Artificial aging conditions for Artemisia argyi leaves based on quality-inflammation-quality marker transformation.

BACKGROUND: Appropriate conditions for storage of Artemisia argyi leaves reduce irritation during treatment and increase the active ingredient content. Naturally aged A. argyi leaves (≥1 year) are optimal for moxibustion; however, this process is time-consuming and costly. A comprehensive understanding of the conditions for artificial aging of A. argyi leaves and the mechanism of quality-marker conversion are required to guarantee A. argyi quality and moxibustion efficacy. OBJECTIVE: To identify the optimal conditions for artificial aging of A. argyi leaves and clarify the mechanism of quality-marker conversion. METHOD: Gas chromatography (GC), high-performance liquid chromatography (HPLC), colorimeter (CD), and near-infrared spectroscopy (NIRS) were used to determine the chemical composition of A. argyi leaves before and after artificial and natural (1 year) aging and to determine the optimal artificial aging conditions. The effects of both artificially and naturally aged A. argyi leaves were then evaluated in a mouse model of ulcerative colitis (UC). The main chemical components of aged A. argyi leaves were then analyzed to determine quality-markers and the transformation mechanism. RESULTS: Comprehensive analysis of volatile and non-volatile components, color values, and characteristic near-infrared spectra revealed that the quality of artificially aged A. argyi leaves was similar to that of naturally aged A. argyi leaves. In the mouse model, artificially and naturally aged A. argyi leaves not only improved the symptoms of UC with the same therapeutic effects, but also safeguarded the barrier of the colonic mucosa and prevented the release of colitis-related substances. In addition, the content of caffeic acid converted from L-phenylalanine in A. argyi leaves increased during the aging process. CONCLUSION: Conditions for artificial aging of A. argyi leaves were identified for the first time, and the equivalent efficacy of artificially aged A. argyi leaves and naturally aged A. argyi leaves for improving UC was confirmed. This method for artificial aging of A. argyi leaves not only reduces the time and cost associated with this process, but also provides technical support to ensure the quality and stability of artificially aged A. argyi leaves. In addition, caffeic acid was identified as a potential quality-marker for establishing standards and specifications for aging A. argyi leaves for the first time, and its possible transformation mechanism was preliminarily elucidated.

Mechanism of Shenfu Injection in Treating Ischemic Stroke Elucidated using Network Pharmacology and Experimental Validation.

BACKGROUND: Shenfu injection was derived from the classical Chinese medicine formula 'Shenfu decoction', which was widely used in the treatment of cardiovascular and cerebrovascular diseases in clinical practice. OBJECTIVES: Predict the main active ingredients, core targets, and related signaling pathways of Shenfu injection in the treatment of ischemic stroke. METHODS: Databases were used to collect the active ingredients and target information of Shenfu injection; GO and KEGG pathway enrichment analyses were performed using the David database. The effects of Shenfu injection on core targets were verified using molecular docking and in vivo experiments. RESULTS: The predicted results identified 44 active ingredients and 635 targets in Shenfu injection, among which 418 targets, including TNF, IL-6, MAPK1, and MAPK14, were potential targets for the treatment of ischemic stroke. Molecular docking revealed that the active ingredients had good binding to IL-6, MAPK1, and MAPK14. In vivo experiments demonstrated that Shenfu injection significantly improved the pathological damage due to ischemic stroke, promoted the expression of tight junction proteins, and inhibited MMP-2 and MMP-9 expressions, thereby reducing BBB permeability. Animal experiments revealed that Shenfu injection could inhibit p38、JNK and ERK phosphorylation. CONCLUSIONS: Mechanism of Shenfu injection in treating ischemic stroke may be via inhibition of the inflammatory factors levels and protecting the BBB, thereby warranting subsequent studies and highlighting its potential as a reference for new drug development.

Numerical studies of indoor particulate and gaseous micropollutant transport and its impact on human health in densely-occupied spaces.

Micropollutants (MPs) have increasingly become a matter of concern owing to potential health risks associated with human inhalation exposure, particularly in densely-occupied indoor environments. This study employed numerical simulations in a traditional built indoor workspace and a public transport cabin to elucidate the transport dynamics and health impacts of particulate and gaseous type of indoor MPs on varying groups of occupants. The risk of infection from pathogen-bearing MPs was evaluated in the workspace using the integrated Eulerian-Lagrangian and modified Wells-Riley model. In the cabin environment, the health impact of inhaled TVOC within the human nasal system was assessed via the integrated nasal-involved manikin model and cancer/non-cancer risk model. The results demonstrated that when ventilation layout was in favour of restricting particulate MPs spread, considerably high health risks (up to 17.22% infection possibility) were generally found in near-fields of emission source (< 2.25 m). Conversely, if the ventilated flow interacts robustly with emission source, every occupant has a minimum 5% infection risk. Incorporating the nasal cavity in the human model offers a nuanced understanding of gaseous MP distributions post-inhalation. Notably, the olfactory and sinus regions displayed heightened vulnerability to TVOC exposure, with a 62.5%-108% concentration increase compared to other nasal areas. Cancer risk assessment plausibly explained the rising occurrence of brain and central nervous system cancer for aircrew members. Non-cancer risk was found acceptable. This study was expected to advance the understanding of environmental pollution and the health risks tied to indoor MPs in densely-populated environments.

Atractylodes lancea Rhizome Polysaccharide Alleviates Immunosuppression and Intestinal Mucosal Injury in Mice Treated with Cyclophosphamide.

Plant-derived polysaccharides, such as Atractylodes lancea rhizome polysaccharide (ALP), are good immune regulators. However, the immune regulatory mechanism of the ALP is unknown. This study aimed to evaluate the effects of ALP on the intestinal mucosal barrier and intestinal mucosal immunity of immunosuppressed mice. We also compared the activity of raw Atractylodes lancea rhizome polysaccharide (SALP) with wheat bran processed bran-fried Atractylodes lancea rhizome polysaccharide (FALP; both at 1.2 g/kg/d for mice). Our results showed that ALP effectively increased the immune organ index and blood cell count, stimulated the secretion of cytokines, and promoted the expression of occludin and zonula occludens-1 (ZO-1). ALP also promoted the expression of T cells and the secretion of sIgA. Furthermore, ALP alleviated the gut microbiota disorder in Cy-treated mice and increased the relative abundances of Lactobacillus and Faecalibaculum. ALP reversed the decrease in the level of SCFAs and promoted the expression of G protein-coupled receptor 43 (GPR43). To our knowledge, this study was the first to explore how the ALP protects the intestinal mucosal barrier and enhances intestinal mucosal immunity by alleviating the gut microbiota imbalance and metabolic disorders of SCFAs. FALP was more therapeutic than SALP, suggesting that FALP could be developed as a promising functional food component.

Polygonum Cuspidatum Alcohol Extract Exerts Analgesic Effects via the MAPK/ERK Signaling Pathway.

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.

Atractylenolide III Ameliorates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting the PI3K/AKT Pathway and Regulating Glutamine Metabolism.

Liver fibrosis is one of the leading causes of hepatic sclerosis and hepatocellular carcinoma worldwide. However, the complex pathophysiological mechanisms of liver fibrosis are unknown, and no specific drugs are available to treat liver fibrosis. Atractylenolide III (ATL III) is a natural compound isolated from the plant Atractylodes lancea (Thunb.) DC. that possesses antioxidant properties and the ability to inhibit inflammatory responses. In this study, cholestatic hepatic fibrosis was induced in mice using a bile duct ligation (BDL) model and treated with 10 mg/kg and 50 mg/kg of ATL III via gavage for 14 days. ATL III significantly reduced the liver index, lowered serum ALT and AST levels, and reduced liver injury in bile-duct-ligated mice. In addition, ATL III significantly attenuated histopathological changes and reduced collagen deposition. ATL III reduced the expression of fibrosis-related genes α-smooth muscle actin (α-SMA), Collagen I (col1a1), Collagen IV (col4a2), and fibrosis-related proteins α-SMA and col1a1 in liver tissue. Using RNA sequencing (RNA-seq) to screen molecular targets and pathways, ATL III was found to affect the PI3K/AKT singling pathway by inhibiting the phosphorylation of PI3K and AKT, thereby ameliorating BDL-induced liver fibrosis. Gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of ATL III on liver metabolites in BDL mice. ATL III further affected glutamine metabolism by down-regulating the activity of glutamine (GLS1) and glutamine metabolism. ATL III further affected glutamine metabolism by down-regulating the activity of glutaminase (GLS1), as well as glutamine metabolism. Therefore, we conclude that ATL III attenuates liver fibrosis by inhibiting the PI3K/AKT pathway and glutamine metabolism, suggesting that ATL III is a potential drug candidate for treating liver fibrosis.

Semi-surrogate modelling of droplets evaporation process via XGBoost integrated CFD simulations.

The applications of machine learning (ML) based approach are emerging as possible tools to accelerate CFD simulations. This study proposed a semi-surrogate model for CFD with integration of the cutting-edge ML algorithm, eXtreme Gradient Boosting (XGB), which enlightened a possible pathway to effectively and efficiently solve and predict those costly but highly repetitive fluid dynamics-related problems. Droplet evaporation, a complex but essential phenomenon in respiratory droplets transport, was studied as the practical case using the proposed model. Droplets evaporation and dynamic size distributions were firstly tracked under various combinations of indoor humidity and temperature using traditional Eulerian-Lagrangian CFD framework, followed by generating several datasets for XGB training. The trained XGB was then used to interpret the evaporated droplets size over time under new combinations of indoor conditions. Outcomes revealed that well-trained XGB-base semi-surrogate model was capable of interpreting complex non-linear relationships between droplets dynamic parameters (diameter and time) and indoor parameters (humidity and temperature). For each specific parameter, the predictive error of well-trained XGB could retain below 5 % and its prediction speed was found nearly 1 million times faster than that of new CFD simulations. Successful applications of XGB in conjunction with CFD demonstrated its great potential on providing rapid and more efficient predictions of complex, costly and repetitive fluid dynamics-related phenomenons (e.g. droplets evaporation). Also, the XGB predicted droplets evaporation data from this study could be further applied as initial conditions into new simulations via the User-defined function (UDF).

Total and regional microfiber transport characterization in a 15th - Generation human respiratory airway.

Fiber transport and deposition in the complete respiratory airway is of great significance for human health risk assessment. Thus far, the literature has mainly focused on limited branches of the upper airway and assumes spherical particles by neglecting fiber anisotropy. To fill the gap, this paper utilized an extended realistic respiratory airway from the nasal cavity to the distal bronchial tracts, up to the 15th generation. Fibers with aerodynamic diameters from 2 to 12 µm and aspect ratios of 1, 10, and 50 were released at the inlet of the respiratory airway model, and the coupled translational and rotational motion were computed. Overall and regional fiber deposition fractions, including the nasal cavities, laryngeal airway, and lungs were predicted and compared with earlier numerical results. The study also investigated: 1) secondary flow and distributions of the fibers at the lower respiratory airway entrance; 2) upstream conditions toward fiber deposition efficiencies; 3) fiber deposition patterns and detailed deposition fractions in the five lobes. Utilizing the realistic fiber transport model, the current study found that the upstream airway geometry and the flow condition have a significant impact on the fiber transport and deposition in the downstream airway regions. The fiber depositions in the lower and middle lobes are sensitive to the fiber aerodynamic diameter, but insensitive in the upper lobes. This study expects to generate innovative knowledge on the unique fiber motion characteristics toward potential inhalation health risks.

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach.

Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies < -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI.

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

Numerical modelling of micron particle inhalation in a realistic nasal airway with pediatric adenoid hypertrophy: A virtual comparison between pre- and postoperative models.

Adenoid hypertrophy (AH) is an obstructive condition due to enlarged adenoids, causing mouth breathing, nasal blockage, snoring and/or restless sleep. While reliable diagnostic techniques, such as lateral soft tissue x-ray imaging or flexible nasopharyngoscopy, have been widely adopted in general practice, the actual impact of airway obstruction on nasal airflow and inhalation exposure to drug aerosols remains largely unknown. In this study, the effects of adenoid hypertrophy on airflow and micron particle inhalation exposure characteristics were analysed by virtually comparing pre- and postoperative models based on a realistic 3-year-old nasal airway with AH. More specifically, detailed comparison focused on anatomical shape variations, overall airflow and olfactory ventilation, associated particle deposition in overall and local regions were conducted. Our results indicate that the enlarged adenoid tissue can significantly alter the airflow fields. By virtually removing the enlarged tissue and restoring the airway, peak velocity and wall shear stress were restored, and olfactory ventilation was considerably improved (with a 16∼63% improvement in terms of local ventilation speed). Furthermore, particle deposition results revealed that nasal airway with AH exhibits higher particle filtration tendency with densely packed deposition hot spots being observed along the floor region and enlarged adenoid tissue area. While for the postoperative model, the deposition curve was shifted to the right. The local deposition efficiency results demonstrated that more particles with larger inertia can be delivered to the targeted affected area following Adenoidectomy (Adenoid Removal). Research findings are expected to provide scientific evidence for adenoidectomy planning and aerosol therapy following Adenoidectomy, which can substantially improve present clinical treatment outcomes.

A spatiotemporal assessment of occupants' infection risks in a multi-occupants space using modified Wells-Riley model.

Escalating demands of assessing airborne disease infection risks had been awakened from ongoing pandemics. An inhalation index linked to biomedical characteristics of pathogens (e.g. TCID 50 for coronavirus delta variant) was proposed to quantify human uptake dose. A modified Wells-Riley risk-assessment framework was then developed with enhanced capability of integrating biological and spatiotemporal features of infectious pathogens into assessment. The instantaneous transport characteristics of pathogens were traced by Eulerian-Lagrangian method. Droplets released via speaking and coughing in a conference room with three ventilation strategies were studied to assess occupants' infection risks using this framework. Outcomes revealed that speaking droplets could travel with less distance (0.5 m) than coughing droplets (1 m) due to the frequent interaction between speaking flow and thermal plume. Quantified analysis of inhalation index revealed a higher inhalation possibility of droplets with nuclei size smaller than 5 µ m , and this cut-off size was found sensitive to ventilation. With only 60-second exposure, occupants in the near-field of host started to have considerable infection risks (approximately 20%). This risk was found minimising over distance exponentially. This modified framework demonstrated the systematic analysis of airborne transmission, from quantifying particle inhalation possibility, targeting specific disease's TCID 50 , to ultimate evaluation of infection risks.

Atractylenolide-1 affects glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI to inhibit the proliferation and invasion of human triple-negative breast cancer cells.

Atractylenolide-1 (AT-1) is a major octanol alkaloid isolated from Atractylodes Rhizoma and is widely used to treat various diseases. However, few reports have addressed the anticancer potential of AT-1, and the underlying molecular mechanisms of its anticancer effects are unclear. This study aimed to assess the effect of AT-1 on triple-negative breast cancer (TNBC) cell proliferation and migration and explore its potential molecular mechanisms. Cell invasion assays confirmed that the number of migrating cells decreased after AT-1 treatment. Colony formation assays showed that AT-1 treatment impaired the ability of MDA-MB-231 cells to form colonies. AT-1 inhibited the expression of p-p38, p-ERK, and p-AKT in MDA-MB-231 cells, significantly downregulated the proliferation of anti-apoptosis-related proteins CDK1, CCND1, and Bcl2, and up-regulated pro-apoptotic proteins Bak, caspase 3, and caspase 9. The gas chromatography-mass spectroscopy results showed that AT-1 downregulated the metabolism-related genes TPI1 and GPI through the glycolysis/gluconeogenesis pathway and inhibited tumor growth in vivo. AT-1 affected glycolysis/gluconeogenesis by downregulating the expression of TPI1 and GPI, inhibiting the proliferation, migration, and invasion of (TNBC) MDA-MB-231 cells and suppressing tumor growth in vivo.

Scutellaria baicalensis Pith-decayed Root Inhibits Macrophage-related Inflammation Through the NF-κB/NLRP3 Pathway to Alleviate LPS-induced Acute Lung Injury.

Acute lung injury (ALI) is one of the representative "lung heat syndromes" in traditional Chinese medicine (TCM). Scutellaria baicalensis is an herbal medicine used in TCM for treating lung diseases, due to its remarkable anti-inflammatory and antiviral effects. When used in TCM, S. baicalensis root is divided into two categories: S. baicalensis pith-not-decayed root (SN) and S. baicalensis pith-decayed root (SD). Compared to SN, SD has a better effect on lung diseases. We constructed a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model to study the pharmacodynamic mechanism of SD. The ethanolic extract of Scutellaria baicalensis pith-decayed root (EESD) significantly affected LPS-induced ALI by reducing alveolar interstitial thickening, pulmonary edema, and other pathological symptoms, decreasing the infiltration of inflammatory cells, especially macrophages, and inhibiting IL-1ß, TNF-α, and IL-6 transcription and translation. Furthermore, in the THP-1 macrophage model induced by LPS, EESD inhibited the expression of phosphorylated nuclear factor inhibitory protein alpha (p-IκBα), phosphorylated nuclear factor-κB P65 (p-p65), cleaved-caspase-1, cleaved-IL-1ß protein, and the release of inflammatory factors in the NF-κB/NLRP3 pathway, inhibiting macrophage function. In vivo experiments yielded similar results. Therefore, the present study clarified the potential of EESD in the treatment of ALI and revealed its potential pharmacodynamic mechanism by inhibiting the NF-κB/NLRP3 inflammasome pathway and suppressing the pro-inflammatory phenotype activation of lung tissue macrophages.

A pH-sensitive field-effect transistor for monitoring of cancer cell external acid environment.

The external acid environment of cancer cells is different from that of normal cells, making a profound impact on cancer progression. Here we report a simple poly-l-lysine-modified graphene field-effect transistor (PLL@G-FET) for in situ monitoring of extracellular acidosis around cancer cells. PLL is a well-known material with good biocompatibility and is rich in amino groups that are sensitive to hydrogen ions. After a simple drop-casting of PLL on the reduced graphene oxide (RGO) FET surface, the PLL@G-FET was able to realize the real-time monitoring of the localized pH change of cancer cells after the cancer cells were grown on the device. The PLL@G-FET sensor achieved a Nernstian value of 52.9 mV/pH in phosphate buffer saline from pH 4.0 to 8.0. In addition, the sensor exhibited excellent biocompatibility as well as good anti-interference ability in the cell culture medium. Furthermore, the device was used to real-time monitor the extracellular pH changes of MCF-7 cells under the intervention of different concentrations of drugs. This developed pH-sensitive FET provides a new method to study the extracellular acid environment in situ and helps us to enhance our understanding of cancer cell metabolism.

Protective Effects of Atractylodis lancea Rhizoma on Lipopolysaccharide-Induced Acute Lung Injury via TLR4/NF-κB and Keap1/Nrf2 Signaling Pathways In Vitro and In Vivo.

Acute lung injury (ALI) is a syndrome caused by an excessive inflammatory response characterized by intractable hypoxemia both inside and outside the lung, for which effective therapeutic drugs are lacking. Atractylodis rhizoma, a traditional Chinese medicine, has excellent anti-inflammatory and antiviral properties in addition to protecting the integrity of the cellular barrier. However, few studies of Atractylodis rhizoma for the treatment of ALI have been published, and its mechanism of action remains unclear. In the present study, the chemical composition of the ethanolic extract of Atractylodis rhizoma (EEAR) was initially clarified by high performance liquid chromatography (HPLC), after which it was studied in vivo using a lipopolysaccharide (LPS)-induced ALI rat model. Treatment with EEAR significantly reduced the lung wet/dry (W/D) ratio, neutrophil infiltration, and malondialdehyde (MDA) and myeloperoxidase (MPO) formation, and enhanced superoxide dismutase (SOD) and glutathione (GSH) depletion in rats with ALI, thereby improving lung barrier function and effectively reducing lung injury. In addition, EEAR significantly reduced histopathological changes, decreased the expression of inflammatory factors (such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), inducible nitric oxide synthase (INOS), and cyclooxygenase-2 (COX-2)), and inhibited the activation of the NF-κB signaling pathway, thus reducing inflammation. In addition, EEAR was found to also reduce oxidative stress in ALI by upregulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins heme oxygenase-1 (HO-1) and NADPH quinone acceptor oxidoreductase 1 (NQO-1). EEAR also reduced LPS-induced inflammatory factor expression in THP-1 cells in vitro by inhibition of the NF-κB signaling pathway, and reduced damage from lipopolysaccharide (LPS)-induced oxidative stress in THP-1 cells by promoting the expression of Nrf2 and its downstream targets HO-1 and NQO-1, the molecular mechanism of which was consistent with in vivo observations. Therefore, we conclude that EEAR attenuates oxidative stress and inflammatory responses via TLR4/NF-κB and Keap1/Nrf2 signaling pathways to alleviate LPS-induced ALI, suggesting that Atractylodis rhizoma is a potential drug candidate for the treatment of ALI.

Ganfule capsule alleviates bile duct ligation-induced liver fibrosis in mice by inhibiting glutamine metabolism.

Background: Liver fibrosis is a pathological outcome of a variety of liver diseases, and it can also progress into liver cirrhosis and liver cancer. Specific liver antifibrotic drugs have not been clinically approved yet. Studies have demonstrated the protective effects of Ganfule capsule (GFL) on the liver and its therapeutic potential in hepatic cancer. However, the mechanism of GFL is not clear in the treatment of liver fibrosis. Objective: This article aims to study the protective effect of GFL on liver fibrosis and its possible mechanism. Methods: The cholestatic liver fibrosis model was prepared by subjecting C57BL/6 mice to bile duct ligation (BDL). The GFL groups were treated with different concentrations of GFL for 14 days. Pathological analysis, serum biochemical index detection, metabonomic analysis, immunohistochemistry, Western blot, and real-time PCR were carried out. Results: GFL could alleviate liver injury and liver fibrosis caused by BDL in mice. Metabonomic analysis of mice serum showed postoperative metabolic disorder, which could be alleviated by GFL through glutamine metabolism; valine, leucine, and isoleucine biosynthesis; aminoacyl-tRNA biosynthesis; and other metabolic pathways. GFL affected glutamine metabolism by inhibiting the activity of glutaminase 1 (GLS1). The activation of GLS1 is regulated by the NF-κB pathway, and experiments showed that GFL could inhibit IκB-α and NF-κB p65 phosphorylation. Conclusion: This study confirms the protective effect of GFL on liver injury and shows that GFL inhibits glutamine metabolism, which was correlated with the NF-κB pathway, and eventually alleviates liver fibrosis. These results are conducive to the development of new therapeutic drugs for liver fibrosis.

Detailed comparative analysis of environmental microparticle deposition characteristics between human and monkey nasal cavities using a surface mapping technique.

Inhaled particulate matter is associated with nasal diseases such as allergic rhinitis, rhinosinusitis and neural disorders. Its health risks on humans are usually evaluated by measurements on monkeys as they share close phylogenetic relationship. However, the reliability of cross-species toxicological extrapolation is in doubt due to physiological and anatomical variations, which greatly undermine the reliability of these expensive human surrogate models. This study numerically investigated in-depth microparticle transport and deposition characteristics on human and monkey (Macaca fuscata) nasal cavities that were reconstructed from CT-images. Deposition characteristics of 1-30µm particles were investigated under resting and active breathing conditions. Similar trends were observed for total deposition efficiencies and a single correlation using Stokes Number was fitted for both species and both breathing conditions, which is convenient for monkey-human extrapolation. Regional deposition patterns were carefully compared using the surface mapping technique. Deposition patterns of low, medium and high inertial particles, classified based on their total deposition efficiencies, were further analyzed in the 3D view and the mapped 2D view, which allows locating particle depositions on specific nasal regions. According to the particle intensity contours and regional deposition profiles, the major differences were observed at the vestibule and the floor of the nasal cavity, where higher deposition intensities of medium and high inertial particles were shown in the monkey case than the human case. Comparisons of airflow streamlines indicated that the cross-species variations of microparticle deposition patterns are mainly contributed by two factors. First, the more oblique directions of monkey nostrils result in a sharper airflow turn in the vestibule region. Second, the monkey's relatively narrower nasal valves lead to higher impaction of medium and high inertial particles on the nasal cavity floor. The methods and findings in this study would contribute to an improved cross-species toxicological extrapolation between human and monkey nasal cavities.

[Active ingredients and in vitro anti-inflammatory effects of Polygoni Cuspidati Rhizoma et Radix decoction pieces by integrated processing and traditional processing: a comparative analysis].

The present study explored the differences in active ingredients and in vitro anti-inflammatory effects of the decoction pieces by integrated processing(IPDP) and traditional processing(TPDP) of Polygoni Cuspidati Rhizoma et Radix(PCRER).The content of polydatin, resveratrol, emodin-8-O-ß-D-glucoside, emodin, and physcion in IPDP and TPDP was determined by high-performance liquid chromatography(HPLC).The inflammation model was induced by lipopolysaccharide(LPS) in RAW264.7 cells.The mRNA levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in 60% ethanol extracts of IPDP and TPDP of different concentrations(5 and 10 µg·mL~(-1)) were determined by PCR.The results showed that the content of polydatin and emodin-8-O-ß-D-glucoside in IPDP was significantly higher than that in TPDP, while the content of resveratrol, emodin, and physcion was higher in TPDP.The anti-inflammatory results showed that ethanol extracts of IPDP of different concentrations(5 and 10 µg·mL~(-1)) significantly inhibited the increase in the mRNA levels of IL-1ß and TNF-α induced by LPS, whereas TPDP only had a significant inhibitory effect on IL-1ß.This study preliminarily showed that the total content of five active ingredients in IPDP was higher than that in TPDP, and IPDP was superior to TPDP in anti-inflammatory activity in vitro, which provided an experimental basis for the production and application of IPDP.

Ultrasensitive detection of exosomal miRNA with PMO-graphene quantum dots-functionalized field-effect transistor biosensor.

Compared with the conventional DNA probe immobilization on the planar surface, nanoparticles-based DNA probes enable more RNA molecules to be anchored to the sensor surface, thereby improving the detection sensitivity. In this work, we report phosphorodiamidate morpholino oligomers (PMO)-graphene quantum dots (GQDs)-functionalized reduced graphene oxide (RGO) field effect transistor (FET) biosensors for ultrasensitive detection of exosomal microRNAs. After the RGO FET sensor was fabricated, polylysine (PLL) film was deposited onto the RGO surface. GQDs-PMO hybrid was prepared and covalently bound to PLL surface, enabling detection of exosomal microRNAs (miRNAs). The method achieved a detection limit as low as 85 aM and high specificity. Furthermore, the FET sensor was able to detect exosomal miRNAs in plasma samples and distinguish breast cancer samples from healthy samples. Compared with other methods, we use GQDs to further improve the sensitivity of FET, making it a potential tool for early diagnosis of breast cancer.