Five new eremophilane-type sesquiterpenes from the fresh roots of Rehmannia glutinosa.

Five undescribed eremophilane-type sesquiterpenes, remophilanetriols E-I (1-5), along with seven known compounds (6-12) were isolated from the fresh roots of Rehmannia glutinosa. Their structures were characterized by extensive spectroscopic data analysis and their absolute configurations were determined by comparing their calculated electronic circular dichroism (ECD) spectra and experimental ECD spectra. The anti-pulmonary fibrosis activities of all compounds were evaluated in vitro by MTT methods, and compounds 2, 8, 10, and 12 exhibited excellent anti-pulmonary fibrosis activities. In addition, compound 2 can reduce the levels of ROS and apoptosis in TGF-ß1-induced BEAS-2B cells.

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

AIMS: The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. METHODS: A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. RESULTS: Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. CONCLUSION: The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

Changes of soil nutrients and organic carbon fractions in Caragana korshinskii forests with different restoration years in mountainous areas of southern Ningxia, China.

Vegetation restoration can effectively enhance soil quality and soil organic carbon (SOC) sequestration. In this study, the distribution characteristics of soil nutrients and SOC along soil profile (0-100 cm), and their responses to restoration years (16, 28, 38 years) were studied in Caragana korshinskii plantations in the southern mountainous area of Ningxia, compared with cropland and natural grassland. The results showed that: 1) the contents of SOC, soil total nitrogen (TN), total phosphorus (TP), particulate organic carbon (POC), mineral-associated organic carbon (MAOC) and the proportion of particulate organic carbon to total organic carbon (POC/SOC) all decreased with increasing soil depth. The ratio of mineral-associated organic carbon to total organic carbon (MAOC/SOC) exhibited an opposite trend. 2) The contents of SOC, TN, TP, C:P, N:P, POC and MAOC gra-dually decreased as the restoration years increased. However, the C:N ratio showed no significant change. The POC/SOC ratio initially increased and then decreased, while the MAOC/SOC ratio decreased initially and then increased. 3) In three different types of vegetation, POC, MAOC, and SOC showed a highly significant positive linear correlation, with the increase in SOC mainly depended on the increase in MAOC. The SOC, TN, TP, POC and MAOC contents in natural grassland and C. korshinskii plantations were significantly higher than those in cropland. In conclusion, soil nutrients and POC and MAOC contents of C. korshinskii plantations gradually decreased with the increases in restoration years. However, when compared with cropland, natural grassland and C. korshinskii plantations demonstrated a greater capacity to maintain and enhance soil nutrient and carbon storage.

Functional Identification of HhUGT74AG11-A Key Glycosyltransferase Involved in Biosynthesis of Oleanane-Type Saponins in Hedera helix.

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.

[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

The anti-cholestatic effects of Coptis chinensis Franch. alone and combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley: dual effects on fecal metabolism and microbial diversity.

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms. Methods: Rats with α-naphthylisothiocyanate (ANIT, 50 mg/kg)-induced cholestasis were administered low (0.3 g/kg) and high (0.6 g/kg) doses of CF, as well as CF combined with TR at doses of 0.6 g/kg and 0.9 g/kg, respectively. The anti-cholestatic effects of these treatments were assessed by determining their anti-inflammatory, hypolipidemic, and anti-oxidative stress properties. Additionally, fecal metabolomics and fecal microorganisms were analyzed. Results: Low dose CF had a more potent hypolipidemic effect than high dose CF, whereas high dose CF had more potent anti-inflammatory and anti-oxidative stress effects. Combination with TR enhanced the hypolipidemic effect, but antagonized the anti-inflammatory effect, of CF. Analyses of fecal metabolomics and fecal microorganisms showed differences in the regulation of lipid- and amino acid metabolism-related pathways, including pathways of linoleic acid, tyrosine, and arachidonic acid metabolism, and amino acid biosynthesis between different doses of CF as well as between different doses of CF in combination with TR. These differences may contribute to differences in the anti-cholestatic effects of these preparations. Conclusion: CF dose influences its anti-cholestatic efficacy. The combination with TR had synergistic or antagonistic effects on the properties of CF, perhaps by altering fecal metabolism and fecal microbial homeostasis.

Effects of mindful breathing training combined with diary-based rehabilitation guidance in lung cancer patients undergoing surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Lung cancer surgery patients experience severe physical and mental symptoms, which seriously affect their quality of life and prognosis. Mindful breathing training is a promising strategy to improve their symptoms, but its effectiveness is affected by training compliance, and diary-based rehabilitation instruction has been shown to help improve training compliance. Therefore, the aim of this study was to evaluate the effects of mindful breathing training combined with diary-based rehabilitation guidance on improving perioperative outcomes in lung cancer surgery patients. MATERIALS AND METHODS: This single-center, assessor-blinded, prospective, three-arm randomized controlled trial was conducted from November 1, 2021 to November 1, 2022. Patients diagnosed with primary non-small cell lung cancer and scheduled for thoracoscopic surgery were randomly allocated to the combined intervention group, the mindful breathing group or the control group, with 34 patients in each group. The control group received routine care, while the mindful breathing group received mindful breathing training and routine care. The combined intervention group received both mindful breathing training and diary-based rehabilitation guidance, along with routine care. RESULTS: The per-protocol analysis revealed that patients in the mindful breathing group experienced statistically significant improvements in dyspnea, fatigue and anxiety. Patients in the combined intervention group had statistically significant improvements in dyspnea, fatigue, anxiety, depression, exercise self-efficacy and training compliance. CONCLUSION: This study provides evidence that mindful breathing training combined with diary-based rehabilitation guidance can be effective in improving perioperative outcomes in lung cancer patients. It can be applied in clinical practice in the future.

Exploring the mechanism of Erteng-Sanjie capsule in treating gastric and colorectal cancers via network pharmacology and in-vivo validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The Erteng-Sanjie capsule (ETSJC) has therapeutic effects against gastric cancer (GC) and colorectal cancer (CRC). However, its underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: To explore the pharmacological mechanism of ETSJC against GC and CRC via network pharmacology and in-vivo validation. MATERIALS AND METHODS: Data on the ingredients of ETSJC were obtained from the TCMSP and HERB databases. Further, details on the related targets of the active ingredients were collected from the HERB and SwissTargetPrediction databases. The targets in GC and CRC, which were screened from the OMIM, GeneCards, and TTD databases, were uploaded to STRING for a separate protein-protein interaction network analysis. The common targets shared by ETSJC, GC, and CRC were then screened. Cytoscape and STRING were used to construct the networks of herbs-compounds-targets and PPI. Metascape was utilized to analyze the enrichment of the GO and KEGG pathways. Molecular docking was used to validate the potential binding mode between the core ingredients and targets. Finally, the predicted results were verified with animal experiment. RESULTS: Eight core ingredients (resveratrol, quercetin, luteolin, baicalein, delphinidin, kaempferol, pinocembrin, and naringenin) and six core targets (TP53, SRC, PIK3R1, AKT1, MAPK3, and STAT3) were filtered via network analysis. The molecular mechanism mainly involved the positive regulation of various processes such as cell migration, protein phosphorylation, and the PI3K-Akt signaling pathway. Molecular docking revealed that the core ingredients could be significantly combined with all core targets. The animal experiment revealed that ETSJC could suppress proliferation and promote apoptosis of both GC and CRC tumor cells by regulating the PI3K/Akt signaling pathway. CONCLUSIONS: Multiple targets (TP53, SRC, AKT1, and STAT3) were important in GC and CRC. ETSJC could act on these targets and engage in different pathways against GC and CRC. Simultaneously, inhibiting the PI3K/Akt signaling pathway was a promising therapeutic mechanism for treating GC and CRC.

Visual analysis on clinical randomized controlled trial of fire needle based on VOSviewer and CiteSpace. / 基于VOSviewer与CiteSpaceçš„ç«é’ˆä¸´åºŠéšæœºå¯¹ç §è¯•éªŒç ”ç©¶å¯è§†åŒ–åˆ†æž.

To analyze the research hotspots, frontiers and trends of fire needle clinical randomized controlled trial (RCT) literature in the past 10 years by using bibliometrics and knowledge mapping methods. Six Chinese and English databases including CNKI, Wanfang, VIP, SinoMed, PubMed and Web of Science ( WOS ) were searched for RCT research literature on fire needle. CiteSpace V6.1.R6 and VOSviewer V1.6.18 software were used to analyze the cooperation network, keyword co-occurrence, keyword clustering, keyword timeline, keyword emergence, etc., and to draw a visual knowledge map. A total of 1 973 Chinese articles and 3 English articles were included. The top three institutions that publish articles were Guangzhou University of CM, Heilongjiang University of CM and Beijing Hospital of TCM Affiliated to Capital Medical University. The fire needle was often combined with acupuncture, cupping and bloodletting therapy in the treatment of acne, vitiligo, lumbar disc herniation, herpes zoster, stroke sequelae, facial paralysis, knee osteoarthritis and so on. The research frontiers included the combined application of fire needle and other therapies, clinical mechanism research and efficacy evaluation index research. In the future, we should expand the dominant diseases, optimize the research design, strengthen the cooperation between the teams, and carry out high-level clinical research.

Selection and Verification of Standardized Reference Genes of Angelica dahurica under Various Abiotic Stresses by Real-Time Quantitative PCR.

In traditional Chinese medicine, Angelica dahurica is a valuable herb with numerous therapeutic applications for a range of ailments. There have not yet been any articles on the methodical assessment and choice of the best reference genes for A. dahurica gene expression studies. Real-time quantitative PCR (RT-qPCR) is widely employed as the predominant method for investigating gene expression. In order to ensure the precise determination of target gene expression outcomes in RT-qPCR analysis, it is imperative to employ stable reference genes. In this study, a total of 11 candidate reference genes including SAND family protein (SAND), polypyrimidine tract-binding protein (PTBP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), TIP41-like protein (TIP41), cyclophilin 2 (CYP2), elongation factor 1 α (EF1α), ubiquitin-protein ligase 9 (UBC9), tubulin ß-6 (TUB6), thioredoxin-like protein YLS8 (YLS8), and tubulin-α (TUBA) were selected from the transcriptome of A. dahurica. Subsequently, three statistical algorithms (geNorm, NormFinder, and BestKeeper) were employed to assess the stability of their expression patterns across seven distinct stimulus treatments. The outcomes obtained from these analyses were subsequently amalgamated into a comprehensive ranking using RefFinder. Additionally, one target gene, phenylalanine ammonia-lyase (PAL), was used to confirm the effectiveness of the selected reference genes. According to the findings of this study, the two most stable reference genes for normalizing the expression of genes in A. dahurica are TIP41 and UBC9. Overall, our research has determined the appropriate reference genes for RT-qPCR in A. dahurica and provides a crucial foundation for gene screening and identifying genes associated with the biosynthesis of active ingredients in A. dahurica.

Aggregating intrinsic information to enhance BCI performance through federated learning.

Insufficient data is a long-standing challenge for Brain-Computer Interface (BCI) to build a high-performance deep learning model. Though numerous research groups and institutes collect a multitude of EEG datasets for the same BCI task, sharing EEG data from multiple sites is still challenging due to the heterogeneity of devices. The significance of this challenge cannot be overstated, given the critical role of data diversity in fostering model robustness. However, existing works rarely discuss this issue, predominantly centering their attention on model training within a single dataset, often in the context of inter-subject or inter-session settings. In this work, we propose a hierarchical personalized Federated Learning EEG decoding (FLEEG) framework to surmount this challenge. This innovative framework heralds a new learning paradigm for BCI, enabling datasets with disparate data formats to collaborate in the model training process. Each client is assigned a specific dataset and trains a hierarchical personalized model to manage diverse data formats and facilitate information exchange. Meanwhile, the server coordinates the training procedure to harness knowledge gleaned from all datasets, thus elevating overall performance. The framework has been evaluated in Motor Imagery (MI) classification with nine EEG datasets collected by different devices but implementing the same MI task. Results demonstrate that the proposed framework can boost classification performance up to 8.4% by enabling knowledge sharing between multiple datasets, especially for smaller datasets. Visualization results also indicate that the proposed framework can empower the local models to put a stable focus on task-related areas, yielding better performance. To the best of our knowledge, this is the first end-to-end solution to address this important challenge.

Effect of apple high-methoxyl pectin on heat-induced gelation of silver carp myofibrillar protein.

The effect of adding apple high-methoxy pectin (HMP) (0-3 mg∙mL-1) on heat-induced gel characteristics of low concentration silver carp myofibrillar protein (MP) (15 mg∙mL-1) was studied. It was found that the hardness of gel increased by 20.6 times with adding 2 mg∙mL-1 HMP. Besides, HMP aided in the development of disulfide bonds and the aggregation of hydrophobic groups. During gel formation, the maximal storage modulus (G') of samples supplemented with 2 mg·mL-1 HMP was raised by a factor of 2.7. Of note, the images of SEM showed that protein and water were tightly combined with a proper amount of HMP and made its pores more uniform and dense. Meantime, the addition of moderate amounts of HMP enabled the formation of gels with favorable texture and performance at low concentration of MP was identified, which could provide a theoretical reference for the design and production of flesh low-calorie food gel.

Antifungal mechanism of rose, mustard, and their blended essential oils against Cladosporium allicinum isolated from Xinjiang naan and its storage application.

AIMS: To reveal the inhibition mechanism of rose, mustard, and blended essential oils against Cladosporium allicinum isolated from Xinjiang naan, and investigate the effect of the three essential oils on oxidative damage and energy metabolism. METHODS AND RESULTS: Rose and mustard essential oils significantly inhibited mycelial growth and spore viability in a dose-dependent relationship. After essential oil treatment, the cell membrane permeability was altered, and significant leakage of intracellular proteins and nucleic acids occurred. SEM observations further confirmed the disruption of cell structure. ROS, MDA, and SOD measurements indicated that essential oil treatment induced a redox imbalance in C. allicinum, leading to cell death. As for energy metabolism, essential oil treatment significantly reduced Na+K+-ATPase, Ca2+Mg2+-ATPase, MDH activity, and CA content, impairing metabolic functions. Finally, storage experiments showed that all three essential oils ensured better preservation of naan, with mustard essential oil having the best antifungal effect. CONCLUSIONS: Rose and mustard essential oils and their blends can inhibit C. allicinum at multiple targets and pathways, destroying cell morphological structure and disrupting metabolic processes.

Effects and core patterns of Chinese herbal medicines on hematologic manifestations in systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of Chinese herbal medicines (CHMs) on hematologic manifestations in patients with systemic lupus erythematosus (SLE). DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Airiti Library were searched for the period January 2000 to February 2022. STUDY SELECTION: RCTs involving CHMs in patients with SLE with available hematologic data. DATA EXTRACTION: The primary outcomes included white blood cell (WBC) count, hemoglobin level, and platelet count. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. Sensitivity analysis of RCTs with abnormal hematologic data before intervention was performed to verify the robustness of the results. Subgroup analysis was also applied for results with high heterogenicity. Core patterns of used herbal drug pairs had also been analyzed and visualized. DATA SYNTHESIS: Fifteen RCTs involving 1183 participants were included. The effects of elevating WBC count (weighted mean difference [WMD]: 0.69; 95% confidence interval [CI]: 0.33-1.06; p <0.001), hemoglobin levels (WMD: 0.64; 95% CI: 0.31-0.97; p <0.001), and platelet count (WMD: 0.61; 95% CI: 0.48-0.74; p <0.001) in the CHM group were significantly greater than those in the control group. In total, 23 single herbs and 152 herbal drug pairs were identified for core patterns network analysis. CONCLUSIONS: We demonstrated significantly superior therapeutic effects achieved with CHMs and conventional therapy regarding leukopenia, anemia, and thrombocytopenia compared to that of conventional therapy alone in patients with SLE.

Causal relationships between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers: univariable and multivariable Mendelian randomization.

PURPOSE: Coffee intake and apolipoprotein B levels have been linked to gastric, colorectal, and esophageal cancers in numerous recent studies. However, whether these associations are all causal remains unestablished. This study aimed to assess the potential causal associations of apolipoprotein B and coffee intake with the risk of gastric, colorectal, and esophageal cancers using Mendelian randomization analysis. METHODS: In this study, we utilized a two-sample Mendelian randomization analysis to access the causal effects of coffee intake and apolipoprotein B on gastric, colorectal, and esophageal cancers. The summary statistics of coffee intake (n = 428,860) and apolipoprotein B (n = 439,214) were obtained from the UK Biobank. In addition, the summary statistics of gastric cancer, colorectal cancer, and esophageal cancer were obtained from the FinnGen biobank (n = 218,792). Inverse variance weighted, MR-Egger, weighted median, and weighted mode were applied to examine the causal relationship between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. Steiger filtering and bidirectional mendelian randomization analysis were performed to evaluate the possible reverse causality. RESULTS: The result of the inverse variance weighted method indicated that apolipoprotein B levels were significantly associated with a higher risk of gastric cancer (OR = 1.392, 95% CI 1.027-1.889, P = 0.0333) and colorectal cancer (OR = 1.188, 95% CI 1.001-1.411, P = 0.0491). Furthermore, multivariable Mendelian randomization analysis also revealed a positive association between apolipoprotein B levels and colorectal cancer risk, but the effect of apolipoprotein B on gastric cancer risk disappeared after adjustment of coffee intake, body mass index or lipid-related traits. However, we did not discover any conclusive evidence linking coffee intake to gastric, colorectal, or esophageal cancers. CONCLUSIONS: This study suggested a causal association between genetically increased apolipoprotein B levels and higher risk of colorectal cancer. No causal relationship was observed between coffee intake and gastric, colorectal, or esophageal cancers.

TMT-based proteomics analysis identifies the interventional mechanisms of Qijia Rougan decoction in improving hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qijia Rougan decoction (QJ), consisting of eight herbs and two animal drugs, is an effective traditional Chinese medicine with hepatoprotective and antifibrotic effects. However, its underlying action mechanism remains unclear. AIM OF THE STUDY: To explore the mechanism underlying the treatment of liver fibrosis in rats by QJ. MATERIALS AND METHODS: Rats with fibrosis were constructed using carbon tetrachloride (CCl4). The QJ was orally administered to fibrotic rats. Hepatic pathological changes were evaluated using hematoxylin and eosin and Masson's trichrome staining. The differentially expressed proteins (DEPs) in QJ were analyzed using quantitative proteomics. Subsequently, the underlying mechanisms in liver fibrosis after QJ treatment were validated using Western blotting. RESULTS: The QJ markedly improved liver function and attenuated fibrotic progression. Based on the tandem mass-tag based (TMT) proteomics, we identified 818 common DEPs between QJ vs Model and Model vs Control, including 296 upregulated and 522 downregulated DEPs, which mostly participate in metabolic pathways, oxidation-reduction reactions, and collagen biosynthetic processes. In addition, we found that QJ reduced hepatocellular death by inhibiting the expression of caspase proteins, repressing pro-apoptotic proteins, and promoting anti-apoptotic proteins. We further demonstrated that QJ suppressed the Akt/mTOR pathway. CONCLUSION: QJ exerted hepatoprotective effects in CCl4-induced rats through multi-pathway regulation. This study provides protein information on liver fibrosis treated with QJ.

Intestinal Microbiota and Metabolomics Reveal the Role of Auricularia delicate in Regulating Colitis-Associated Colorectal Cancer.

BACKGROUND: The edible fungus Auricularia delicate (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer (CAC) and the underlying mechanisms remain unexplored. (2) Methods: The inhibitory effect of ADe on CAC was investigated using a mouse model induced by azoxymethane/dextran sulfate sodium. RESULTS: ADe effectively suppressed the growth and number of intestinal tumors in mice. Intestinal microbiota analyses revealed that ADe treatment increased Akkermansia and Parabacteroides while it decreased Clostridium, Turicibacter, Oscillospira, and Desulfovibrio. ADe regulated the levels of 2'-deoxyridine, creatinine, 1-palmitoyl lysophosphatidylcholine, and choline in serum. Furthermore, the levels of these metabolites were associated with the abundance of Oscillospira and Paraacteroides. ADe up-regulated the free fatty acid receptor 2 and ß-Arrestin 2, inhibited the nuclear factor kappa B (NF-κB) pathway, and significantly attenuated the levels of inflammatory cytokines, thereby mitigating the inflammatory in CAC mice. CONCLUSIONS: The protective effect of ADe in CAC mice is associated with the regulation of intestinal microbiota, which leads to the inhibition of NF-kB pathway and regulation of inflammation.

Postoperative Effects of Cinobufacini Capsules on Pain Reduction, Mitigation of Oxidative Stress, Immune Modulation, and Inflammatory Response in Differentiated Thyroid Cancer.

Objective: This study aimed to evaluate the impact of cinobufacini capsules in patients who underwent total thyroidectomy for differentiated thyroid cancer (DTC). Methods: A prospective cohort study was conducted, and a total of 120 DTC patients were selected. The patients were divided into two groups: a control group receiving standard postoperative treatment (n = 60) and a cinobufacini group receiving cinobufacini capsules in addition to standard treatment (n = 60). Various assessments were conducted, including pain evaluation, lymphocyte subset measurement, as well as the quantification of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), free sulfhydryl (-SH) levels, and lipid hydroperoxides (LOOH) in serum. Results: Both groups experienced reduced pain levels after one month of treatment, with the cinobufacini group demonstrating a more significant reduction. In comparison to the control group, one month of cinobufacini treatment resulted in substantial increases in NK cell activity, percentages of NK cells, activated NK cells, and CD8+ T-cells. It also led to the mitigation of oxidative stress and inflammation response. Conclusions: These findings indicate that cinobufacini may serve as an adjunctive therapy for DTC patients, offering benefits in pain management, immune modulation, and reducing inflammation and oxidative stress after surgery.

Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants.

Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the chemical compounds, there is little research about the functions of other contents in medicinal plants. Extracellular vesicles (EVs) are functionally active, nanoscale, membrane-bound vesicles secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular vesicles (PDEVs) also have been implicated to play an important role in therapeutic application. PDEVs were reported to have physical and chemical properties similar to mammalian EVs, which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. Besides these properties, PDEVs also exhibit unique advantages, especially intrinsic bioactivity, high stability, and easy absorption. PDEVs were found to be transferred into recipient cells and significantly affect their biological process involved in many diseases, such as inflammation and tumors. PDEVs also could offer unique morphological and compositional characteristics as natural nanocarriers by innately shuttling bioactive lipids, RNA, proteins, and other pharmacologically active substances. In addition, PDEVs could effectively encapsulate hydrophobic and hydrophilic chemicals, remain stable, and cross stringent biological barriers. Thus, this study focuses on the pharmacological action and mechanisms of PDEVs in therapeutic applications. We also systemically deal with facets of PDEVs, ranging from their isolation to composition, biological functions, and biotherapeutic roles. Efforts are also made to elucidate recent advances in re-engineering PDEVs applied as stable, effective, and non-immunogenic therapeutic applications to meet the ever-stringent demands. Considering its unique advantages, these studies not only provide relevant scientific evidence on therapeutic applications but could also replenish and inherit precious cultural heritage.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.