The improvement effect and metabolic mechanism of Echinops sphaerocephalus extract on osteoporosis model rat / 中国药房

OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group， model group， Gushukang group， E. sphaerocephalus high-dose， medium-dose and low- dose groups， with 6 rats in each group. Except for blank group， other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection， E. sphaerocephalus high-dose， medium-dose and low-dose groups were given drugs intragastrically at dose of 878， 439， 219.5 mg/kg， respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically， once a day， for consecutive 8 weeks. After last administration， blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline （HYP）， alkaline phosphatase （ALP）] and oxidative stress indexes [total antioxidant capacity （TAOC）， superoxide dismutase （SOD）， malondialdehyde （MDA）] in serum of rats. Positron emission tomography/computedtomography （PET/CT） was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile， metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group， HYP， ALP， MDA， ratio of bone surface to bone volume （BS/BV）， and trabecular separation （Tb·Sp） in model group were significantly increased （P＜0.05）， while TAOC， SOD， bone mineral density （BMD）， bone volume fraction （BVF）， trabecular E-mail：Xpfdc153@163.com thickness （Tb·Th） and trabecular number （Tb·N） were significantly decreased （P＜0.05）. Compared with model group， above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus， 18 metabolites such as arachidonic acid， phenylalanine， tyrosine， tryptophan， isoleucine and uric acid in the serum of rats changed significantly， involving 15 metabolic pathways such as arachidonic acid， phenylalanine and tyrosine， of which arachidonic acid metabolism， phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure， which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.

Application of virus-induced gene silencing technology to investigate the phytochrome metabolism mechanism: a review / 生物工程学报

Color is an important indicator for evaluating the ornamental traits of horticultural plants, and plant pigments is a key factor affecting the color phenotype of plants. Plant pigments and their metabolites play important roles in color formation of ornamental organs, regulation of plant growth and development, and response to adversity stress. It has therefore became a hot topic in the field of plant research. Virus-induced gene silencing (VIGS) is a vital genomics tool that specifically reduces host endogenous gene expression utilizing plant homology-dependent defense mechanisms. In addition, VIGS enables characterization of gene function by rapidly inducing the gene-silencing phenotypes in plants. It provides an efficient and feasible alternative for verifying gene function in plant species lacking genetic transformation systems. This paper reviews the current status of the application of VIGS technology in the biosynthesis, degradation and regulatory mechanisms of plant pigments. Moreover, this review discusses the potential and future prospects of VIGS technology in exploring the regulatory mechanisms of plant pigments, with the aim to further our understandings of the metabolic processes and regulatory mechanisms of different plant pigments as well as improving plant color traits.

Advances on the production of organic acids by yeast / 生物工程学报

Organic acids are organic compounds that can be synthesized using biological systems. They often contain one or more low molecular weight acidic groups, such as carboxyl group and sulphonic group. Organic acids are widely used in food, agriculture, medicine, bio-based materials industry and other fields. Yeast has unique advantages of biosafety, strong stress resistance, wide substrate spectrum, convenient genetic transformation, and mature large-scale culture technology. Therefore, it is appealing to produce organic acids by yeast. However, challenges such as low concentration, many by-products and low fermentation efficiency still exist. With the development of yeast metabolic engineering and synthetic biology technology, rapid progress has been made in this field recently. Here we summarize the progress of biosynthesis of 11 organic acids by yeast. These organic acids include bulk carboxylic acids and high-value organic acids that can be produced naturally or heterologously. Finally, future prospects in this field were proposed.

Research progress of the regulatory role of autophagy in metabolic liver diseases / 中华肝脏病杂志

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.

Metabolic regulation and drug target discovery researches in China: Progress and prospect / 中国临床药理学与治疗学

Metabolic regulation is an important mechanism by which organisms adapt to changes in the internal and external environment. Metabolic small molecules function as versatile messengers involved in signaling networks and organ crosstalk, which carries great implications for understanding physiological processes, revealing disease mechanisms and discovering drug targets. In this review, we present an overview of the main progresses in metabolic regulation and drug target discovery researches in China, and look forward to its future direction, which may provide a reference for the drug development endeavor based on metabolic regulation.

ATP regulation strategy and its application in the synthesis of microbial metabolites / 生物工程学报

Cofactor engineering, as a new branch of metabolic engineering, mainly involves ATP/ADP, NADH/NAD⁺, NADPH/NADP⁺ and other cofactors. Cofactor engineering can maximize metabolic flow by directly regulating the concentration and form of the cofactor of key enzymes in cells, and quickly direct carbon flow to target metabolites. ATP, as an important cofactor, is involved in many enzyme-catalyzed reactions in microbial cells, and leads to the restriction of the distribution of metabolic pathways by connecting or linking them into a complex network. Therefore, ATP regulation strategy is expected to be a favorable tool for industrial strain modification, to improve the concentration and production capacity of target metabolites, strengthen microbial tolerance to the environment and promote substrate utilization rate. The present review focuses on the recently used effective ATP regulation strategies and the effects of ATP regulation on cell metabolism in order to provide references for the efficient construction of microbial cell factories.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera / 中国天然药物

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.

Research Development in Biosynthesis and Metabolic Regulation of Tetracyclic Triterpenoid Saponins in Medicinal Plants / 世界科学技术-中医药现代化

Triterpenoid saponins is an important secondary metabolites in medicinal plants, and the tetracyclic triterpenoid saponins, as one of the main categories, have very high medicinal value and market demand. However, there is no systematic review on the research. Thus, the elucidation of the biosynthetic pathway and metabolism of the medicinal plant tetracyclic triterpenoid saponins has important theoretical significance and broad application prospects.In this review, the biosynthetic pathway and metabolic regulation of medicinal plant of tetracyclic triterpenoid saponins were discussed. My focus in this paper was to introduce the research development of several metabolic biosynthetic pathways of tetracyclic triterpenoid saponins centered on dammarane type, and the gene improvement by methods such as metabolic pathway and other technological methods. This study provides references on secondary metabolic framework of medicinal plants of tetracyclic triterpenoid saponins, accurately locating secondary metabolism and its key enzymes, and promoting the sustainable uses of medicinal plant resources.

Applications progress of stable isotopic tracer technique in metabolic regulation of endogenous substances / 中草药

With the rapid development of high-sensitivity detection methods, stable isotope tracing technique has received increasing attention. Stable isotope tracing technique can accurately track the activity of labeled compounds in the body through the tracer atoms and determine their specific metabolic pathways based on the distribution of isotopic peaks of the intermediate metabolites. By calculating the flux, the metabolic pathways are analyzed to provide a basis for the study of disease mechanism and drug metabolism. In recent years, the technique has a wide application in the field of biomedicine. This paper summarizes the applications of stable isotopic tracer technique in the metabolic regulation of endogenous substances such as carbohydrate metabolism, lipid metabolism, amino acid metabolism, hormone metabolism, nucleic acid metabolism, and so on.

Traditional Chinese Practice, A Promising Integrative Intervention for Chronic Non-Infectious Disease Management / 中国结合医学杂志

The number of people with chronic diseases rises rapidly in recent years worldwide. Except for drug medication, mind-body exercises are indispensable for chronic disease management. Traditional Chinese practice (TCP), as an integrative intervention, is known as an effective means to keep in good health and fitness, as well as help regulate emotion. This paper introduces the domestic and overseas studies on effectiveness of TCP for chronic diseases, and explores the key action links from three aspects, including functional training of multiple-joint guided by consciousness, relieving psychological risk factors, improving respiratory and digestive function, blood and lymph circulation through respiratory training, and regulation of nerve, metabolic, and immune system. Finally, the authors discussed how to integrate TCP in the chronic disease management, and put forward that the practice methods and evaluation standard should be assessed academically.

Research progress on metabolic regulation of artemisinin / 中草药

Artemisinin is widely used for the treatment of malaria. Artemisia annua fielded low artemisinin, which was far behind the requirements. The study on the metabolic regulation of A. annua is an effective way to improve the yield of artemisinin. Metabolic regulation of artemisinin is an effective approach to improve the yield of artemisinin. In this paper, the variety of factors that affect artemisinin content was summarized, including biosynthesis in artemisinin and its branch pathway of key enzyme genes, transcription factors, phytohormones, environmental stress, induction factors, trichomes, etc. By reviewing the research progress of these factors in metabolic regulation of artemisinin, new strategies in conventional secondary metabolic engineering were generalized based on artemisinin and its branch biosynthesis pathway and fresh metabolic engineering based on trichomes. These strategies enriched the pathway in metabolic regulation of artemisinin and put forward a new idea to cultivate transgenic strain of A. annua with good quality and high yield.

Cloning of FPS gene and its role in regulation of alkaloid synthesis in Fritillaria thunbergii / 中草药

Objective: Farnesyl pyrophosphate synthase (FPS) gene of Fritillaria thunbergii was cloned and the correlation between the expression content of gene and alkaloid accumulation was analyzed to explore the role of FPS gene in the regulation of alkaloid synthesis and metabolism. Methods: In this study, the new bulbs and different tissues of Fritillaria thunbergii varieties "Narrow leaf" "Broad leaf" and "New Meiyuan" were used to clone the full-length sequence of FPS gene via RACE technology. RT-qPCR and HPLC-ELSD technology was used to determine the expression of FPS in 10 different developmental stages and the content of alkaloid (Peimine and Verticinone), respectively. Finally, the correlation was analyzed. Results: The full-length cDNA sequence of FPS gene was 1 629 bp. Open Reading Frame (ORF) was 1 056 bp and encoded 351 amino acids. Among them, the tissue specific expression trends of FPS gene were same, flowers had the highest expression level, followed by the new bulb. The results of correlation analysis showed thatthe content Peimine and Verticinone had significant positive correlation with the expression level of FPS gene in "Broad leaf" and "New Meiyuan" (The correlation coefficients were 0.289 and 0.613, 0.427 and 0.622, respectively);FPS gene expression and alkaloid content in different tissues had a positive correlation (The correlation coefficients were 0.057 and 0.476, 0.085 and 0.495, 0.375 and 0.432, respectively). Conclusion: The full-length sequence of FPS gene was successfully cloned in this study. The FPS gene involved in the regulation of alkaloid synthesis and metabolism.

A new method of RNAi vector construction and its application of secondary metabolism regulation of plants / 中草药

RNA interference (RNAi) technology has strong specificity, high inhibitory efficiency, large-scale operation application, and good repeatability, and it can perform Mendelian mode of inheritance in plants, which is widely used in the validation of gene function and metabolic regulation. In plant metabolic engineering, the RNAi method can inhibit the synthesis of product, change the distribution of metabolic flux, and regulate the synthesis of the target product. This review summarized the current progress and study strategy of RNAi in plant metabolic regulation. RNAi mechanism and characteristics, optimal strategy of vector structure, efficient RNAi vector construction method, and application progress in the regulation of metabolism were reviewed, in order to lay the theoretical foundation and technical reference of RNAi technology of metabolic engineering control.

Advances in study on secondary metabolic engineering of alkaloids in medicinal plants / 中草药

Since the weak research basis on metabolic pathway and regulation mechanism of medicinal plants, obtaining valuable secondary metabolites from medicinal plants by metabolic engineering technology is seriously impacted. Alkaloids are nitrogen heterocyclic compounds in medicinal plants, which have pharmacological effects, such as anti-tumor, anti-microbial, anti-hypotensive, spasmolysis analgesia, etc. It is valuable for optimizing the germplasm resource of medicinal plants and their sustainable development by using metabolic engineering methods to influence the metabolic pathways in order to increase the content of secondary metabolites. The synthetic metabolic pathways about alkaloids of medicinal plants were reviewed in this paper, as well as research methods and regulation strategies, for giving some references to relative studies on alkaloids from medicinal plants.

Advance in biosynthesis of terpenoid indole alkaloids and its regulation in Catharanthus roseus / 中国中药杂志

Catharanthus roseus can produce a variety of terpenoid indole alkaloids (TIA), most of which exhibit strong pharmacological activities. Hence, biosynthesis and regulation of TIA have received recent attention. 3α (S)-strictosidine is an important node in TIA biosynthesis, which is a condensation product of secologanin and tryptamine. The former is produced in iridoid pathway, and the latter is produced in indole pathway. Vindoline and catharanthine, which are produced respectively by 3α (S)-strictosidine via multi-step enzymatic reaction, can form α-3, 4-anhydrovinblastine by the condensation reaction. Then, vinblastine and vincristine are generated from α-3, 4-anhydrovinblastine. Many transcription factors are involved in the regulation of TIA synthesis, such as AP2/ERF and WRKY. Illumination of biosynthetic pathway has laid a foundation for the study of synthetic biology. Today, 3α (S)-strictosidine and vindoline have been synthesized in heterologous hosts Saccharomyces cerevisiae.Research about synthetic biology and the regulation mechanisms will provide a guidance for the production and development of TIA drugs in C. roseus.

Application of metabolic regulation in the antibiotic biosynthesis of actinomycetes / 中国药科大学学报

@#The secondary metabolites of actinomycetes are rich and diverse, which have become important sources of antibiotics and their lead compounds. The study of microbial secondary metabolism is focused on metabolic regulation of antibiotic biosynthesis in actinomycetes by genetic manipulation. On the basis of the advances of recent years, this paper summarizes the application progress of metabolic regulation used for improving biosynthesis of antibiotics in actinomycetes, concluding of regulating the expression of regulatory genes, increasing the copy numbers of gene clusters and heterologous expression, over-expressing the resistance genes and transfer gene, improving precursor metabolic flux, and ribosome engineering.

Effect of special anti-fatigue foods on military physical performance capacity / 军事医学

Objective To assess the series of special anti-fatigue foods including JuntiⅠ, JuntiⅡ, JuntiⅢ, and Jun-tiⅣon military physical performance capacity .Methods Fifty-four soldiers , selected from a border defense troop , were randomly designated to control group , trial group 1 and trial group 2.Subjects of two trial groups were supplied with No .1 nutritional package ( including JuntiⅠ, Ⅲand Ⅳ) and No.2 nutritional package ( including Junti Ⅱ, Ⅲand Ⅳ),re-spectively, while no additional nutritional supplements were added in control group .After 7 days’ supplementation, a hard military exercise was performed to induce fatigue and an increasing load test was used to assess physical activity .RPE scale, exhaustive time and time taken to reach the 75% maximal heart rate were recorded while serum markers , such as glucose, lactate, BUN, LDH,and CK, were detected after test .Moreover, serum lactate and fatigue recovery scale were determined on the evening of the same day and the next morning .Results Prolonged exhaustive time and time taken to reach the 75%maximal heart rate and elevated RPE scores at 6 min were detected in both two trial groups compared with the control group .Meanwhile , after the increasing load test , elevated glucose concentration and reduced lactate , BUN, LDH and CK were also observed in both trial groups .Moreover, serum lactate of both trial groups was quickly recovered on the evening of the same day compared with the control group , and the next morning , serum lactate was even much lower in trial groups than in control group .The fatigue recovery scores were higher in trial groups at both time points .Meanwhile, there was no difference of such indexes between the two trial groups .Conclusion Through the combination use , the series of special anti-fatigue foods, inclucling No.1 and No.2 nutritional packages , can significantly improve the soldiers′physi-cal performance capacity , delay the physical fatigue emergence , promote physical activity recovery and prevent military training injury.

Effect of Insulin on the Differential Expression of VLDL Receptor Isoforms of SGC7901 Cell and Its Biological Implication / 华中科技大学学报（医学）（英德文版）

This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication. In vitro,moderately or poorly-differentiated human gastric adenocarcinoma cell line SGC7901 was incubated with insulin for different lengths of time, and then the expression of protein and RNA level in VLDLR subtypes were detected by Western blotting and real-time PCR, respectively. The results showed that, at certain time interval, insulin could down-regulate expression of type Ⅰ VLDLR and up-regulate the expression of type Ⅱ VLDLR in SGC7901 cells, at both protein and RNA level.We are led to conclude that insulin serves as a regulator in maintaining the balance between glucose and lipid metabolism in vivo, possibly through its effect on the differential expression of VLDLR subtypes.

Metabolic Regulation of Cell Growth and Antimicrobial Metaboliteof the F0238 / 微生物学通报

Metabolic regulation of cell growth and antimicrobial metabolite of the F0238 was carried out in this study.The proper compositions of the culture medium and technological conditions for its fermentation were investigated.The results showed that the optimum conditions for the growth of the strain and its production of kojic acid were PDA medium with starch 2% as C source, peptone 0.2% as N source, and temperature 28℃, culture time 5 day (144 h), culture volume 80mL/500mL Erlenmeyer flask. Under above conditions, the dynamic curve of fermentation was obtained by an automatic mini-bioreactor of 10L and indicated a trend of decreasing pH, DO and residual sugar and increasing biomass and kojic acid production by F0238.