Cloning, Expression Characteristics of Farnesyl Pyrophosphate Synthase Gene from Platycodon grandiflorus and Functional Identification in Triterpenoid Synthesis.

Platycodon grandiflorus is a medicinal plant whose main component is platycodins, which have a variety of pharmacological effects and nutritional values. The farnesyl pyrophosphate synthase (FPS) is a key enzyme in the isoprenoid biosynthesis pathway, which catalyzes the synthesis of farnesyl diphosphate (FPP). In this study, we cloned the FPS gene from P. grandiflorus (PgFPS) with an ORF of 1260 bp, encoding 419 amino acids with a deduced molecular weight and theoretical pI of 46,200.98 Da and 6.52, respectively. The squalene content of overexpressed PgFPS in tobacco leaves and yeast cells extract was 1.88-fold and 1.21-fold higher than that of the control group, respectively, and the total saponin content was also increased by 1.15 times in yeast cells extract, which verified the biological function of PgFPS in terpenoid synthesis. After 48 h of MeJA treatment and 6 h of ethephon treatment, the expression of the PgFPS gene in roots and stems reached its peak, showing a 3.125-fold and 3.236-fold increase compared to the untreated group, respectively. Interestingly, the expression of the PgFPS gene in leaves showed a decreasing trend after exogenous elicitors treatment. The discovery of this enzyme will provide a novel perspective for enhancing the efficient synthesis of platycodins.

Genome-wide identification and expression pattern analysis of the GRF transcription factor family in Astragalus mongholicus.

BACKGROUND: Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. METHODS AND RESULTS: This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. CONCLUSIONS: The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.

Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

The complete chloroplast genome sequence of Jacobaea cannabifolia.

Jacobaea cannabifolia is a widely used medicinal plant. The total length of the chloroplast genome was 151,390 bp, and it comprised a large single-copy (LSC, 83,432 bp) region, a small single-copy (SSC, 18,304 bp) region, and a pair of inverted repeats (IRs, 49,654 bp). A total of 130 coding genes were annotated, including 88 protein-coding genes, 8 rRNA genes, and 34 tRNA genes. A phylogenetic tree was showed that J. cannabifolia and other species of the same genus clustered together.

Biosynthesized tumor acidity and MMP dual-responsive plant toxin gelonin for robust cancer therapy.

Among all kinds of anticancer agents, small molecule drugs produce an unsatisfactory therapeutic effect due to the lack of selectivity, notorious drug resistance and side effects. Therefore, researchers have begun to pay extensive attention to macromolecular drugs with high efficacy and specificity. As a plant toxin, gelonin exerts potent antitumor activity via inhibiting intracellular protein synthesis. However, gelonin lacks a translocation domain, and thus its poor cellular uptake leads to low outcomes of antitumor response. Here, tumor acidity and matrix metalloproteinase (MMP) dual-responsive functional gelonin (Trx-PVGLIG-pHLIP-gelonin, TPpG), composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP), an MMP-responsive motif PVGLIG hexapeptide and gelonin, was innovatively proposed and biologically synthesized by a gene recombination technique. TPpG exhibited good thermal and serum stability, showed MMP responsiveness and could enter tumor cells under weakly acidic conditions, especially for MMP2-overexpressing HT1080 cells. Compared to low MMP2-expressing MCF-7 cells, TPpG displayed enhanced in vitro antitumor efficacy to HT1080 cells at pH 6.5 as determined by different methods. Likewise, TPpG was much more effective in triggering cell apoptosis and inhibiting protein synthesis in HT1080 cells than in MCF-7 cells. Intriguingly, with enhanced stability and pH/MMP dual responsiveness, TPpG notably inhibited subcutaneous HT1080 xenograft growth in mice and no noticeable off-target side effect was observed. This ingeniously designed strategy aims at providing new perspectives for the development of a smart platform that can intelligently respond to a tumor microenvironment for efficient protein delivery.

A review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of the Astragalus memeranaceus.

Astragali Radix (Huangqi) is mainly distributed in the Northern Hemisphere, South America, and Africa and rarely in North America and Oceania. It has long been used as an ethnomedicine in the Russian Federation, Mongolia, Korea, Kazakhstan, and China. It was first recorded in the Shennong Ben Cao Jing and includes the effects of reinforcing healthy qi, dispelling pathogenic factors, promoting diuresis, reducing swelling, activating blood circulation, and dredging collaterals. This review systematically summarizes the botanical characteristics, phytochemistry, traditional uses, pharmacology, and toxicology of Astragalus to explore the potential of Huangqi and expand its applications. Data were obtained from databases such as PubMed, CNKI, Wan Fang Data, Baidu Scholar, and Google Scholar. The collected material also includes classic works of Chinese herbal medicine, Chinese Pharmacopoeia, Chinese Medicine Dictionary, and PhD and Master's theses. The pharmacological effects of the isoflavone fraction in Huangqi have been studied extensively; The pharmacological effects of Huangqi isoflavone are mainly reflected in its anti-inflammatory, anti-tumor, anti-oxidant, anti-allergic, and anti-diabetic properties and its ability to treat several related diseases. Additionally, the medicinal uses, chemical composition, pharmacological activity, toxicology, and quality control of Huangqi require further elucidation. Here, we provide a comprehensive review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of Astragalus to assist future innovative research and to identify and develop new drugs involving Huangqi.

[Retracted] miR­148a suppresses human renal cell carcinoma malignancy by targeting AKT2.

Following the publication of the above paper, an interested reader drew to our attention that the western blot data shown in Fig. 7, the scratch­wound assay data in Fig. 2D and the cell invasion assay data in Fig. 2E were strikingly similar to data that had already been published in different articles by different authors from different research institutions, or which were already under consideration for publication elsewhere. Independently of the reader's enquiry, the authors contacted the Editorial Office to request that the paper be retracted on account of the fact that they were unable to reproduce the results presented in Fig. 2. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Oncology Reports, and in line with the authors' own request, the Editor has decided that this paper should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 147­154, 2017; DOI: 10.3892/or.2016.5257].

Molecularly engineered tumor acidity-responsive plant toxin gelonin for safe and efficient cancer therapy.

Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomes and inhibiting protein synthesis. Nonetheless, its poor internalization ability to tumor cells has compromised the therapeutic promise of gelonin. In this study, a tumor acidity-responsive intracellular protein delivery system ─ functional gelonin (Trx-pHLIP-Gelonin, TpG) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP) and gelonin, was designed and obtained by genetic recombination technique for the first time. TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cell proliferation via triggering cell apoptosis and inhibiting protein synthesis. Most importantly, treatment by intravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much more effective than gelonin in curtailing tumor growth rates with negligible toxicity. Collectively, our present work suggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficient delivery of other bioactive substances to acidic diseased tissues.

miR-148a suppresses human renal cell carcinoma malignancy by targeting AKT2.

MicroRNA-148a (miR-148a) has been reported to be deregulated in different tumor types, whereas the biological function of miR-148a in renal cell carcinoma (RCC) largely remains unexplored. In the present study we investigated the clinical significance, biological effects, and the underlying molecular mechanisms of miR-148 in RCC. Here, we showed that miR-148a was significantly downregulated in RCC tissues and cell lines. Low expression of miR-148a in RCC tissues was associated with large tumor size, advanced TNM stage, and lymph node metastasis. Functional assays revealed that overexpression of miR-148a significantly inhibited RCC cell proliferation, colony formation, migration and invasion in vitro and suppressed RCC xenograft tumor growth in vivo. In addition, using quantitative RT-PCR (qRT-PCR), western blot analysis and luciferase reporter assays, AKT2 was confirmed to be a direct target of miR-148a. AKT2 expression was upregulated, and was negatively correlated with miR-148a expression in RCC tissues (r=-0.641, P<0.001). Silencing of AKT2 phenotypically copied miR-148a-induced phenotypes, whereas re-expression of AKT2 reversed the suppressive effects of miR-148a in RCC cells. Further mechanistic investigations showed that miR-148a exerted its antitumor activity via inhibition of the AKT pathway in vitro and in vivo. Taken together, these findings suggest that miR-148a functions as tumor suppressor in RCC by targeting AKT2.