Research progress on phenotype and function of microglia / 中国药理学通报

Microglia are the central nervous system's resident myeloid-derived immune cells, which play a major role in the innate and acquired immunological responses of brain. In the maintenance of brain tissue function under both healthy and pathological conditions, microglia take a protective or damaging role, depending on cell phenotypes and functions. The traditional microglia classification of pro- or anti-inflammatory phenotypes refers to the profile of macrophages, hence the term “brain macrophages:has been drawn. More microglia phenotypes are being discovered as new technologies and research methods are developed, and the newly discovered microglia phenotypes are often disease-, brain region-, and function-specific, providing an important foundation for studying the pathological processes underlying the development of specific diseases and developing appropriate interventions. Here, we provide a retrospective review of recent advances in the study of phenotype and function of microglia, and analyze the microglial cell lineage composition and its heterogeneous function.

Growth differentiation factor 15 and obesity / 中国药理学通报

Growth differentiation factor 15(GDF15) is a member of transforming growth factor β superfamily. Animal studies find that GDF15, bounding with centrally expressed receptors, reduces body weight by inhibiting food intake and by enhancing energy metabolism. In addition, GDF15 is also involved in the effects of tumor cachexia and platinum-based chemotherapy on body weight. GDF15 and its receptor could be potential targets for the treatment of such diseases.

Study on protective effect of pedunculoside on acute myocardial ischemia/reperfusion injury in rats / 中国药理学通报

Aim To explore the protective effect of pedunculoside (PE) on myocardial ischemia/reperfusion injury. Methods Rat model of acute myocardial ischemia reperfusion injury was prepared by ligating the left anterior descending coronary artery (LAD) of the heart for 30 min and reperfusion for 24 h, and the rats were randomly divided into seven groups (re = 10): sham group (Sham), acute myocardial ischemia reperfusion injury model group (M), captopril group (Capt), metoprolol group (MT), PE low, medium and high dosage groups (2. 5, 5 and 10 mg · kg

Network pharmacology-based study on mechanisms of Huanglian Jiedu Decoction impact on macrophage inflammation response / 药学学报

This study was designed to explore the impact of Huanglian Jiedu Decoction (HLJDT) on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for "multi-component, multi-target and multi-pathway", which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by PharmMapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active componenttarget-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.

Network pharmacology-based study on intervention mechanism of Huanglian Jiedu decoction in the treatment of Alzheimer's disease / 药学学报

This study was designed to explore the "multi-components, multi-targets and multi-pathways" intervention mechanism of Huanglian Jiedu decoction (HLJDD) in the treatment of Alzheimer's disease (AD) by pharmacological network technology, which may establish a foundation for drug development and innovative research. Seventeen active constituents of HLJDD with anti-AD activities were submitted to PharmMapper and Molecule Annotation System (MAS 3.0) bioinformatics softwares to predict the target proteins and carry out related KEGG pathways annotation respectively. The network of "active compound-target-pathway" was constructed and analyzed using the Cytoscape 3.4.0 software. The results suggest that 47 pathways are affected by the 17 active components through 59 target proteins, in which 4 target proteins are related to AD and 2 pathways related to neuroinflammation, respectively. The effect of HLJDD on AD may be dependent on clearing/reducing β-amyloid protein, inhibiting Tau hyperphosphorylation, anti-inflammation and immunoregulation.

Mechanism of treatment effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats based on metabolomic approach / 中国中药杂志

The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry method（UPLC-Q-TOF/MS）, Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database. The 20 potential biomarkers were found in the urine of rats with cerebral ischemia, which mainly involved in the neurotransmitter regulation, amino acid metabolism, energy metabolism, lipid metabolism and so on. Those metabolic pathways were disturbed in cerebral ischemia model rats, the principal component analysis showed that the normal and cerebral ischemia model is clearly distinguished, and the compound can be given to the normal state of change after HL, HQ, LQ administration. This study index the interpretation of cerebral ischemia rat metabolism group and mechanism, the embodiment of metabonomics can reflect the physiological and metabolic state, which can better reflect the traditional Chinese medicine as a whole view, system view and the features of multi ingredient synergistic or antagonistic effects.

Study of effect of tongsaimai tablets on experimental diabetic foot model rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of Tongsaimai (TSM) tablets in treating foot trauma of diabetic foot (DF) model rats, and discuss its potential mechanism.</p><p><b>METHOD</b>Male SD rats were selected to duplicate the diabetic foot ulcer model and randomly divided into the blank control group, the model group, the metformin treatment group, and TSM 12.44, 6.22, 3.11 g x kg(-1) groups (n = 10). The healing of ulcer wounds were observed on day 1, 4, 8, 13 and 18. After 18 days, a histopathologic examination was conducted for ulcer tissues. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by hydroxylamine and TBA methods. The content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined with the radioimmunoassay. The immunohistochemical method was used to observe the expression of vascular endothelial growth factor (VEGF) in ulcer tissues and the number of capillary vessels.</p><p><b>RESULT</b>TSM could alleviate the pathological changes of diabetic foot rats, accelerate the ulcer healing on 4, 8, 13, 18 d, reduce MDA, IL-6, TNF-alpha, VEGF content in rat serum at 18 d (after the rehabilitation period), and enhance the SOD content. Specifically, the TSM 12.44 g x kg(-1) group showed significant differences compared with the model group (P < 0.05, P < 0.01). At 18 d after the treatment (the late rehabilitation period), the VEGF expression of TSM 12.44, 6.22 g x kg(-1) groups and the number of blood capillaries of the TSM 12.44 g x kg(-1) group were significantly lower than that of the model group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>TSM could promote the foot wound healing of DF model rats, reduce MDA, IL-6 and TNF-alpha levels in serum, increase the SOD content and decrease the VEGF expression and the number of blood capillaries in the late rehabilitation period. Its action mechanism may be related to the inhibition of oxidative stress injury and the inflammatory cell infiltration.</p>

Study on PK/PD model for traditional Chinese medicine biopharmaceutics based on principle of "correspondence of prescriptions and syndromes" / 中国中药杂志

In the principle of "correspondence of prescription and syndrome", this article focuses on key technical issues of traditional Chinese medicine (TCM) biopharmaceutis by using the integrated pharmacokinetic and pharmacodynamic model: (1) As the prescription formulation and compatibility of TCM compounds could be influential to the in vivo pharmacokinetics of chemical components of TCMs, and closely related to therapeutic and adverse effects, how to describe these actions in a biopharmaceutics model? (2) As there are differences between pharmacokinetic processes in the normal and pathological states, how to express characteristic "syndromes" in an animal model? (3) As prescriptions work to reduce and transform syndromes, how o confirm the type and amount of effective substances in case of physiological and pathological indicators and drug distribution in a dynamic corresponding state. In response to the above key issues, we proposed the TCM biopharmaceutic study model based on PK/PD. (1) The integrity of TCMs was better expressed with the effect at the core, supplemented with the component pharmacokinetics; (2) An integrated pharmacokinetic and pharmacodynamic system was established on the basis of pharmacokinetics and pharmacodynamics of many major effective components; (3) AK/PD mathematical function with the three-phase synchronous characterization of "time-concentration-effect" was established by using the data mining techniques, to explore the biopharmaceutic principle of "correspondence of prescriptions and syndromes", in which prescriptions are only required for syndromes, whereas no prescription is required in case of no syndrome.

Effects of nitrogen fertilization strategies on nitrogen use efficiency in physiology, recovery, and agronomy and redistribution of dry matter accumulation and nitrogen accumulation in two typical rice cultivars in Zhejiang, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Field experiments were conducted in farmers' rice fields in 2001 and 2002 to study the effects of nitrogen (N) management strategies on N use efficiency in recovery (RE), agronomy (AE) and physiology (PE) and redistribution of dry matter accumulation (DMA) and nitrogen accumulation (NA) in two typical rice cultivars in Jinhua, Zhejiang Province. This study aimed mainly at identifying the possible causes of poor fertilizer N use efficiency (NUE) of rice in Zhejiang by comparing farmers' fertilizer practice (FFP) with advanced site-specific nutrient management (SSNM) and real-time N management (RTNM). The results showed that compared to FFP, SSNM and RTNM reduced DMA and NA before panicle initiation and increased DMA and NA at post-flowering. There is no significant difference between SSNM and FFP in post-flowering dry matter redistribution (post-DMR) and post-flowering nitrogen redistribution (post-NR). These results suggest that high input rate of fertilizer N and improper fertilizer N timing are the main factors causing low NUE of irrigated rice in the farmer's routine practice of Zhejiang. With SSNM, about 15% of the current total N input in direct-seeding early rice and 45% in single rice could be reduced without yield loss in Zhejiang, China.

Potential production simulation and optimal nutrient management of two hybrid rice varieties in Jinhua, Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Potential growth of two widely-grown hybrid rice varieties in the Jinhua district of Zhejiang Province, Shanyou63 for mid-rice and Xieyou46 for late rice, was simulated using a crop growth model of WOFOST. Parameters of the rice growth in WOFOST were calibrated through field experiments from 1999 to 2002 in Jinhua. The potential yield simulated with WOFOST was about 12 t/ha for Shanyou63 and 10 t/ha for Xieyou46, which are in good agreement with the highest recorded yield obtained in this area. Under farmers practice, current yield is about 7.5 t/ha for Shanyou63 and 6.5 t/ha for Xieyou46. There is a gap between the actual rice yield and the potential yield for these two hybrid rice varieties grown in this area. The attainable target yields were set to 70% to 75% of their potential yields for the two varieties. A recently developed software "Nutrient Decision Support System (NuDSS)" for irrigated rice was used to optimize nutrient management for these two rice varieties. According to NuDSS, the optimal fertilizer N requirement for the target yields was about 150 kg/ha for Shanyou63 and about 120 kg/ha for Xieyou46, which were only about 70% of the fertilizer N application under current farmers' practice. Comparing with farmers' practice, there is great potential to increase actual rice yields and to reduce fertilizer N use rates by improving rice crop management practice in Jinhua.

Studies on nutrient uptake of rice and characteristics of soil microorganisms in a long-term fertilization experiments for irrigated rice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The ecosystem characteristics of soil microorganism and the nutrient uptake of irrigated rice were investigated in a split-block experiment with different fertilization treatments, including control (no fertilizer application), PK, NK, NP, NPK fertilization, in the main block, and conventional rice and hybrid rice comparison, in the sub block. Average data of five treatments in five years indicated that the indigenous N supply (INS) capacity ranged from 32.72 to 93.21 kg/ha; that indigenous P supply (IPS) capacity ranged from 7.42 to 32.25 kg/ha; and that indigenous K supply (IKS) capacity ranged from 16.24 to 140.51 kg/ha, which showed that soil available nutrient pool depletion might occur very fast and that P, K deficiency has become a constraint to increasing yields of consecutive crops grown without fertilizer application. It was found that soil nutrient deficiency and unbalanced fertilization to rice crop had negative effect on the diversity of the microbial community and total microbial biomass in the soil. The long-term fertilizer experiment (LTFE) also showed that balanced application of N, P and K promoted microbial biomass growth and improvement of community composition. Unbalanced fertilization reduced microbial N and increased C/N ratio of the microbial biomass. Compared with inbred rice, hybrid rice behavior is characterized by physiological advantage in nutrient uptake and lower internal K use efficiency.