Changes in chemical components and hepatoprotective effect of red Panax notoginseng processed by aspartic acid impregnation treatment.

BACKGROUND: Red Panax notoginseng (RPN) is one of the major processed products of P. notoginseng (PN), with more effective biological activities. However, the traditional processing method of RPN has some disadvantages, such as low conversion rate of ginsenosides and long processing time. RESULTS: In this work, we developed a green, safe, and efficient approach for RPN processing by aspartic acid impregnation pretreatment. Our results showed that the optimized temperature, steaming time, and concentration of aspartic acid were 120 °C, 1 h, and 3% respectively. The original ginsenosides in PN treated by aspartic acid (Asp-PN) were completely converted to rare saponins at 120 °C within just 1 h. The concentration of the rare ginsenosides in Asp-PN was two times higher than that in untreated RPN. In addition, we examined the protective effect of RPN and Asp-PN on acetaminophen-induced liver injury in a mouse model. The results showed that Asp-PN has significantly more potent hepatoprotective action than the RPN. The hepatoprotection of Asp-PN in acetaminophen-induced hepatotoxicity may be due to its anti-oxidative stress, anti-apoptotic, and anti-inflammatory activities. CONCLUSION: These results indicated that aspartic acid impregnation pretreatment may provide an effective method to shorten the steaming time, improve the conversion rate of ginsenosides, and enhance hepatoprotective activity of RPN. © 2024 Society of Chemical Industry.

Phytochemistry of Red Ginseng, a Steam-Processed Panax ginseng.

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

A light-activatable theranostic combination for ratiometric hypoxia imaging and oxygen-deprived drug activity enhancement.

While performing oxygen-related tumour treatments such as chemotherapy and photodynamic therapy, real-time monitoring hypoxia of tumour is of great value and significance. Here, we design a theranostic combination for light-activated ratiometric hypoxia imaging, hypoxia modulating and prodrug activation. This combination consisted of an oxygen-sensitive near-infrared-emitting ratiometric phosphorescence probe and a hypoxia-activated prodrug-loaded covalent organic framework. In this combination, the probe plays two roles, including quantitative monitoring of oxygen concentration by ratiometric imaging and consuming the oxygen of tumour under light excitation by photodynamic therapy. Meanwhile, the enhanced hypoxia microenvironment of tumour can raise the cytotoxicity of prodrug loaded in covalent organic framework, resulting in boosting antitumour therapeutic effects in vivo. This theranostic combination can precisely provide therapeutic regime and screen hypoxia-activated prodrugs based on real-time tumour hypoxia level, offering a strategy to develop hypoxia mediated tumour theranostics with hypoxia targeted prodrugs.

Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A1c and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A1c concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A1c and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845.

Emerging insights into inflammatory bowel disease from the intestinal microbiota perspective: a bibliometric analysis.

Background: Inflammatory bowel disease (IBD) has caused severe health concerns worldwide. Studies on gut microbiota have provided new targets for preventing and treating IBD. Therefore, it is essential to have a comprehensive understanding of the current status and evolution of gut microbiota and IBD studies. Methods: A bibliometric analysis was performed on documents during 2003-2022 retrieved from the Scopus database, including bibliographical profiles, citation patterns, and collaboration details. Software programs of VOSviewer, CiteSpace, and the Bibliometrix R package visually displayed the mass data presented in the scientific landscapes and networks. Results: 10479 publications were retrieved, showing a steadily growing tendency in interest. Xavier Ramnik J. group led the total number of publications (73 papers) and 19787 citations, whose productive work aroused widespread concern. Among the 1977 academic journals, the most prolific ones were Inflammatory Bowel Diseases, Frontiers in Immunology, and Nutrients. Research outputs from the United States (US, 9196 publications), China (5587), and Italy (2305) were highly ranked. Conclusion: Our bibliometric study revealed that the role of gut microbiota has become a hot topic of IBD research worldwide. These findings are expected to improve understanding of research characteristics and to guide future directions in this field.

Comparative whole-genome analysis of China and global epidemic Pseudomonas aeruginosa high-risk clones.

OBJECTIVES: The various sequence types (STs) of Pseudomonas aeruginosa (P. aeruginosa) high-risk clones (HiRiCs) have been sporadically reported in China, but the systematic analysis of genomes for these STs remains limited. This study aimed to address the evolutionary pathways underlying the emergence of HiRiCs and their routes of dissemination from Chinese and global perspectives. METHODS: The phylogenetic analysis was performed based on 416 newly sequenced clinical P. aeruginosa strains from Guangdong (GD), published genome sequences of 282 Chinese isolates, and 868 HiRiCs isolates from other countries. The genomic comparison study of global HiRiC ST244 was conducted to detect the model of global dissemination and local separation driven by association regional-specific antibiotic resistance genes. Furthermore, the evolutionary route of the emerging, China-specific HiRiC ST1971 was explored using Most Recent Common Ancestor (MRCA) analysis. RESULTS: Based on comparative genomics analysis, we found a clear geographical separation of ST244 isolates, yet with an association between ST244 isolates from GD and America. We identified a set of 38 AMR genes that contribute to the geographical separation in ST244, and we identified genetic determinants either positively (MexB) and negatively (opmD) associated with GD ST244. For the China-unique HiRiC ST1971, its evolutionary history across different continents before emerging as ST1971 in China was also deduced. CONCLUSION: This study provides insight into the specific genetics underlying regional differences among globally disseminated P. aeruginosa HiRiCs (ST244) as well as new understanding of the dissemination and evolution of a regional HiRiC (ST1971). Understanding the genetics of these and other HiRiCs may assist in controlling their emergence and further spread.

Acanthopanax senticosus Harms improves Parkinson's disease by regulating gut microbial structure and metabolic disorders.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with an increasing prevalence as the population ages, posing a serious threat to human health, but the pathogenesis remains uncertain. Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) (aqueous ethanol extract), a Chinese herbal medicine, provides obvious and noticeable therapeutic effects on PD. To further investigate the ASH's mechanism of action in treating PD, the structural and functional gut microbiota, as well as intestinal metabolite before and after ASH intervention in the PD mice model, were examined utilizing metagenomics and fecal metabolomics analysis. α-syn transgenic mice were randomly divided into a model and ASH groups, with C57BL/6 mice as a control. The ASH group was gavaged with ASH (45.5 mg/kg/d for 20d). The time of pole climbing and autonomous activity were used to assess motor ability. The gut microbiota's structure, composition, and function were evaluated using Illumina sequencing. Fecal metabolites were identified using UHPLC-MS/MS to construct intestinal metabolites. The findings of this experiment demonstrate that ASH may reduce the climbing time of PD model mice while increasing the number of autonomous movements. The results of metagenomics analysis revealed that ASH could up-regulated Firmicutes and down-regulated Actinobacteria at the phylum level, while Clostridium was up-regulated and Akkermansia was down-regulated at the genus level; it could also recall 49 species from the phylum Firmicutes, Actinobacteria, and Tenericutes. Simultaneously, metabolomics analysis revealed that alpha-Linolenic acid metabolism might be a key metabolic pathway for ASH to impact in PD. Furthermore, metagenomics function analysis and metabolic pathway enrichment analysis revealed that ASH might influence unsaturated fatty acid synthesis and purine metabolism pathways. These metabolic pathways are connected to ALA, Palmitic acid, Adenine, and 16 species of Firmicutes, Actinobacteria, and Tenericutes. Finally, these results indicate that ASH may alleviate the movement disorder of the PD model, which may be connected to the regulation of gut microbiota structure and function as well as the modulation of metabolic disorders by ASH.

Effects of Curcuminoids and Surfactant-Formulated Curcumin on Chemo-Resistant Colorectal Cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related death in the United States, and chronic gut inflammation is a risk factor for CRC initiation and development. Curcuma longa L., or turmeric, has become one of the most studied herbal medicines in recent years due to its anticancer potentials. It is generally accepted that the major component in turmeric is curcuminoids, and the active constituent in curcuminoids is curcumin. However, unprocessed curcumin is characterized by poor water solubility, which means low bioavailability in humans. To increase the bioavailability of curcumin, in this study, we utilized a novel surfactant-formulated curcumin (CuminUP60[Formula: see text]) and evaluated its CRC chemopreventive activities. Compared with the chemo-sensitive CRC cell line HCT-116, the management of the CRC SW-480 cell line is a challenge, since the latter is chemo-resistant. In other words, these cancer cells resist the effects of the chemotherapy. Using the newly formulated CuminUP60[Formula: see text] water solution, this study demonstrated its strong antiproliferative effects on the SW-480 cells in a dose- and time-dependent manner. This new formulation induced early apoptosis and arrested the cell cycle in the G2/M phase via the upregulation of cyclin B1. We also observed that this new formulation possessed inhibitory effects on Th17 cell differentiation, which regulates the body's immune response against gut malignancies. In summary, our results exhibited a potential clinical utility of the surfactant-formulated curcumin in chemo-resistant colorectal cancer management.

Pharmacological Effects of Ginseng: Multiple Constituents and Multiple Actions on Humans.

Ginseng is a very commonly used natural product in the world, and its two main species are Asian ginseng and American ginseng. Ginseng is an adaptogenic botanical that reportedly protects the body against stress, stabilizes physiological processes, and restores homeostasis. Previously, different animal models and contemporary research methodologies have been used to reveal ginseng's biomedical activities in different body systems and the linked mechanisms of actions. However, human clinical observation data on ginseng effects have attracted more attention from the general public and medical community. In this paper, after an introduction of the phytochemistry of ginseng species, we review positive ginseng clinical studies, mainly conducted in developed countries, performed over the past 20 years. The reported effects of ginseng are presented in several sections, and conditions impacted by ginseng include diabetes; cardiovascular disorders; cognition, memory, and mood; the common cold and flu; cancer fatigue and well-being; quality of life and social functioning, etc. Administration of ginseng demonstrated a good safety record in humans. Although encouraging beneficial effects obtained from clinical data, using the study treatment regimen, the reported ginseng effects in general only ranged from mild to moderate. Nonetheless, these beneficial effects of ginseng could be a valuable add-on therapy for patients receiving standard drug treatments. Additionally, as a dietary supplement, ginseng possesses an important role in maintaining and promoting human health. We believe that the quality of future ginseng trials should be improved, particularly by providing detailed herbal phytochemistry and quality control information. With solid effectiveness data obtained from a well-designed, carefully executed ginseng clinical trial, this meritoriously herbal medicine will be widely used by consumers and patients.

Cross-modal enhancement of spatially unpredictable visual target discrimination during the attentional blink.

The attentional blink can be substantially reduced by delivering a task-irrelevant sound synchronously with the second target (T2) embedded in a rapid serial visual presentation stream, which is further modulated by the semantic congruency between the sound and T2. The present study extended the cross-modal boost during attentional blink and the modulation of audiovisual semantic congruency in the spatial domain by showing that a spatially uninformative, semantically congruent (but not incongruent) sound could even improve the discrimination of spatially unpredictable T2 during attentional blink. T2-locked event-related potential (ERP) data yielded that the early cross-modal P195 difference component (184-234 ms) over the occipital scalp contralateral to the T2 location was larger preceding accurate than inaccurate discriminations of semantically congruent, but not incongruent, audiovisual T2s. Interestingly, the N2pc component (194-244 ms) associated with visual-spatial attentional allocation was enlarged for incongruent audiovisual T2s relative to congruent audiovisual and unisensory visual T2s only when they were accurately discriminated. These ERP findings suggest that the spatially extended cross-modal boost during attentional blink involves an early cross-modal interaction strengthening the perceptual processing of T2, without any sound-induced enhancement of visual-spatial attentional allocation toward T2. In contrast, the absence of an accuracy decrease in response to semantically incongruent audiovisual T2s may originate from the semantic mismatch capturing extra visual-spatial attentional resources toward T2.

Mapping the regulatory effects of herbal organic compounds on gut bacteria.

Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.

Probiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.

Background: Probiotics play a vital role in treating immune and inflammatory diseases by improving intestinal barrier function; however, a comprehensive evaluation is missing. The present study aimed to explore the impact of probiotics on the intestinal barrier and related immune function, inflammation, and microbiota composition. A systematic review and meta-analyses were conducted. Methods: Four major databases (PubMed, Science Citation Index Expanded, CENTRAL, and Embase) were thoroughly searched. Weighted mean differences were calculated for continuous outcomes with corresponding 95% confidence intervals (CIs), heterogeneity among studies was evaluated utilizing I2 statistic (Chi-Square test), and data were pooled using random effects meta-analyses. Results: Meta-analysis of data from a total of 26 RCTs (n = 1891) indicated that probiotics significantly improved gut barrier function measured by levels of TER (MD, 5.27, 95% CI, 3.82 to 6.72, P < 0.00001), serum zonulin (SMD, -1.58, 95% CI, -2.49 to -0.66, P = 0.0007), endotoxin (SMD, -3.20, 95% CI, -5.41 to -0.98, P = 0.005), and LPS (SMD, -0.47, 95% CI, -0.85 to -0.09, P = 0.02). Furthermore, probiotic groups demonstrated better efficacy over control groups in reducing inflammatory factors, including CRP, TNF-α, and IL-6. Probiotics can also modulate the gut microbiota structure by boosting the enrichment of Bifidobacterium and Lactobacillus. Conclusion: The present work revealed that probiotics could improve intestinal barrier function, and alleviate inflammation and microbial dysbiosis. Further high-quality RCTs are warranted to achieve a more definitive conclusion. Clinical trial registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281822, identifier CRD42021281822.

Hypoxia-responsive Immunostimulatory Nanomedicines Synergize with Checkpoint Blockade Immunotherapy for Potentiating Cancer Immunotherapy.

Inducing cell death while simultaneously enhancing antitumor immune responses is a promising therapeutic approach for multiple cancers. Celastrol (Cel) and 7-ethyl-10-hydroxycamptothecin (SN38) have contrasting physicochemical properties, but strong synergy in immunogenic cell death induction and anticancer activity. Herein, a hypoxia-sensitive nanosystem (CS@TAP) was designed to demonstrate effective immunotherapy for colorectal cancer by systemic delivery of an immunostimulatory chemotherapy combination. Furthermore, the combination of CS@TAP with anti-PD-L1 mAb (αPD-L1) exhibited a significant therapeutic benefit of delaying tumor growth and increased local doses of immunogenic signaling and T-cell infiltration, ultimately extending survival. We conclude that CS@TAP is an effective inducer of immunogenic cell death (ICD) in cancer immunotherapy. Therefore, this study provides an encouraging strategy to synergistically induce immunogenic cell death to enhance tumor cytotoxic T lymphocytes (CTLs) infiltration for anticancer immunotherapy.

Phenylboronic acid-modified nanoscale multi-arm polymers for tumor-targeted therapy.

Unimolecular polymer nanomaterials (UPNs) have well-defined structures, desirable stability and designable functional groups, and hence exhibit great application potential in drug delivery. However, the syntheses of UPNs are generally time-consuming and tedious, which greatly limit their applications. In this paper, we present the preparation of a ß-cyclodextrin-cored star-shaped polymer with 21 poly(tert-butyl acrylate) arms. This polymer was facilely synthesized by one-step atom transfer radical polymerization (ATRP). After cleaving the tert-butyl ester protecting groups, the abundant carboxylic acid side groups were used to incorporate doxorubicin (DOX), phenylboronic acid (PBA) groups and poly(ethylene glycol) (PEG) to achieve drug loading and tumor drug delivery. Due to the tumor-targeting ability of the PBA groups, this UPN-based nanomedicine showed high tumor accumulation, penetration and therapeutic efficacy.

Specific capture and determination of glycoprotein using a hybrid epitopes and monomers-mediated molecular-imprinted polymer enzyme-free electrochemical biosensor.

A novel molecular-imprinted polymer (MIP)-based enzyme-free biosensor was created for the selective detection of glycoprotein transferrin (Trf). For this purpose, MIP-based biosensor for Trf was prepared by electrochemical co-polymerization of novel hybrid monomers 3-aminophenylboronic acid (M-APBA) and pyrrole on a glassy carbon electrode (GCE) modified with carboxylated multi-walled carbon nanotubes (cMWCNTs). Hybrid epitopes of Trf (C-terminal fragment and glycan) have been selected as templates. The produced sensor exhibited great selective recognition ability toward Trf under optimal preparation conditions, offering good analytical range (0.125-1.25 µM) with a detection limit of 0.024 µM. The proposed hybrid epitope in combination with hybrid monomer-mediated imprinting strategy was successfully applied to detect Trf in spiked human serum samples, with recoveries and relative standard deviations ranging from 94.7 to 106.0% and 2.64 to 5.32%, respectively. This study provided a reliable protocol for preparing hybrid epitopes and monomers-mediated MIP for the synergistic and effective determination of glycoprotein in complicated biological samples.

Ginseng-Containing Sijunzi Decoction Ameliorates Ulcerative Colitis by Orchestrating Gut Homeostasis in Microbial Modulation and Intestinal Barrier Integrity.

Ulcerative colitis (UC) has become a global epidemic, and the lack of an effective cure highlights the necessity and urgency to explore novel therapies. Sijunzi Decoction (SJZD), a classical Chinese herbal formula, has been comprehensively applied and clinically proven effective in treating UC; however, the pharmacological mechanism behind its therapeutic benefits is largely obscure. Here, we find that SJZD can restore microbiota homeostasis and intestinal barrier integrity in DSS-induced colitis. SJZD significantly alleviated the colonic tissue damage and improved the goblet cell count, MUC2 secretion, and tight junction protein expressions, which indicated enhanced intestinal barrier integrity. SJZD remarkedly suppressed the abundance of phylum Proteobacteria and genus Escherichia-Shigella, which are typical features of microbial dysbiosis. Escherichia-Shigella was negatively correlated with body weight and colon length, and positively correlated with disease activity index and IL-1[Formula: see text]. Furthermore, through gut microbiota depletion, we confirmed that SJZD exerted anti-inflammatory activities in a gut microbiota-dependent manner, and fecal microbiota transplantation (FMT) validated the mediating role of gut microbiota in the SJZD treatment of UC. Through gut microbiota, SJZD modulates the biosynthesis of bile acids (BAs), especially tauroursodeoxycholic acid (TUDCA), which has been identified as the signature BA during SJZD treatment. Cumulatively, our findings disclose that SJZD attenuates UC via orchestrating gut homeostasis in microbial modulation and intestinal barrier integrity, thus offering a promising alternative approach to the clinical management of UC.

The Small-Molecule compound baicalein alleviates experimental autoimmune encephalomyelitis by suppressing pathogenetic CXCR6+ CD4 cells.

CXC chemokine receptor6 (CXCR6)-based immunotherapy plays a significant role in autoimmune diseases, however, little is known about possible small compounds that inhibit pathogenic CXCR6+ T cells for treating multiple sclerosis (MS). Baicalein, a flavonoid isolated from Scutellarin baicalensis (Huang Qin), was shown to exert therapeutic effects on MS, but the underlying mechanisms are largely unknown. In the current study, we found that baicalein inhibited Th1 and Th17 differentiation in vitro. Oral administration of baicalein (25 mg/kg) significantly reduced the disease severity and the infiltration process, decreased the extent of demyelination in EAE, and selectively blocked IL-17A production and specific antibodies (IgG and IgG3) in MOG35-55-induced specific immune responses. In addition, the expression of CD4 cell effectors (CD44hiCD62Llow) and pathogenic Th17 cells was decreased by baicalein treatment. Furthermore, baicalein treatment largely decreased CXCR6+ CD4 and CD8 cells and prominently inhibited CXCR6+ Th17 cells in EAE. Taken together, the findings of this study suggest for the first time that baicalein may ameliorate EAE by suppressing pathogenetic CXCR6+ CD4 cells.

Genomic basis of the giga-chromosomes and giga-genome of tree peony Paeonia ostii.

Tree peony (Paeonia ostii) is an economically important ornamental plant native to China. It is also notable for its seed oil, which is abundant in unsaturated fatty acids such as α-linolenic acid (ALA). Here, we report chromosome-level genome assembly (12.28 Gb) of P. ostii. In contrast to monocots with giant genomes, tree peony does not appear to have undergone lineage-specific whole-genome duplication. Instead, explosive LTR expansion in the intergenic regions within a short period (~ two million years) may have contributed to the formation of its giga-genome. In addition, expansion of five types of histone encoding genes may have helped maintain the giga-chromosomes. Further, we conduct genome-wide association studies (GWAS) on 448 accessions and show expansion and high expression of several genes in the key nodes of fatty acid biosynthetic pathway, including SAD, FAD2 and FAD3, may function in high level of ALAs synthesis in tree peony seeds. Moreover, by comparing with cultivated tree peony (P. suffruticosa), we show that ectopic expression of class A gene AP1 and reduced expression of class C gene AG may contribute to the formation of petaloid stamens. Genomic resources reported in this study will be valuable for studying chromosome/genome evolution and tree peony breeding.

Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics.

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography-mass spectrometry-based (UHPLC-MS/MS-based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.