Ginsenoside Rg1 treatment protects against cognitive dysfunction via inhibiting PLC-CN-NFAT1 signaling in T2DM mice

Xianan Dong,Liangliang Kong,Lei Huang,Yong Su,Xuewang Li,Liu Yang,Pengmin Ji,Weiping Li,Weizu Li The Korean Society of Ginseng 2023 Journal of Ginseng Research Vol.47 No.3

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

Cloning and functional characterization of two GsSnRK1 gene promoters from wild soybean

Chen Jun,Li Qiang,Zhang Pengmin,Lu Haoran,Bian Ya,Jian Yi,Wang Yizhu,Ding Xiaodong,Xiao Jialei 한국식물생명공학회 2021 Plant biotechnology reports Vol.15 No.5

Sucrose non-fermenting-related protein kinase 1 (SnRK1) belongs to a plant serine/threonine protein kinase family, and is part of a large interactive network of signaling pathways in plants to regulate many aspects of growth and development, and its gene expressions are highly responsive to multiple external stimuli. To functionally characterize the role of different SnRK1 members in wild soybean and identify the expression patterns of novel SnRK1 promoters for transgenic research, in this study, we performed an in silico analysis of the SnRK1 gene family in wild soybean and found GsSnRK1.1 and GsSnRK1.2 are main SnRK1 isoforms in wild soybean. The promoter fragments of both GsSnRK1.1 and GsSnRK1.2 were isolated, and a series of 5′-deletion and the full-length versions of both GsSnRK1.1 and GsSnRK1.2 promoters were fused with GUS reporter gene to generate expression vectors. The GUS activities in different tissues of seedling and adult growth stages of transgenic Arabidopsis plants were determined, and the GUS activities in transgenic Arabidopsis plants under NaCl, NaHCO3, PEG, ABA, MeJA and SA were also analyzed. The results showed that GsSnRK1.1 and GsSnRK1.2 genes have different expression patterns and both promoters may contain enhancers and silencers. In addition, NaCl, NaHCO3, ABA, MeJA, and PEG treatments enhanced, whereas SA treatment decreased the GUS activity under the control of both GsSnRK1.1 and GsSnRK1.2 promoters, which may be due to the distributions of various cis-elements in both GsSnRK1.1 and GsSnRK1.2 promoter regions. These results will contribute to a better understanding of the underlying mechanisms of GsSnRK1 genes in response to various abiotic stresses, and as stress-inducible promoters, GsSnRK1.1 and GsSnRK1.2 promoters can be candidates for practical application in agriculture.

Characterization of Phenolic Compounds and Active Anthocyanin Degradation in Crabapple (Malus orientalis) Flowers

Rana Naveed Ur Rehman,Yaohua You,Chengquan Yang,Abdul Rehman Khan,Pengmin Li,Fengwang Ma 한국원예학회 2017 Horticulture, Environment, and Biotechnology Vol.58 No.4

The red coloration of young crabapple (Malus orientalis) flowers results from their high cellular concentrationof anthocyanins. As the petals grow larger, the color fades, which is commonly regarded as being caused by floraltissue expansion diluting the anthocyanin levels in larger cells. We hypothesized that the anthocyanins are degradeddue to hydrogen peroxide (H2O2) and that the concentrations of each phenolic intermediate depends on the physiologicalgrowth of flower petals. A high-performance liquid chromatography (HPLC) analysis was performed to characterizethe identities and concentrations of the diverse array of phenolics present during different growth stages in the crabappleflowers. The concentrations of gallic acid, caffeic acid, syringic acid, chlorogenic acid, phloridzin, procyanidin B1,procyanidin B2, and catechin significantly increased throughout development, while epicatechin and cyanidin-3-galactosidelevels declined. Most flavonols (quercetin-3-xyloside, quercetin-3-rhaminose, quercetin-3-glucoside, and quercetin-3-arabinoside)increased until the fourth stage, after which they declined suddenly. Likewise, cyanidin-3-galactoside degraded sharplyat stage III, exhibiting reciprocal relationship with H2O2 concentration. Our results suggest that the concentrations ofphenolic compounds are congruent with their functional activities in floral tissues, and that their systematicfluctuation mainly depends on environmental cues and physiological imbalances, not merely petal expansion. Theresults of this study will be useful for better understanding the physiological changes in phenolic content andanthocyanin degradation that occur during flower development.

Phenolic compounds as biochemical markers of senescence in woody ornamental flowers of Malus crabapple

Rana Naveed Ur Rehman,Yaohua You,Sajid Ali,Yule Wang,Lei Zhang,Pengmin Li,Fengwang Ma 한국원예학회 2018 Horticulture, Environment, and Biotechnology Vol.59 No.1

Polyphenol intermediates accumulate predominantly in peripheral parts of floral tissues and play various roles in tissuehomeostasis. A limited ornamental flower shelf life is caused by early tissue senescence, otherwise known as programmedcell death (PCD), which is characterized by processes such as DNA degradation, reduction in protein content and others. However, the role of polyphenols during PCD is poorly understood. In this study, we evaluated polyphenols as potentialbiochemical markers during developmental changes associated with PCD. Malus crabapple flowers were exposed to low(LT = 13 ± 2 °C), room (RT = 23 ± 2 °C), and high (HT = 30 ± 2 °C) temperatures to induce different levels of PCD. HTtreatment was associated with enhanced H2O2and MDA content, which subsequently caused lower protein concentrationand induced DNA degradation. Conversely, substantially higher protein content, lesser DNA degradation, and lower H2O2and MDA accumulation were observed following RT and LT treatments. Furthermore, significantly higher concentrationsof phenolic acids, flavanols, and anthocyanins were observed following both RT and LT treatments, more so for the latter,due to up-regulation of structural genes such as MpPAL, MpDFR, MpLDOX, and MpUFGT. Similarly, following HT treatmentthat induced a higher rate of PCD, the accumulation of dihydrochalcone and flavonols was significantly enhanced andassociated with increased expression of MpCHS and MpFLS. Phenolic contents are determined via precise regulation of ahighly conserved set of structural genes, indicating their functional importance. Therefore, it was assumed that individualphenolic intermediates or discrete diverse classes of polyphenol compounds may be utilized as biochemical markers of PCDin woody ornamental flowers of Malus crabapple.

Characterization of quercetin and its glycoside derivatives in Malus germplasm

Lei Zhang,Qipeng Xu,Yaohua You,Weifeng Chen,Zhengcao Xiao,Pengmin Li,Fengwang Ma 한국원예학회 2018 Horticulture, Environment, and Biotechnology Vol.59 No.6

Quercetin and its glycoside derivatives were identifi ed and quantifi ed using high-performance liquid chromatograph (HPLC)and liquid chromatograph/mass spectrometer/mass spectrometer (LC/MS/MS) in the leaves, flowers, and fruits of 22 Malusgenotypes. In all genotypes, small amounts of quercetin aglycone were present, with water-soluble glycoside forms were themost abundant in diff erent Malus plant tissues, including quercetin-3-galactoside, quercetin-3-rutinoside, quercetin-3-glucoside,quercetin-3-xyloside, quercetin-3-arabinoside, and quercetin-3-rhamnoside. Among these six quercetin glycosides,quercetin-3-galactoside was the common form in Malus plants, except in the leaves and flowers of M. ceracifolia and M. magdeburgensis , and in the fruits of M. micromalus ‘Haihong Fruit’, where there was a higher concentration of quercetin-3-glucoside. Among the diff erent tissues tested, leaves contained the highest concentration of quercetin and its glycosides,while fruits contained the lowest concentrations of these compounds. Among the genotypes we analyzed, no specifi c genotypeconsistently contained the highest concentration of quercetin and its glycoside derivatives. M. domestica ‘Honeycrisp’had the highest total compound concentration (approximately 1600 mg kg −1 ), whereas M. hupehensis contained the lowestin its fruits. In contrast, the concentration of total quercetin and its glycosides was more than 5000 mg kg −1 in the leaves ofeight genotypes and greater than 2500 mg kg −1 in the flowers of seven species. In general, the concentration of quercetinand its glycoside derivatives depended on the species and tissue type. These results may provide useful information for theevaluation and selection of edible Malus fruits and the materials for quercetin glycoside extraction.

Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer

Huan Peng,Jun Ying,Jia Zang,Hao Lu,Xiaokai Zhao,Pengmin Yang,Xintao Wang,Jieyi Li,Ziying Gong,Daoyun Zhang,Zhiguo Wang 대한암학회 2023 Cancer Research and Treatment Vol.55 No.4

Purpose Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. Materials and Methods Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. Results APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. Conclusion APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.