Pterostilbene alleviated cerebral ischemia/reperfusion-induced blood-brain barrier dysfunction via inhibiting early endothelial cytoskeleton reorganization and late basement membrane degradation.

Pterostilbene, an important analogue of the star molecule resveratrol and a novel compound naturally occurring in blueberries and grapes, exerts a significant neuroprotective effect on cerebral ischemia/reperfusion (I/R), but its mechanism is still unclear. This study aimed to follow the molecular mechanisms behind the potential protective effect of pterostilbene against I/R induced injury. For fulfilment of our aim, we investigated the protective effects of pterostilbene on I/R injury caused by middle cerebral artery occlusion (MCAO) in vivo and oxygen-glucose deprivation (OGD) in vitro. Machine learning models and molecular docking were used for target exploration and validated by western blotting. Pterostilbene significantly reduced the cerebral infarction volume, improved neurological deficits, increased cerebral microcirculation and improved blood-brain barrier (BBB) leakage. Machine learning models confirmed that the stroke target MMP-9 bound to pterostilbene, and molecular docking demonstrated the strong binding activity. We further found that pterostilbene could depolymerize stress fibers and maintain the cytoskeleton by effectively increasing the expression of the non-phosphorylated actin depolymerizing factor (ADF) in the early stage of I/R. In the late stage of I/R, pterostilbene could activate the Wnt pathway and inhibit the expression of MMP-9 to decrease the degradation of the extracellular basement membrane (BM) and increase the expression of junction proteins. In this study, we explored the protective mechanisms of pterostilbene in terms of both endothelial cytoskeleton and extracellular matrix. The early and late protective effects jointly maintain BBB stability and attenuate I/R injury, showing its potential to be a promising drug candidate for the treatment of ischemic stroke.

Integrating transcriptomics and metabolomics to analyze quinoa (Chenopodium quinoa Willd.) responses to drought stress and rewatering.

The crop production of quinoa (Chenopodium quinoa Willd.), the only plant meeting basic human nutritional requirements, is affected by drought stress. To better understand the drought tolerance mechanism of quinoa, we screened the drought-tolerant quinoa genotype "Dianli 129" and studied the seedling leaves of the drought-tolerant quinoa genotype after drought and rewatering treatments using transcriptomics and targeted metabolomics. Drought-treatment, drought control, rewatering-treated, and rewatered control were named as DR, DC, RW, and RC, respectively. Among four comparison groups, DC vs. DR, RC vs. RW, RW vs. DR, and RC vs. DC, we identified 10,292, 2,307, 12,368, and 3 differentially expressed genes (DEGs), and 215, 192, 132, and 19 differentially expressed metabolites (DEMs), respectively. A total of 38,670 genes and 142 pathways were annotated. The results of transcriptome and metabolome association analysis showed that gene-LOC110713661 and gene-LOC110738152 may be the key genes for drought tolerance in quinoa. Some metabolites accumulated in quinoa leaves in response to drought stress, and the plants recovered after rewatering. DEGs and DEMs participate in starch and sucrose metabolism and flavonoid biosynthesis, which are vital for improving drought tolerance in quinoa. Drought tolerance of quinoa was correlated with gene expression differences, metabolite accumulation and good recovery after rewatering. These findings improve our understanding of drought and rewatering responses in quinoa and have implications for the breeding of new drought-tolerance varieties while providing a theoretical basis for drought-tolerance varieties identification.

Advanced Research in Cellular Pharmacokinetics and its Cutting-edge Technologies.

Pharmacokinetics (PK), as a significant part of pharmacology, runs through the overall process of the preclinical and clinical research on drugs and plays a significant role in determining the material basis of efficacy and mechanism research. However, due to the limitations of classical PK, cellular PK was put forward and developed rapidly. Many novel and original technologies have been innovatively applied to cellular PK research, thereby providing powerful technical support. As a novel field of PK research, cellular PK expands the research object and enriches the theoretical framework of PK. It provides a new perspective for elucidating the mechanism of drug action and the dynamic process of drug in the body. Furthermore, it provides a scientific basis and guiding significance for the development of new drugs and clinical rational drug use. Cellular PK can explain the dynamic process of certain drugs (e.g., antineoplastic drugs and antibiotics) and the disposition kinetics characteristics in some specific tissues (e.g., brain and tumor) in a clearer and more accurate manner. It is a beneficial supplement and the perfection of traditional PK. In the future, traditional and cellular PKs will complement each other well and improve into an all-around research system in drug developments. Briefly, this paper reviews the conceptual development of cellular PK and key associated technologies, explores its main functions and applications, and looks forward to the important pioneering significance and promising value for the development of PK.

Transcriptomics Integrated With Widely Targeted Metabolomics Reveals the Mechanism Underlying Grain Color Formation in Wheat at the Grain-Filling Stage.

Colored wheat grains have a unique nutritional value. To elucidate the color formation mechanism in wheat seeds, comprehensive metabolomic and transcriptomic analyses were conducted on purple (Dianmai 20-1), blue (Dianmai 20-8), and white (Dianmai 16) wheat at the grain-filling stage. The results showed that the flavonoid biosynthesis pathway was closely related to grain color formation. Among the 603 metabolites identified in all varieties, there were 98 flavonoids. Forty-six flavonoids were detected in purple and blue wheat, and there were fewer flavonoids in white wheat than in colored wheat. Integrated transcriptomic and metabolomic analyses showed that gene expression modulated the flavonoid composition and content, resulting in different metabolite levels of pelargonidin, cyanidin, and delphinidin, thus affecting the color formation of wheat grains. The present study clarifies the mechanism by which pigmentation develops in wheat grains and provides an empirical reference for colored wheat breeding.

Recent Advances in Synthesis, Bioactivity, and Pharmacokinetics of Pterostilbene, an Important Analog of Resveratrol.

Pterostilbene is a natural 3,5-dimethoxy analog of resveratrol. This stilbene compound has a strong bioactivity and exists widely in Dalbergia and Vaccinium spp. Besides natural extraction, pterostilbene can be obtained by biosynthesis. Pterostilbene has become popular because of its remarkable pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammation, and neuroprotection. Pterostilbene can be rapidly absorbed and is widely distributed in tissues, but it does not seriously accumulate in the body. Pterostilbene can easily pass through the blood-brain barrier because of its low molecular weight and good liposolubility. In this review, the studies performed in the last three years on resources, synthesis, bioactivity, and pharmacokinetics of pterostilbene are summarized. This review focuses on the effects of pterostilbene on certain diseases to explore its targets, explain the possible mechanism, and look for potential therapeutic applications.

Advances in Biosynthesis, Pharmacology, and Pharmacokinetics of Pinocembrin, a Promising Natural Small-Molecule Drug.

Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy and a two-phase pH fermentation strategy. Pinocembrin poses an interest for its remarkable pharmacological activities, such as neuroprotection, anti-oxidation, and anti-inflammation. Studies have shown that pinocembrin works excellently in treating ischemic stroke. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Given its significant efficacy in cerebral ischemia, pinocembrin has been approved by China Food and Drug Administration (CFDA) as a new treatment drug for ischemic stroke and is currently in progress in phase II clinical trials. Research has shown that pinocembrin can be absorbed rapidly in the body and easily cross the blood-brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body. Pinocembrin has also been found to play a role in Parkinson's disease, Alzheimer's disease, and specific solid tumors, but its mechanisms of action require in-depth studies. In this review, we summarized the latest 10 years of studies on the biosynthesis, pharmacological activities, and pharmacokinetics of pinocembrin, focusing on its effects on certain diseases, aiming to explore its targets, explaining possible mechanisms of action, and finding potential therapeutic applications.