Metabolomic and chemometric analyses of St. John's wort and related Asian Hypericum species linked to bioactivity.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises. AIM OF THE STUDY: The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds. MATERIALS AND METHODS: Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds. RESULTS: In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity. CONCLUSIONS: This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.

Polyhydroxybutyrate synthesis in Camelina: Towards coproduction of renewable feedstocks for bioplastics and fuels.

Plant-based co-production of polyhydroxyalkanoates (PHAs) and seed oil has the potential to create a viable domestic source of feedstocks for renewable fuels and plastics. PHAs, a class of biodegradable polyesters, can replace conventional plastics in many applications while providing full degradation in all biologically active environments. Here we report the production of the PHA poly[(R)-3-hydroxybutyrate] (PHB) in the seed cytosol of the emerging bioenergy crop Camelina sativa engineered with a bacterial PHB biosynthetic pathway. Two approaches were used: cytosolic localization of all three enzymes of the PHB pathway in the seed, or localization of the first two enzymes of the pathway in the cytosol and anchoring of the third enzyme required for polymerization to the cytosolic face of the endoplasmic reticulum (ER). The ER-targeted approach was found to provide more stable polymer production with PHB levels up to 10.2% of the mature seed weight achieved in seeds with good viability. These results mark a significant step forward towards engineering lines for commercial use. Plant-based PHA production would enable a direct link between low-cost large-scale agricultural production of biodegradable polymers and seed oil with the global plastics and renewable fuels markets.

[Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures].

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

Morphological, physiological, and secondary metabolic responses of Taraxacum officinale to salt stress.

Salt stress has a major effect on growth and secondary metabolism in medicinal plants, however, the effect of salt stress on Taraxacum officinale F. H. Wigg. is still scarce. In this study, we evaluated the effects of salt stress on the physiology, morphology, phenolic acid accumulation, and expression of genes involved in phenolic acid biosynthesis in T. officinale. We found that plants grew well at 1 g kg-1 NaCl, and the state of photosystem Ⅱ (PSⅡ) and the organization of the chloroplasts at 0.5 g kg-1 NaCl showed no significant differences compared with the control. However, 2 g kg-1 and 4 g kg-1 NaCl inhibited growth and accelerated leaf senescence. At 4 g kg-1 NaCl, the fresh and dry weights decreased to 28% and 42% of the control, while chlorosis and necrosis were observed on the leaves. Furthermore, up-regulation of the expression of ToC3'H corresponded with an increase in the levels of caffeoylquinic acids (chlorogenic acid and isochlorogenic acid A) at NaCl concentration ≤ 1 g kg-1. Expressions of four phenolic acid biosynthesis genes, ToC4H, To4CL, ToHCT, and ToHQT, were down-regulated with increasing NaCl concentrations, consistent with the observed decreases in caftaric and cichoric acids. In summary, cultivation of T. officinale under mild salt stress (NaCl ≤ 1 g kg-1) is feasible and facilitates the accumulation of caffeoylquinic acids; thus this species may be recommended for saline soils.

Comparative analysis of the structure and function of rhizosphere microbiome of the Chinese medicinal herb Alisma in different regions.

Rhizoma Alismatis, a commonly used traditional Chinese medicine, is the dried tuber of Alisma orientale and Alisma A. plantago-aquatica, mainly cultivated in Fujian and Sichuan provinces (China), respectively. Studies have shown that the rhizosphere microbiome is a key factor determining quality of Chinese medicinal plants. Here we applied metagenomics to investigate the rhizosphere microbiome of Alisma in Fujian and Sichuan, focusing on its structure and function and those genes involved in protostane triterpenes biosynthesis. The dominant phyla were Proteobacteria, Actinobacteria, Chloroflexi, Acidobacteria, and Gemmatimonadetes. Compared with Fujian, the rhizosphere of Sichuan has a greater α diversity and stronger microbial interactions but significantly lower relative abundance of archaea. Microbes with disease-suppressing functions were more abundant in Sichuan than Fujian, but vice versa for those with IAA-producing functions. Gemmatimonas, Anaeromyxobacter, and Pseudolabrys were the main contributors to the potential functional difference in two regions. Genes related to protostane triterpenes biosynthesis were enriched in Fujian. Steroidobacter, Pseudolabrys, Nevskia, and Nitrospira may contribute to the accumulation of protostane triterpenes in Alisma. This work fills a knowledge gap of Alisma's rhizosphere microbiome, providing a valuable reference for studying its beneficial microorganisms.

Tuina combined with physical therapy for spasticity of poststroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Limb spasms are a common complication of stroke. It not only affects the quality of life of stroke survivors, but also brings an economic burden. Tuina combined with physical therapy is widely used in the rehabilitation of poststroke spasticity. However, there is no supporting evidence for its efficacy and safety. This study aimed to evaluate the effectiveness and safety of Tuinas combined with physical therapy in the treatment of spasticity after stroke. METHODS: Literature will be collected from the following databases: China Biology Medicine (CBM), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), PubMed, Embase, Cochrane Library, and Web of Science; We will include randomized controlled trials of Tuina combined with physical therapy for poststroke spasticity range from the establishment to May 1, 2021. There were no limitations to the publication time, and the language was limited to Chinese and English. The primary outcome was evaluated using the Modified Ashworth scale, and the secondary outcomes were the simplified Fugl-Meyer Assessment scale, Modified Barthel Index, Functional Independence Measurement (FIM), and Visual Analog Scale. RevMan V.5.4.1 software was used for the meta-analysis. The Cochrane Intervention System Evaluation Manual analyzes the risk of bias, and the recommended grading assessment, development and evaluation are used to assess the quality of evidence. ETHICS AND DISSEMINATION: This study will be based on published systematic review studies, no ethical approval is required and the results of the study will be published in a peer-reviewed scientific journal. SYSTEMATIC REVIEW REGISTRATION: INPLASY2021110064.

Tuina combined with diet and exercise for simple obesity: A protocol for systematic review.

BACKGROUND: The incidence of simple obesity is increasing annually, with the number of obese people in all age groups increasing significantly. Obesity has become an important public health concern. Simple obesity affects not only appearance but also health. Obesity has an increasing impact on individuals, families, and society. Therefore, the treatment of obesity is becoming increasingly important. Prior studies have shown that Tuina combined with diet and exercise is capable of producing improvements in body weight and fasted health markers. In recent years, there are many clinical studies on the intervention of simple obesity by Tuina combined with diet and exercise, however, no study systematically evaluated the clinical efficacy. The purpose of this study is to evaluate its effects of Tuina combined with diet and exercise on people with simple obesity. METHODS: We will search the following electronic databases: PubMed, EMBASE, MEDLINE, Web of science, Cochrane Library, WanFang Data, CBM, CNKI, and VIP from the inception of the coverage of these databases to December 2021. Randomized controlled clinical trials related to Tuina combined with diet and exercise intervention on simple obesity will be included. Cochrane's collaboration tool will be used to assess the quality of the studies. RevMan 5.3 software will be used for the data analysis. RESULTS: This study will provide a standardized evaluation for the efficacy of Tuina combined with diet and exercise for simple obesity. CONCLUSION: The conclusion of this study will provide evidence for the safety and effectiveness of Tuina combined with diet and exercise on weight loss. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: INPLASY202210079.

Efficacy and safety of tuina for senile insomnia: A protocol for systematic review and meta-analysis.

BACKGROUND: Insomnia is a common diseases of the elderly, tuina is a widely used treatment. At present, there is a lack of supportive evidence on efficacy and safety of tuina for senile insomnia. The purpose of this systematic review is to assess the effectiveness and safety of tuina therapy in the treatment of senile insomnia. METHODS: Literature on tuina for senile insomnia in the PubMed, EMBASE, Web of Science, Cochrane, China National Knowledge Infrastructure Database, Wanfang, Chinese Scientific and Journal Database, Japanese medical database, Korean Robotics Institute Summer Scholars, and Thai-Journal Citation Index Center will be conducted to search from the creation of these databases. We will search the databases from the beginning to January 2022. The primary outcome was the Pittsburgh Sleep Quality Index score, and the secondary outcomes included clinical efficacy and safety. RevMan 5.4.1 will be used for the meta-analysis. RESULTS: This study aimed to will prove the effectiveness and safety of tuina therapy for the treatment of insomnia in the elderly. CONCLUSION: This study provides up-to-date evidence of the effectiveness and safety of tuina for the treatment of senile insomnia. INPLASY REGISTRATION NUMBER: INPLASY2021110063. ETHICS AND COMMUNICATION: This systematic review will evaluate the effectiveness and safety of massage therapy for insomnia in the elderly population. As all the included data have been published, systematic reviews do not require ethical approval.

Nutraceutical Study on Maianthemum atropurpureum, a Wild Medicinal Food Plant in Northwest Yunnan, China.

Maianthemum atropurpureum (Franch) LaFrankie (Asparagaceae), called nibai in Tibetan or dongka in Drung or zhu-ye-cai in local Chinese, is a wild vegetable consumed by the Tibetan people and other ethnic groups in Northwest Yunnan, China. It is also a traditional medicinal plant used by different linguistic groups for antimicrobial purposes. However the nutritional and phytochemical compositions of this important medicinal food plant have not been well studied previously. In this study, the nutrient content for nibai was determined by the China National Standards (GB) methods, and the phytochemical analysis involved multiple chromatographic and spectral methods including LC-TOF-MS analysis. Dried nibai is a rich source of protein (ca. 24.6%), with 18 of the 21 common amino acids. The amino acid content of nibai can reach up to 17.9/100 g, with the essential amino acids as major contributors, corresponding to 42.3% of the total amino acids. Nibai contains rich mineral elements, dietary fiber, vitamins, ß-carotene, carbohydrates, and lipids. The phytochemical content of nibai was examined by conventional isolation strategies, as well as HR-ESI-TOF-MS to detect and identify 16 compounds including nine steroid saponins and seven flavonoids. Among these compounds, uridine, adenosine, guanosine, and ß-methyl-6-methyl-d-glucopyranoside were found from the genus Maianthemum for the first time. These results help to demonstrate that the local people's practice of consuming Maianthemum atropurpureum is reasonable due to its high levels of vitamins, minerals, essential amino-acids, and phytochemicals. Nibai may be further developed in Tibet and surrounding regions, and beyond as a health food, nutraceutical, and/or dietary supplement product.

From Folk Taxonomy to Species Confirmation of Acorus (Acoraceae): Evidences Based on Phylogenetic and Metabolomic Analyses.

Plants in Acorus have been used as herbal medicine by various linguistic groups for thousands of years. Arguments of taxonomy of Acorus among scientists resulted in confusions and misuses of Acorus plants. The present study used different methods to investigate the classification of the genus, based on folk taxonomy. The relationships among Acorus species were revealed through phylogenetic analyses by constructing the Maximum Likelihood and Bayesian phylogenetic analyses based on sequences of two chloroplast regions (trnL-trnF and rbcL). All samples named with two so-called synonyms, Acorus macrospadiceus (Yamam.) F. N. Wei and Y. K. Li and Acorus tatarinowii Schott collected from different habitats, were clustered into separate groups, which revealed that they represented two independent species. Multivariate statistical analysis of metabolites from different Acorus populations were carried out based on UPLC-QTOF-MS data. Three independent analysis, principal component analysis, heat-map analysis, and hierarchical cluster analysis, showed that A. macrospadiceus and A. tatarinowii are different from two recognized species in the genus, A. calamus L. and A. gramineus Aiton. The results of phylogenetics and chemotaxonomy, together with morphological and ecological evidences, were consistent with traditional knowledge of local people related to Acorus taxa, which proved the significance of parataxonomy. Multiple evidences including morphological, ecological, folk taxonomic, phylogenetic, and chemical taxonomic results suggested that there are four species in the genus Acorus.

Near-infrared fluorescence imaging in immunotherapy.

Near-infrared (NIR) light possesses many suitable optophysical properties for medical imaging including low autofluorescence, deep tissue penetration, and minimal light scattering, which together allow for high-resolution imaging of biological tissue. NIR imaging has proven to be a noninvasive and effective real-time imaging methodology that provides a high signal-to-background ratio compared to other potential optical imaging modalities. In response to this, the use of NIR imaging has been extensively explored in the field of immunotherapy. To date, NIR fluorescence imaging has successfully offered reliable monitoring of the localization, dynamics, and function of immune responses, which are vital in assessing not only the efficacy but also the safety of treatments to design immunotherapies optimally. This review aims to provide an overview of the current research on NIR imaging of the immune response. We expect that the use of NIR imaging will expand further in response to the recent success in cancer immunotherapy. We will also offer our insights on how this technology will meet rapidly growing expectations in the future.

Ethnopharmacology of Hypericum species in China: A comprehensive review on ethnobotany, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum species have been used traditionally as astringent, antipyretic, diuretic, antiphlogistic, analgesic, and antidepressant in Europe, America, Africa, and Asia. One of the most extensively investigated medicinal herbs, H. perforatum L. (St. John's wort), is widely used in many countries to treat mild to moderate mental depression. Hypericum species are abundant throughout China, including 30 used as ethnomedicines. There are limited publications describing the ethnobotanical uses and biological activities associated with Hypericum species in China. Some reported activities include the treatment of wounds and bruises, irregular menstruation, dysentery, hepatitis, mastitis, jaundice, hemoptysis, and epistaxis. AIM OF THE REVIEW: This review aims to critically examine how Hypericum species are used ethnomedicinally in China, to see if the ethnobotanical data may be useful to help prioritize Hypericum species and certain phytochemical constituents that may be new drug leads, and consider the focus and lack of the phytopharmacological study on Hypericum species in China. MATERIALS AND METHODS: Classic medicinal books and ethnomedicinal publications were reviewed for the genus Hypericum (called jin si tao in Chinese). In addition, relevant information about ethnobotany, phytochemistry, and pharmacology were from online databases including SciFinder, Science Direct, PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI). "Hypericum", "", "ethnobotany", "traditional use", "ethnomedicine", "phytochemistry", "pharmacology" and "bioactivity" were used as keywords when searching the databases. Thus, available articles from 1959 to 2019 were collected and analyzed. RESULTS: Among 64 Hypericum species recorded in China, 30 have been used as ethnomedicines by 15 linguistic groups such as Dai, Dong, Han, Miao, and Mongolian people. Hypericum species in China possess traditional uses which are also mirrored in Europe, America, Africa, and other countries in Asia. However, there are some unique ethnomedicinal uses in China. For example, several Hypericum species are used as a local remedy in southwest China, and H. attenuatum Fisch. ex Choisy is used to treat cardiac disorders in northeast China. Antitumor, anti-inflammatory, antimicrobial, neuroprotective, antidepressant, hepatoprotective, cardioprotective, and antiviral activities have been reported in numerous biological studies. The main phytochemical constituents in Hypericum consist of phloroglucinols, naphthodianthrones, xanthones, flavonoids, and terpenoids. CONCLUSIONS: There is a rich traditional knowledge regarding the ethnomedicinal uses of Hypericum species in China. Through phytochemical and pharmacological studies, several medicinal Hypericum from China have yielded many bioactive phytochemicals, possessing antitumor, anti-inflammatory, antimicrobial, and neuroprotective properties. Hypericum species from China are potential sources of drugs to fight cancer and other chronic diseases. Remarkably, nearly half of Hypericum species in China have rarely been studied, and their ethnomedicinal potential have not been scientifically evaluated. Thus, in vitro mechanistic studies, in vivo pharmacology, and clinical efficacy are all needed, prioritizing those studies that relate most closely with their traditional uses. In addition, a comprehensive plant-resource evaluation, quality control, and toxicology studies are needed.

Cytotoxic Xanthones from Hypericum stellatum, an Ethnomedicine in Southwest China.

Hypericum stellatum, a species endemic to China, is used to treat hepatitis by several ethnic groups in Guizhou Province. This research was inspired by the traditional medicinal usage of H. stellatum, and aims to explore the phytochemistry and bioactivity of H. stellatum to explain why local people in Guizhou widely apply H. stellatum for liver protection. In this study, two new prenylated xanthones, hypxanthones A (8) and B (9), together with seven known compounds, were isolated from the aerial parts of the plant. Spectroscopic data as well as experimental and calculated ECD spectra were used to establish the structures of these compounds. Six xanthones isolated in this study, together with four xanthones previously isolated from H. stellatum, were evaluated for their growth-inhibitory activities against five human liver carcinoma cell lines to analyze the bioactivity and structure-activity relationship of xanthones from H. stellatum. Isojacareubin (6) showed significant cytotoxicity against five human liver carcinoma cell lines, with an IC50 value ranging from 1.41 to 11.83 µM, which was stronger than the positive control cisplatin (IC50 = 4.47-20.62 µM). Hypxanthone B (9) showed moderate cytotoxicity to three of the five cell lines. Finally, structure-activity analysis revealed that the prenyl and pyrano substituent groups of these xanthones contributed to their cytotoxicity.

Roles of Cytosolic Glutamine Synthetases in Arabidopsis Development and Stress Responses.

Glutamine (Gln) has as a central role in nitrogen (N) and carbon (C) metabolism. It is synthesized during assimilation of ammonium by cytosolic and plastidial glutamine synthetases (GS; EC 6.1.1.3). Arabidopsis thaliana has five cytosolic GS (GS1) encoding genes designated as GLN1;1-GLN1;5 and one plastidial GS (GS2) gene. In this report that concerns cytosolic GS, we show by analyzing single, double and triple mutants that single genes were dispensable for growth under laboratory conditions. However, loss of two or three GS1 isoforms impacted plant form, function and the capacity to tolerate abiotic stresses. The loss of GLN1;1, GLN1;2 and GLN1;3 resulted in a significant reduction of vegetative growth and seed size. In addition, we infer that GLN1;4 is essential for pollen viability but only in the absence of GLN1;1 and GLN1;3. Transcript profiling revealed that expression of GLN1;1, GLN1;2, GLN1;3 and GLN1;4 was repressed by salinity and cold stresses. Among all single gln1 mutants, growth of gln1;1 seedlings showed an enhanced sensitivity to the GS inhibitor phosphinothricin (PPT), as well as to cold and salinity treatments, suggesting a non-redundant role for GLN1;1. Furthermore, the increased sensitivity of gln1;1 mutants to methyl viologen was associated with an accelerated accumulation of reactive oxygen species (ROS) in the thylakoid of chloroplasts. Our data demonstrate, for the first time, an involvement of the cytosolic GS1 in modulating ROS homeostasis in chloroplasts. Collectively, the current study establishes a link between cytosolic Gln production and plant development, ROS production and stress tolerance.

[Chemical constituents of Hypericum stellatum and their antioxidant bioactivities].

Hypericum stellatum is an important ethnomedicinal plant endemic to southwest China. Ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to analyze the chemical constituents of H. stellatum. Seventeen compounds from H. stellatum were tentatively identified using UPLC-Q-TOF-MS data. Antioxidant activity and total phenolic content were investigated by DPPH assay and Folin-Ciocalted methods. The EtOAc extract with high total phenolic content showed prominent antioxidant activity. The EtOAc extract of H. stellatum was separated and purified by column chromatography, including silica gel, Sephedex LH-20, and RP-HPLC. The isolates were defined by 1D, 2D NMR data. As a result, ten compounds were isolated and assigned as quercetin (Ⅰ), quercetin 3-O-ß-D-glucopyranoside (Ⅱ), 1,3,6,7-tetrahydroxylxanthone (Ⅲ), 1,3,5,6-tetrahydroxyxanthone (Ⅳ), 1,3,7-trihydroxyxanthone (Ⅴ), 3, 6, 7-trihydroxy-1-methoxyxanthone (Ⅵ), calycinoxanthon D (Ⅶ), caffeic acid ethyl ester (Ⅷ), chlorogenic acid (Ⅸ) and chlorogenic acid ethyl ester (Ⅹ). This is the first report on chemical constituents and bioactivity of H. stellatum. The antioxidant activity of chemical constituents was tentatively found, which provided a foundation for further researches on the genus Hypericum and the traditional uses of H. stellatum.

Camelina sativa, an oilseed at the nexus between model system and commercial crop.

The rapid assessment of metabolic engineering strategies in plants is aided by crops that provide simple, high throughput transformation systems, a sequenced genome, and the ability to evaluate the resulting plants in field trials. Camelina sativa provides all of these attributes in a robust oilseed platform. The ability to perform field evaluation of Camelina is a useful, and in some studies essential benefit that allows researchers to evaluate how traits perform outside the strictly controlled conditions of a greenhouse. In the field the plants are subjected to higher light intensities, seasonal diurnal variations in temperature and light, competition for nutrients, and watering regimes dictated by natural weather patterns, all which may affect trait performance. There are difficulties associated with the use of Camelina. The current genetic resources available for Camelina pale in comparison to those developed for the model plant Arabidopsis thaliana; however, the sequence similarity of the Arabidopsis and Camelina genomes often allows the use of Arabidopsis as a reference when additional information is needed. Camelina's genome, an allohexaploid, is more complex than other model crops, but the diploid inheritance of its three subgenomes is straightforward. The need to navigate three copies of each gene in genome editing or mutagenesis experiments adds some complexity but also provides advantages for gene dosage experiments. The ability to quickly engineer Camelina with novel traits, advance generations, and bulk up homozygous lines for small-scale field tests in less than a year, in our opinion, far outweighs the complexities associated with the crop.

Sodium humate accelerates cutaneous wound healing by activating TGF-ß/Smads signaling pathway in rats.

Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague-Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-ß1, 2, 3 (TGF-ß1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-ß/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing.

Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).

The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•- quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 µM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63-5.00 µM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.

Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway.

Baicalein, a widely used Chinese herbal medicine, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain poorly understood. Therefore, the purpose of this study was to assess the anti-metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays utilized in both HCC cell lines and in an animal model, we found that baicalein inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after treatment with baicalein for 24 hours, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (u-PA) expression as well as proteinase activity in hepatocellular carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent fashion. Moreover, baicalein treatment dramatically decreased the levels of the phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked the anti-metastatic effects of baicalein. Combined treatment with an ERK inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP-9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the invasive capabilities of MHCC97H cells were also inhibited. In conclusion, baicalein inhibits tumor cell invasion and metastasis by reducing cell motility and migration via the suppression of the ERK pathway, suggesting that baicalein is a potential therapeutic agent for HCC.

Traditional herbal medicine: a review of potential of inhibitory hepatocellular carcinoma in basic research and clinical trial.

Although significantly develops in hepatocellular carcinoma (HCC), features of HCC remain an aggressive cancer with a dismal outcome. Traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), is one of the most popular complementary and alternative medicine modalities worldwide. The use of heat-clearing and detoxicating (Chinese named qingre jiedu) CHM has attracted great attention as an alternative antitumor including HCC considering its low toxicity and high activity. Together these reports indicate that CHM is a promising anti-HCC herbal remedy in basic research. For patients with advanced HCC, CHM including formula and single combined with transcatheter arterial chemoembolization or chemotherapy is able to decrease tumor growth and the side effect of toxicity and improve overall survival, quality of life, and immune function. Due to its abundance, low cost, and safety in consumption, CHM remains a species with tremendous potential for further investigation in HCC.