ultra-high-performance-liquid-chromatography-mass-spectrometry-self

Ultra High-Performance Liquid Chromatography-Mass Spectrometry and Self-established Database Analysis of Chinese Herbal Medicine Components

Chinese herbal medicine is complex and has numerous unknown compounds, making qualitative research crucial. Ultra-high-performance liquid chromatography ...

high-resolution-tandem-mass-spectrometry-for-studying-chemical

High-resolution Tandem Mass Spectrometry for Studying Chemical Constituents of <em>Gynura bicolor DC</em>

The separation and analysis of the desired chemical components are important subjects for the fundamental research of traditional Chinese medicine (TCM). ...

technical-approach-for-structural-analysis-an-unknown-compound

Technical Approach for Structural Analysis of an Unknown Compound in Huoxiang Zhengqi Oral Liquid based on Linear Ion Trap Mass Spectrometry

Chinese herbal compounds (CHCs) play an irreplaceable role in Chinese medicine, and identifying their complex constituents has been a significant research ...

The Src-homology 2 domain-containing phosphatase 2 (SHP2), encoded by PTPN11, has been reported oncogenic tyrosine phosphatase associated with various tumors and played critical roles in many cell signaling events. Targeting SHP2 by small molecules may be a promising way for cancer therapy. Herein, a new abietane diterpenoid, named 3-acetoxylteuvincenone G (3-AG), was isolated from the whole plants of Ajuga ovalifolia var. calantha. The structure of the new compound was elucidated by means of extensive spectroscopic analyses. Using recombinant enzyme activity assay and cellular thermal shift assay, we found that 3-AG was a selective inhibitor of SHP2. Molecular docking suggested 3-AG displayed an orientation favorable to nucleophilic attack in the catalytic domain of SHP2. 3-AG suppressed A549 cell proliferation (IC = 10.79 ± 0.14 μM), invasion and induced cell apoptosis through SHP2/ERK1/2 and SHP2/AKT pathways. In summary, 3-AG, a potent, selective, and efficacious SHP2 inhibitor, may be a promising small molecule to treat human lung epithelial cancer.

A new abietane diterpenoid from Ajuga ovalifolia var. calantha induces human lung epithelial A549 cell apoptosis by inhibiting SHP2.

Aloe-emodin (AE) is among the primary bioactive anthraquinones present in traditional Chinese medicinal plants such as Rheum palmatum L. Multidrug resistance protein 2 (ABCC2/ MRP2) is an important efflux transporter of substances associated with cellular oxidative stress. However, the effects of traditional Chinese medicine on this protein remain unclear.

Aloe-emodin induces hepatotoxicity by the inhibition of multidrug resistance protein 2.

The glyoxalase system is a ubiquitous enzymatic network which plays important roles in biological life. It consists of glyoxalase 1 (GLO1), glyoxalase 2 (GLO2), and reduced glutathione (GSH), which perform an essential metabolic function in cells by detoxifying methylglyoxal (MG) and other endogenous harmful metabolites into non-toxic d-lactate. MG and MG-derived advanced glycation endproducts (AGEs) are associated with various diseases, such as diabetes, cardiovascular disease, neurodegenerative disorders and cancer, and GLO1 is a key rate-limiting enzyme in the anti-glycation defense. The abnormal activity and expression of GLO1 in various diseases make this enzyme a promising target for drug design and development. This review focuses on the regulatory mechanism of GLO1 in diverse pathogenic conditions with a thorough discussion of GLO1 regulators since their discovery, including GLO1 activators and inhibitors. The different classes, chemical structure and structure-activity relationship are embraced. Moreover, assays for the discovery of small molecule regulators of the glyoxalase system are also introduced in this article. Compared with spectrophotometer-based assay, microplate-based assay is a more simple, rapid and quantitative high-throughput method. This review will be useful to design novel and potent GLO1 regulators and hopefully provide a convenient reference for researchers.

Glyoxalase system: A systematic review of its biological activity, related-diseases, screening methods and small molecule regulators.

MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.

Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of β-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression.

Three chalcone derivatives, abelmanihotols A-C , and nine known compounds were isolated from  seeds, and their structures were determined using HRESIMS and NMR spectroscopic analysis. Compound  exhibited the most potent inhibitory effect (IC = 4.79 ± 0.72 μM) against lipopolysaccharide (LPS)-induced NO release in THP-1 cells, and ignificantly inhibited interleukin 1β (IL-1β) secretion, which is stimulated by LPS plus nigericin (IC = 11.86 ± 1.20 μM), ATP or MSU, in THP-1 cells. A preliminary mechanism of action study indicated that compound  blocked the formation of nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome formation by suppressing apoptosis-associated speck-like protein oligomerization, thereby attenuating caspase-1 activation and IL-1β release. These results reveal that compound  is not only a potent and efficacious NLRP3 inflammasome inhibitor but also a promising drug for the treatment of NLRP3-related diseases.

Chalcone Derivatives From  Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization.

The Src-homology 2 domain-containing phosphatase 2 (SHP2), which is encoded by PTPN11, participates in many cellular signaling pathways and is closely related to various tumorigenesis. Inhibition of the abnormal activity of SHP2 by small molecules is an important part of cancer treatment. Here, three abietane diterpenoids, named compounds -, were isolated from  var. . Spectroscopic analysis was used to identify the exact structure of the compounds. The enzymatic kinetic experiment and the cellular thermal shift assay showed compound  selectively inhibited SHP2 activity in vitro. Molecular docking indicated compound  targeted the SHP2 catalytic domain. The predicted pharmacokinetic properties by SwissADME revealed that compound  passed the majority of the parameters of common drug discovery rules. Compound  restrained A549 proliferation (IC = 8.68 ± 0.96 μM), invasion and caused A549 cell apoptosis by inhibiting the SHP2-ERK/AKT signaling pathway. Finally, compound  (Ajuforrestin A) is a potent and efficacious SHP2 inhibitor and may be a promising compound for human lung epithelial cancer treatment.

Ajuforrestin A, an Abietane Diterpenoid from  var. , Induces A549 Cell Apoptosis by Targeting SHP2.

With high mortality and morbidity rates, lung cancer (LC) has become one of the major threats to human health. The treatment strategies for LC currently face issues, such as drug resistance and body tolerance. Traditional Chinese medicine (TCM) is characterized by novel pharmacological mechanisms, low toxicity, and limited side effects. TCM includes a substantial number of biologically active ingredients, several of which are effective monomeric agents against LC. An increasing number of researchers are focusing their efforts on the discovery of active anti-cancer ingredients in TCM.

Traditional Chinese Medicine has great potential as candidate drugs for lung cancer: A review.

Extrinsic injury can evoke intrinsic stimulation and subsequently initiate the physiological repair process. This study aims to investigate whether clinically acceptable micro-injury could be used to create local stimuli to induce hair regeneration and vitiligo repigmentation. A novel device was designed and manufactured to precisely control the micro-injury parameters. Then the most appropriate extent of micro-injury without over-damaging the skin was evaluated. Finally, the effects of micro-injury on hair regeneration and vitiligo repigmentation were examined by macroscopic observation, histological staining, gene and protein expression analysis. We discover that proper micro-injury effectively induces hair regeneration by activating the hair follicle stem cell proliferation and migration downwards to the hair matrix, finally shifting the hair follicle stage from telogen into anagen. On vitiligo model mice, micro-injury also induces the hair follicle melanocyte stem cells to migrate upwards to the interfollicular epidermis, activating and giving rise to melanocytes to repopulate the vitiligo lesion. Mechanistic analysis indicates that the canonical Wnt/β-catenin pathway plays a key role in the micro-injury-induced repair process. This study demonstrates that micro-injury has great potential in inducing hair regeneration and vitiligo repigmentation, laid a foundation to develop a micro-injury-based treatment method in alopecia and vitiligo.

Micro-Injury Induces Hair Regeneration and Vitiligo Repigmentation Through Wnt/β-Catenin Pathway.

Aged cells have declined regenerative ability when subjected to environmental insult. Here we elucidate the mechanism by which mechanical stimulus induces hair regeneration at the microenvironmental regulation level using the hair plucking and organoid culture models. We observed that the skin cells harvested from post-plucking day 3 (PPD3) have the best self-organizing ability during skin organoid culture and have the highest hair regeneration upon transplantation. By bulk RNA sequencing (RNA-seq) and single-cell RNA-seq analysis and  hybridization, we identified that the chemokine signaling pathway genes including CCL2 are significantly increased in the skin at PPD3 and in skin organoid cultures. Immunostaining shows that the PPD3 skin epithelial cells have increased multipotency, which is verified by the ability to self-organize to form epidermal aggregates during organoid culture. By adding CCL2 recombinant protein to the organoid culture using an environmental reprogramming protocol, we observed the PPD0 adult skin cells, which lose their regenerative ability can self-organize in organoid culture and regenerate hair follicles robustly upon transplantation. Our study demonstrates that CCL2 functions in immune regulation of hair regeneration under mechanical stimulus, and enhances cell multipotency during organoid culture. This provides a therapeutic potential for future clinical application.

Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles.

 Stem cells self-organize to form organoids that generate mini-organs that resemble the physiologically-developed ones. The mechanism by which the stem cells acquire the initial potential for generating mini-organs remains elusive. Here we used skin organoids as an example to study how mechanical force drives initial epidermal-dermal interaction which potentiates skin organoids to regenerate hair follicles.  Live imaging analysis, single-cell RNA-sequencing analysis, and immunofluorescence were used to analyze the contractile force of dermal cells in skin organoids. Bulk RNA-sequencing analysis, calcium probe detection, and functional perturbations were used to verify that calcium signaling pathways respond to the contractile force of dermal cells.  mechanical loading experiment was used to prove that the stretching force triggers the epidermal Piezo1 expression which negatively regulates dermal cell attachment. Transplantation assay was used to test the regenerative ability of skin organoids.  We found that dermal cell-derived contraction force drives the movement of dermal cells surrounding the epidermal aggregates to trigger initial mesenchymal-epithelial interaction (MEI). In response to dermal cell contraction force, the arrangement of the dermal cytoskeleton was negatively regulated by the calcium signaling pathway which further influences dermal-epidermal attachment. The native contraction force generated from the dermal cell movement exerts a stretching force on the adjacent epidermal cells, activating the stretching force sensor Piezo1 in the epidermal basal cells during organoid culture. Epidermal Piezo1 in turn drives strong MEI to negatively regulate dermal cell attachment. Proper initial MEI by mechanical-chemical coupling during organoid culture is required for hair regeneration upon transplantation of the skin organoids into the back of the nude mice.  Our study demonstrated that mechanical-chemical cascade drives the initial event of MEI during skin organoid development, which is fundamental to the organoid, developmental, and regenerative biology fields.

ArticleTotal : 3	Year
Publication title Cited by 1	2023
Publication title	2024
Publication title	2026

Article	Year
A new abietane diterpenoid from Ajuga ovalifolia var. calantha induces human lung epithelial A549 cell apoptosis by inhibiting SHP2. Fitoterapia\| PubMed ID: 31954180	2020
Aloe-emodin induces hepatotoxicity by the inhibition of multidrug resistance protein 2. Phytomedicine : international journal of phytotherapy and phytopharmacology\| PubMed ID: 32028185	2020
Glyoxalase system: A systematic review of its biological activity, related-diseases, screening methods and small molecule regulators. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 32858501	2020
Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels. Virus research\| PubMed ID: 33775754	2021
Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression. Die Pharmazie\| PubMed ID: 34481532	2021
Chalcone Derivatives From Seeds Restrain NLRP3 Inflammasome Assembly by Inhibiting ASC Oligomerization. Frontiers in pharmacology\| PubMed ID: 35873581	2022
Ajuforrestin A, an Abietane Diterpenoid from var. , Induces A549 Cell Apoptosis by Targeting SHP2. Molecules (Basel, Switzerland)\| PubMed ID: 36080236	2022
Traditional Chinese Medicine has great potential as candidate drugs for lung cancer: A review. Journal of ethnopharmacology\| PubMed ID: 36162545	2023
Micro-Injury Induces Hair Regeneration and Vitiligo Repigmentation Through Wnt/β-Catenin Pathway. Stem cells and development\| PubMed ID: 35044224	2022
Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles. Molecular therapy. Nucleic acids\| PubMed ID: 37020681	2023
Mechanical force drives the initial mesenchymal-epithelial interaction during skin organoid development. Theranostics\| PubMed ID: 37284452	2023

Deming Liu

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