Active metabolites and potential mechanisms of Notopterygium incisum against obstructive sleep apnea Syndrome (OSAS): network analysis and experimental assessment.

Background: Notopterygium incisum K.C. Ting ex H.T. Chang, a synonym of Hansenia weberbaueriana (Fedde ex H. Wolff) Pimenov & Kljuykov, is an anti-inflammatory medicinal plant. Although abrnotopterol has been reported to be its primary active metabolite, the other metabolites and their mechanisms of action remain unclear. This study aims to investigate the potential mechanisms by which its active metabolites treat Obstructive Sleep Apnea Syndrome (OSAS) through network analysis and experimental assessment. Methods: The metabolites and potential targets of Notopterygium incisum were extracted from public databases. We searched for OSAS-related genes in the Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Cytoscape 3.9.0 was used to construct the drug-target-disease network and screen for hub genes. Human bronchial epithelial (HBE) cells were cultivated in normoxia and chronic intermittent hypoxia (CIH) medium for 24 h. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E2 (PGE2) were quantified using enzyme-linked immunosorbent assay (ELISA). Prostaglandin-endoperoxide synthase 2(PTGS2) mRNA was detected using RT-qPCR, while PTGS2 and nuclear factor-kappa B (NF-κB) proteins were identified using Western blot analysis. Co-Immunoprecipitation (CoIP) and Western blotting were utilized to evaluate the ubiquitination of PTGS2 in HBE cells. Results: Pterostilbene and notopterol, isolated from Notopterygium incisum, had potential therapeutic effects on OSAS. The PTGS2 and estrogen receptor alpha (ESR1) hub genes were associated with OSAS. The pathway enrichment analysis focuses on the NF-κB, apoptosis, and HIF-1A pathways. In response to CIH, pterostilbene and notopterol decreased IL-6, TNF-α, and PGE2 levels. The NF-κB pathway was activated by an increase in PTGS2 levels. Pterostilbene promoted proteasome-mediated ubiquitination of PTGS2 protein and reduced PTGS2 levels, inhibiting the NF-κB pathway. Conclusion: This study reveals the active metabolites of Notopterygium incisum and hub genes involved in treating OSAS, which provide a basis for the follow-up development and exploitation of the botanical drug.

Ferulic Acid Induces Autophagy and Apoptosis in Colon Cancer CT26 Cells via the MAPK Pathway.

Ferulic acid (FA) is a bioactive compound found in traditional Chinese herbal medicine; for example, it is present in Xinjiang Ferula, but also in strong-flavor Chinese baijiu. FA has been shown to play a crucial role in treating oxidative stress, skin whitening, and eye diseases. In this study, the potential role of FA as a means of inducing apoptosis and inhibiting colon cancer induced by the transplantation of CT26 cells was investigated. The results show that FA adjuvant treatment caused an upregulation in the expression of genes related to autophagy while simultaneously suppressing the expression of inflammatory response elements and improving the bodyweight, glutamic pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST) in vivo. Furthermore, FA inhibited the proliferation of CT26 cells and induced apoptosis, specifically by activating the phosphorylation of ERK and JNK to enhance the essential proteins BCL-2 and BAX in the apoptosis pathway. These results suggest that FA could be a promising auxiliary therapeutic agent for the treatment of colon cancer. Further research is needed to better understand the mechanisms underlying the beneficial effects of FA and its synergistic effects with other compounds.

An optimized machine learning method for predicting wogonin therapy for the treatment of pulmonary hypertension.

Human health is at risk from pulmonary hypertension (PH), characterized by decreased pulmonary vascular resistance and constriction of the pulmonary vessels, resulting in right heart failure and dysfunction. Thus, preventing PH and monitoring its progression before treating it is vital. Wogonin, derived from the leaves of Scutellaria baicalensis Georgi, exhibits remarkable pharmacological activity. In this study, we examined the effectiveness of wogonin in mitigating the progression of PH in mice using right heart catheterization and hematoxylin-eosin (HE) staining. As an alternative to minimize the possibility of harming small animals, we present a scientifically effective feature selection method (BSCDWOA-KELM) that will allow us to develop a novel simpler noninvasive prediction method for wogonin in treating PH. In this method, we use the proposed enhanced whale optimizer (SCDWOA) in conjunction with the kernel extreme learning machine (KELM). Initially, we let SCDWOA perform global optimization experiments on the IEEE CEC2014 benchmark function set to verify its core advantages. Lastly, 12 public and PH datasets are examined for feature selection experiments using BSCDWOA-KELM. As shown in the experimental results for global optimization, the proposed SCDWOA has better convergence performance. Meanwhile, the proposed binary SCDWOA (BSCDWOA) significantly improves the ability of KELM to classify data. By utilizing the BSCDWOA-KELM, key indicators such as the Red blood cell (RBC), the Haemoglobin (HGB), the Lymphocyte percentage (LYM%), the Hematocrit (HCT), and the Red blood cell distribution width-size distribution (RDW-SD) can be efficiently screened in the Pulmonary hypertension dataset, and one of its most essential points is its accuracy of greater than 0.98. Consequently, the BSCDWOA-KELM introduced in this study can be used to predict wogonin therapy for treating pulmonary hypertension in a simple and noninvasive manner.

[Design and development of a multifunctional moxibustion treatment machine based on heat-sensitive moxibustion therapy].

A multifunctional moxibustion treatment machine is designed and developed to assist the heat-sensitive moxibustion therapy. Through the motion control of the stepping motor by programmable logic controller (PLC), the automatic control is obtained for the acupoint detection of heat-sensitive moxibustion therapy and the manual operation of moxibustion. The skin temperature is monitored in real-time, using infrared non-contact temperature measurement technology. Based on the deviation of the temperature set value and the monitoring one, the distance between the moxibustion device and the exerted region is adjusted automatically by PLC so that the temperature is controlled practically. The multifunctional moxibustion treatment machine based on the heat-sensitive moxibustion therapy is capable of the operation control of mild moxibustion, circling moxibustion, sparrow-pecking moxibustion and along-meridian moxibustion techniques, as well as real-time monitoring of skin temperature. The temperature change curve of this machine is coincident with that obtained by the manual operation of heat-sensitive moxibustion. This multifunctional moxibustion treatment machine assists the delivery of heat-sensitive moxibustion therapy and it is satisfactory in temperature control and precise in operation.

Microfluidics-enabled Serial Assembly of Lipid-siRNA-sorafenib Nanoparticles for Synergetic Hepatocellular Carcinoma Therapy.

Multi-component nanoparticles (mNPs) hold great potential for disease prevention and treatment. However, a major barrier is the lack of versatile platforms to accommodate steps of assembly processes of mNPs. Here the microfluidics-enabled serial assembly (MESA) of mNPs is presented. The microfluidic chip, as a mini-conveyor of initial materials, sequentially enables the assembly of sorafenib supramolecule, electrostatic adsorption of siRNA, and surface assembly of protective lipids. The produced lipid-siRNA-sorafenib nanoparticles (LSS NPs) have ultrahigh encapsulation efficiencies for sorafenib (≈100%) and siRNA (≈95%), which benefit from the accommodation of both fast and slow processes on the chip. Although carrying negative charges, LSS NPs enable cytosolic delivery of agents and high gene silencing efficiency within tumor cells. In vivo, the LSS NPs delivering hypoxia-induced factor (HIF1α)-targeted siRNA efficiently regress tumors of Hep3B xenograft and hepatocellular carcinoma patient-derived primary cells xenograft (PDCX) and finally extend the average survival of PDCX mice to 68 days. Thus, this strategy is promising as a sorafenib/siRNA combination therapy, and MESA can be a universal platform for fabricating complex nanosystems.

Randomised, controlled crossover trial of intermittent and continuous transcutaneous electrical stimulation of the genioglossus muscle for obstructive sleep apnoea.

PURPOSE: Continuous transcutaneous electrical stimulation (CTES) of the genioglossus muscle may benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of intermittent transcutaneous electrical stimulation (ITES) for OSA is unclear. METHODS: This was a randomised, controlled, crossover study to compare the effects of ITES and CTES of the genioglossus muscle. Over three single-night sessions, participants were alternately subjected to three genioglossus stimulation modalities during sleep (sham, CTES and ITES). The apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI) were used for OSA diagnosis and to evaluate efficacy. A responder was defined as an individual with a ≥50% reduction in AHI together with <10 AHI events per hour and/or an ODI reduction of ≥25% between sham stimulation and electrical stimulation nights. RESULTS: Fifteen men with OSA completed the study. Compared with sham, the median AHI with ITES decreased by 13.3 events/hour (95% CI 3.1 to 23.5, p=0.030) and by 7.3 events/hour (95% CI -3.9 to 18.5, p=0.825) with CTES. The median ODI was reduced by 9.25 events/hour (95% CI 0.5 to 18.0) with ITES and 3.3 events/hour (95% CI -5.6 to 12.2) with CTES; however, there was no significant difference between groups. Furthermore, ITES outperformed CTES with respect to longest apnoea duration (median (95% CI), 9.5 (0.0 to 19.0), p=0.011)) and the highest sleep efficiency (12.2 (2.7 to 21.7), p=0.009). Of the 15 participants, 8 responded to ITES and 3 responded to CTES (p=0.058), of whom all eight cases and two out of three cases had ODIs <5 events/hour, respectively. All participants tolerated ITES well. CONCLUSIONS: ITES improved upper airway obstruction in patients with OSA, suggesting that further prospective validation of the intermittent approach is warranted. TRIAL REGISTRATION NUMBER: ChiCTR2100050138.

Synchronous Extraction, Antioxidant Activity Evaluation, and Composition Analysis of Carbohydrates and Polyphenols Present in Artichoke Bud.

This study investigated the optimization of ultrasonic-assisted aqueous two-phase synchronous extraction of carbohydrates and polyphenols present in artichoke bud, evaluated their antioxidant activities in vitro, and analyzed the composition of carbohydrates and polyphenols by high-performance liquid chromatography (HPLC). The powder mass, ultrasonic time, ammonium sulfate concentration, and alcohol-water ratio were considered the influencing factors based on the single-factor experiment results, and a dual-response surface model was designed to optimize the synchronous extraction process to extract carbohydrates and polyphenols. The antioxidant activity was evaluated by measuring the scavenging capacity of ABTS+· and DPPH· and the reducing capacity of Fe3+. The optimal process conditions in this study were as follows: the powder mass of 1.4 g, ammonium sulfate concentration of 0.34 g/mL, alcohol-water ratio of 0.4, and ultrasonic time of 43 min. The polyphenol content in artichoke bud was 5.32 ± 0.13 mg/g, and the polysaccharide content was 74.78 ± 0.11 mg/g. An experiment on in vitro antioxidant activity showed that both carbohydrates and polyphenols had strong antioxidant activities, and the antioxidant activity of polyphenols was stronger than that of carbohydrates. The HPLC analysis revealed that the carbohydrates in artichoke bud were mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, and the molar ratio was 10.77:25.22:2.37:15.74:125.39:48.62:34.70. The polyphenols comprised chlorogenic acid, 4-dicaffeoylquinic acid, caffeic acid, 1,3-dicaffeoylqunic acid, isochlorogenic acid B, isochlorogenic acid A, cynarin, and isochlorogenic acid C, and the contents were 0.503, 0.029, 0.022, 0.017, 0.008, 0.162, 1.621, 0.030 mg/g, respectively. This study also showed that the carbohydrates and polyphenols in artichoke bud could be important natural antioxidants, and the composition analysis of HPLC provided directions for their future research. Carbohydrates and polyphenols in artichoke buds can be separated and enriched using the optimized process technology, and it is an effective means of extracting ingredients from plants.

Radix Asteris: Traditional Usage, Phytochemistry and Pharmacology of An Important Traditional Chinese Medicine.

Radix Asteris (RA), also known as 'Zi Wan', is the dried root and rhizome of Aster tataricus L. f., which has been used to treat cough and asthma in many countries such as China, Japan, Korea and Vietnam. This article summarizes the available information on RA in ancient Chinese medicine books and modern research literature: its botanical properties, traditional uses, chemical composition, pharmacological activity, toxicity and quality control. Studies have shown that RA extracts contain terpenes, triterpenoid saponins, organic acids, peptides and flavonoids, and have various pharmacological activities such as anti-inflammatory, anti-tumor, anti-oxidation, and anti-depression. RA is considered to be a promising medicinal plant based on its traditional use, chemical constituents and pharmacological activities. However, there are few studies on its toxicity and the consistency of its components, which indicates the need for further in-depth studies on the toxicity and quality control of RA and its extracts.

Investigation of Lonicera japonica Flos against Nonalcoholic Fatty Liver Disease Using Network Integration and Experimental Validation.

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components-targets-pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD.

Intake of Vitamin B12 and Folate and Biomarkers of Nutrient Status of Women within Two Years Postpartum.

Background: Little is known about variation in vitamin B12 and folate status among Chinese women 2 years postpartum. This study assessed intake of vitamin B12 and folate and biomarkers of nutrient status among Chinese women postpartum. Methods: Demographic information, multi-/single-nutrient supplementation, dietary data, serum vitamin B12 and serum folate were assessed in 982 women within 2 years postpartum, using ten investigation sites in Zhejiang Province from the National Nutritional Study 2016−2017, which is a nationally representative cross-sectional study, to form a representative provincial sample of Zhejiang Province. The dietary diversity score (DDS) was used for assessing the dietary pattern. Results: Vitamin B12 increased slightly at the early stage of postpartum and then dropped over time. Serum folate level elevated with postpartum time. The median serum vitamin B12 concentration was 494.59 (373.21−650.20) pg/mL, and folate was 7.58 (5.02−10.34) ng/mL. Correspondingly, vitamin B12 levels suggesting marginal deficiency (200−300 pg/mL) and deficiency (<200 pg/mL) resulted as 9.27% and 3.26%, respectively, and folate level suggesting deficiency (<3 ng/mL) was 9.16%. Multi-/single-nutrient supplementation during pregnancy was associated with log-transformed serum vitamin B12 and folate level after adjusting for potential confounders (vitamin B12: ß (SE) = 0.124 (0.028), p < 0.001; folate: 0.128 (0.035), <0.001). Additionally, postpartum nutrient supplementation was associated with log-transformed serum folate level, especially for lactating women (ß (SE) = 0.204 (0.062), p = 0.001). Increased DDS was significantly associated with elevated serum vitamin B12 and folate levels (vitamin B12: ß (SE) = 0.028 (0.011), p = 0.011; folate: 0.030 (0.014), 0.031). In addition, age and educational level were influencing factors for serum vitamin B12 and folate concentrations among postpartum women. Conclusion: Serum vitamin B12 level decreased and folate level increased with postpartum age among Chinese women. Nutrient supplementation during pregnancy was related to elevated serum vitamin B12 and folate concentrations. Postpartum nutrient supplementation was associated with the increased serum folate level of lactating women. Dietary diversity was related to increased serum vitamin B12 and folate levels, especially among postpartum women with younger age and lower educational level.

Molecular and Supramolecular Approach to Highly Photocytotoxic Phthalocyanines with Dual Cell Uptake Pathways and Albumin-Enhanced Tumor Targeting.

Phototherapy for non-invasive cancer treatment has been extensively studied. An urgent challenge in phototherapy application is to fabricate appropriate targeted agents to achieve efficient therapeutic effect. Herein, a molecular and supramolecular approach for targeting phototherapy was reasonably designed and realized through the axial sulfonate modification of silicon(IV) phthalocyanines (Pcs), followed by supramolecular interaction with albumin. This approach can not only improve the photoactivities (e.g., fluorescence emission and reactive oxygen species production) of the Pcs but also enhance their tumor targeting. Most importantly, one of the deigned Pcs (4) can target HepG2 cells through dual cell pathways, leading to an extremely high phototoxicity with an EC50 (i.e., concentration of Pcs to kill 50% of cells under light irradiation) value of 2.0 nM. This finding presents a feasible strategy to realize efficient targeting phototherapy.

Garlic polysaccharides: A review on their extraction, isolation, structural characteristics, and bioactivities.

Garlic has been considered as a source of highly promising functional food and traditional herbal medicine for thousands of years. Garlic polysaccharides is one of the important effective components of garlic, which has various bioactivities, including immune-enhancing, hepatoprotective, and antioxidant. Garlic polysaccharides is mainly composed of monosaccharides, such as Fru, Glc, and Gal, having a (2 â†’ 1)-linked ß-D-Fruf backbone with (2 â†’ 6)-linked ß-D-Fruf side chains. With great marketing potential and development prospects, garlic polysaccharides has drawn much attention from researchers worldwide. Therefore, this review aimed at providing systematic and current information on the extraction, isolation, structural characteristics, and bioactivities of garlic polysaccharides to support their further application as therapeutic agents and functional foods.

Comparison of adjuvant pharmaceuticals for caudal block in pediatric lower abdominal and urological surgeries: A network meta-analysis.

STUDY OBJECTIVE: Caudal block helps relieve pain after sub-umbilical surgery in pediatric patients; however, the duration for which it exerts its analgesic effect is limited. The addition of certain adjuvant agents to local anesthetics (LAs) that are used to administer caudal block can prolong postoperative analgesia. Therefore, we aimed to compare the efficiencies and side effects of caudal adjuvants in the settings of pediatric lower abdominal and urological surgeries. DESIGN: A network meta-analysis (NMA). PATIENTS: One hundred and twelve randomized controlled trials (RCTs) involving 6800 pediatric patients were included in the final analysis. INTERVENTIONS: Different adjuvant agents, namely clonidine, dexamethasone, dexmedetomidine, fentanyl, ketamine, magnesium, midazolam, morphine, neostigmine, and tramadol. MEASUREMENTS: The primary outcome was the duration of analgesia. The secondary outcomes included the requirement for additional analgesia, analgesic consumption, and postoperative complications. The effects and rankings were evaluated using NMA and the surface under the cumulative ranking curve scores, respectively. RESULTS: Neostigmine, dexmedetomidine, and dexamethasone were found to be the three most effective adjuvants that prolong the duration of analgesia for caudal block, and these adjuvants extended this duration by 8.9 h (95% confidence interval [CI], 7.1-10.7), 7.3 h (95% CI, 6.0-8.6), and 5.9 h (95% CI, 4.0-7.7), respectively. Caudal neostigmine was associated with an increase in the incidence of postoperative nausea and vomiting, whereas dexmedetomidine and dexamethasone showed no postoperative complications. CONCLUSIONS: This NMA provided evidence and suggested that dexmedetomidine and dexamethasone may be the most beneficial adjuvant pharmaceutics adding to LAs for caudal block in children. However, given the off-label status of caudal dexmedetomidine and dexamethasone, further high-quality RCTs are still warranted, especially to determine whether delayed neurological complications will occur.

New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation.

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K+ channels to restrain Ca2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development.

Targeted fully endoscopic visualized laminar trepanning approach under local anaesthesia for resection of highly migrated lumbar disc herniation.

PURPOSE: To introduce a new fully endoscopic visualized laminar trepanning approach with a periendoscopic trephine under local anesthesia for resection of highly migrated lumbar disc herniation (LDH) and report the clinical outcomes of one year follow-up. METHODS: Twenty-one patients with highly migrated LDH who underwent percutaneous endoscopic lumbar discectomy via the laminar trepanning approach from June 2019 to August 2020 were retrospectively reviewed. Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms-Pain Interference (PI) and Physical Function (PF) were selected as outcome measures. The operating duration and complication were documented. RESULTS: The average age of the 21 patients (15 males, 6 females) was 37.8 ± 6.0 years (29-52 years). Disc migration originated from L4/5 in 19 patients, L5/S1 in two patients. The mean operative duration was 54.1 ± 9.0 minutes (42-79 min). All patients were followed up to 12 months after the operation. PROMIS PI T-scores decreased significantly from pre-operatively mean 68.6 ± 2.4 to 54.4 ± 1.9 (P < 0.001) and 47.1 ± 4.3 (P < 0.001) at six weeks and 12 months, respectively. PROMIS PF T-scores improved significantly from pre-operatively mean 26.7 ± 4.7 to 44.3 ± 4.2(P < 0.001) and 58.4 ± 4.0 (P < 0.001) at six weeks and 12 months, respectively. No complications and disc herniation recurrences occurred. CONCLUSION: The targeted full endoscopic laminar trepanning under local anesthesia with a visualized periendoscopic trephine offers a safe, efficient and cost-effective option for the resection of highly migrated LDH.

Integrating 16S sequencing and metabolomics study on anti-rheumatic mechanisms against collagen-induced arthritis of Wantong Jingu Tablet.

Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, was reported to relieve the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism was not completely understood. The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo. The effects of WJT on joint pathology, as well as the levels of Bax, Bcl-2, caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1ß, and IL-6 were measured using collagen-induced arthritis (CIA) rats. The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method, respectively. We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis, inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines. WJT, in part, relieved the gut microbiota dysbiosis, especially bacterial phylum Bacteroidetes, Tenericutes and Deferribacteres, as well as bacterial genus Vibrio, Macrococcus and Vagococcus. 3'-N-debenzoyl-2'-deoxytaxol, tubulysin B, and magnoline were significantly associated with the specific genera. We identified serotonin, glutathione disulfide, N-acetylneuraminic acid, naphthalene and thromboxane B2 as targeted molecules via metabolomics. Our findings contributed to the understanding of RA pathogenesis, and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.

Volatile Analysis of Wuliangye Baijiu by LiChrolut EN SPE Fractionation Coupled with Comprehensive GC×GC-TOFMS.

Wuliangye baijiu is one of the most famous Chinese liquors with a protected geographical indication. This study used LiChrolut® EN-based solid-phase extraction (SPE) and fractionation combined with comprehensive two-dimensional chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) to unveil its volatile composition. The volatiles were isolated with LiChrolut® EN-based SPE and traditional liquid-liquid extraction (LLE). The neutral/basic fractions from LLE and the SPE were fractionated on a LiChrolut® EN SPE column and analyzed by comprehensive GC×GC-TOFMS. Compared with LLE, more esters and alcohols were detected in the SPE-based extraction. The SPE fractionation and GC×GC-TOFMS analysis resulted in the identification of about 500 volatile compounds in more than 3000 peaks of the Wuliangye baijiu. The approach simplifies the complex baijiu composition into functional group-based fractions for reliable identification and analysis. This study provided a confidence volatile identification approach for Chinese baijiu based on the SPE fractionation GC×GC-TOFMS.

Structural elucidation of flavonoids from Shatianyu (Citrus grandis L. Osbeck) pulp and screening of key antioxidant components.

The Citrus genus is a good source of dietary flavonoids, which have many health benefits. As a representative citrus fruit, the flavonoids composition in Shatianyu (Citrus grandis L. Osbeck) pulp remains to be investigated. In the present study, 11 flavonoids were isolated and identified from Shatianyu pulp flavonoid extracts (SPFEs). Among them, 4 flavonoids were previously undescribed and 2 flavonoids were firstly isolated from pummelo. The cellular antioxidant activity (CAA) and oxygen radical absorbance capacity (ORAC) of isolated compounds were evaluated. Naringin and rhoifolin showed the highest ORAC activity, and the presence of a 3-hydroxy-3-methylglutaryl or a 4'-glucose decreased the ORAC activity of flavonoids. The contribution of isolated flavonoids to the holistic antioxidant activity of SPFEs was determined by an online knockout method. Melitidin, bergamjuicin and naringin contributed most to ORAC activity, while bergamjuicin, melitidin and apigenin-4'-O-ß-d-glucopyranosyl-7-O-α-l-rhamnopyranosyl-(1 â†’ 2)-[6″-O-(3- hydroxy-3-methylgltaryl)]-ß-d-glucopyranoside contributed most to CAA activity.

Integrating 16S sequencing and metabolomics study on anti-rheumatic mechanisms against collagen-induced arthritis of Wantong Jingu Tablet / 中国天然药物

Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, was reported to relieve the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism was not completely understood. The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo. The effects of WJT on joint pathology, as well as the levels of Bax, Bcl-2, caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were measured using collagen-induced arthritis (CIA) rats. The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method, respectively. We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis, inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines. WJT, in part, relieved the gut microbiota dysbiosis, especially bacterial phylum Bacteroidetes, Tenericutes and Deferribacteres, as well as bacterial genus Vibrio, Macrococcus and Vagococcus. 3'-N-debenzoyl-2'-deoxytaxol, tubulysin B, and magnoline were significantly associated with the specific genera. We identified serotonin, glutathione disulfide, N-acetylneuraminic acid, naphthalene and thromboxane B2 as targeted molecules via metabolomics. Our findings contributed to the understanding of RA pathogenesis, and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.

Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.