Mechanism analysis of Buyang Huanwu decoction in treating atherosclerosis based on network pharmacology and in vitro experiments.

Atherosclerosis (AS) is one of the main risk factors of ischemic cardiovascular and cerebrovascular diseases. Buyang Huanwu decoction (BYHWT) is a classic Chinese medicine prescription that is used for treating AS. However, the underlying pharmacological mechanism remains unclear. This study aims to clarify the molecular mechanism of BYHWT in treatment of AS through network pharmacology and in vitro experiments. Molecular structure information and targets of core components of BYHWT were obtained from PubChem and UniProtKB databases. Genes involved in AS were obtained from DisGeNet, GeneCards and OMIM databases. The core targets of BYHWT in AS treatment were identified by protein-protein interaction (PPI) network analysis with STRING platform, and analyzed by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the core targets and the bioactive ingredients. HUVEC viability, inflammatory response and mRNA expression levels of core target genes were evaluated by cell counting kit 8 assay, enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. A total of 60 candidate compounds and 325 predicted target genes were screened. PPI network analysis suggested that TP53, SRC, STAT3, and AKT1 may be the core targets. BYHWT in AS treatment was associated with 46 signaling pathways. GA120, baicalein, and 3,9-di-o-methylnissolin had good binding affinity with core target proteins. Baicalein treatment could significantly promoted the viability and repress the inflammatory response of HUVEC cells stimulated by ox-LDL. In addition, Baicalein can regulate the expression of core targets including AKT1, MAPK1, PIK3CA, JUN, TP53, SRC, EGFR, and ESR1. In conclusion, BYHWT and its main bioactive component baicalein, inhibit inflammatory response and modulate multiple downstream genes of endothelial cells, and show good potential to block the progression of AS and cardiovascular/cerebrovascular diseases.

Baiheqingjin formula reduces inflammation in mice with asthma by inhibiting the PI3K/AKT/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baiheqingjin Decoction (BHQJ), which consists of 7 traditional Chinese herbs including Baibu (Stemona tuberosa Lour.), Hezi (Terminalia chebula Retz.), Mahuang (Ephedra sinica Stapf.), Ziwan (Aster tataricus L. f.), Dilong (Pheretima), Sangbaipi (Morus alba L.), and Xianhecao (Agrimonia pilosa Ledeb.). BHQJ is commonly used for treating cough asthma, and variant cough-variant asthma as it, is effective in improving asthma symptoms and reducing airway inflammation. AIM OF THE STUDY: To investigate the mechanisms of BHQJ in treating allergic asthma. MATERIALS AND METHODS: We collected information about the components and targets of 6 Chinese medicines (excluding Pheretima) from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Additionally, we obtained genes associated with asthma from six disease databases. To create a protein-protein interaction network, we conducted an intersection analysis using differentially expressed genes derived from RNA transcriptome data. Subsequently, we carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To validate the findings from network pharmacology and transcriptomics, we established an allergic asthma mouse model induced by ovalbumin and conducted in vivo experiments. RESULTS: Using network pharmacology and transcriptomics analyses, we identified the pathways including the PI3K/AKT signaling pathway, and NF-κB signaling pathway. Among these, the involvement of the PI3K/AKT/NF-κB signaling pathway in various pathological processes of asthma, such as airway inflammation, smooth muscle contraction, and excessive mucus production, are well-documented. Histopathological examinations indicated that BHQJ had the potential to mitigate inflammatory cell infiltration and the excessive growth of goblet cells in the airways of asthmatic mice, consequently reducing mucus secretion. Results from Western blot demonstrated that BHQJ could inhibit the activation of the PI3K/AKT/NF-κB pathway at the protein levels. Enzyme-linked immunosorbent assay findings revealed that BHQJ could reduce the production of typical "type 2 asthma" cytokines and immunoglobulin (Ig) E in the blood. These discoveries imply that BHQJ has the potential to reduce the release of inflammatory cytokines and suppress the overactivation of the PI3K/AKT/NF-κB signaling pathway, thus offering a therapeutic approach for asthma. CONCLUSION: Our research offers initial insights into the fundamental mechanisms through which BHQJ treats asthma. This study reveals the potential mechanism of BHQJ in treating asthma, particularly its role in reducing inflammatory cytokines, mucus production, and cell infiltration, as well as inhibiting the expression of PI3K/AKT/P65 phosphorylated protein. These findings indicate the potential of BHQJ in treating asthma. In summary, our study provides preliminary insights into the asthma treatment mechanism of BHQJ and provides guidance for future research.

Electroacupuncture ameliorates hepatic defects in a rat model of polycystic ovary syndrome induced by letrozole and a high-fat diet.

BACKGROUND: This study was designed to evaluate the effects of low-frequency electroacupuncture (EA) on glucose and lipid disturbances in a rat model of polycystic ovary syndrome (PCOS) characterized by insulin resistance (IR) and hepatic steatosis. METHODS: The PCOS rat model was induced by continuous administration of letrozole (LET) combined with a high-fat diet (HFD). Female Sprague-Dawley rats were divided into the following four groups: control, control + EA, LET + HFD and LET + HFD + EA. EA was administered five or six times a week with a maximum of 20 treatment sessions. Body weight, estrous cyclicity, hormonal status, glucose and insulin tolerance, lipid profiles, liver inflammation factors, liver morphology and changes in the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway were evaluated. RESULTS: The rat model presented anovulatory cycles, increased body weight, elevated testosterone, abnormal glucose and lipid metabolism, IR, liver inflammation, hepatic steatosis and dysregulation of the insulin-mediated PI3-K/Akt signaling axis. EA reduced fasting blood glucose, fasting insulin, area under the curve for glucose, homeostasis model assessment of IR indices, triglycerides and free fatty acids, and alleviated hepatic steatosis. Furthermore, low-frequency EA downregulated mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6, upregulated mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α, increased protein expression of phosphorylated (p)-Akt (Ser473), p-glycogen synthase kinase (GSK) 3ß (Ser9) and glucose transporter 4 (GLUT4), increased the ratio of p-GSK3ß to GSK3ß and downregulated protein expression of GSK3ß. CONCLUSION: An obese PCOS rat model with IR and hepatic steatosis was successfully established by the combination of LET and HFD. EA improved dysfunctional glucose and lipid metabolism in this PCOS-IR rat model, and the molecular mechanism appeared to involve regulation of the expression of key molecules of the PI3-K/Akt insulin signaling pathway in the liver.

Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

[Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina].

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 µg·g~(-1)) was higher than that in GFA(0.03-10.41 µg·g~(-1)) and GS(0.04-13.66 µg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

Noninvasive Strategies for the Treatment of Tiny Liver Cancer: Integrating Photothermal Therapy and Multimodality Imaging EpCAM-Guided Nanoparticles.

Surgical resection and ablation therapy have been shown to achieve the purpose of a radical cure for liver cancer with a size of less than 3 cm; however, tiny liver cancer lesions of diameters smaller than 2 cm remain challenging to diagnose and cure due to the failure of the generation of new blood vessels within tumors. Emerging evidence has revealed that optical molecular imaging combined with nanoprobes can detect tiny cancer from the perspective of molecular and cellular levels and kill cancer cells by the photothermal effect of nanoparticles in real time, thereby achieving radical goals. In the present study, we designed and synthesized multicomponent and multifunctional ICG-CuS-Gd@BSA-EpCAM nanoparticles (NPs) with a potent antineoplastic effect on tiny liver cancer. Using subcutaneous and orthotopic liver cancer xenograft mouse models, we found that the components of the NPs, including ICG and CuS-Gd@BSA, showed synergistic photothermal effects on the eradication of tiny liver cancer. We also found that the ICG-CuS-Gd@BSA-EpCAM NPs exhibited triple-modal functions of fluorescence imaging, magnetic resonance imaging, and photoacoustic imaging, with targeted detection and photothermal treatment of tiny liver cancer under near-infrared light irradiation. Together, our study demonstrates that the ICG-CuS-Gd@BSA-EpCAM NPs in combination with optical imaging technique might be a potential approach for detecting and noninvasively and radically curing tiny liver cancer by the photothermal effect.

Romboutsia lituseburensis JCM1404 supplementation ameliorated endothelial function via gut microbiota modulation and lipid metabolisms alterations in obese rats.

Our previous study revealed moderate-intensity exercise improved endothelial function associated with decreasing Romboutsia in rats on a high-fat diet. However, whether Romboutsia influences endothelial function remains unclear. The aim of this study was to determine the effects of Romboutsia lituseburensis JCM1404 on the vascular endothelium of rats under standard diet (SD) or high-fat diet (HFD). Romboutsia lituseburensis JCM1404 had a better improvement effect on endothelial function under HFD groups, while no significant effect on small-intestinal and blood vessel morphology. HFD significantly decreased villus height of small intestine and increased outer diameter and media thickness of the vascular tissue. After the treatments by R. lituseburensis JCM1404, the expression of claudin5 was increased in the HFD groups. Romboutsia lituseburensis JCM1404 was found to increase alpha diversity in the SD groups, with an increase in beta diversity in the HFD groups. The relative abundance of Romboutsia and Clostridium_sensu_stricto_1 was decreased significantly in both diet groups after R. lituseburensis JCM1404 intervention. The functions of human diseases and endocrine and metabolic diseases significantly downregulated in the HFD groups by Tax4Fun analysis. Furthermore, we found Romboutsia was significantly associated with bile acids, triglycerides, amino acids and derivatives and organic acids and derivatives in the SD groups, while Romboutsia was significantly associated with triglycerides and free fatty acid in the HFD groups. Romboutsia lituseburensis JCM1404 significantly upregulated several metabolism-related pathways by KEGG analysis in the HFD groups, including glycerolipid metabolism, cholesterol metabolism, regulation of lipolysis in adipocytes, insulin resistance, fat digestion and absorption, thermogenesis. Overall, R. lituseburensis JCM1404 supplementation ameliorated endothelial function via gut microbiota modulation and lipid metabolisms alterations in obese rats.

Toxic metals and the risks of sludge from the treatment of wastewater from beryllium smelting.

The release of highly toxic beryllium in sludge (BCS) produced by physico-chemical treatment of beryllium-containing wastewater from Be smelting production has become a growing concern with the widespread use of Be in the defense industry. This work investigated the potential mobility of Be in BCS. The toxicity characteristic leaching procedure (TCLP) of BCS showed that the amount of leached Be was up to 202 mg L-1, which exceeded the regulated limit by nearly 10,000 times. The chemical fractionation analysis further revealed that the excessive amount of Be leached from BCS was contributed to the high content of acid-soluble fraction and reducible fraction of Be, which accounted for over 70% of the Be content. The results obtained from mineralogical automatic analyzer (MLA) showed that gypsum (23.23%) and epidote (19.55%) were the two major mineralogical phases of BCS. Both were small and loosely structured agglomerated particles with a D50 of 6.61 µm and 3.31 µm. ToF-SIMS results revealed that the Be distribution on the surface of BCS particles was relatively dispersed, with no aggregation or encapsulation. Be co-precipitated with gypsum and chlorite in the form of unstable Be(OH)2, which attached to the surface of these small particles. The unstable state of Be and the small size, loose structure and high liberation of the host material phases are the main reasons for the high leaching mobility of Be. The results of the risk assessment indicated that BCS posed an extremely high potential ecological risk, with Be being the most significant contributor.

[Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry].

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Structural characterization and anti-osteoporosis effects of polysaccharide purified from Eucommia ulmoides Oliver cortex based on its modulation on bone metabolism.

EuOCP3, with a molecular weight of 38.1 kDa, is an acidic polysaccharide purified from Eucommia ulmoides Oliver cortex. Herein, we determined that the main backbone of EuOCP3 was predominantly composed of →4)-α-GalpA-(1 â†’ 4)-α-GalpA-(1→, →4)-α-GalpA-(1 â†’ 5)-α-Araf-(1→, →4)-α-GalpA-(1 â†’ 2)-α-Rhap-(1→, and →4)-α-GalpA-(1 â†’ 5)-α-Araf-(1 â†’ 2)-α-Rhap-(1 â†’ repeating blocks, which were connected by →2,3,5)-α-Araf-(1→. The side chains, substituted at C-2 and C-5 of →2,3,5)-α-Araf-(1→, contained T-ß-Araf→ and T-ß-Araf â†’ 4)-α-GalpA-(1 â†’ residues. In dexamethasone (Dex)-induced osteoporosis (OP) mice, EuOCP3 treatment restored cortical bone thickness, increased mineralized bone area, enhanced the number of osteoblasts, and decreased the number of osteoclasts on the surface of cortical bone. Combining analysis of gut microflora, serum metabolite profiles, and biological detection results, we demonstrated that EuOCP3 regulated the abundance of specific species within the gut microflora, such as g_Dorea and g_Prevotella, and ameliorated oxidative stress. In turn, enhancement of osteogenic function and restoration of bone metabolism via the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway was indicated. The current findings contribute to understanding the potential of EuOCP3 in anti-OP treatment.

Qi Gong Wan ameliorates adipocyte hypertrophy and inflammation in adipose tissue in a PCOS mouse model through the Nrf2/HO-1/Cyp1b1 pathway: Integrating network pharmacology and experimental validation in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Initially recorded in Yifang Jijie (an ancient Chinese text), Qi Gong Wan (QGW) is used to treat obese women with infertility. QGW can help promote follicular development and maturation, regulate the balance of serum hormones between testosterone and estradiol, enhance endometrial receptivity, improve waist circumference, and ameliorate insulin resistance. It contains eight herbs: Pinellia ternata (Thunb.) Makino (Banxia), Citrus maxima (Burm.) (Juhong), Poria cocos (Schw.) Wolf. (Fuling), Atractylodes macrocephala Koidz (Baizhu), Cyperus rotundus L. (Xiangfu), Conioselinum anthriscoides 'Chuanxiong' (Chuanxiong), Massa Medicata Fermentata (Shenqu), and Glycyrrhiza uralensis Fisch. ex DC. (Gancao). However, the underlying mechanism of how QGW affects women with PCOS remains unclear. AIM OF THE STUDY: QGW has been widely used to treat PCOS patients with obesity clinically. This study was designed to identify its chemical and pharmacological properties. MATERIALS AND METHODS: Network pharmacology was used to predict the active compounds, potential targets, and pathways of QGW. Female C57BL/6J mice were injected with letrozole and fed a high-fat diet to establish a PCOS-insulin resistance (PCOS-IR) model. Body weight, estrous cycles, ovarian pathology, and serum insulin resistance were measured. qRT-PCR was used to examine the inflammation-related and steroid hormone biosynthesis-related mRNA expression in adipose tissue. Western blotting was used to determine the protein levels of Nrf2, HO-1, and Cyp1b1 in adipose tissue. Molecular docking was used to reveal the key chemical compounds of QGW. RESULTS: Network pharmacology revealed a total of 91 active ingredients in QGW that were associated with 167 targets. QGW could potentially treat PCOS-IR via nitrogen metabolism, steroid hormone biosynthesis, and ovarian steroidogenesis pathways. In the PCOS-IR mouse model, we found that QGW decreased the mean diameter of adipocytes and the total adipocyte area. Furthermore, QGW was found to significantly lower the expression of inflammation-related genes including Tnfɑ and C4a/b and the steroid hormone biosynthesis-related gene Cyp1b1. QGW showed a tendency to improve cystic follicles, fasting insulin, and HOMA-IR index in the PCOS-IR mouse model. Combining these findings with the results of KEGG analysis, we conclude that QGW promotes the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue under conditions of PCOS. Molecular docking revealed that rutin, nicotiflorin, and baicalein may be the key chemical compounds of QGW through which it improves adipocyte hypertrophy and inflammation. CONCLUSIONS: QGW improved adipocyte hypertrophy and inflammation in the PCOS-IR mouse model by activating the Nrf2/HO-1/Cyp1b1 pathway to protect adipose tissue. Our work thus provides a new research avenue for the study of traditional Chinese medicine in the treatment of PCOS.

Piperlongumine overcomes imatinib resistance by inducing proteasome inhibition in chronic myelogenous leukemia cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., an herbal medicine used in India and other Asian countries, is prescribed routinely for a range of diseases, including tumor. Piperlongumine, a natural product isolated from Piper longum L., has received widespread attention due to its various pharmacological activities, such as anti-inflammatory, antimicrobial, and antitumor effects. AIM OF THE STUDY: Chronic myelogenous leukemia (CML) is a hematopoietic disease caused by Bcr-Abl fusion gene, with an incidence of 15% in adult leukemias. Targeting Bcr-Abl by imatinib provides a successful treatment approach for CML. However, imatinib resistance is an inevitable issue for CML treatment. In particular, T315I mutant is the most stubborn of the Bcr-Abl point mutants associated with imatinib resistance. Therefore, it is urgent to find an alternative approach to conquer imatinib resistance. This study investigated the role of a natural product piperlongumine in overcoming imatinib resistance in CML. MATERIALS AND METHODS: Cell viability and apoptosis were evaluated by MTS assay and Annexin V/propidium iodide counterstaining assay, respectively. Levels of intracellular signaling proteins were assessed by Western blots. Mitochondrial membrane potential was reflected by the fluorescence intensity of rhodamine-123. The function of proteasome was detected using 20S proteasomal activity assay, proteasomal deubiquitinase activity assay, and deubiquitinase active-site-directed labeling. The antitumor effects of piperlongumine were assessed with mice xenografts. RESULTS: We demonstrate that (i) Piperlongumine inhibits proteasome function by targeting 20S proteasomal peptidases and 19S proteasomal deubiquitinases (USP14 and UCHL5) in Bcr-Abl-WT and Bcr-Abl-T315I CML cells; (ii) Piperlongumine inhibits the cell viability of CML cell lines and primary CML cells; (iii) Proteasome inhibition by piperlongumine leads to cell apoptosis and downregulation of Bcr-Abl; (iv) Piperlongumine suppresses the tumor growth of CML xenografts. CONCLUSIONS: These results support that blockade of proteasome activity by piperlongumine provides a new therapeutic strategy for treating imatinib-resistant CML.

Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina / 中国中药杂志

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 μg·g~(-1)) was higher than that in GFA(0.03-10.41 μg·g~(-1)) and GS(0.04-13.66 μg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

Corrigendum: Construction of a three-level enteral nutrition nursing system under the "Internet + medical" mode and an evaluation of its effect in clinical application.

[This corrects the article DOI: 10.3389/fpubh.2022.976276.].

Construction of a three-level enteral nutrition nursing system under the "Internet + medical" mode and an evaluation of its effect in clinical application.

Objective: This study aimed to explore the construction of a three-level enteral nutrition nursing system under the "Internet + medical" mode and the clinical application effect. Methods: A total of 40 nurses from four primary and secondary hospitals in Jiangxi Province and 100 patients treated with enteral nutrition between January 2020 and December 2021 were enrolled in this study. Patients in the control group received routine enteral nutrition nursing. In the study group, a three-level enteral nutrition nursing system was applied under the "Internet + medical" mode to train and guide the implementation of clinical enteral nutrition. The changes in nurses' cognition and behavior in enteral nutrition safety nursing, comprehensive core competence before and after training, and the effect of enteral nutrition nursing were compared between the two groups. Results: After 3 months of training, nurses' cognition and behavior scores in enteral nutrition safety nursing were higher than those before training (t = 11.780, P < 0.05), and nurses' core competence scores were higher than before training (P < 0.05). After 1 week of nursing, the nutritional risk screening 2002 (NRS2002) score decreased, and the levels of albumin and hemoglobin increased in both groups (P < 0.05). However, after 1 week of nursing, the NRS2002 score of the study group (2.89 ± 0.75) was lower than that of the control group (3.25 ± 0.82), and the levels of albumin (39.89 ± 3.21) and hemoglobin (119.57 ± 8.78) were higher in the study group than in the control group (albumin 36.25 ± 3.45, hemoglobin 113.66 ± 9.55) (P < 0.05). Conclusion: Three-level enteral nutrition nursing linkage assisted by the "Internet + medical" mode can improve the cognition and behavior of medical staff in enteral nutrition safety nursing, as well as the comprehensive core competence of nurses, achieving good clinical effects.

Novel mechanisms underlying inhibition of inflammation-induced angiogenesis by dexamethasone and gentamicin via PI3K/AKT/NF-κB/VEGF pathways in acute radiation proctitis.

Acute radiation proctitis (ARP) is one of the most common complications of pelvic radiotherapy attributed to radiation exposure. The mechanisms of ARP are related to inflammation, angiogenesis, and so on. In this study we evaluated the effect of dexamethasone (DXM) combined with gentamicin (GM) enema on ARP mice, and explored its possible mechanisms by transcriptome sequencing, western blot and immunohistochemistry. C57BL/6 mice were randomly divided into 3 groups: healthy control group, ARP model group, and DXM + GM enema treatment group. ARP mice were established by using a single 6 MV X-ray dose of 27 Gy pelvic local irradiation. Transcriptome sequencing results showed that 979 genes were co-upregulated and 445 genes were co-downregulated in ARP mice compared to healthy mice. According to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, we firstly found that PI3K/AKT/NF-κB/VEGF pathways were mostly correlated with the inflammation-induced angiogenesis in ARP mice. PI3K/AKT pathway leads to the activation of NF-κB, which promotes the transcription of VEGF and Bcl-2. Interestingly, symptoms and pathological changes of ARP mice were ameliorated by DXM + GM enema treatment. DXM + GM enema inhibited inflammation by downregulating NF-κB and upregulating AQP3, as well as inhibited angiogenesis by downregulating VEGF and AQP1 in ARP mice. Moreover, DXM + GM enema induced apoptosis by increasing Bax and suppressing Bcl-2. The novel mechanisms may be related to the downregulation of PI3K/AKT/NF-κB/VEGF pathways.

The efficacy and safety of Zengxiao Jiandu decoction combined with definitive concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a randomized, double-blind, placebo-controlled clinical trial.

Background: Traditional Chinese medicine (TCM) makes a synergistic and attenuative effect when combined with chemoradiotherapy. However, strong evidence-based studies are lacking. The study sought to investigate whether Zengxiao Jiandu decoction as an adjunctive therapy is superior to definitive concurrent chemoradiotherapy (DCCRT) alone in unresectable, locally advanced (LA), stage III non-small cell lung cancer (NSCLC). Methods: Patients with unresectable LA-NSCLC were randomly assigned to receive DCCRT either combined with Zengxiao Jiandu decoction (TCM arm) or placebo therapy (Control arm), by computer-generated random assignment lists using a central randomization system. The patients were routinely followed-up every 3 months for the first 2 years after the therapy, and every 6 months for the subsequent 3 years, or earlier if clinically indicated. The primary endpoint was grade ≥3 chemoradiotherapy-related toxicities, while secondary endpoints included the completion rate of chemoradiotherapy, the clinical objective response rate (ORR), and survival. The placebo achieved full consistency in color, aroma, taste and appearance with the Zengxiao Jiandu decoction. Results: From February 2019 to December 2020, 163 patients were randomly allocated to TCM arm (n=82) or Control arm (n=81). Fifty-nine (72.0%) patients in TCM arm finished chemoradiotherapy per protocol and 79 (96.3%) received protocol-specified Zengxiao Jiandu decoction. Forty-two patients in Control arm finished chemoradiotherapy per protocol. The incidence of grade ≥3 chemoradiotherapy-related toxicities was higher in Control arm than TCM arm (44.4% vs. 31.7%, P=0.094). Grade ≥3 radiation pneumonitis occurred more frequently in Control arm than TCM arm (13.6% vs. 3.7%, P=0.024). The completion rate of the protocol-specified chemotherapy was significantly higher in TCM arm than Control arm (79.3% vs. 64.2%, P=0.033), but the completion rates of the definitive-dose radiotherapy were similar. There were no significant differences in ORR between the 2 arms. The progression-free survival (PFS) of TCM arm was significantly better than Control arm (median PFS, 12.0 vs. 9.0 months, P=0.035). However, Zengxiao Jiandu decoction was not found to produce any significant benefit in overall survival. Conclusions: The Zengxiao Jiandu decoction adjunctive therapy, as compared to DCCRT alone, reduced grade ≥3 radiation pneumonitis, improved the completion rate of DCCRT, and prolonged PFS for unresectable LA-NSCLC. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031667.

Effect of Perioperative Comprehensive Nursing Intervention on Transcatheter Arterial Chemoembolization in Patients with Primary Hepatic Carcinoma.

Objective: To study and analyze the effect of perioperative comprehensive nursing intervention on transcatheter arterial chemoembolization (TACE) in patients with primary hepatic carcinoma (PHC). Methods: One hundred and ten patients with PHC diagnosed in our hospital from May 2019 to January 2022 were randomly selected and divided into a control group (n = 55) and an observation group (n = 55) by random number sorting according to odd and even numbers. Patients in the control group received conventional nursing interventions and those in the observation group received comprehensive nursing interventions. The two groups were compared in terms of surgical status, quality of life (QoL), and nursing satisfaction. Results: The operation time, postoperative bed rest time, and hospital stay in the observation group were significantly (P < 0.05) shorter than those in the control group; the observation group had significantly (P < 0.05) higher scores of quality of life, including somatic function, emotional function, role function, social function, and cognitive function than the control group; chemotherapy adverse reactions including fever, abdominal pain, urinary retention, and gastrointestinal reactions in the observation group were significantly less than those in the control group (P < 0.05); the total incidence of complications in the observation group was significantly (P < 0.05) lower than that in the control group. The total satisfaction with nursing care in the observation group was significantly (P < 0.05) higher than that in the control group. Conclusion: The perioperative application of comprehensive nursing intervention in TACE for patients with PHC aids in the smooth operation, improves patients' QoL, lowers the risk of chemotherapy reactions and complications, and enhances patient satisfaction and nursing quality. These advantages justify a wider perioperative application of comprehensive nursing intervention in TACE clinical practice.

Medicinal Plants for the Treatment of Gastrointestinal Cancers From the Metabolomics Perspective.

Gastrointestinal cancer (GIC), primarily including colorectal cancer, gastric cancer, liver cancer, pancreatic cancer, and esophageal cancer, is one of the most common causes of cancer-related deaths with increasing prevalence and poor prognosis. Medicinal plants have been shown to be a great resource for the treatment of GIC. Due to their complex manifestations of multi-component and multi-target, the underlying mechanisms how they function against GIC remain to be completely deciphered. Cell metabolism is of primary importance in the initialization and development of GIC, which is reported to be a potential target. As an essential supplement to the newest "omics" sciences, metabolomics focuses on the systematic study of the small exogenous and endogenous metabolites involved in extensive biochemical metabolic pathways of living system. In good agreement with the systemic perspective of medicinal plants, metabolomics offers a new insight into the efficacy assessment and action mechanism investigation of medicinal plants as adjuvant therapeutics for GIC therapy. In this review, the metabolomics investigations on metabolism-targeting therapies for GIC in the recent 10 years were systematically reviewed from five aspects of carbohydrate, lipid, amino acid, and nucleotide metabolisms, as well as other altered metabolisms (microbial metabolism, inflammation, and oxidation), with particular attention to the potential of active compounds, extracts, and formulae from medicinal plants. Meanwhile, the current perspectives and future challenges of metabolism-targeting therapies of medicinal plants for GIC were also discussed. In conclusion, the understanding of the action mechanisms of medicinal plants in GIC from the metabolomics perspective will contribute to the clinical application of potential candidates from the resourceful medicinal plants as novel and efficient adjuvant therapeutics for GIC therapy.

Chemical Constituent Analysis of Ranunculus sceleratus L. Using Ultra-High-Performance Liquid Chromatography Coupled with Quadrupole-Orbitrap High-Resolution Mass Spectrometry.

Ranunculus sceleratus L.(RS) has shown various pharmacological effects in traditional Chinese medicine. In our previous study, the positive therapeutic effect on α-naphthylisothiocyanate induced intrahepatic cholestasis in rats was obtained using TianJiu treatment with fresh RS. However, the chemical profile of RS has not been clearly clarified, which impedes the research progress on the therapeutic effect of RS. Herein, an ultra-high performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method was developed to rapidly separate and identify multiple constituents in the 80% methanol extract of RS. A total of sixty-nine compounds (19 flavonoids, 22 organic acids, 6 coumarins, 4 lignans, 14 nitrogenous compounds, and 4 anthraquinones) were successfully characterized. A total of 12 of these compounds were unambiguously identified by standard samples. Their mass spectrometric fragmentation pathways were investigated. It is worth noting that flavonoids and lignans were identified for the first time in RS. In this study, we successfully provide the first comprehensive report on identifying major chemical constituents in RS by UHPLC-Q-Orbitrap HRMS. The obtained results enrich the RS chemical profile, paving the way for further phytochemical study, quality control, and pharmacological investigation of RS.