New eremophilane-type sesquiterpenes from Synotis solidaginea.

Eleven new highly oxygenated eremophilane-type sesquiterpenoids were isolated from the whole plant of Synotis solidaginea, including two pairs of C-8 S/R epimers. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configurations of 1 and 9 were confirmed by single-crystal X-ray crystallography using Cu Kα radiation. All the isolates were tested for the inhibition of LPS-stimulated NO production in macrophage-like mouse monocytic leukemia RAW264.7 cells. Compound 1 exhibited weak inhibitory effects with an IC50 of 71.2 µM.

The Active Ingredient Catalpol in Rehmannia glutinosa Reduces Blood Glucose in Diabetic Rats via the AMPK Pathway.

Background: Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic. Methods: The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed. Results: Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL. Conclusion: As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.

Does an antihypertensive diet cost more? Analysis from the Chinese Heart-Healthy diet trial.

OBJECTIVE: To determine whether the Chinese heart-healthy diet (Sichuan cuisine version) (CHH diet-SC) was more expensive than the conventional Sichuan diet and explore the food groups and nutrients that mainly affected the cost of CHH diet-SC. DESIGN: Cost analysis of 4-week intervention diets in the Sichuan center representing southwestern China in the CHH diet study. SETTING: A multicentre, parallel-group, single-blind, randomised feeding trial evaluating the efficacy of lowering blood pressure with the cuisine-based CHH diet. PARTICIPANTS: Totally, fifty-three participants with hypertension aged 25-75 years in the Sichuan center were randomised into the control group (n 26) or the CHH diet-SC group (n 27). RESULTS: The CHH diet-SC was more expensive than the control diet (¥27·87 ± 2·41 v. ¥25·18 ± 2·79 equals $3·90 ± 0·34 v. $3·52 ± 0·39, P < 0·001), and the incremental cost-effectiveness ratio for a 1-mm Hg systolic blood pressure reduction was ¥9·12 ($1·28). Intakes and the cost of seafood, dairy products, fruits, soybeans and nuts, whole grains and mixed beans were higher for the CHH diet-SC than for the control diet (P < 0·001). Intakes of vitamin B1, vitamin B6, vitamin C, Mg and phosphorus were positively correlated with the cost (P < 0·05). CONCLUSIONS: The CHH diet-SC costs more than the conventional Sichuan diet, partly due to the high cost of specific food groups. Positive correlations between the intakes of vitamin B1, vitamin B6, vitamin C, Mg, phosphorus and the dietary cost could be a direction to adjust the composition within the food groups to reduce the cost of the CHH diet-SC.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

Transcriptomic profiling and the first spatial expression analysis of candidate genes in the salivary gland of the East Asian medicinal leech, Hirudo nipponia.

Hirudo nipponia, a blood-sucking leech native to East Asia, possesses a rich repertoire of active ingredients in its saliva, showcasing significant medical potential due to its anticoagulant, anti-inflammatory, and antibacterial effects against human diseases. Despite previous studies on the transcriptomic and proteomic characteristics of leech saliva, which have identified medicinal compounds, our knowledge of tissue-specific transcriptomes and their spatial expression patterns remains incomplete. In this study, we conducted an extensive transcriptomic profiling of the salivary gland tissue in H. nipponia based on de novo assemblies of tissue-specific transcriptomes from the salivary gland, teeth, and general head region. Through gene ontology (GO) analysis and hierarchical clustering, we discovered a novel set of anti-coagulant factors-i.e., Hni-Antistasin, Hni-Ghilanten, Hni-Bdellin, Hni-Hirudin-as well as a previously unrecognized immune-related gene, Hni-GLIPR1 and uncharacterized salivary gland specific transcripts. By employing in situ hybridization, we provided the first visualization of gene expression sites within the salivary gland of H. nipponia. Our findings expand on our understanding of transcripts specifically expressed in the salivary gland of blood-sucking leeches, offering valuable resources for the exploration of previously unidentified substances with medicinal applications.

Enhancement of volatile fatty acids production through anaerobic co-digestion of navel orange residue and waste activated sludge: Effect of pre-treatment and substrate proportions.

In this study, the co-digestion system with Navel orange residues (NOR) and Waste activated sludge (WAS) was established, by pre-treating the NOR and setting different volatile solids (VS) ratios of NOR to WAS to motivate the production of volatile fatty acids (VFA). The pre-treatment method (pH 7 and temperature 70 °C) promoted the release of dissolved organic matter, and the concentration of soluble chemical oxygen demand (SCOD) increased by 45.56% compared with the untreated group (pH 3 and temperature 20 °C). In the co-digestion system, the highest VFA yield (5716.69 mg/L) was obtained at VS ratio of 2. When the VS ratio was increased to 4, the imbalance in proportions of carbon and nitrogen affected VFA production, and the high concentration of essential oils (EO) present in the NOR inhibited the methane production; the cumulative yield of methane gas decreased by 24.10% compared with the yield obtained when the VS ratio was 2. Analysis of microbial community revealed that an increase in the number of VFA-producing microbial populations and the abundance of Methanobacteria resulted in the accumulation of acetic acid. This study demonstrated that co-digestion of NOR with WAS improve VFA production, thus realizing the utilization of solid wastes and reducing environmental pollution.

Dual Stimuli-Responsive Micelles for Imaging-Guided Mitochondrion-Targeted Photothermal/Photodynamic/Chemo Combination Therapy-Induced Immunogenic Cell Death.

Introduction: As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies. Methods: In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core. Results: In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities. Conclusion: In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.

The therapeutic effect of wasp venom (Vespa magnifica, Smith) and its effective part on rheumatoid arthritis fibroblast-like synoviocytes through modulating inflammation, redox homeostasis and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is related to the aberrant proliferation of fibroblast-like synoviocytes (FLS). Wasp venom (WV, Vespa magnifica, Smith), an insect secretion, has been used to treat RA in Chinese Jingpo national minority's ancient prescription. However, the potential mechanisms haven't been clarified. AIM OF THE STUDY: The purposes of this paper were two-fold. First, to investigate which was the best anti-RA effective part of WV-I (molecular weight less than 3 kDa), WV-II (molecular weight 3-10 kDa) and WV-III (molecular weight more than 10 kDa) that were separated from WV. Second, to explore the underlying molecular mechanism of WV and WV-II that was best effective part in RA. MATERIALS AND METHODS: The wasps were electrically stimulated and the secretions were collected. WV-I, WV-II and WV-III were acquired by ultracentrifuge method according to molecular weight. Next, WV, WV-I, WV-II and WV-III were identified by HPLC. Functional annotation and pathway analysis of WV used to bioinformatics analysis. RNA-seq analyses were constructed to identify differentially expressed genes (DEGs). GO and KEGG pathway analyses were performed by Metascape database. STRING was used to analyze the PPI network from DEGs. Next, PPI network was visualized using Cytoscape that based on MCODE. The pivotal genes of PPI network and MCODE analysis were verified by qRT-PCR. Subsequently, MH7A cells were performed by MTT assay to evaluate the ability of inhibiting cell proliferation. Luciferase activity assay was conducted in HepG2/STAT1 or HepG2/STAT3 cells to assess STAT1/3 sensitivity of WV, WV-I, WV-II and WV-III. Additionally, interleukin (IL)-1ß and IL-6 expression levels were detected by ELISA kits. Intracellular thioredoxin reductase (TrxR) enzyme was evaluated by TrxR activity assay kit. ROS levels, lipid ROS levels and Mitochondrial membrane potential (MMP) were assessed by fluorescence probe. Cell apoptosis and MMP were measured by using flow cytometry. Furthermore, the key proteins of JAK/STAT signaling pathway, protein levels of TrxR and glutathione peroxidase 4 axis (GPX4) were examined by Western blotting assay. RESULTS: RNA-sequencing analysis of WV displayed be related to oxidation-reduction, inflammation and apoptosis. The data displayed that WV, WV-II and WV-III inhibited significantly cells proliferation in human MH7A cell line compared to WV-I treatment group, but WV-III had no significant suppressive effect on luciferase activity of STAT3 compared with IL-6-induced group. Combined with earlier reports that WV-III contained major allergens, we selected WV and WV-II further to study the mechanism of anti-RA. In addition, WV and WV-II decreased the level of IL-1ß and IL-6 in TNF-α-induced MH7A cells via inactivating of JAK/STAT signaling pathway. On the other hand, WV and WV-II down-regulated the TrxR activity to produce ROS and induce cell apoptosis. Furthermore, WV and WV-II could accumulate lipid ROS to induce GPX4-mediated ferroptosis. CONCLUSIONS: Taken together, the experimental results revealed that WV and WV-II were potential therapeutic agents for RA through modulating JAK/STAT signaling pathways, redox homeostasis and ferroptosis in MH7A cells. Of note, WV-II was an effective part and the predominant active monomer in WV-II will be further explored in the future.

Rapid recognition and targeted isolation of potential anti-breast cancer xanthones in Hypericum bellum Li by "seed" mass spectra-based molecular networking and in silico MS/MS fragmentation.

INSTRUCTION: Hypericum bellum Li is rich in xanthones with various bioactivities, especially in anti-breast cancer. While the scarcity of mass spectral data of xanthones in Global Natural Products Social Molecular Networking (GNPS) libraries have challenged the rapid recognition of xanthones with similar structures. OBJECTIVE: This study is aimed to enhance the molecular networking (MN)-based dereplication and visualisation ability of potential anti-breast cancer xanthones from H. bellum to overcome the scarcity of xanthones mass spectral data in GNPS libraries. Separating and purifying the MN-screening bioactive xanthones to verify the practicality and accuracy of this rapid recognition strategy. METHODOLOGY: A combined strategy of "seed" mass spectra-based MN, in silico annotation tools, substructure identification tools, reverse molecular docking, ADMET screening, molecular dynamics (MDs) simulation experiments, and an MN-oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti-breast cancer xanthones in H. bellum. RESULTS: A total of 41 xanthones could only be tentatively identified. Among them, eight xanthones were screened to have potential anti-breast cancer activities, and six xanthones that were initially reported in H. bellum were obtained and verified to have good binding abilities with their paired targets. CONCLUSION: This is a successful case study that validated the application of "seed" mass spectral data could overcome the drawbacks of GNPS libraries with limited mass spectra and enhance the accuracy and visualisation of natural products (NPs) dereplication, and this rapid recognition and targeted isolation strategy can be also applicable for other types of NPs.

Effect of Tiaoshen Changzhi acupuncture on behavior and striatum ΔFosB in rats with levodopa-induced dyskinesias.

This study aims to study the effffects of Tiaoshen Changzhi acupuncture on behavior and striatum ΔFosB in rats with Levodopa-induced Dyskinesias (LIDs). In this experimental study, Levodopa-induced Dyskinesia (LID) rat models were established by 6-OHDA double-target injection and randomly assigned to six groups, with ten rats in each group. The rats were subjected to difffferent interventions for 28 days, and their behavior was observed. Additionally, the content of ΔFosB, a marker of neuronal activation, in the rat striatum was detected by immunohistochemistry and qRT-PCR. In contrallateral rotation behavior experiment and AIM experiment, the score of the model group was significantly increased, compared with the model group, the score of the Western medicine group, the ordinary acupuncture group and the Tiaoshen Changzhi group was significantly decreased (P < 0.01), the score of the Western medicine group and the Tiaoshen Changzhi group was significantly lower than the ordinary acupuncture group (P < 0.01), there was no statistical significance between the Western medicine group and the Tiaoshen Changzhi group (P>0.05). In the left forelimb function test, the score of the model group was significantly decreased, and compared with the model group, the left forelimb function score of the Western medicine group, the ordinary acupuncture group and the Tiaoshen Changzhi group were significantly increased (P < 0.01). The left forelimb function score of the Western medicine group and the Tiaoshen Changzhi group was higher than the ordinary acupuncture group (P < 0.05, P < 0.01). There was no statistical significance between Western medicine group and Tiaoshen Changzhi group (P > 0.05). After treatment, the content of ΔFosB in the striatum of the Western medicine group, the ordinary acupuncture group and the Tiaoshen Changzhi acupuncture group all decreased, the Western medicine group was better than the ordinary acupuncture group (P < 0.01), and the Tiaoshen Changzhi acupuncture group was better than the ordinary acupuncture group (P < 0.05). Tiaoshen Changzhi acupuncture can improve the behavioral performance of LID rats, reduce abnormal involuntary movement and contralateral rotation behavior and enhance the motor function of the left forelimb of rats. One of its therapeutic mechanisms for LID may be to reduce the expression level of ΔFosB in the striatum of LID rats, thereby reducing the symptoms of LID rats.

Danggui Buxue decoction ameliorates mitochondrial biogenesis and cognitive deficits through upregulating histone H4 lysine 12 acetylation in APP/PS1 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Buxue decoction (DBD) is a classic herbal decoction consisting of Astragali Radix (AR) and Angelica Sinensis Radix (ASR) with a 5:1 wt ratio, which can supplement 'blood' and 'qi' (vital energy) for the treatment of clinical diseases. According to Traditional Chinese Medicine (TCM) theory, dementia is induced by Blood deficiency and Qi weakness, which causes a decline in cognition. However, the underlying mechanisms of DBD improving cognition deficits in neurodegenerative disease are no clear. AIM OF THE STUDY: This study aims at revealing the underlying mechanisms of DBD plays a protective role in the cognitive deficits and pathology process of Alzheimer's disease (AD). MATERIALS AND METHODS: The APP/PS1 (Mo/HuAPP695swe/PS1-dE9) double transgenic mice were adopted as an experimental model of AD. Qualitative and quantitative analysis of 3 compounds in DBT was analyzed by HPLC. Morris water maze test, Golgi staining and electrophysiology assays were used to evaluate the effects of DBD on cognitive function and synaptic plasticity in APP/PS1 mice. Western blot, immunofluorescence and Thioflavin S staining were used for the pathological evaluation of AD. Monitoring the level of ATP, mitochondrial membrane potential, SOD and MDA to evaluate the mitochondrial function, and with the usage of qPCR and CHIP for the changes of histone post-translational modification. RESULTS: In the current study, we found that DBD could effectively attenuate memory impairments and enhance long-term potentiation (LTP) with concurrent increased expression of memory-associated proteins. DBD markedly decreased Aß accumulation in APP/PS1 mice by decreasing the phosphorylation of APP at the Thr668 level but not APP, PS1 or BACE1. Further studies demonstrated that DBD restored mitochondrial biogenesis deficits and mitochondrial dysfunction. Finally, the restored mitochondrial biogenesis and cognitive deficits are under HADC2-mediated histone H4 lysine 12 (H4K12) acetylation at the peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) and N-methyl-D-aspartate receptor type 2B (GluN2B) promoters. CONCLUSIONS: These findings reveal that DBD could ameliorate mitochondrial biogenesis and cognitive deficits by improving H4K12 acetylation. DBD might be a promising complementary drug candidate for AD treatment.

Imagined object files: Visual imagery produces partial repetition costs where perception does not.

The present study explored whether object (or event) files can be formed that integrate color imagery and perceptual location features. To assess this issue, a cue-target procedure was used whereby color imagery was cued to be generated at a particular location in space, which was then followed by a perceptual color discrimination task. Partial repetition costs (PRCs) were then measured by varying the overlap of the color and location features of the cue and target to evaluate whether an object/event file was formed. Robust PRCs were observed when imagery was generated at a location, supporting the idea that imagery and perception can be incorporated into a common event file. It was also revealed that the PRC effects for perceptual color cues were tenuous-they did not reach significance in the present study. Overall, the present study indicates that imagery can produce stronger binding effects than perception, offering important insights into the role that active engagement plays in the formation of object/event files.

Ultrasound-Based Risk Stratification System for the Assessment of Partially Cystic Thyroid Nodules.

OBJECTIVE: To develop and validate a risk stratification system for the prediction of malignancy in partially cystic thyroid nodules (PCTNs). METHODS: We retrospectively reviewed the sonography data of patients with PCTNs from 2 medical centers-Hangzhou Traditional Chinese Medicine Hospital and Hangzhou First People's Hospital-from January 2020 to December 2021. The independent risk factors for malignant PCTNs were evaluated using the univariate and multivariate logistic regression analyses. The nomogram prediction efficiency was assessed using the area under the curve and calibration curves. The decision curve analysis was used to determine the clinical value of the predictive model. RESULTS: A total of 285 patients were enrolled in this retrospective study, and of 301 PCTNs, 242 were benign and 59 were malignant. Younger age, hypoechoic, irregular margin, and microcalcifications were found to be the independent risk factors for malignant PCTNs. The area under the curve, sensitivity, and specificity were 0.860, 77.1%, and 84.7% in the training data set and 0.897, 91.7%, and 87.0% in the external validation data set, respectively. The total point of nomogram was >161, which showed the best to predict malignancy in PCTNs. CONCLUSION: Our findings demonstrated that the risk stratification system for the assessment of PCTNs showed good prediction capacities.

[Effect of electroacupuncture at "Zusanli" (ST36) and "Tianshu" (ST25) on intestinal function and autonomic nerve balance in rats with irritable bowel syndrome].

OBJECTIVE: To study whether electroacupuncture (EA) of "Zusanli" (ST36) combined with "Tianshu" (ST25) has a synergistic effect in regulating the colonic function and autonomic nerve balance in rats with irritable bowel syndrome (IBS). METHODS: Male Wistar rats were randomly divided into control, model, EA-ST36, and EA-ST36+ST25 groups, with 14 rats in each group. The IBS model was established by using water avoidance stress method. The visceral hypersensitivity was measured using the abdominal wall retraction reflex (AWR). The rectus abdominis electromyogram (EMG), intestinal electrical activity, and electrocardiogram (ECG) were recorded using a PowerLab data acquisition and analysis system. The contents of serum cAMP and cGMP were determined by ELISA, the expression levels of colonic tyrosine hydroxylase (TH) and choline acetyl-transferase (ChAT) proteins were determined by immunofluorescence staining and Western blot, respectively. RESULTS: Compared with the control group, the model group had an evident increase in the levels of AWR, LF, LF/HF, ChAT protein expression, cAMP and cGMP contents and cAMP/cGMP ratio (P<0.001, P<0.05), and a marked decrease in the levels of HF, frequency of slow waves of intestinal EMG, visceral pain threshold (PT), immunoactivity and expression of TH protein (P<0.05, P<0.001). In contrast to the model group, the levels of AWR, LF, LF/HF, ChAT protein expression and immunoactivity, cAMP and cGMP contents and ratio of cAMP/cGMP were significantly reduced (P<0.001, P<0.05, P<0.01), whereas the levels of frequency of slow waves of intestinal EMG, PT, and the immunoactivity and expression of TH were considerably increased (P<0.001, P<0.05) in both EA-ST36 and EA-ST36+ST25 groups. CONCLUSION: EA of both ST36 and ST36+ST25 can relieve visceral pain, and reduce sympathetic activity to improve autonomic nerve balance, but without apparent synergistic effect between EA-ST36 and EA-ST25 in rats with IBS.

Sodium houttuyfonate against cardiac fibrosis attenuates isoproterenol-induced heart failure by binding to MMP2 and p38.

BACKGROUND: Heart failure (HF), caused by stress cardiomyopathy, is a major cause of mortality. Cardiac fibrosis is an essential structural remodeling associated with HF; therefore, preventing cardiac fibrosis is crucial to decelerating the progression of HF. Sodium houttuyfonate (SH), an extract of Houttuynia cordata, has a potent therapeutic effect on hypoxic cardiomyocytes in a myocardial infarction model. PURPOSE: To investigate the preventative and therapeutic effects of SH during isoproterenol (ISO)-induced HF and explore the pharmacological mechanism of SH in alleviating HF. METHODS: We analyzed the overlapping target genes between SH and cardiac fibrosis or HF using a network pharmacology analytical method. We verified the suppressive effect of SH on ISO-induced proliferation and activation of cardiac fibroblasts by immunohistochemical staining and histological analysis in an isoproterenol-induced HF mouse model. Additionally, we investigated the effect of SH by evaluating fibrosis and cardiac remodeling markers. To further decipher the pharmacological mechanism of SH against cardiac fibrosis and HF, we performed a molecular docking analysis between SH and hub common target genes. RESULTS: There were 20 overlapping target genes between SH and cardiac fibrosis and 32 overlapping target genes between SH and HF. The 16 common target genes of SH against cardiac fibrosis and HF included MMP2 (matrix metalloproteinase 2), and p38. SH significantly inhibited the ISO- or TGF-ß-induced expression of Col1α (collagen 1), α-SMA (smooth muscle actin), MMP2, TIMP2 (tissue inhibitor of metalloproteinase 2), TGF-ß (transforming growth factor), and Smad2 phosphorylation. Moreover, both ISO- and TGF-ß-induced p38 phosphorylation was inhibited. Molecular docking analysis showed that SH forms a stable complex with MMP2 and p38. CONCLUSIONS: In addition to protecting cardiomyocytes, SH directly inhibits cardiac fibroblast activation and proliferation by binding to MMP2 and p38, subsequently delaying cardiac fibrosis and HF progression. Our prevention- and intervention-based approaches in this study showed that SH inhibited the development of stress cardiomyopathy-mediated cardiac fibrosis and HF when SH was administered before or after the initiation of cardiac stress.

Effects of fermented broccoli stem and leaf residue on growth performance, serum characteristics and meat quality of growing pigs.

The aim of this study was to evaluate the effects of fermented broccoli stem and leaf residue (FBR) on the growth performance, serum biochemical characteristics, and meat quality of growing pigs. A total of 72 growing pigs (Durox × Landrace × Yorkshire) were subjected to three dietary treatments with different levels (0%, 5% and 10%) of FBR with three replicates for an experimental period of 70 day. The average daily feed intake of growing pigs was higher (p < 0.05) in the 5% FBR treatment compared with the control group (0% FBR). The serum urea nitrogen content in growing pigs was lower (p < 0.05) in the 5% and 10% FBR treatments. The lightness value was higher (p < 0.05) in the longissimus dorsi muscle of pigs fed 5% and 10% FBR diets compared with the control group, and the yellowness value was increased in pigs fed the 10% FBR diet compared with pigs fed the control diet. Overall, the beneficial effects of FBR supplementation on serum biochemical parameters, and meat colour without undermining the growth performance indicate that up to 10% FBR could be used in diets to enhance the production of growing pigs.

Association between Oral Chinese Herbal Medicine and Recurrence and Metastasis in Patients with Stages II and III Colorectal Cancer: A Cohort Study in China.

Background: To evaluate the associations between long-term oral Chinese herbal medicines (CHMs) and recurrence and metastasis (R&M) in patients with stage II and III colorectal cancer (CRC). Furthermore, we aimed to determine the correlation between different syndrome patterns and prognosis and summarized the regularities among CHMs prescriptions, providing reference for clinical practice. Methods: An ambispective cohort study was conducted. All CRC patients who sought evaluation and treatment at Xiyuan Hospital and Beijing Cancer Hospital from August 2014 to August 2016 were included. In this study, "whether patients voluntarily take CHMs" was taken as the exposure factor, and the exposure degree was "the duration of CHM use." Stratification was performed according to the duration of TCM use to determine the relationship with R&M of CRC. The primary outcome was disease-free survival. Patients who had R&M of CRC after taking CHMs for ≥6 months were defined as "worst patients." R software was used for statistical analysis. The Kaplan-Meier method and Cox regression analysis were used to determine the prognosis. IBM SPSS was used to model a priori association rules; drug use rules were analyzed on this basis. Results: A total of 186 patients with stage II and III CRC after radical resection were enrolled. All patients reached the study endpoint by August 2021. The difference in disease-free survival between the two groups was most significant when the cutoff value for CHMs was 18 months (P = 0.0012). Multivariate analysis showed that 18 CHMs were independent protective factors for R&M of CRC (P = 0.001, HR = 0.20, 95% CI = 0.08-0.53). The ratio of Pi (spleen) and Shen (kidney) deficiency in the worst cases was higher than patients without R&M (P = 0.018). Sijunzi and Liuwei Dihuang decoctions were the most frequently used prescriptions in the anti-R&M phase. Conclusion: CHMs complying with the "Jianpi Bushen" principle may attenuate the risk of R&M in patients with stage II and III CRC. Pi (spleen) and Shen (kidney) deficiency in patients receiving TCM intervention for the first time within 6 months of radical resection may be associated with a higher CRC R&M rate. Further research is warranted to validate these findings and elucidate underlying biological mechanisms.

Analysis of the Relationship between Nutritional Status and Bone Age and Sexual Development in Children and Adolescents.

Purpose: To observe the correlation between nutritional status, bone age, and sexual development in children and adolescents. Methods: 895 children and adolescents who underwent physical examination in the growth and development clinic and height clinic of our hospital from 2019 to 2021 were selected as the research objects. The subjects were divided into emaciation group, normal group, overweight group, and obesity group. The bone age level, bone age assessment, sexual development, and early maturity rate of each group were compared. Results: The bone age difference (BAD) of the overweight and obesity groups was higher than that of the normal group, and the BAD of the obesity group was higher than that of the emaciation group (P < 0.05). Compared with the normal group, the risk of advancement of bone age in the overweight group increased by 2.674 times (male) and 1.908 times (female), the risk of advancement of bone age in the obesity group increased by 6.376 times (male) and 14.687 times (female), the risk of retardation of bone age in the emaciation group increased by 2.150 times (male) and 3.092 times (female). Whether it was male or female, the sexual development of overweight and obese was higher than that of the normal weight group in the same age group. Among female children, the sexual precocious puberty rate of the overweight + obesity group is higher. Conclusion: The nutritional status of children and adolescents is closely related to their bone age and sexual development.

Global analysis of qualitative and quantitative metabolism of Notoginsenoside R1 in rat liver-brain-gut axis based on LC-IT-TOF/MS combing mMDF strategy.

BACKGROUND: The metabolism study of active components for traditional Chinese medicine (TCM) in target organs is conducive to clarify the authentic active ingredients. Notoginsenoside R1 (NG-R1), one of the bioactive components of Panax notoginsenoside (PNS), is commonly acknowledged as the characteristic marker of PNS. However, the metabolism of NG-R1 in target organs has not been clarified yet due to the lack of robust technique and approach. PURPOSE: The present study aimed to develop a reliable and efficient strategy and technology for revealing the qualitative and quantitative metabolism of active components of TCMs in target organs, and to clarify the biotransformation of NG-R1 in liver-brain-intestinal axis. METHODS: The metabolic transformation of NG-R1 in the brain gut axis was investigated in the in vitro incubation system of fresh rat brain, liver homogenate, and intestinal flora. To quickly lock the target metabolites, we set the mass defect filter (MDF) in different ranges to screen metabolites with different molecular weight (MW). This strategy was defined as multi-stage MDF (mMDF). In addition, we performed relative quantitative analysis on all metabolites according to the peak area acquired by LC-IT-TOF/MS to overcome the challenge that metabolites are difficult to be quantified due to the lack of standards. RESULTS: When MDF was set at 0.50 to 0.65 to screen metabolites with MW of 900 to 1200 Da, 6 novel metabolites were quickly found, and then identified as glucuronic acid binding, oxidation, dehydrogenation, methylation and hydrogenation products according to their LC and MS characteristics. When setting MDF at 0.42 - 0.52, 6 metabolites with MW of 600 to 900 Da were effectively screened and identified as Rg1, NG-R2, Rh1, Rg1+CH2+2H and Rg1+CH2. To screen the metabolites with MW of 300 to 600 Da, MDF was set at 0.25 - 0.42, and 4 novel metabolites were screened rapidly. The results of quantitative metabolism suggested that intestinal flora was the main metabolic site of NG-R1 in rat, and more than 60% of NG-R1 was converted to Rg1 by deglycosylation in the intestinal flora. CONCLUSION: The mMDF strategy can significantly improve the research efficiency of qualitative metabolism of saponins. Although NG-R1 could be transformed into a variety of metabolites in rat liver and brain homogenate, it still existed mainly in prototype form. In the rat flora, NG-R1 mainly existed in the form of deglycosylated metabolite Rg1.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis.

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.