Integrated transcriptome and metabolome analysis provide insights into the mechanism of saponin biosynthesis and its role in alleviating cadmium-induced oxidative damage in Ophiopogon japonicum.

Zhe-Maidong, a cultivar of Ophiopogon japonicus is a prominent traditional herbal medicine rich in saponins. This study explored the mechanism of saponin biosynthesis and its role in alleviating Cd-induced oxidative damage in the Zhe-Maidong cultivar using three experimental groups undergoing Cd stress. In the Cd-contaminated soil treatment, total saponins were 1.68 times higher than those in the control. The saponin content in the Cd-2 and Cd-3 treatments was approximately twice as high as that in the Cd-CK treatment. These findings revealed that Cd stress leads to total saponin accumulation. Metabolomic analysis identified the accumulated saponins, primarily several monoterpenoids, diterpenoids, and triterpenoids. The increased saponins exhibited an antioxidant ability to prevent the accumulation of Cd-induced reactive oxygen species (ROS). Subsequent saponin application experiments provided strong evidence that saponin played a crucial role in promoting superoxide dismutase (SOD) activity and reducing ROS accumulation. Transcriptome analysis revealed vital genes for saponin synthesis under Cd stress, including SE, two SSs, and six CYP450s, positively correlated with differentially expressed metabolite (DEM) levels in the saponin metabolic pathway. Additionally, the TF-gene regulatory network demonstrated that bHLH1, bHLH3, mTERF, and AUX/IAA transcript factors are crucial regulators of hub genes involved in saponin synthesis. These findings significantly contribute to our understanding of the regulatory network of saponin synthesis and its role in reducing oxidative damage in O. japonicum when exposed to Cd stress.

Reinforcing the immunogenic cell death to enhance cancer immunotherapy efficacy.

Immunogenic cell death (ICD) has been a revolutionary modality in cancer treatment since it kills primary tumors and prevents recurrent malignancy simultaneously. ICD represents a particular form of cancer cell death accompanied by production of damage-associated molecular patterns (DAMPs) that can be recognized by pattern recognition receptors (PRRs), which enhances infiltration of effector T cells and potentiates antitumor immune responses. Various treatment methods can elicit ICD involving chemo- and radio-therapy, phototherapy and nanotechnology to efficiently convert dead cancer cells into vaccines and trigger the antigen-specific immune responses. Nevertheless, the efficacy of ICD-induced therapies is restrained due to low accumulation in the tumor sites and damage of normal tissues. Thus, researchers have been devoted to overcoming these problems with novel materials and strategies. In this review, current knowledge on different ICD modalities, various ICD inducers, development and application of novel ICD-inducing strategies are summarized. Moreover, the prospects and challenges are briefly outlined to provide reference for future design of novel immunotherapy based on ICD effect.

The anticancer potential of the dietary polyphenol rutin: Current status, challenges, and perspectives.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Dynamic changes of metabolic profile and taste quality during the long-term aging of Qingzhuan Tea: The impact of storage age.

Qingzhuan tea (QZT) with longer aging year is usually believed to have higher quality and commercial value. In this study, a 20 years sequence of aged QZT were subjected to an electronic tongue and liquid chromatography-mass spectrometry to investigate the effect of storage age on its metabolic profile and taste quality. The changes in both taste quality and metabolic profile exhibited a parabolic trend in the 20 years of QZT aging and reached the maximum at the 10th year. A total of 47 compounds were identified as critical metabolites responsible for the age variation of QZT quality, with the methylation of catechins, glycosylation of flavonoids, degradation of flavoalkaloids, biosynthesis of triterpenoids, and formation of theabrownins. These results suggested that the taste of QZT was improved after 10 years of storage, with the reduction of bitterness and astringency and a general increase of key quality-related compounds.

Optimization and Characterization of Microwave-Assisted Hydro-Distillation Extraction of Essential Oils from Cinnamomum camphora Leaf and Recovery of Polyphenols from Extract Fluid.

In this study, the efficiency of microwave-assisted hydro-distillation (MAHD) to extract essential oil from Cinnamomum camphora leaf, and the recovery of polyphenols from extract fluid were investigated. The effects of microwave power, liquid-to-material ratio, and extraction time on the extraction efficiency were studied by a single factor test as well as the response surface methodology (RSM) based on the central composite design method. The optimal extraction conditions were a microwave power of 786.27 W, liquid-to-material ratio of 7.47:1 mL/g, and extraction time of 35.57 min. The yield of essential oil was 3.26 ± 0.05% (w/w), and the recovery of polyphenols was 4.97 ± 0.02 mg gallic acid equivalent/g dry weight under the optimal conditions. Furthermore, the comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) was used to characterize the essential oils of fresh and fallen leaves, and 159 individual compounds were tentatively identified, accounting for more than 89.68 and 87.88% of the total contents, respectively. The main ingredients include sabinene, l-ß-pinene, ß-myrcene, α-terpineol, 3-heptanone, and ß-thujene, as well as δ-terpineol and 3-heptanone, which were first identified in C. camphora essential oil. In conclusion, the MAHD method could extract essential oil from C. camphora with high efficiency, and the polyphenols could be obtained from the extract fluid at the same time, improving the utilization of C. camphora leaf.

Distinct Changes of Metabolic Profile and Sensory Quality during Qingzhuan Tea Processing Revealed by LC-MS-Based Metabolomics.

Qingzhuan tea (QZT) is a unique type of dark tea exclusively produced in Hubei Province of China. In the current study, liquid chromatography-mass spectrometry (LC-MS) coupled with multivariate analysis was applied to characterize the chemical composition of QZT and investigate the effect of QZT processing on its metabolic profile and sensory quality. The contents of polyphenols and flavonoids decreased significantly while the polysaccharides content remained stable, while the theabrownin content inversely increased during QZT processing. LC-MS-based metabolomics analyses revealed that the tea sample after microbial fermentation (MFT) was dramatically different from the sample before microbial fermentation (UFT), while MFT was very similar to QZT. A total of 102 compounds were identified as critical metabolites responsible for metabolic changes caused by QZT processing, with the contents of catechins and flavonoids significantly decreased, and some novel phenolic acids and catechin derivatives were formed. The sensory quality of QZT was mainly formed during microbial fermentation, which greatly reduced the astringency and bitterness of raw tea leaves and produced its characteristic woody and stale aroma as well as mellow taste. These results suggested that microbial fermentation is the critical process in changing the metabolic profile of raw tea leaves and forming the sensory quality of QZT.

Yin Yang 1 protein ameliorates diabetic nephropathy pathology through transcriptional repression of TGFß1.

Transforming growth factor-ß1 (TGFß1) has been identified as a major pathogenic factor underlying the development of diabetic nephropathy (DN). However, the current strategy of antagonizing TGFß1 has failed to demonstrate favorable outcomes in clinical trials. To identify a different therapeutic approach, we designed a mass spectrometry-based DNA-protein interaction screen to find transcriptional repressors that bind to the TGFB1 promoter and identified Yin Yang 1 (YY1) as a potent repressor of TGFB1. YY1 bound directly to TGFB1 promoter regions and repressed TGFB1 transcription in human renal mesangial cells. In mouse models, YY1 was elevated in mesangial cells during early diabetic renal lesions and decreased in later stages, and knockdown of renal YY1 aggravated, whereas overexpression of YY1 attenuated glomerulosclerosis. In addition, although their duration of diabetic course was comparable, patients with higher YY1 expression developed diabetic nephropathy more slowly compared to those who presented with lower YY1 expression. We found that a small molecule, eudesmin, suppressed TGFß1 and other profibrotic factors by increasing YY1 expression in human renal mesangial cells and attenuated diabetic renal lesions in DN mouse models by increasing YY1 expression. These results suggest that YY1 is a potent transcriptional repressor of TGFB1 during the development of DN in diabetic mice and that small molecules targeting YY1 may serve as promising therapies for treating DN.

Melatonin alleviates aluminium toxicity through modulating antioxidative enzymes and enhancing organic acid anion exudation in soybean.

Aluminium (Al) toxicity is a major chemical constraint limiting plant growth and production on acidic soils. Melatonin (N-acetyl-5-methoxytryptamine) is a ubiquitous molecule that plays crucial roles in plant growth and stress tolerance. However, there is no knowledge regarding whether melatonin is involved in plant responses to Al stress. Here, we show that optimal concentrations of melatonin could effectively ameliorate Al-induced phytotoxicity in soybean (Glycine max L.). The concentration of melatonin in roots was significantly increased by the 50µM Al treatment. Such an increase in endogenous melatonin coincided with the upregulation of the gene encoding acetyltransferase NSI-like (nuclear shuttle protein-interacting) in soybean roots. Supplementation with low concentrations of melatonin (0.1 and 1µM) conferred Al resistance as evident in partial alleviation of root growth inhibition and decreased H2O2 production: in contrast, high concentrations of melatonin (100 and 200µM) had an opposite effect and even decreased root growth in Al-exposed seedlings. Mitigation of Al stress by the 1µM melatonin root treatment was associated with enhanced activities of the antioxidant enzymes and increased exudation of malate and citrate. In conclusion, melatonin might play a critical role in soybean resistance to Al toxicity.

Nitrate reductase-mediated NO production enhances Cd accumulation in Panax notoginseng roots by affecting root cell wall properties.

Panax notoginseng (Burk) F. H. Chen is a traditional medicinal herb in China. However, the high capacity of its roots to accumulate cadmium (Cd) poses a potential risk to human health. Although there is some evidence for the involvement of nitric oxide (NO) in mediating Cd toxicity, the origin of Cd-induced NO and its function in plant responses to Cd remain unknown. In this study, we examined NO synthesis and its role in Cd accumulation in P. notoginseng roots. Cd-induced NO production was significantly decreased by application of the nitrate reductase inhibitor tungstate but not the nitric oxide synthase inhibitor L-NAME (N(G)-methyl-l-arginine acetate), indicating that nitrate reductase is the major contributor to Cd-induced NO production in P. notoginseng roots. Under conditions of Cd stress, sodium nitroprusside (SNP, an NO donor) increased Cd accumulation in root cell walls but decreased Cd translocation to the shoot. In contrast, the NO scavenger cPTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) and tungstate both significantly decreased NO-increased Cd retention in root cell walls. The amounts of hemicellulose 1 and pectin, together with pectin methylesterase activity, were increased with the addition of SNP but were decreased by cPTIO and tungstate. Furthermore, increases or decreases in hemicellulose 1 and pectin contents as well as pectin methylesterase activity fit well with the increased or decreased retention of Cd in the cell walls of P. notoginseng roots. The results suggest that nitrate reductase-mediated NO production enhances Cd retention in P. notoginseng roots by modulating the properties of the cell wall.

Role of the plasma membrane H(+)-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency.

Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H(+)-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H(+)-ATPase in organic acid exudation under Al toxicity and P deficiency conditions.