Mechanism exploration of SanShi ShengXin Ointment in the treatment of pressure ulcers based on network pharmacology and molecular docking.

BACKGROUND: To explore the active ingredients, prospective targets, and action mechanisms of SanShi ShengXin Ointment in the treatment of pressure ulcers (PU) based on the network pharmacology technique and molecular docking technology. METHODS: The active ingredients and action targets of Sanshishengxin Ointment were searched through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform. The PU-related targets were retrieved from the GeneCards and DisGeNET databases. The intersection target genes of disease and drugs were obtained. The "disease-drug-active ingredient-target" was constructed using Cytoscape software. The intersection target genes were imported into the String database to construct a protein-protein interaction network for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The Auto Dock software was used for relevant molecular docking. RESULTS: A total of 78 active ingredients of SanShi ShengXin Ointment were obtained, corresponding to 539 target genes. There were 5896 PU-related target genes, and 373 intersection target genes of disease and drugs were obtained, such as STAT3, TP53, JUN, MAPK3, CTNNB1, involving PI3K-Akt, TNF, MAPK, and other related signaling pathways. CONCLUSION: Based on network pharmacology and molecular docking analyses, this study demonstrates that SanShi ShengXin Ointment can treat PU through multicomponent, multitarget, and multipathway. .

Phillygenin prevents osteoclast differentiation and bone loss by targeting RhoA.

Forsythia suspensa tea is a popular traditional Chinese medicine decoction for its healthy and therapeutic benefits. However, its effects in bone metabolism were not clear. In recent study, we uncovered anti-osteoclastogenesis property of Phillygenin (Phi), a compound abundant in Forsythia suspensa leaves, and aimed to investigate the effect and mechanism of Phi on bone metabolism in vivo and in vitro. Lipopolysaccharides-induced murine calvaria osteolysis and ovariectomy-induced bone loss animal models were used to identify the bone-protective effect of Phi in vivo and micro-CT, pQCT, and TRAP staining were applied. We used CCK8, TUNEL, BrdU, and TRAP staining to evaluate the efficacy of Phi on the proliferation and formation of OCs in primary mBMMs. RNA sequence, activity-based protein profiling, molecular docking, G-LISA, and WB were used to inspect the target and underlying mechanism of Phi's actions in mBMMs. We found Phi significantly inhibited bone resorption in vivo and inhibited mBMMs osteoclastogenesis in vitro. Ras homolog gene family member A (RhoA) was identified as the direct target of Phi. It counteracted the effects of RhoA activator and acted as a RhoA inhibitor. By targeting RhoA, Phi modulated Rho-associated coiled-coil containing protein kinase 1 (ROCK1) activity and regulated its downstream NF-κB/NFATc1/c-fos pathway. Furthermore, Phi depressed the disassembling of F-actin ring through cofilin and myosin1a. Our findings provided Phi as a potential option for treating bone loss diseases by targeting RhoA and highlighted the importance of F. suspensa as a preventive approach in bone disorders.

Design strategies for enhancing antitumor efficacy through tumor microenvironment exploitation using albumin-based nanosystems: A review.

The tumor microenvironment (TME) is a complex and dynamic system that plays a crucial role in regulating cancer progression, treatment response, and the emergence of acquired resistance mechanisms. The TME is usually featured by severe hypoxia, low pH values, high hydrogen peroxide (H2O2) concentrations, and overproduction of glutathione (GSH). The current development of intelligent nanosystems that respond to TME has shown great potential to enhance the efficacy of cancer treatment. As one of the functional macromolecules explored in this field, albumin-based nanocarriers, known for their inherent biocompatibility, serves as a cornerstone for constructing diverse therapeutic platforms. In this paper, we present a comprehensive overview of the latest advancements in the design strategies of albumin nanosystems, aiming to enhance cancer therapy by harnessing various features of solid tumors, including tumor hypoxia, acidic pH, the condensed extracellular matrix (ECM) network, excessive GSH, high glucose levels, and tumor immune microenvironment. Furthermore, we highlight representative designs of albumin-based nanoplatforms by exploiting the TME that enhance a broad range of cancer therapies, such as chemotherapy, phototherapy, radiotherapy, immunotherapy, and other tumor therapies. Finally, we discuss the existing challenges and future prospects in direction of albumin-based nanosystems for the practical applications in advancing enhanced cancer treatments.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Omega-3 polyunsaturated fatty acids in the prevention of relapse in patients with stable bipolar disorder: A 6-month pilot randomized controlled trial.

This study investigated the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in relapse prevention of bipolar disorder (BD), addressing the shortcomings of current medications. Thirty-one stable BD patients were randomized to receive n-3 PUFAs or placebo for 6 months and intergroup differences in the incidence of the recurrence of bipolar depression were assessed. Differences in depression severity, manic symptoms, and routine biochemical parameters were also assessed. Interestingly, n-3 PUFAs demonstrated a favorable preventive effect on bipolar depression recurrence (p=0.005; Log-Rank) and reduced depression severity compared to placebo, and were well-tolerated, suggesting their potential as a safe prophylactic therapy for BD.

Clerodane diterpenoids with in-vitro anti-neuroinflammatory activity from the tuberous root of Tinospora sagittata (Menispermaceae).

Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.

Evaluating the effects of tannic acid on rabbit growth performance, digestibility, antioxidant status, intestinal morphology and caecal fermentation and microbiota.

The objective of this study was to assess the effects of dietary supplementation with tannic acid (TA) on the growth performance, digestibility, antioxidant status, intestinal morphology and the caecal fermentation and microbiota in rabbits. A total number of 120 Ira rabbits (30 days of age) were randomly allotted to four dietary treatment groups: TA 0 (control), TA 0.75, TA 1.5 and TA 3, administered basal diets with 0, 0.75, 1.5 and 3 g TA/kg of feed for 28 days. Compared to the control group, dietary 3 g TA/kg inclusion decreased the average daily feed intake (p < 0.05). No significant differences were found in the digestibility among the groups (p > 0.05). Serum total antioxidant capacity was significantly higher in the 3 g/kg TA group than in the other groups (p < 0.05). There was a significant increase in the concentration of propionic acid and butyric acid in the 3 g/kg TA group. The addition of TA had no effect on villus height and crypt depth of small intestine (p > 0.05). The 16S rRNA high-throughput sequencing results showed that at the phylum level, dietary 3 g/kg TA increased the abundance of Bacteroidetes in the caecum of rabbits (p < 0.05). Based on the results, dietary TA is effective in antioxidant capacity of rabbits, improving caecal fermentation and optimizing the caecal microflora. However, the appropriate dosage supplementation of TA in rabbits needs further research.

A review of the research progress on Pinellia ternata (Thunb.) Breit.: Botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.

Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.

Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1ß, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Study on neural entrainment to continuous speech using dynamic source connectivity analysis.

Objective.Many recent studies investigating the processing of continuous natural speech have employed electroencephalography (EEG) due to its high temporal resolution. However, most of these studies explored the response mechanism limited to the electrode space. In this study, we intend to explore the underlying neural processing in the source space, particularly the dynamic functional interactions among different regions during neural entrainment to speech.Approach.We collected 128-channel EEG data while 22 participants listened to story speech and time-reversed speech using a naturalistic paradigm. We compared three different strategies to determine the best method to estimate the neural tracking responses from the sensor space to the brain source space. After that, we used dynamic graph theory to investigate the source connectivity dynamics among regions that were involved in speech tracking.Main result.By comparing the correlations between the predicted neural response and the original common neural response under the two experimental conditions, we found that estimating the common neural response of participants in the electrode space followed by source localization of neural responses achieved the best performance. Analysis of the distribution of brain sources entrained to story speech envelopes showed that not only auditory regions but also frontoparietal cognitive regions were recruited, indicating a hierarchical processing mechanism of speech. Further analysis of inter-region interactions based on dynamic graph theory found that neural entrainment to speech operates across multiple brain regions along the hierarchical structure, among which the bilateral insula, temporal lobe, and inferior frontal gyrus are key brain regions that control information transmission. All of these information flows result in dynamic fluctuations in functional connection strength and network topology over time, reflecting both bottom-up and top-down processing while orchestrating computations toward understanding.Significance.Our findings have important implications for understanding the neural mechanisms of the brain during processing natural speech stimuli.

Fabrication of Black Silicon Microneedle Arrays for High Drug Loading.

Silicon microneedle (Si-MN) systems are a promising strategy for transdermal drug delivery due to their minimal invasiveness and ease of processing and application. Traditional Si-MN arrays are usually fabricated by using micro-electro-mechanical system (MEMS) processes, which are expensive and not suitable for large-scale manufacturing and applications. In addition, Si-MNs have a smooth surface, making it difficult for them to achieve high-dose drug delivery. Herein, we demonstrate a solid strategy to prepare a novel black silicon microneedle (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The proposed strategy consists of a simple fabrication of plain Si-MNs and a subsequent fabrication of black silicon nanowires. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching. The nanowire structures were then prepared on the surfaces of the plain Si-MNs to form the BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag+ and HF concentrations during Ag nanoparticle deposition and [HF/(HF + H2O2)] ratio during Ag-catalyzed chemical etching, on the morphology and properties of the BSi-MNs were investigated in detail. The results show that the final prepared BSi-MN patches exhibit an excellent drug loading capability, more than twice that of plain Si-MN patches with the same area, while maintaining comparable mechanical properties for practical skin piercing applications. Moreover, the BSi-MNs exhibit a certain antimicrobial activity that is expected to prevent bacterial growth and disinfect the affected area when applied to the skin.

Spontaneous Internal Electric Field in Heterojunction Boosts Bifunctional Oxygen Electrocatalysts for Zinc-Air Batteries: Theory, Experiment, and Application.

Heterojunctions are a promising class of materials for high-efficiency bifunctional oxygen electrocatalysts in both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, the conventional theories fail to explain why many catalysts behave differently in ORR and OER, despite a reversible path (* O2 ⇋* OOH⇋* O⇋* OH). This study proposes the electron-/hole-rich catalytic center theory (e/h-CCT) to supplement the existing theories, it suggests that the Fermi level of catalysts determines the direction of electron transfer, which affects the direction of the oxidation/reduction reaction, and the density of states (DOS) near the Fermi level determines the accessibility for injecting electrons and holes. Additionally, heterojunctions with different Fermi levels form electron-/hole-rich catalytic centers near the Fermi levels to promote ORR/OER, respectively. To verify the universality of the e/h-CCT theory, this study reveals the randomly synthesized heterostructural Fe3 N-FeN0.0324 (Fex N@PC with DFT calculations and electrochemical tests. The results show that the heterostructural F3 N-FeN0.0324 facilitates the catalytic activities for ORR and OER simultaneously by forming an internal electron-/hole-rich interface. The rechargeable ZABs with Fex N@PC cathode display a high open circuit potential of 1.504 V, high power density of 223.67 mW cm-2 , high specific capacity of 766.20 mAh g-1 at 5 mA cm-2 , and excellent stability for over 300 h.

Self-Assembly of Selenium-Doped Carbon Quantum Dots as Antioxidants for Hepatic Ischemia-Reperfusion Injury Management.

Hepatic ischemia-reperfusion injury (HIRI) is a critical complication after liver surgery that negatively affects surgical outcomes of patients with the end-stage liver-related disease. Reactive oxygen species (ROS) are responsible for the development of ischemia-reperfusion injury and eventually lead to hepatic dysfunction. Selenium-doped carbon quantum dots (Se-CQDs) with an excellent redox-responsive property can effectively scavenge ROS and protect cells from oxidation. However, the accumulation of Se-CQDs in the liver is extremely low. To address this concern, the fabrication of Se-CQDs-lecithin nanoparticles (Se-LEC NPs) is developed through self-assembly mainly driven by the noncovalent interactions. Lecithin acting as the self-assembly building block also makes a pivotal contribution to the therapeutic performance of Se-LEC NPs due to its capability to react with ROS. The fabricated Se-LEC NPs largely accumulate in the liver, effectively scavenge ROS and inhibit the release of inflammatory cytokines, thus exerting beneficial therapeutic efficacy on HIRI. This work may open a new avenue for the design of self-assembled Se-CQDs NPs for the treatment of HIRI and other ROS-related diseases.

Investigating the Mechanism of Action of Schisandra chinensis Combined with Coenzyme Q10 in the Treatment of Heart Failure Based on PI3K-AKT Pathway.

Purpose: To study the active components, drug targets and mechanism of Schisandra chinensis (S.chinensis) combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF). Methods: Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which S.chinensis combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of S. chinensis combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot. Results: Network pharmacology combined with experimental validation suggests that the mechanism of action of S.chinensis combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, S. chinensis combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1ß and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of S.chinensis and CQ10 was more effective compared with CQ10 alone, ie, the ability of S.chinensis combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway. Conclusion: The therapeutic effect of S.chinensis combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.

Gastrodia elata BI.:A Comprehensive Review of Its Traditional Use, Botany, Phytochemistry, Pharmacology, and Pharmacokinetics.

Materials and Methods: This article collects information from relevant documents, including scientific papers, books, and dissertations concerning Gastrodia elata BI. Results: To date, research on Gastrodia elata BI. has identified about 100 active compounds. Many compounds in Gastrodia elata BI. have biological activities, such as sedation and hypnosis, anticonvulsion, improvement of learning and memory, protection of neurons, antidepressive effects, lowering of blood pressure, promotion of angiogenesis, protection of cardiomyocytes, antiplatelet aggregation, anti-inflammatory activity, and amelioration of labor pains. Conclusion: Although many traditional uses of this plant have been confirmed, it is necessary to continue to study the relationship between its structure and function, clarify the mechanisms of pharmacological effects, and explore new clinical applications so as to better delineate the quality control standards for Gastrodia elata BI.

Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation.

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.

[Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells].

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Structure, anti-fatigue activity and regulation on gut microflora in vivo of ethanol-fractional polysaccharides from Dendrobium officinale.

This study was to investigate the antifatigue, prebiotic effects and their relationships to the structure properties of three ethanol precipitated polysaccharides from Dendrobium officinale (EPDO), as EPDO-40, EPDO-60 and EPDO-80. EPDOs with anti-fatigue activity were screened out by forced swimming test, and blood lactic acid (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), liver glycogen, muscle glycogen, and intestinal microflora were investigated. Results showed that purified EPDO-60, 277.3 kDa, with a backbone consisted of 4-Manp and 4-Glcp. EPDO-60 had the best anti-fatigue activity, because it could significantly prolong the forced swimming time, as well as down-regulating the levels of BLA and BUN, increasing SOD. Proportions of Bacteroidetes and Firmicutes and abundance of Lactobacillus and Bifidobacterium in gut microflora increased after treated with EPDO-60. Accordingly, EPDO-60 could affect the community structure of gut microflora, leading to promote the balance of oxidation and antioxidation, and accelerated the fatigue metabolism in vivo.