Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

[Comparison of transcriptome of Atractylodes lancea rhizome and exploration of genes for sesquiterpenoid biosynthesis].

This study compared the transcriptome of Atractylodes lancea rhizome at different development stages and explored genes encoding the key enzymes of the sesquiterpenoid biosynthesis pathway. Specifically, Illumina NovaSeq 6000 was employed for sequencing the cDNA libraries of A. lancea rhizome samples at the growth stage(SZ), flowering stage(KH), and harvesting stage(CS), respectively. Finally, a total of 388 201 748 clean reads were obtained, and 16 925, 8 616, and 13 702 differentially expressed genes(DEGs) were identified between SZ and KH, KH and CS, and SZ and CS, separately. Among them, 53 genes were involved in the sesquiterpenoid biosynthesis pathways: 9 encoding 6 enzymes of the mevalonic acid(MVA) pathway, 15 encoding 7 enzymes of the 2-C-methyl-D-erythritol-4-phosphate(MEP) pathway, and 29 of sesquiterpenoid and triterpenoid biosynthesis pathway. Weighted gene co-expression network analysis(WGCNA) yielded 12 genes related to sesquiterpenoid biosynthesis for the SZ, 1 gene for the KH, and 1 gene for CS, and several candidate genes for sesquiterpenoid biosynthesis were discovered based on the co-expression network. This study laid a solid foundation for further research on the sesquiterpenoid biosynthesis pathway, analysis of the regulation mechanism, and mechanism for the accumulation of sesquiterpenoids in A. lancea.

[Effects and mechanisms of nitrogen fertilizers on soil and tritrophic interactions in Chinese medicinal plants ecosystem].

Nitrogen is one of the most frequently used fertilizers in growth of Chinese medicinal plants(CMP). As in many other ecosystems, CMP ecosystem is also composed of plant-herbivore-natural enemy(tritrophic) interactions. Nitrogen fertilizer influences the growth and reproduction of CMP, and it is also able to heavily shape the ecosystem functions of CMP ecosystem through bottom-up forces. Understanding the specific effects of nitrogen fertilizer towards each trophic level will be beneficial to improve the resistance of CMP to herbivore and enhance the control efficiency of nature enemies to herbivore, and eventually, maximize the yield and quality of CMP. Most papers published on nitrogen use in plants focused mainly on the impact of nitrogen fertilization on CMP yield and quality. Influences of nitrogen application on CMP ecosystem get little attention at present. Therefore, this review summed up the potential effects of nitrogen fertilization on CMP ecosystem from perspectives of soil and tritrophic interactions. First of all, nitrogen fertilizer might decrease soil microbial biomass and altered the community structures of soil bacteria, fungi and protozoa. Negative effects of nitrogen fertilizer were found on biodiversity of soil bacteria and protozoa. Different fungi species respond differently to nitrogen fertili-zers. Nitrogen deposition can also decrease the soil pH. Decreases in soil microbial diversity and soil acidification can cause negative effects on CMP growth. In addition, nitrogen fertilizer could regulate the pest resistance of CMP including constitutive and inducible resistance. Both positive and negative effects of nitrogen application were found on pest resistance of CMP. Moreover, the development and predation of natural enemies were influenced by nitrogen deposition. Nitrogen influences natural enemies in many ways including plant volatiles, plant nutrient and structure and the supplementary food quality. Nectar and honeydew of plants and preys serve as important food source for natural enemies especially in early season when preys are still not available. Finally, the interactions between herbivores and their natural enemies were also shaped by nitrogen fertilizer in many aspects like increasing the nutritional content of prey and changing control efficiency of natural enemies. Some herbivores have evolved a strategy to sequester secondary metabolites which they absorbed from plant during their feeding. Studies showed that sequestration efficiency of secondary metabolites in prey could also be regulated by nitrogen. Parasitic, emergence, reproduction rate and longevity of parasites were found positively correlated with nitrogen deposition. Hopefully this study will shed light on practicable and economical application of nitrogen in cultivation of CMP.

[Effects of ecological factors on shape and ginsenoside of Panax ginseng].

The ecological environment is closely related to the growth and quality of authentic medicinal materials. Ginseng is very strict with its natural environment and grows mostly in the damp valleys of forests, and the appearance and chemical composition of ginseng under different growth environments are very different. This article reviews the effects of different ecological factors(including light, temperature, altitude, moisture, soil factors, etc.)on the appearance and chemical composition(mainly ginsenosides) of ginseng. Through systematic review, it is found that soil physical factors are the most important ecological factors that affect the appea-rance of ginseng, and soil bulk density plays a key role; temperature affects ginsenosides in ginseng medicinal materials The dominant ecological factors for the accumulation of chemical ingredents; strong light, high altitude, high soil moisture, low soil nutrient and strong acid soil can influence the accumulation of secondary metabolites in ginseng. Environmental stress can also stimulate the formation and accumulation of secondary metabolites in medicinal plants. Appropriate low temperature stress, high or low water stress, acid or alkali stress can also promote the accumulation of ginsenosides. This article systematically reviews the ecological factors that affect the appearance and chemical composition of ginseng, and clarifies the dominant ecological factors and limiting factors for the formation of ginseng's appearance and quality, as well as beneficial environmental stress factors, in order to provide a theoretical basis for ginseng ecological planting and ginseng quality improvement.

[Construction of pharmacophore model and its application in identification of effective components of Chinese medicine].

The effective material basis of Chinese medicine is the key and difficult point in the quality control and modernization research of Chinese medicine. With the increasing application of pharmacophore-based virtual screening in computer-aided drug design, it is possible to employ this technology in the modernization of Chinese medicine. Based on the systematic research method of the pharmacophore model, the present study systematically reviewed the pharmacophore-based technologies and strategies in the identification of active components in Chinese medicine.

[Preliminary study on memory function of Sorbus aucuparia suspension cell to biotic stress].

Plants have a memory function for the environmental stress they have suffered. When they are subjected to repeated environmental stress, they can quickly and better activate the response and adaptation mechanism to environmental stress, thus realizing long-term stable reproduction. However, most of the relevant studies are applied to crops and Arabidopsis thaliana rather than medicinal plants about the improvement of plant growth status and the effect on phytoalexin biosynthesis. In this study, yeast extract(YE) was used as an elicitor to simulate biotic stress, and the changes in biomass and the content of some secondary metabolites were measured by giving repeated stresses to Sorbus aucuparia suspension cell(SASC). The results showed that the accumulation levels of biomass and some secondary metabolites in SASC subjected to repeated stress are significantly increased at some time points compared with single stress. A phenomenon that SASC can memorize biotic stress is confirmed in this study and influences phytoalexin accumulation in SASC. Furthermore, the work laid the groundwork for research into the transgenerational stress memory mechanism of medicinal plant.

[Extraction and separation, structure analysis and biological activity of polysaccharides from Atractylodis Rhizoma].

Atractylodis Rhizoma(AR) is a traditional Chinese medicinal material for food and medicine, with the functions of eli-minating dampness, strengthening the spleen, expelling wind evil and dispersing cold. AR contains a variety of compounds, including sesquiterpenoids, alkynes, triterpenoids, aromatic glycosides, polysaccharides and so on. At present, the researches on AR mainly focus on volatile components, with relatively fewer researches on non-volatile components. Polysaccharide from Atractylodis Rhizoma(ARP) is an important material basis among non-volatile components for the efficacy. Due to its many biological activities such as immunomodulatory activity, anti-tumors, anti-virus and anti-oxidation, ARP has certain research value and potential. The diversity of the polysaccharide structure is the basis for biological functions, but it also increases the difficulty of carbohydrate research. The research on the extraction, separation, purification, structure and activity of ARP is in the preliminary exploration stage, still with many shortcomings. Herein, recent advancements in the extraction, purification, structural characteristics and biological activities of ARP were summarized in this article to provide scientific reference for the in-depth systematic research of ARP and the development of AR resources.

[Current situation of nitrogen application and its effects on yield and quality of Chinese materia medica].

Nitrogen fertilizer has been the long-lasting crucial component in cultivation of Chinese materia medica(CMM) and crops for its profound effects on enhancing the productivity. In consideration of its role in better production, intensive and excessive application of N fertilizer is often found in CMM cultivation. Therefore, firstly, this review summarized various concentrations of N application with regards to different CMM and districts from the literatures published in the last two decades. The recommended concentration of nitrogen application of forty seven CMM species were covered in this review. We found that the optimum rates of nitrogen fertili-zer for different medicinal plants species were varied in the range between 0-1 035.55 kg·hm~(-2). Most of the optimum rates of nitrogen fertilizer for CMM in published researches fell between 100-199 kg·hm~(-2). The optimum rate of nitrogen fertilizer is not only related to amount of nitrogen required for different medicinal plants but also to soil fertilities of different fields. In addition, we outlined the diffe-rent effects of proper and excessive nitrogen deposition on yield of CMM. Proper nitrogen deposition benefits the yield of CMM, howe-ver, excessive nitrogen use accounts for a decrease in CMM yield. We elucidated that nutritional content, water use efficiencies, and photosynthesis capacity were major influencing factors. Researches showed that proper nitrogen fertilizer could promote the water use efficiencies of plants and boost photosynthesis. Consequently, the yield of CMM can be enhanced after nitrogen deposition. However, negative effects of nitrogen fertilizer were also found on plant including producing toxic substances to the soil and causing severe pest damages. Lastly we analyzed the impact of N fertilizer application on secondary metabolites which accounts for a large part of active pharmaceutical ingredients of CMM. It usually caused an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. The potential underlying mechanisms are the different synthetic pathways of these metabolites and the plant nutritional status. Synthesis of non-nitrogen-containing secondary metabolites like phenols can be inhibited after nitrogen application because of the competition of the same precursor substances between metabolites synthesis and plant growth. To sum up, impacts and mechanisms of nitrogen fertilizer on yield and quality enhancement of CMM were discussed in this review. Negative effects of excessive nitrogen application on CMM should be paid special attention in CMM cultivation and prescription fertilization based on the field soil quality is strongly recommended. Overall, this review aims to provides insights on improving the proper application of N fertilizer in the cultivation of CMM.

[Effects and mechanisms of nitrogen application on stress resistance of Chinese materia medica].

Nitrogen fertilizers play an important role in the regulation of plant stress resistance. Impacts of nitrogen fertilizers on abiotic stress resistance and biotic stress resistance of Chinese materia medica(CMM) were summarized in this study. Adequate nitrogen application improves the abiotic stress resistance and weed resistance of CMM, however adverse effect appears when excess nitrogen is used. Generally, pest resistance decreases along with nitrogen deposition, while effects of nitrogen application on disease resistance vary with different diseases. Mechanisms underlying the impact of nitrogen fertilizers on plant stress resistance were also elucidated in this study from three aspects including physical defense mechanisms, biochemistry mechanisms and molecular defense mechanisms. Nitrogen availability modulates physical barrier of CMM like plant growth, formation of lignin and wax cuticle, and density of stomata. Growth of CMM promoted by nitrogen fertilizer may cause some decrease in pest resistance of CMM due to an increase in hiding places for pest along with plant growth. High ambient humidity caused by excessive plant growth facilitates the growth and development of CMM pathogen. Nitrogen application can also interfere with the accumulation of lignin in CMM which makes CMM more vulnerable to pest and pathogen attack. Stomatal closing delays due to nitrogen application is also a causal factor of increasing pathogen infection after nitrogen deposition. Biochemical defenses of plants are mainly achieved through nutrient elements, secondary metabolites, defense-related enzymes and proteins. Nutritional level of CMM and various antioxidant enzymes and resistance-related protein activities are elevated along with nitrogen deposition. These antioxidant enzymes can reduce the damage of reactive oxygen species content produced by plant in response to adversity and therefore enhance stress resistance of CMM. Researches showed that nitrogen application could also cause an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. Nitrogen-mediated molecular defense mechanisms includes multiple plant hormones and nitric oxide signals. Plant hormones related to plant defense like salicylic acid, jasmonic acid and abscisic acid can be modulated by nitrogen application. Negative effect of nitrogen deposition was found on salicylic acid accumulation and the expression of related plant disease resistance genes. However, jasmonic acid level can be elevated by nitrogen. Nitric oxide signals constitute an important part of nitrogen mediated defense mechanisms. Nitric oxide signaling is related to many aspects of plant immunity. The roles of nitrogen fertilizers in CMM stress resistance are complex and may vary with different CMM varieties and environments. Further studies are urgently needed to provide a comprehensive understanding of how to improve stress resistance of CMM by using fertilizers.

[Construction status and development strategy of GAP bases for Chinese herbal medicine].

Good agricultural practices(GAP) for Chinese herbal medicine(CHM) is the source of quality control in the production of CHM. To ensure the safety, efficacy, and quality of Chinese herbal and natural medicine, the international community has been exploring the implementation of GAP for CHM. The implementation of GAP for CHM has a far-reaching impact, and the scale planting of CHM has been expanding. However, the medicinal materials produced by the GAP bases for CHM still cannot fully meet the market demand, and the output and quality of CHM remain to be improved. This paper summarizes construction status of GAP bases for CHM.The 129 companies that passed the certification during the implementation of GAP for CHM included 196 GAP bases, forming the scale CHM production zone with Sichuan province, Yunnan province, Jilin province, Henan province, and Shandong province as the core.The total area of GAP bases for CHM in China is about 250 000-500 000 Mu(1 Mu≈667 m2), which is still less than 1% of the total production area of CHM. The international agricultural production quality management strategies are all market-oriented behaviors.Drawing on the international good agricultural and collection practice(GACP) and hazard analysis critical control point(HACCP) as well as the relevant policies of Chinese quality management of CHM, we put forward feasible suggestions for the further implementation of GAP for CHM:(1)The market rules and international experience should be followed and employed to promote GAP management of CHM and third-party implementation of GAP certification;(2)The sound development of GAP for CHM should be boosted with the HACCP management system and the revision of GAP for CHM;(3)The implementation of policies and standards should be stepped up to facilitate the building of a whole-course traceability system for the production of CHM with high quality and reasonable prices.

[Current status and prospects of implementing GAP in Chinese medicine injection materials].

Chinese medicine injections(CMIs) have higher requirements for quality consistency and controllability than other traditional Chinese medicine products. The implementation of Good Agricultural Practice of Medicinal Plants and Animals(GAP) is an important factor that guarantees the quality stability of raw Chinese medicinal materials and affects the quality of CMIs. Through literature review, data research, expert consultation, and statistical analysis, this paper analyzes the current status of GAP management of key CMIs and the impact of GAP management of raw medicinal materials on the quality consistency and controllability of CMIs. Furthermore, it demonstrates the rationality, necessity, and feasibility of the full implementation of GAP on the basis of CMIs safety re-evaluation.

[Analysis on quality evaluation and control methods of Chinese medicine polysaccharide].

Chinese medicine polysaccharide is an important active biological macromolecule, which has a broad application prospect. However, there are still many deficiencies in the quality evaluation and control of polysaccharides. Based on the existing problems in the quality control of traditional Chinese medicine polysaccharides, current review analyzes the methods of extraction, separation and purification, characteristic identification, content determination and structure analysis of Chinese medicine polysaccharides, and draws the following conclusions: ①Based on the clinical application of Chinese medicine, decoction is recommended as the extraction method in the basic study of effective substances of Chinese medicine polysaccharides; ②On the basis of impurity removal, HPGPC can achieve the separation, purification and content determination of Chinese medicine polysaccharides at the same time, supplemented by MS or NMR can achieve the quantitative and qualitative analysis of Chinese medicine polysaccharides; ③Based on the characteristic identification, select the suitable pure polysaccharide, dextran or monosaccharide reference; ④HPSEC-MALLS-RID is specific, accurate, and beneficial to the study of structure-activity mechanism of polysaccharides. The review suggested that the comprehensive evaluation and control of the quality of Chinese medicine polysaccharides should be based on extraction, separation and purification, on the premise of characteristic identification, on the basis of content determination, supplemented by structural analysis, which is to provide useful reference for the quality research of Chinese medicine polysaccharides.

[Strategies for medicinal plants adapting environmental stress and "simulative habitat cultivation" of Dao-di herbs].

This paper analyzed life form, habitats and environmental stresses of medicinal plants and algal fungi collected in Chinese Pharmacopoeia(2015). ①It was found that only 0.94% of the medicinal plants mainly cultivated in field. The most common habitats of medicinal plants are divided into two types: those whose natural habitats are forest margins/undergrowth(about 42.53%) and those whose natural habitats are roadside, hillside, wasteland/sand(about 43.78%). The former mainly faces environmental stresses such as weak light, pests and diseases; the latter often faces the main environmental stresses of drought, strong light, ultraviolet radiation, high temperature, low temperature(day and night or annual temperature difference is large), nutrient deficiency, pests and so on. ②Based on analyzing the strategies of medicinal plants to adapt to environmental stresses, it is pointed out that the synthesis and accumulation of secondary metabolites are the most important strategies of medicinal plants to protect against environmental stresses. In the process of long-term adaptation to specific stress, the accumulation of relevant genetic variation and epigenetic inheritance has become an important condition for the formation of quality of medicinal plants. ③It is proposed that "simulative habitat cultivation" has obvious advantages in balancing growth and secondary metabolism and guaranting the quality of traditional Chinese medicinal materials.

[Pattern and matching technology of ecological planting for Chinese materia medica based on system level].

The ecological agriculture of Chinese materia medica(CMM) has become the most dynamic and promising new field in the global ecological agriculture. The development of ecological planting of CMM has become the national strategy of Chinese traditional medicine agriculture. It has been highly valued and has flourished throughout the country, and has formed some more mature ecological planting models of CMM. Based on the system level, this paper sorts out the common ecological cultivation patterns of CMM, and obtains five basic patterns: landscape pattern at the ecological landscape level, circulation pattern at the ecosystem level, stereo model at the bio-community level, biodiversity patterns at the level of biological populations and well-established models at the level of biological individuals. On this basis, eight common ecological planting techniques of CMM were obtained, includingwild tending techniques, fine agricultural farming techniques, directional cultivation techniques, soil improvement techniques, soil testing and fertilization techniques, mycorrhizal cultivation techniques, green control technology for pests and diseases and facility cultivation techniques.This paper aims to provide theoretical basis for scientific research and popularization and application of CMM ecological planting.

[Pattern of ecological planting for Chinese materia medica based on regional distribution].

As an environment-friendly agriculture, ecological agriculture of Chinese materia medica(CMM) is being implemented in all parts of the country. Due to the stronger dependence on natural environmental conditions, ecological agriculture of CMM shows obvious regional differences in production practice. More mature CMM ecological planting patterns representative of each region were collected. It was found that common types of patterns in various regions of the country mainly included intercropping,intercropping,rotation planting mode, undergrowth planting mode, wild tending planting mode and landscape ecological planting mode. Based on the Construction Plan of National Dao-di Herbs Production Base(2018-2025) and Chinese Medicine Division, this paper systematically sorts out the pattern of ecological planting of CMM in the 8-avenue medicinal materials production areas according to the varieties and regions. The specific pattern of ecological planting of CMM included the ginseng undergrowth planting pattern in northeastern China, the bionics wild ecological planting of the Forsythia suspensa in northern China, the Fritillaria thunbergii-rice rotation in eastern China, the imitation wild planting pattern under the Polygonatum cyrtonema in central China, the planting pattern of the Fructus amomi under forest in southern China, the Ligusticum chuanxiong-rice rotation pattern in the Southwest, wild tending of Glycyrrhiza uralensis in the Northwest, and rhubarb imitation wild planting pattern in Qinghai-Tibet area. Finally, it is expected to provide reference for the screening and popularization of ecological planting patterns of other CMMs in various distribution areas.

[Land use strategy of ecological agriculture of Chinese materia medica in future development].

With the rapid development of comprehensive health industry, the demand for Chinese medicinal materials is increasing. There is also a growing demand for land for the cultivation of Chinese medicinal materials.Based on the analysis of the demand characteristics of planting habitats for Chinese medicinal herbs, this paper finds that compared with the cultivated environment, the wild environment is more conducive to the improvement of the quality and stress resistance of medicinal plants. The eco-planting for Chinese medicinal materials is the only way to achieve high quality, efficient and sustainable production of traditional Chinese medicine. Therefore, according to the habitat distribution characteristics of wild medicinal plants, combined with the current situation of land resource utilization in China and the increasing demand for land for Chinese herbal medicine cultivation, the land use strategy of Chinese herbal medicine ecological agriculture was proposed. ① To vigorously develop underwood planting and change the existing field cultivation mode. ② To make full use of mountainous areas and barren slopes to carry out wild planta tending or planting imitates wild condition. ③ According to the development law and biological characteristics of medicinal plants, the land resources should be developed and used rationally according to local conditions.This can not only meet the requirements of the specific growth environment of Chinese medicinal materials, realize the sustainable development of the Chinese medicinal materials industry, but also increase the economic income of people in mountainous areas, provide scientific and effective solutions for the land use of Chinese medicinal materials, and also have important significance for the protection of wild Chinese medicinal materials.

[Cultivation strategy on cluster brand of ecological agriculture of Dao-di herbs].

The cluster brand is the embodiment of the core competitiveness of an industry. Developing and cultivating cluster brand of ecological agriculture of Dao-di herbs not only helps to optimize the value chain of the Chinese medicinal materials(CMMs) industry cluster, realize the value-added of the CMMs industry cluster, but also enhance the visibility and influence of the industrial cluster, enhance the core competitiveness of the industrial cluster. This has important practical significance for promoting the "orderly" "safe" and "effective" development of the Dao-di herbs. Based on the industry development status of CMMs, this article introduces several concepts related to cluster brands and their relationships, and focuses on the cultivation models and strategies of cluster brand in the CMMs industry. Based on the current status of the development of the CMMs industry, this article introduces several concepts related to cluster brands and their interrelationships. It discusses the cultivation models and strategies of cluster brands in the CMMs industry, industry associations, Chinese medicine companies and individual growers as the support, insists on the ecological cultivation of authentic medicinal materials and the cultivation of cluster brands. Finally, it points out the direction for the high-quality development of the ecological agriculture of CMMs.

Echinacoside Alleviates Hypoxic-Ischemic Brain Injury in Neonatal Rat by Enhancing Antioxidant Capacity and Inhibiting Apoptosis.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of death and disability in neonatal or perinatal all over the world, seriously affecting children, families and society. Unfortunately, only few satisfactory therapeutic strategies have been developed. It has been demonstrated that Echinacoside (ECH), the major active component of Cistanches Herba, exerts many beneficial effects, including antioxidative, anti-apoptosis, and neuroprotective in the traditional medical practice in China. Previous research has demonstrated that ECH plays a protective effect on ischemic brain injury. This study aimed to investigate whether ECH provides neuroprotection against HIBD in neonatal rats. We subjected 120 seven-day-old Sprague-Dawley rats to cerebral hypoxia-ischemia (HI) and randomly divided into the following groups: sham group, HI group and ECH (40, 80 and 160 mg/kg, intraperitoneal) post-administration group. After 48 h of HI, 2,3,5-Triphenyltetrazolium chloride, Hematoxylin-Eosin and Nissl staining were conducted to evaluate the extent of brain damage. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) production were assessed to determine the antioxidant capacity of ECH. TUNEL staining and Western blot analysis was performed to respectively estimate the extent of brain cell apoptosis and the expression level of the apoptosis-related proteins caspase-3, Bax, and Bcl-2. Results showed that ECH remarkably reduced the brain infarct volume and ameliorated the histopathological damage to neurons. ECH post-administration helped recovering the antioxidant enzyme activities and decreasing the MDA production. Furthermore, ECH treatment suppressed neuronal apoptosis in the rats with HIBD was by reduced TUNEL-positive neurons, the caspase-3 levels and increased the Bcl-2/Bax ratio. These results suggested that ECH treatment was beneficial to reducing neuronal damage by attenuating oxidative stress and apoptosis in the brain under HIBD.

Synthesis and identification of quinoline derivatives as topoisomerase I inhibitors with potent antipsoriasis activity in an animal model.

Psoriasis is a chronic inflammatory and immune-mediated skin disease. Although certain agents have shown clinical success in treating psoriasis, development of safe and effective strategies for the treatment of this condition remains important. Research suggests that DNA topoisomerase I (Topo I) inhibitors may have potent psoriasis-ameliorating effects. Here, 25 quinoline derivatives were synthesized and identified as Topo I inhibitors. These compounds inhibited the 12-O-tetradecanoylphorbol-13-acetate-induced mouse ear inflammation. The most potent analogs, 5i and 5l, suppressed the expression of inflammatory cytokines in lipopolysaccharide-stimulated HaCaT cells. Additionally, the lead compounds significantly improved imiquimod-induced psoriasis-like inflammation in mice. Moreover, the expression levels of cytokines and inflammatory mediators, such as interleukin (IL)-17A, IL-22, IL-23, nuclear factor-κB subunit p65, tumor necrosis factor-α, and interferon-γ, were dramatically inhibited in the dorsal skin of 5i- and 5l-treated mice. These findings indicate that the inhibition of Topo I activity may potentially be an effective strategy for psoriasis treatment.

Synthesis and biological evaluation of novel carbazole-rhodanine conjugates as topoisomerase II inhibitors.

In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 µM. Mechanism study revealed that these compounds may function as Topo II catalytic inhibitors. It was found that the electron-withdrawing groups on the phenyl ring of compounds played an important role on enhancing both enzyme inhibition and cytotoxicity.