higher than that in all other groups at 3 days after injury and the level in bTBI injury and drowning groups was higher than that in normal group ( P<0.05 or 0.01); the level of hippocampal glycine in bTBI plus drowning group was lower than that in normal group ( P<0.05), but there was no statistical difference among bTBI, drowning or normal groups (all P>0.05); the concentration of hippocampal GABA had no statistical difference among all groups (all P>0.05). In addition, the concentration of GRP78 in bTBI injury, drowning and bTBI injury plus drowning groups were increased compared with normal group ( P<0.05 or 0.01), but did not statistically differ from each other (all P>0.05). The concentration of caspase-12 in drowning and bTBI plus drowning groups were increased compared with normal group ( P<0.05 or 0.01), but was not statistically different from each other ( P>0.05), and its concentration in bTBI plus drowning group was increased compared with bTBI group ( P<0.05). In Western blotting, the level of Bcl-2 in bTBI plus drowning group was decreased compared with all other groups at 3 days after injury, and the level in bTBI and drowning groups were decreased compared with normal group, but a much lower level was observed in drowning group than that in bTBI group ( P<0.05 or 0.01); the level of Bax in bTBI plus drowning group was increased compared with all other groups at 3 days after injury, and the level in drowning group was increased compared with normal group ( P<0.05 or 0.01), with no statistical difference between bTBI and drowning groups ( P>0.05). The ratio of Bcl-2 to Bax in bTBI plus drowning group was decreased compared with all other groups, while the ratio in bTBI and drowning groups were decreased compared with normal group, showing a much lower level in drowning group than that in bTBI group ( P<0.05 or 0.01). Also, the level of caspase-3 in drowning and bTBI plus drowning groups were increased compared with normal and bTBI groups ( P<0.05 or 0.01), but there was no statistical difference between drowning and bTBI plus drowning groups ( P>0.05). Conclusions:Non-fatal drowning can aggravate hippocampal neuron damage in bTBI rats and cause memory, emotion and other cognitive dysfunction. The mechanism may involve the imbalance of hippocampal neurotransmitters glutamate and glycine, which activates the downstream pro-apoptotic pathway through ERS in the early stage of injury to induce hippocampal neuron apoptosis.
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This paper was aimed to study the molecular mechanism of acupoint biology effect on acupuncture experiment articles.The acupuncture experiment articles in CNKI,Wanfang Data Resource Library and the China Biomedical Literature Database (CBM) were searched.The literature on acupoint and related genes were selected according to the literature inclusion criteria and exclusion criteria.The acupoint and corresponding genes in the literature were collected and analyzed by software written in Python,Cytoscape 3.3.0 and MECODE algorithm.The results showed that 2136 articles were collected,with 233 acupoints and 793 genes.Acupoints in the top 10 frequency were ST36 (Zusanli),GV20 (Baihui),PC6 (Neiguan),GV26 (Shuigou),GV14 (Dazhui),SP6 (Sanyinjiao),BL23 (Shenshu),LI11 (Quchi),GV16 (Fengfu) and GB34 (Yanglingquan).Genes in the top 10 frequency were BCL2,FOS,BDNF,Bax,CASP3,TNFA,GFAP,NGF,HSP70 and IL1B.Acupoint-groups in the top 5 frequency were GV14 (Dazhui)-GV20 (Baihui),GV26 (Shuigou)-GV20 (Baihui),GV20 (Baihui)-ST36 (Zusanli),SP6 (Sanyinjiao)-ST36 (Zusandi),PC6 (Neiguan)-GV26 (Shuigou).ST36 (Zusanli) was in the center of the acupoint-gene network.Through module analyzing,there were some genes belong to different pathways and some acupoints in one network module.It was concluded that ST36 (Zusanli) was the core acupoint in the acupoint experiment study,the stomach meridian of foot Yangming may be closely related with the metabolic pathway.This finding may provide new research ideas for clinical and experimental research.
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Objective To study computer toxicity prediction technology and predict the acute toxicity of Chinese materia medica; To provide a new way and method for safety evaluation of traditional Chinese medicine. Methods First, Mold2 software (version 2.0.0) was used to calculate molecular descriptors of 7409 chemical components. After preliminary screening of molecular descriptors, quantitative structure-activity relationship (QSAR) models were built up with Random Forest (RF) for screening the optimum prediction model. From the 83 kinds of toxic Chinese materia medica in Chinese Pharmacopoeia (2010 edition), acute toxicity of 60 kinds of Chinese materia medica reported from monomer structure (1692 chemical components) were under prediction.Results Totally 7409 pieces of data were obtained. When the descriptors were 52, RF modeling accuracy and Kappa were the highest, 0.712 and 0.436 respectively. Compound clusters were divided into 3 types according to optimum molecule descriptors (52). The accuracy and Kappa of the optimum model for the first type of compounds were 0.666 and 0.476 respectively; the accuracy and Kappa of the optimum model for the second type of compounds were 0.804 and 0.381 respectively; the accuracy and Kappa of the optimum model for the third type of compounds were 0.709 and 0.373 respectively. It was predicted that 60 kinds of Chinese materia medica containing 0 violent toxic compound, 2 high toxic compounds, 172 medium toxic compounds and 1518 low toxic compound.Conclusion QSAR model for prediction study on acute toxicity of chemical components of Chinese mareria medica can provide references combination medication and experimental studies.
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Using the methods of informetrics analysis, articles retrieved from the database of CNKI were statistically analyzed on development course and knowledge system, so as to reflect the overall situation of pharmacognostical studies by molecular biotechnology. The result shows that the research on pharmacognosy by molecular biotechnology is an inter-disciplinary research area, the major research fields can be divided into 7 categories, including molecular identification of Chinese medicinal materials, molecular systematics and genetic diversity analysis of Chinese medicinal materials, biosynthesis and bioregulation of secondary metabolites in medicinal plants, molecular mechanism and genetic basis of Dao-di Herbs, and tissue culture and molecular breeding in medicinal plants. The research on pharmacognosy by molecular have achieved remarkable progress in recent 20 years, and have broad development prospects.
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The method of bibliometrics was used to analyze the literature about the application of molecular biotechnique to pharmacognosy which were searched and obtained from the CNKI database and Shanghai intellectual property information platform from the year 1995 to 2015.It was found that 22 462 articles were published and the 63% were funded, 50 core institutions and 888 authors, 18 core journals were engaged in this subject.496 items of patents were authorized and 90 kinds of Chinese Materia Medica were involved.In the view of the quantity and quality of published literature, the scale and influence of journals, institutions, and the extent of subject categories have made remarkable achievement. Molecular pharmacognosy has completed the germination stage of a new subject, and has been in a relatively mature and stable development status.
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This study collected 1995-2014 molecular pharmacognosy study, a total of 595 items, funded by Natural Science Foundation of China (NSFC). TDA and Excel software were used to analyze the data of the projects about general situation, hot spots of research with rank analytic and correlation analytic methods. Supported by NSFC molecular pharmacognosy projects and funding a gradual increase in the number of, the proportion of funds for pharmaceutical research funding tends to be stable; mainly supported by molecular biology methods of genuine medicinal materials, secondary metabolism and Germplasm Resources Research; hot drugs including Radix Salviae Miltiorrhizae, Radix Rehmanniae, Cordyceps sinensis, hot contents including tanshinone biosynthesis, Rehmannia glutinosa continuous cropping obstacle.
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Objective To investigate the effect of endogenous electric fields on proliferation and migration of epidermal stem cells (EpSCs) in vitro.Methods EpSCs in the first passage were cultured on simulated endogenous electric field.Galvanic stimulation set at an intensity of 0 mV/mm (Group Ⅰ),100 mV/mm (Group Ⅱ) and 200 mV/mm(Group Ⅲ) was given twice a day for 3 days with each time continuing 1 hour and resting 1 hour.Effect of bio-electric field on cell proliferation was measured by direct cell counting in fixed visual field.Repeated experiment but continued stimulation for 3 hours was performed.Live cell migration was monitored to determine the effect of bio-electric field on the process of cell migration.Results For the EpSCs cultured in endogenous bio-electric simulation platform for 24,48 and 72 hours,cell proliferation rate was the highest in Group Ⅲ [(107.4 ±21.9)％,(270.2 ± 71.4) ％,(544.0 ± 95.1) ％] (P ＜ 0.01).And higher cell proliferation was observed in Group Ⅰ [(35.1 ± 21.0) ％,(138.6 ± 31.0) ％,(323.5 ± 23.0) ％] than in Group Ⅱ [(66.9 ±24.2) ％,(192.1 ± 36.2) ％,(406.7 ± 50.7) ％] (P ＜ 0.01).After continued galvanic stimulation for 3 hours,cells in Groups Ⅱ and Ⅲ oriented towards cathode,but cells in Group Ⅰ moved randomly.In measurements of track velocity (Vt),displacement velocity (Vd) and electric field migration rate (Vx),Group Ⅲ revealed increased values[(42.5 ± 2.8),(32.3 ± 1.8),(29.7 ± 1.3) μm/h] as compared with Group Ⅰ [(36.2 ±2.2),(23.6 ±2.9),(18.2 ± 1.8) μm/h] and Group Ⅱ [(34.3 ±1.6),(23.8±l.2),(21.2±l.6)μm/h] (P＜0.01).Conclusion In vitro experiments reveal that endogenous electric fields can promote the proliferation of EpSCs and induce oriented movements towards the cathode.
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In order to provide a new way and method for safety evaluation of Chinese materia medica (CMM) and also to provide a reference for conventional animal experiments, computer toxicity prediction technique and method were established to predict the cardiotoxicity of CMM. Mold2 software (version 2.0.0) was used to calculate molecular descriptors of 1034 chemical components. Then, the random forest (RF) method and the support vector machine (SVM) method were used to screen the descriptors. After that, boosting trees method, SVM, regularized discriminant analysis method and RF method were used to build up prediction model, respectively. Finally, the cardiotoxicity of chemical components was predicted by the quantitative structure-activity relationship (QSAR) model with the best accuracy and Kappa value. The results showed that by comparing the accuracy and Kappa value of prediction model, it was found that the RF model was the optimal algorithm model with 86.3%accuracy and the Kappa value of 0. 725. Through the prediction research on chemical components of Chinese herbs with toxicity recorded in the Pharmacopoeia of People’s Republic of China (version2010),suchasEvodia rutaecarpa,North bean root,Murraya incense,some meaningful results had been received. It was concluded that QSAR model on prediction research of chemical components of Chinese herbs provided important references for further experimental studies and clinical researches.