IncRNA XIST Promotes Cardiac Fibrosis in Mice with Diabetic Nephropathy via Sponging miR-106a-5p to Target RUNX1.

Diabetic nephropathy (DN) accompanied by cardiac fibrosis (CF) increases the mortality rate among people with diabetes. This study sought to explore the molecular mechanism of long non-coding RNA X inactive specific transcript (lncRNA XIST) in CF in DN mice. The animal model of DN was established by streptozocin (STZ). The levels of lncRNA XIST, microRNA (miR)-106a-5p, and RUNX family transcription factor 1 (RUNX1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), followed by biochemical analysis, hematoxylin & eosin and Masson staining, echocardiography, and quantification of collagen I, collagen III, α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) levels through qRT-PCR and Western blot assay. The subcellular localization of lncRNA XIST was analyzed by nuclear/cytoplasmic fractionation assay and the bindings of miR-106a-5p to lncRNA XIST and RUNX1 were confirmed by RNA immunoprecipitation and dual-luciferase assays. Functional rescue experiments were performed to validate the role of miR-106a-5p/RUNX1 in CF in DN mice. lncRNA XIST and RUNX1 were elevated while miR-106a-5p was decreased in STZ mice. lncRNA XIST inhibition reduced myocardial injury and collagen deposition, along with decreased levels of fasting blood glucose, serum creatinine, blood urea nitrogen, and urinary microalbumin, collagen I, collagen III, α-SMA, and TGF-ß1. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription. miR-106a-5p downregulation or RUXN1 upregulation reversed the protective role of lncRNA XIST inhibition in STZ mice. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription, thereby aggravating renal dysfunction and CF in DN mice.

JWA inhibits nicotine-induced lung cancer stemness and progression through CHRNA5/AKT-mediated JWA/SP1/CD44 axis.

Cigarette smoking is an independent risk factor for lung cancer. Nicotine, as an addictive substance in tobacco and e-cigarettes, is known to promote tumor progression and metastasis despite being a non-carcinogen. As a tumor suppressor gene, JWA is widely involved in the inhibition of tumor growth and metastasis and the maintenance of cellular homeostasis, including in non-small cell lung cancer (NSCLC). However, the role of JWA in nicotine-induced tumor progression remains unclear. Here, we reported for the first time that JWA was significantly downregulated in smoking-related lung cancer and associated with overall survival. Nicotine exposure reduced JWA expression in a dose-dependent manner. Gene Set Enrichment Analysis (GSEA) analysis showed the tumor stemness pathway was enriched in smoking-related lung cancer, and JWA was negatively associated with stemness molecules CD44, SOX2, and CD133. JWA also inhibited nicotine-enhanced colony formation, spheroid formation, and EDU incorporation in lung cancer cells. Mechanically, nicotine downregulated JWA expression via the CHRNA5-mediated AKT pathway. Lower JWA expression enhanced CD44 expression through inhibition of ubiquitination-mediated degradation of Specificity Protein 1 (SP1). The in vivo data indicated that JAC4 through the JWA/SP1/CD44 axis inhibited nicotine-triggered lung cancer progression and stemness. In conclusion, JWA via down-regulating CD44 inhibited nicotine-triggered lung cancer cell stemness and progression. Our study may provide new insights to develop JAC4 for the therapy of nicotine-related cancers.

JAC4 Inhibits EGFR-Driven Lung Adenocarcinoma Growth and Metastasis through CTBP1-Mediated JWA/AMPK/NEDD4L/EGFR Axis.

Lung adenocarcinoma (LUAD) is the most common lung cancer, with high mortality. As a tumor-suppressor gene, JWA plays an important role in blocking pan-tumor progression. JAC4, a small molecular-compound agonist, transcriptionally activates JWA expression both in vivo and in vitro. However, the direct target and the anticancer mechanism of JAC4 in LUAD have not been elucidated. Public transcriptome and proteome data sets were used to analyze the relationship between JWA expression and patient survival in LUAD. The anticancer activities of JAC4 were determined through in vitro and in vivo assays. The molecular mechanism of JAC4 was assessed by Western blot, quantitative real-time PCR (qRT-PCR), immunofluorescence (IF), ubiquitination assay, co-immunoprecipitation, and mass spectrometry (MS). Cellular thermal shift and molecule-docking assays were used for confirmation of the interactions between JAC4/CTBP1 and AMPK/NEDD4L. JWA was downregulated in LUAD tissues. Higher expression of JWA was associated with a better prognosis of LUAD. JAC4 inhibited LUAD cell proliferation and migration in both in-vitro and in-vivo models. Mechanistically, JAC4 increased the stability of NEDD4L through AMPK-mediated phosphorylation at Thr367. The WW domain of NEDD4L, an E3 ubiquitin ligase, interacted with EGFR, thus promoting ubiquitination at K716 and the subsequent degradation of EGFR. Importantly, the combination of JAC4 and AZD9191 synergistically inhibited the growth and metastasis of EGFR-mutant lung cancer in both subcutaneous and orthotopic NSCLC xenografts. Furthermore, direct binding of JAC4 to CTBP1 blocked nuclear translocation of CTBP1 and then removed its transcriptional suppression on the JWA gene. The small-molecule JWA agonist JAC4 plays a therapeutic role in EGFR-driven LUAD growth and metastasis through the CTBP1-mediated JWA/AMPK/NEDD4L/EGFR axis.

LncRNA NEAT1 ameliorate ischemic stroke via promoting Mfn2 expression through binding to Nova and activates Sirt3.

BACKGROUND: Recent studies revealed that long non-coding RNAs (lncRNAs) have significant roles in regulating the pathogenesis of ischemia stroke, and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell apoptosis. Aberrant expression of NEAT1 was found after the injury of ischemia-reperfusion, but the mechanism was not fully understood. METHODS: The expression of NEAT1 and Mfn2 were detected in BV-2 and N2a cell with or without OGD/R-induced by qRT-PCR. Inflammatory cytokines secretion was detected by enzyme-linked immunosorbent assay (ELISA). The oxidative stress was evaluated by the examination of ROS, MDA and SOD levels. Flow cytometry and apoptosis marker detection by western blot were performed to examined apoptosis. RESULTS: The expression of NEAT1 and Mfn2 were decreased in OGD/R-induced cell model. Overexpression of NEAT1 or Mfn2 reduced oxidative stress and apoptosis by OGD/R-induced in neuronal cells, while knockdown of Sirt3 reversed the protective effect of NEAT1 and Mfn2. NEAT1 stabilized Mfn2 mRNA via recruiting Nova. NEAT1 alleviates the oxidative stress and apoptosis by OGD/R-induced via activating Sirt3. CONCLUSION: LncRNA NEAT1 stabilizes Mfn2 mRNA via recruiting Nova, therefore increase the expression of Mfn2 and alleviates ischemia-reperfusion induced oxidative stress and apoptosis via Mfn2/Sirt3 pathway.

The Association of Blood Urea Nitrogen to Creatinine Ratio and the Prognosis of Critically Ill Patients with Cerebral Infarction: A Cohort Study.

Background: To evaluate the association between blood urea nitrogen (BUN) to creatinine (Cr) (BUN/Cr) ratio and the in-hospital mortality of critically ill patients with cerebral infarction in intensive care unit (ICU). Methods: In this cohort study, the data of 3059 participants with cerebral infarction were collected from the Medical Information Mart for Intensive Care (MIMIC)-III and the MIMIC-IV database. After propensity score matching (PSM) on age and gender, 2085 people were involved in and divided into the alive group (n = 1390) and the dead group (n = 695) based on the results of follow-up. Multivariate logistic analyses were applied to identify the confounders and the association between BUN/Cr and mortality of cerebral infarction. Results: The median follow-up time was 10.5 days. Among 2778 participants, 695 were dead at the end of follow-up. Univariate analysis revealed that BUN/Cr [risk ratio (RR) = 1.01, 95% confidence interval (CI): 1.01-1.02] might be associated with the in-hospital mortality of cerebral infarction patients. After adjusting for respiratory failure, malignant cancer, anticoagulation, liver disease, white blood cell (WBC), red cell distribution width (RDW), glucose, bicarbonate, and temperature, BUN/Cr had week correlation with the increased risk of in-hospital mortality of cerebral infarction patients (RR = 1.01, 95% CI: 1.01-1.02). Conclusion: This study evaluated the association between BUN/Cr and the in-hospital mortality of cerebral infarction patients in ICU and found that BUN/Cr had weak correlation with the increased risk of in-hospital mortality of patients with cerebral infarction in ICU especially in males and those with respiratory failure, malignant cancer, and without liver disease, as well as those receiving anticoagulation.

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker.

Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

The long noncoding RNA CRAL reverses cisplatin resistance via the miR-505/CYLD/AKT axis in human gastric cancer cells.

Emerging evidence has suggested that long noncoding RNAs (lncRNAs) play an essential role in the tumorigenesis of multiple types of cancer including gastric cancer (GC). However, the potential biological roles and regulatory mechanisms of lncRNA in response to cisplatin, which may be involved in cisplatin resistance, have not been fully elucidated. In this study, we identified a novel lncRNA, cisplatin resistance-associated lncRNA (CRAL), that was downregulated in cisplatin-resistant GC cells, impaired cisplatin-induced DNA damage and cell apoptosis and thus contributed to cisplatin resistance in GC cells. Furthermore, the results indicated that CRAL mainly resided in the cytoplasm and could sponge endogenous miR-505 to upregulate cylindromatosis (CYLD) expression, which further suppressed AKT activation and led to an increase in the sensitivity of gastric cancer cells to cisplatin in vitro and in preclinical models. Moreover, a specific small molecule inhibitor of AKT activation, MK2206, effectively reversed the cisplatin resistance in GC caused by CRAL deficiency. In conclusion, we provide the first evidence that a novel lncRNA, CRAL, could function as a competing endogenous RNA (ceRNA) to reverse GC cisplatin resistance via the miR-505/CYLD/AKT axis, which suggests that CRAL could be considered a potential predictive biomarker and therapeutic target for cisplatin resistance in gastric cancer.

Comprehensive investigation of mechanism and effective ingredients of Fangji Huangqi Tang by serum pharmacochemistry and network pharmacology.

Fangji Huangqi Tang (FHT), has been reported to show effects on nephrotic syndrome, but its mechanism of action and bioactive components have not yet been determined. In this study, a method using UPLC-HRMS/MS was established for the detection and identification of the chemical constituents and metabolites absorbed into the blood. Absorbed components in serum were then used for the network pharmacology analysis to deduce the mechanism and effective components. A total of 86 compounds were identified or tentatively characterized. Based on the same instrumental conditions, 85 compounds were found in rat serum after oral administration of FHT, including 22 prototypes and 63 metabolites. Network pharmacology analysis showed that absorbed components, such as (3R)-2',3',4',7-tetrahydroxyisoflavan, astrapterocarpan, cycloastragenol, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, astragaloside IV, astrapterocarpan glucoside and glycyrrhetinic acid, could be responsible for the pharmacological activity of nephrotic syndrome by regulating the VEGF signaling pathway, focal adhesion and MAPK signaling pathway. Furthermore, the pathway-target network showed that the MAPK1, AKT2 and CDC42 were involved in the signal pathways above. This study provides a scientific basis for the mechanism and effective ingredients of FHT.

[Research progress on identification of pharmacodynamic substance basis of traditional Chinese medicine based on target constituent knock-out/knock-in technology].

The effective material basis of traditional Chinese medicine(TCM) is an indispensable part of studies on TCM, and each technology has its advantages and disadvantages. The target constituent knock-out/knock-in technology has attracted much attention since it was proposed because of its unique advantages of regarding the extract of the formula as a whole, which can better reflect the characteristics of multi-component and multi-target integration and regulation of TCM. This method investigated the contribution of target constituent to the overall efficacy of a TCM by analyzing the changes in efficacy of the remaining formula before and after knock-out/knock-in of the target constitution. The application of this model not only facilitates studies of the effective constituents of TCM, but also help to develop the quality control standard of TCM. However, the application of this model is restricted due to the limitation of target constituent separation technology. By reviewing the literatures in recent years, this study summarized the research process and application of this method for a reference.

[Optimization of determination methods of astragaloside â £ and analysis of contents of astragaloside â £ in different origin and grade].

A rapid and accurate method for determination of astragaloside Ⅳ was established,which was further applied to determine the contents of astragaloside Ⅳ in 87 batches of different origin and different grade of Astragali Radix. The ROC curve was used to analyze the contents of astragaloside Ⅳ in different origin. Simultaneous contents of astragaloside Ⅳ in different grade were compared with chemometrics. HPLC-ELSD method was used to determine the contents of astragaloside Ⅳ. A Vensil MP C18 column( 4. 6 mm×250 mm,5 µm) was used with acetonitrile-water( 32 ∶68) as the mobile phase at a flow rateof 1 m L·min-1. The column temperature was 25 ℃ with ELSD parameters as follows: gas flow rate was 2. 5 L·min-1,the drift tube heating temperature was set to 105 ℃,and the gain value was 4. 0. The optimized method avoided the problem that the consumable quality unstable and the recovery rate was not high. The contents determined by the optimized method were higher than the pharmacopoeia method,with less time and high recovery rate. The ROC curve analysis showed that there was no significant difference of contents of astragaloside Ⅳ between the top grade of Shanxi wild-simulated Astragali Radix top and the first grade of Gansu cultivated Astragali Radix. The contents of astragaloside Ⅳ in the second,third and fourth grade of Shanxi wild-simulated Astragali Radix was significantly higher than those of produced from Gansu.There was a significant negative correlation between the contents of astragaloside Ⅳ and grade in Shanxi Astragali Radix. While there was no correlation for Gansu Astragali Radix. This study provided the basis for the quality grade standard of Astragali Radix.

RNF185 modulates JWA ubiquitination and promotes gastric cancer metastasis.

Gastric cancer (GC) is one of the most common malignant cancers worldwide. Metastasis leads to poor prognoses in GC patients in advanced stages. Our previous studies have demonstrated that JWA functions as a tumour suppressor and that low expression of JWA in GC tissues is significantly correlated with shorter overall survival (OS) as well as with advanced clinicopathologic features in patients. However, the mechanism of dysregulation of JWA in cancers is not clear. In the present study, we found that an E3 ubiquitin ligase, RNF185, directly interacted with JWA and promoted its ubiquitination at the K158 site, resulting in subsequent degradation. Moreover, the protein level of RNF185 was negatively correlated with JWA in tumour tissues from GC patients. High RNF185 expression was significantly correlated with shorter OS. Additionally, increased RNF185 expression facilitated GC cell migration in vitro and promoted GC metastasis in vivo by downregulating JWA expression. However, this effect was reversed by replenishment of JWA. In conclusion, our findings highlight the following: (1) RNF185 promotes GC metastasis by mediating JWA degradation via a ubiquitin-proteasome pathway; (2) the K158 site of JWA is essential for its ubiquitination in GC cells. These findings suggest that RNF185 is a novel candidate prognostic marker and potential therapeutic target for GC.

Resveratrol Boosts Cognitive Function by Targeting SIRT1.

Cognitive decline is among the most devastating age-related conditions and is rapidly becoming an important cause of disease burdens worldwide. New strategies for the prevention and management of cognitive decline are needed. Resveratrol, a polyphenolic compound, has been found to enhance brain health through multiple signaling pathways. Optimal SIRT1 activation is the most crucial step in the neuroprotection provided by resveratrol against cognitive impairment. This review discusses several recent developments in our understanding of the mechanisms by which resveratrol delay age-related cognitive decline through SIRT1. The regulatory mechanisms include anti-oxidative, anti-inflammatory, anti-apoptotic processes and autophagy regulation, as well as increases in cerebral blood flow and improvements in the plasticity of synaptic pathways. Resveratrol, as well as novel SIRT1 activators, is likely to provide promising therapeutic strategies for impeding cognitive decline, repairing brain functions, and supporting healthy aging.

Probing the Bi-directional Interaction Between Microglia and Gliomas in a Tumor Microenvironment on a Microdevice.

It has been proven that microglia are involved in both early and late stages of glioma progression and contribute substantially to the tumor mass of gliomas. Because no appropriate in vitro or in vivo investigative approach is available, the dynamic interaction between microglia and gliomas during tumor formation remains unclear. In this study, three types of microfluidic assay were developed to examine the outcomes of the dynamic interaction between microglia and gliomas. Co-migration assay and two-dimensional cell co-culture assay have been used to show that microglial BV-2 cells migrate toward C6 glioma cells and inhibit tumor growth during the early stage of tumorigenesis. However, in three-dimensional cell spheres (three-dimensional cell co-culture assay) that contain a large amount of glioma cells, mimicking the late stage of glioma growth, the phagocytosis of microglia was suppressed, which suggests that glioma cells could reeducate classically activated microglia into a tumor-promoting state at some point during tumor progression. Notably, we found that microglia could contribute to tumor invasion and acquisition of the epithelial-mesenchymal transition phenotype in the glioma microenvironment during the early stage and the late stage of tumor progression. In conclusion, we have developed a potential quantitative method for in vitro study of glioma immunity and provided evidence for the duality of glioma-associated microglia.

Resonance Rayleigh scattering technique as a detection method for the RP-HPLC determination of local anaesthetics in human urine.

A highly selective and sensitive method of reversed phase high-performance liquid chromatography (RP-HPLC) coupled with resonance Rayleigh scattering (RRS) was developed for the determination of procaine, bupivacaine and tetracaine. Separation of three local anaesthetics was achieved at 35 °C on a C18 column. The mobile phase was 30: 70 (v/v) acetonitrile/triethylamine-phosphoric acid buffer (pH 2.9) at flow rate of 0.3 mL/min. The RRS detection was conducted by taking advantage of the strong RRS enhancement of the local anaesthetics with erythrosine reaction in an acidic medium. Under optimum conditions, the limit of detection (S/N = 3) values were in the range of 2.4-11.2 ng/mL. Recoveries from spiked human urine samples were 95.8%-104.5%. The proposed method applied to the determination of local anaesthetics in human urine achieved satisfactory results. In addition, the mechanism of the reaction is fully discussed. Copyright © 2016 John Wiley & Sons, Ltd.

Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx.

BACKGROUND: Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. METHODS: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol. RESULTS: Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 µM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 µM; n = 6). CONCLUSIONS: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.

Enhanced Neuroprotective Effects of Combination Therapy with Bone Marrow-Derived Mesenchymal Stem Cells and Ginkgo biloba Extract (EGb761) in a Rat Model of Experimental Autoimmune Encephalomyelitis.

OBJECTIVES: We investigated whether Ginkgo biloba extract (EGb761) can provide neuroprotective effects and enhance the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model of experimental autoimmune encephalomyelitis (EAE). METHODS: We examined the synergistic action of BMSCs combined with EGb761 treatment in EAE rats. The immunized rats received an intravenous injection of BMSCs or intraperitoneal administration of EGb761 or both on the day of the onset of clinical symptoms and for the following 21 days. Clinical severity scores were recorded daily and histopathological examination of the spinal cord and cytokine concentrations in the serum were studied on days 14 and 31 postimmunization. RESULTS: Our results showed that combined treatment with BMSCs and EGb761 further decreased the disease severity, maximal clinical score and number of infiltrated mononuclear cells, especially CD3-positive T cells. We observed that the demyelination score and the density of axonal loss in the spinal cord were significantly reduced in mice receiving the combination therapy. The serum concentrations of the phosphorylated neurofilament heavy chain, tumor necrosis factor-α and interferon-γ were reduced in the combination-treatment group. CONCLUSION: Our results suggest that combined treatment with BMSCs and EGb761 have a synergistic effect in rats with EAE by inhibiting the secretion of proinflammatory cytokines, demyelination and protecting axons and neurons.

A metabonomic analysis reveals novel regulatory mechanism of Huangqi injection on leucopenia mice.

CONTEXT: Huangqi injection (HQI), extracted from Astragali Radix, which has capability on treating the leucopenia. However, the potential metabolic mechanism is poorly understood. OBJECTIVE: To investigate the effect of HQI on cyclophosphamide (Cy)-induced leucopenia in mice, the nuclear magnetic resonance (NMR)-based metabolomic profiling technique coupled with multivariate statistical analysis was applied. MATERIALS AND METHODS: NMR analysis was used to identify the various compounds of HQI, and high-performance liquid chromatography was applied to determine the contents of major compounds. A experimental mice model of leucopenia induced by Cy and NMR-based metabolomic approach was used to evaluate the pharmacological effect of HQI and to investigate its probable acting mechanism on leucopenia. RESULTS: HQI increased body weight and elevated the white blood cell (WBC), monocytes (MO), neutrophils (NE), and lymphocyte (LY) levels of Cy-treated mice. In addition, the levels of most perturbed endogenous metabolites could be reversed after HQI treatment. Correlations between WBC, MO, NE, LY, and altered metabolite profiles in spleen were greater than that in serum, and the correlation in MO was more evident than those for WBC, NE, and LY. DISCUSSION AND CONCLUSION: HQI showed obvious efficacy on the mice model of leucopenia. And the drug action of HQI on leucopenia was probably related with regulating metabolic pathways of energy metabolism, amino acids metabolism, oxidative stress, and choline metabolism. However, various compounds were present in the HQI, and the bioactive compounds responsible for the drug actions should be further investigated.

[~1H NMR fingerprints of Huangqi injection solution].

The study established the 1H NMR-based fingerprinting and analyzed 8 batches of Huangqi injection solution.1H NMR-based fingerprinting of both primary and secondary metabolites of Huangqi injection were established, and the 1H-1H chemical shift correlation spectroscopy (COSY) and 1H-13C chemical shift correlation spectroscopy (HSQC) were used to identify the chemical components in Huangqi injection solution. Coupled with similarity analysis and relative content determination,8 batches of Huangqi injection solution were analyzed. Twenty-five metabolites (both primary and secondary) were identified, and the significant differences were found in the chemical composition among these Huangqi samples. The content and content variation of the primary metabolites were much higher than those of the secondary metabolites, which was the major cause of the uniformity of the Huangqi injections. The results on the quality variations of Huangqi injections in this study will serve as a basis for improving the quality control.

[Thinking on development of Shanxi Astragali Radix industry].

Shanxi, a traditional production area to produce genuine Astragali Radix of high quality, has experienced major changes in the pattern of resources. This area once accounted for half of Astragali Radix industry, but now only serves as the largest supply area of traditional wild Astragali Radix. Furthermore, the strategic position of Shanxi Astragali Radix industry will become more prominent and more important to economic and social development in face of the diversity of market demands, especially for the strong demands of high-end Astragali Radix. In addition, Astragalus industry involves the simultaneous development of the first, second and tertiary industries in many areas, and it is typical and representative in the traditional Chinese medicine industry development. However, the application and industrial development of Shanxi Astragali Radix have been restricted due to the problems such as blind promotion of transplanting cultivation technology, and lack of science and technology including efficacy investigation, safety evaluation, standardization and controllability studies. Therefore, we would analyze the production history, resource structure, the current situation and progress of industry development, scientific research foundation and existing problem in this paper, and put forward countermeasures for development and technical innovation in order to make Astragali Radix industry bigger and stronger through innovation-driven and make benefits for demos. This thought provides a reference for the exploratory development of other large varieties of Chinese medicinal materials.

Comparison of Two Different Astragali Radix by a ¹H NMR-Based Metabolomic Approach.

Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. The main source of AR in China is the dried root of Astragalus membranaceus var. mongholicus (Bge.) Hsiao, and both cultivated and wild ARs are used clinically. A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. The results showed that SX-AR and GS-AR differed significantly not only in the primary metabolites but also in the secondary metabolites. However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR.