Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection.

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and the background signal readout makes it challenging to achieve glycan quantification. Here we develop SeMOE, a selenium-based metabolic oligosaccharide engineering strategy that concisely combines elemental analysis and MOE,enabling the mass spectrometric imaging of glycome. We also demonstrate that the new-to-nature SeMOE probes allow for detection, quantitative measurement and visualization of glycans in diverse biological contexts. We also show that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. SeMOE thus provides a convenient and simplified method to explore the glyco-world.

Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

[Determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis by gel permeation chromatography-gas chromatography-ion trap mass spectrometry].

With the growing global popularity of traditional medicine and natural drugs， especially in Southeast Asia， the quality of traditional Chinese medicines （TCMs） has attracted the attention of regulators. China's major TCM export destinations， such as South Korea， Japan， and Europe， have formulated strict maximum residue limits （MRLs） of pesticides in TCMs. Therefore， a sensitive and high-throughput method for the simultaneous determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis was established， involving gel permeation chromatography （GPC） coupled with gas chromatography-ion trap mass spectrometry （GC-ITMS）. In this method， the samples were first ground into fine powder and extracted twice with 20 mL acetonitrile in an ultrasonic cleaner for 30 min. After centrifugation for 10 min at 6000 r/min， the supernatants were combined and dried at 40 ℃ using a rotary vacuum evaporator. The residue was re-dissolved in 2 mL ethyl acetate-cyclohexane （1∶1， v/v） and purified by gel permeation chromatography using a 40 cm×20 mm column. The eluent collecting time was optimized as 17-30 min to ensure both the recovery of target compounds and the removal of interferences such as pigments and lipids from the target compounds. The eluent was then dried and re-dissolved with 1 mL toluene for analysis. The 101 pesticide residues were separated using the DB-5MS capillary column and analyzed by ion trap mass spectrometry. The pretreatment conditions and ion trap mass spectrometry parameters were optimized to effectively reduce the interference of complex TCM matrices and greatly improve the quantitative accuracy of the analysis and recovery of the target pesticides. Three spiked levels of 101 pesticides were tested. The average recovery range was 58.3%-108.9% and the relative standard deviations （RSDs） at the three spiked levels （n=10） ranged from 0.4% to 16.5%. The limits of detection （LODs， S/N=3） of the 101 pesticide compounds ranged from 0.2 to 40.0 µg/kg， while the limits of quantification （LOQs， S/N=10） ranged from 0.6 to 120.0 µg/kg， which met the maximum residue limits of China's main TCM export countries and organizations. This rapid analysis method was easy to operate and high throughput， with strong sensitivity and good repeatability. The employment of gel permeation chromatography overcame the drawback of inadequate cleanup of the solid phase extraction column during TCM analysis. The application of ion trap technology further eliminated the interference of matrix impurities and increased the accuracy of the quantitative and qualitative analyses. This method fills the knowledge gap in multiple pesticide residue determination in TCMs using gas chromatography-ion trap mass spectrometry and is a useful and beneficial alternative to current analytical methods of TCMs.

The role of traditional herbal medicine for ischemic stroke: from bench to clinic-A critical review.

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.

[A mini-review on anti-tumor effect of cannabidiol].

Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.

A multi-herb-combined remedy to overcome hyper-inflammatory response by reprogramming transcription factor profile and shaping monocyte subsets.

Traditional Chinese multi-herb-combined prescriptions usually show better performance than a single agent since a group of effective compounds interfere multiple disease-relevant targets simultaneously. Huang-Lian-Jie-Du decoction is a remedy made of four herbs that are widely used to treat oral ulcers, gingivitis, and periodontitis. However, the active ingredients and underlying mechanisms are not clear. To address these questions, we prepared a water extract solution of Huang-Lian-Jie-Du decoction (HLJDD), called it as WEH (Water Extract Solution of HLJDD), and used it to treat LPS-induced systemic inflammation in mice. We observed that WEH attenuated inflammatory responses including reducing production of cytokines, chemokines and interferons (IFNs), further attenuating emergency myelopoiesis, and preventing mice septic lethality. Upon LPS stimulation, mice pretreated with WEH increased circulating Ly6C- patrolling and splenic Ly6C+ inflammatory monocytes. The acute myelopoiesis related transcriptional factor profile was rearranged by WEH. Mechanistically we confirmed that WEH interrupted LPS/TLR4/CD14 signaling-mediated downstream signaling pathways through its nine principal ingredients, which blocked LPS stimulated divergent signaling cascades, such as activation of NF-κB, p38 MAPK, and ERK1/2. We conclude that the old remedy blunts LPS-induced "danger" signal recognition and transduction process at multiple sites. To translate our findings into clinical applications, we refined the crude extract into a pure multicomponent drug by directly mixing these nine chemical entities, which completely reproduced the effect of protecting mice from lethal septic shock. Finally, we reduced a large number of compounds within a multi-herb water extract to seven-chemical combination that exhibited superior therapeutic efficacy compared with WEH.

The enhancement of the perception of saltiness by Sichuan pepper oleoresin in a NaCl model solution.

Health concerns related to the intake of salt have necessitated the investigation into NaCl reduction by examining the cross-modal interaction between the perception of saltiness and pungency elicited by Sichuan pepper oleoresin (Spo). The category scale and the generalized Labeled Magnitude Scale (gLMS) were used to determine the degree to which Spo enhanced the perception of saltiness in the NaCl model solution. Sixty-eight participants were divided into the hyposensitive, semi-sensitive, and hypersensitive groups according to individual exponent. The power functions of saltiness under different pungency carriers were obtained. The level of enhancement varied between the different sensitivity groups and pungency carriers. In the hypersensitive group, the low and strong pungency carriers effectively enhanced the perception of saltiness at low to moderate, and moderate to strong NaCl solutions, respectively. In the semi-sensitive group, low and moderate pungency carriers induced additive effect in the perception of saltiness at full and moderately strong NaCl solutions, respectively. However, the additive effect was inadequate in the hypo-sensitive group. Therefore, the low pungency solution was more feasible for enhancing in the perception of saltiness, while the maximum NaCl reduction percentages corresponded to the hypersensitive and semi-sensitive groups at 38.61% and 39.06%, respectively. This research not only provided insight into the effect of pungency on the perception of saltiness as it related to individual sensitivity, but also presented valuable information regarding flavor when developing food with reduced salt content.

[Preparation of docetaxel-loaded nanomicelles and their anti-Lewis lung cancer effect in vitro].

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-ß-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.