Gastrodin Attenuates Colitis and Prevents Tumorigenesis in Mice by Interrupting TLR4/MD2/NF-ΚB Signaling Transduction.

INTRODUCTION: Chronic inflammation is one of the causative factors for tumorigenesis. Gastrodin is a main active ingredient isolated from Gastrodia elata Blume, a famous medicinal herb with a long edible history. AIM: This study aimed to explore the effects of gastrodin on colitis-associated carcinogenesis (CRC) in mice and to elucidate its potential molecular mechanisms. METHODS: Balb/c mice were induced with azoxymethane (AOM) and dextran sulfate sodium (DSS) for 12 weeks. Gastrodin (50 mg/kg) was administered via oral gavage three times per week until the end of the experiment. Disease indexes, including body weight, bloody diarrhea, colon length, histopathological score, and tumor size, were measured. Tumor cell proliferation was evaluated by BrdU incorporation assay and tumor cell cytotoxicity was assessed by cell counting kit (CCK-8). The expression levels of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-ΚB) signaling molecules, NF-ΚB luciferase, and pro-inflammatory cytokines were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), immunoblotting, immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA), or reporter gene assays. The binding affinity between gastrodin and myeloid differentiation protein-2 (MD2) was analyzed by molecular docking and cellular thermal shift assay (CETSA). RESULTS: Gastrodin administration was demonstrated to mitigate various CRC-related symptoms in mice, including weight loss, diarrhea, and tissue abnormalities. Notably, gastrodin suppressed tumor cell growth during colitis- associated tumorigenesis, resulting in fewer and smaller adenomas in the colon. Unlike irinotecan, a broadspectrum antitumor drug, gastrodin did not exhibit apparent cytotoxicity in various colorectal adenocarcinoma cell lines. Additionally, gastrodin downregulated TLR4/NF-ΚB signaling molecules and pro-inflammatory mediators in mice and macrophages. Molecular docking and CETSA experiments suggested that gastrodin binds to the MD2 protein, potentially interfering with the recognition of lipopolysaccharide (LPS) by TLR4, leading to NF-ΚB pathway inhibition. CONCLUSION: This study provides evidence for the first time that gastrodin attenuated colitis and prevented colitisrelated carcinogenesis in mice, at least partially, by diminishing tumor-promoting cytokines through the interruption of TLR4/MD2/NF-ΚB signaling transduction.

Bionic Bilayer Scaffold for Synchronous Hyperthermia Therapy of Orthotopic Osteosarcoma and Osteochondral Regeneration.

Large osseous void, postsurgical neoplastic recurrence, and slow bone-cartilage repair rate raise an imperative need to develop functional scaffold in clinical osteosarcoma treatment. Herein, a bionic bilayer scaffold constituting croconaine dye-polyethylene glycol@sodium alginate hydrogel and poly(l-lactide)/hydroxyapatite polymer matrix is fabricated to simultaneously achieve a highly efficient killing of osteosarcoma and an accelerated osteochondral regeneration. First, biomimetic osteochondral structure along with adequate interfacial interaction of the bilayer scaffold provide a structural reinforcement for transverse osseointegration and osteochondral regeneration, as evidenced by upregulated specific expressions of collagen type-I, osteopontin, and runt-related transcription factor 2. Meanwhile, thermal ablation of the synthesized nanoparticles and mitochondrial dysfunction caused by continuously released hydroxyapatite induce residual tumor necrosis synergistically. To validate the capabilities of inhibiting tumor growth and promoting osteochondral regeneration of our proposed scaffold, a novel orthotopic osteosarcoma model simulating clinical treatment scenarios of bone tumors is established on rats. Based on amounts of in vitro and in vivo results, an effective killing of osteosarcoma and a suitable osteal-microenvironment modulation of such bionic bilayer composite scaffold are achieved, which provides insightful implications for photonic hyperthermia therapy against osteosarcoma and following osseous tissue regeneration.

A 4D-CBCT correction network based on contrastive learning for dose calculation in lung cancer.

OBJECTIVE: This study aimed to present a deep-learning network called contrastive learning-based cycle generative adversarial networks (CLCGAN) to mitigate streak artifacts and correct the CT value in four-dimensional cone beam computed tomography (4D-CBCT) for dose calculation in lung cancer patients. METHODS: 4D-CBCT and 4D computed tomography (CT) of 20 patients with locally advanced non-small cell lung cancer were used to paired train the deep-learning model. The lung tumors were located in the right upper lobe, right lower lobe, left upper lobe, and left lower lobe, or in the mediastinum. Additionally, five patients to create 4D synthetic computed tomography (sCT) for test. Using the 4D-CT as the ground truth, the quality of the 4D-sCT images was evaluated by quantitative and qualitative assessment methods. The correction of CT values was evaluated holistically and locally. To further validate the accuracy of the dose calculations, we compared the dose distributions and calculations of 4D-CBCT and 4D-sCT with those of 4D-CT. RESULTS: The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) of the 4D-sCT increased from 87% and 22.31 dB to 98% and 29.15 dB, respectively. Compared with cycle consistent generative adversarial networks, CLCGAN enhanced SSIM and PSNR by 1.1% (p < 0.01) and 0.42% (p < 0.01). Furthermore, CLCGAN significantly decreased the absolute mean differences of CT value in lungs, bones, and soft tissues. The dose calculation results revealed a significant improvement in 4D-sCT compared to 4D-CBCT. CLCGAN was the most accurate in dose calculations for left lung (V5Gy), right lung (V5Gy), right lung (V20Gy), PTV (D98%), and spinal cord (D2%), with the relative dose difference were reduced by 6.84%, 3.84%, 1.46%, 0.86%, 3.32% compared to 4D-CBCT. CONCLUSIONS: Based on the satisfactory results obtained in terms of image quality, CT value measurement, it can be concluded that CLCGAN-based corrected 4D-CBCT can be utilized for dose calculation in lung cancer.

[Pathogenesis of chronic heart failure in rats based on ferroptosis-mediated oxidative stress and intervention effect of Shenfu Injection].

This study aims to investigate the pathogenesis of chronic heart failure based on ferroptosis-mediated oxidative stress and predict the targets of Shenfu Injection in treating chronic heart failure. A rat model of chronic heart failure was established by the isoproterenol induction method. According to the random number table method, the modeled rats were assigned into three groups: a model group, a Shenfu Injection group, and a ferrostatin-1(ferroptosis inhibitor) group. In addition, a normal group was designed. After 15 days of intervention, the cardiac mass index and left ventricular mass index were determined. Echocardiography was employed to eva-luate the cardiac function. Hematoxylin-eosin staining and Masson staining were employed to reveal the pathological changes and fibrosis of the heart, and Prussian blue staining to detect the aggregation of iron ions in the myocardial tissue. Transmission electron microscopy was employed to observe the mitochondrion ultrastructure in the myocardial tissue. Colorimetry was adopted to measure the levels of iron metabolism, lipid peroxidation, and antioxidant indicators. Flow cytometry was employed to measure the content of lipid-reactive oxygen species(ROS) and the fluorescence intensity of ROS. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of ferroptosis-related factors in the myocardial tissue. The results showed that the rats in the model group had reduced cardiac function, elevated levels of total iron and Fe~(2+), lowered level of glutathione(GSH), increased malondialdehyde(MDA), decreased superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), and rising levels of ROS and lipid-ROS. In addition, the model group showed fibrous tissue hyperplasia with inflammatory cell infiltration and myocardial fibrosis, iron ion aggregation, and characteristic mitochondrial changes specific for iron death. Moreover, the model group showcased upregulated protein and mRNA levels of p53 and COX2 and downregulated protein and mRNA levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. The intervention with Shenfu Injection significantly improved the cardiac function, recovered the iron metabolism, lipid peroxidation, and antioxidant indicators, decreased iron deposition, improved mitochondrial structure and function, and alleviated inflammatory cell infiltration and fibrosis. Furthermore, Shenfu Injection downregulated the mRNA and protein levels of p53 and COX2 and upregulated the mRNA and protein levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. Shenfu Injection can improve the cardiac function by regulating iron metabolism, inhibiting ferroptosis, and reducing oxidative stress injury.

[Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway].

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

Photothermal antibacterial materials to promote wound healing.

Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance. Photothermal therapy (PTT) is a promising technique that uses photothermal agents (PTAs) to convert near-infrared radiation into heat, which can eliminate bacteria and stimulate tissue regeneration. PTT has the advantages of high efficiency, controllability, and low drug resistance. Hence, nanomaterial-based PTT and its related strategies have been widely explored for wound healing applications. However, a comprehensive review of PTT-related strategies for wound healing is still lacking. In this review, we introduce the physiological mechanisms and influencing factors of wound healing, and summarize the types of PTAs commonly used for wound healing. Then, we discuss the strategies for designing nanocomposites for multimodal combination treatment of wounds. Moreover, we review methods to improve the therapeutic efficacy of PTT for wound healing, such as selecting the appropriate wound dressing form, controlling drug release, and changing the infrared irradiation window. Finally, we address the challenges of PTT in wound healing and suggest future directions.

The Effects of Selenium Supplementation in the Treatment of Autoimmune Thyroiditis: An Overview of Systematic Reviews.

OBJECTIVE: The available evidence on selenium supplementation in the treatment of autoimmune thyroiditis (AIT) was inconclusive. This research serves to assess the effects of selenium supplementation in the treatment of AIT. METHODS: Online databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 10 June 2022. The AMSTAR-2 tool was used to assess the methodological quality of included studies. The information on the randomized controlled trials of the included studies was extracted and synthesized. The GRADE system was used to assess the certainty of evidence. RESULTS: A total of 6 systematic reviews with 75 RCTs were included. Only one study was rated as high quality. The meta-analysis showed that in the levothyroxine (LT4)-treated population, thyroid peroxidase antibody (TPO-Ab) levels decreased significantly in the selenium group at 3 months (SMD = -0.53, 95% CI: [-0.89, -0.17], p < 0.05, very low certainty) and 6 months (SMD = -1.95, 95% CI: [-3.17, -0.74], p < 0.05, very low certainty) and that thyroglobulin antibody (Tg-Ab) levels were not decreased. In the non-LT4-treated population, TPO-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. Tg-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. The adverse effects reported in the selenium group were not significantly different from those in the control group, and the certainty of evidence was low. CONCLUSION: Although selenium supplementation might reduce TPO-Ab levels at 3 and 6 months and Tg-Ab levels at 3 and 6 months in the non-LT4-treated population, this was based on a low certainty of evidence.

"Lifting Yang to Dredging Du Meridian Manipulation" acupuncture alleviates cerebral ischemia-reperfusion injury by mediating the NF-κB pathway.

BACKGROUND: Ischemic stroke is a permanent neurological impairment resulting from the narrowing or blockage of blood vessels in the brain. The effectiveness of "Lifting Yang to Dredging Du Meridian Manipulation" (LYDD) acupuncture in clinical treatment of ischemic stroke patients has been well-established. Nevertheless, its mechanism is still uncertain. METHODS: MCAO/R rat models at different time points of reperfusion (24, 36, 48 and 72 h) were constructed, and LYDD acupuncture treatment was performed. Zea-Longa score and TTC staining were used for assessing neurological impairment and cerebral infarct in rats, respectively. The pathological changes of cerebral tissue in each group were observed by HE and Nissl's staining. Cerebral tissue from each group was subjected to RNA-seq, and differentially expressed genes (DEGs) were performed for GO and KEGG enrichment analysis, and hub gene was identified based on the String database and MCODE algorithm. RESULTS: LYDD acupuncture treatment significantly reduced Zea-Longa score, dry-wet weight ratio, infarct area, inflammatory factor levels (IL-1ß and TNF-α), cerebral lesions, number of Nissl body and neuronal apoptosis in the MCAO/R model at different time points of reperfusion. A total of 3518 DEGs were identified in the MCAO/R model compared to the control group, and 3461 DEGs were present in the treatment group compared to the MCAO/R model, and they may be implicated in neurotransmitter transmission, synaptic membrane potential, cell junctions, inflammatory response, immune response, cell cycle, and ECM. The expression trends of BIRC3, LTBR, PLCG2, TLR4 and TRADD mRNAs in the Hub gene were consistent with the RNA-seq results, and LYDD acupuncture treatment significantly inhibited MCAO/R-induced p65 nuclear translocation. CONCLUSIONS: LYDD acupuncture ameliorates cerebral ischemia-reperfusion injury by inhibiting NF-κB pathway activity.

N-3 Polyunsaturated Fatty Acids in Elderly with Mild Cognitive Impairment: A Systemic Review and Meta-Analysis.

BACKGROUND: Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function. Supplementation of n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial to delay the decline of cognitive function in the elderly. OBJECTIVE: To investigate the effectiveness of docosapentaenoic acid (DHA) or/and eicosapentaenoic acid (EPA) supplements in the elderly with MCI. METHODS: Eight electronic databases, PubMed, Cochrane Library, Embase, VIP, SinoMed, Web of Science, CNKI, and WANFANG DATA, were searched for related articles from inception until January 2022. Subgroup analyses and sensitivity analyses were performed to detect confounding variables. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots. Stata12.0 was used for Begg's and Egger's test to quantify whether publication bias. Linear relationship between global cognition and covariates was examined in meta-regression analysis. RESULTS: Twelve studies (n = 1,124) were included. The methodological quality of research is mostly medium. Compared with placebo, n-3PUFAs supplements have benefits on global cognition [SMD = 0.51, 95% CI(0.12, 0.91), p = 0.01]. No significant differences were observed between intervention group and placebo on language fluency, executive functions, and depression. CONCLUSION: Our findings indicated DHA and/or EPA supplements have benefits on global cognition, and it may also reduce the level of blood amyloid-ß (Aß)-related biomarkers (e.g., Aß 40, Aß 42) and inflammatory factors (e.g., 1L-6, 1L-10). Since there are only two relative articles, more research is needed in the future to clarify the relationship.

[Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway].

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1ß, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1ß, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1ß and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

[Protective effect of Shenfu Injection on rats with chronic heart failure based on HMGB1/TLR4/NF-κB signaling pathway].

The study aimed to explore the mechanism and targets of Shenfu Injection in the regulation of inflammatory injury in chronic heart failure rats based on the high mobility group box-1/Toll like receptor 4/nuclear factor kappa-B(HMGB1/TLR4/NF-κB) signaling pathway. The rat model of chronic heart failure was established using isoproterenol. The modeled rats were divided into three groups by random number table: the model group, Shenfu group and glycopyrrolate group, and the normal group was also set. The rats were administrated for 15 consecutive days, and on the following day after the last administration, they were sacrificed for sample collection. The cardiac mass index and left ventricular mass index of the rats in each group were measured, and the echocardiogram was used to analyze the cardiac function indices, and ELISA to test the inflammatory indices in rat serum. The pathological morphology and fibrosis status of rat heart tissues were observed by HE staining and Masson staining, respectively. The content of HMGB1 was determined by immunofluorescence staining. The protein and mRNA expression of HMGB1/TLR4/TLR4 signaling pathway was detected by Western blot and RT-qPCR, respectively. The results showed that the chronic heart failure rat model was successfully prepared. The rats in the model group had reduced cardiac function, increased levels of HMGB1 and inflammatory factors(P<0.05), and elevated protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), with fibrous connective tissue hyperplasia, inflammatory cell infiltration and severe fibrosis. Shenfu Injection improved cardiac function, decreased the levels of HMGB1 and inflammatory factors(P<0.05) and the protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), ameliorated interstitial fibrous connective tissue hyperplasia and inflammatory cell infiltration, and reduced fibrosis. In conclusion, Shenfu Injection can reduce inflammatory damage and improve cardiac function in chronic heart failure rats by regulating the HMGB1/TLR4/NF-κB signaling pathway.

Sex-Related Differences on Chemical Composition, Anatomy, Histochemistry, and Biological Activities of Juniperus rigida.

Sex-related differences on phenolic profiles, chemical composition of essential oils, anatomy, histochemistry and biological activities (antioxidant and antibacterial activities) of Juniperus rigida needles collected from Yijun and Fugu region were first studied. In two regions, female and male had similar contents of total phenolic and total flavonoid. 10 phenolic compounds were analyzed by RP-HPLC, amentoflavone content was significantly higher in female than male in Yijun, and chlorogenic acid content was significantly higher in female than male in Fugu. 30 compounds (over 0.5 %) were detected in the essential oils, and the total contents of female were lower than male in Yijun. This difference mainly comes from Germacrene D, which was about twice as high in male as in female. Male needles had significantly larger mechanical tissue and phloem in Yijun. Histochemical analysis indicated that the phenols were stored in epidermal cells, sponge tissue, endodermis cells, edge of resin duct, stomatal bands, and the flavonoids were stored in epidermal cells, endodermis cells, edge of resin duct, stomatal bands. No sex-related differences were found in histochemical analysis, antioxidant activities (ABTS, FRAP) and antibacterial activities (9 strains). This preliminary study provided a reference for production practice and theoretical research of J. rigida.

Supramolecular erythrocytes-hitchhiking drug delivery system for specific therapy of acute pneumonia.

Acute pneumonia is an inflammatory syndrome often associated with severe multi-organ dysfunction and high mortality. The therapeutic efficacy of current anti-inflammatory medicines is greatly limited due to the short systemic circulation and poor specificity in the lungs. New drug delivery systems (DDS) are urgently needed to efficiently transport anti-inflammatory drugs to the lungs. Here, we report an inflammation-responsive supramolecular erythrocytes-hitchhiking DDS to extend systemic circulation of the nanomedicine via hitchhiking red blood cells (RBCs) and specifically "drop off" the payloads in the inflammatory lungs. ß-cyclodextrin (ß-CD) modified RBCs and ferrocene (Fc) modified liposomes (NP) were prepared and co-incubated to attach NP to RBCs via ß-CD/Fc host-guest interactions. RBCs extended the systemic circulation of the attached NP, meanwhile, the NP may get detached from RBCs due to the high ROS level in the inflammatory lungs. In acute pneumonia mice, this strategy delivered curcumin specifically to the lungs and effectively alleviated the inflammatory syndrome.

Spermine-Responsive Intracellular Self-Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer.

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

High-throughput LC-MS method for the rapid characterisation and comparative analysis of multiple ingredients of four hawthorn leaf extracts.

INTRODUCTION: The comprehensive component characterisation of Chinese herbal medicine is the premise of effectively driving the discovery of pharmacodynamic substances or new drugs in recent years. OBJECTIVE: To use the high-throughput liquid chromatography-mass spectrometry (LC-MS) approach to systematically characterise phytochemical compounds from four hawthorn leaf extracts, along with evaluating their classification. METHODS: In the present study, the compounds from 50% ethanol extract, macro porous resin extract, ethyl acetate extract and standard decoction of hawthorn leaves were completely analysed by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). RESULTS: Eight-nine compounds were putatively identified by comparison with secondary MS data and available references. Of these compounds identified, 56 compounds were found for the first time in hawthorn leaves, which was somewhat inconsistent with the findings of other studies. It could be inferred that falconoid, organic acids and nitrogenous compounds were the most abundant in 50% ethanol extract and standard decoction extract, which were considered as better choices for extracting hawthorn leaves. CONCLUSIONS: This work developed a simple, accurate and rapid method for the compound identification of hawthorn leaves, which laid the basis for further discovering pharmacodynamic material basis or new drugs from hawthorn leaves.

[Traditional Chinese medicine network pharmacology: development in new era under guidance of network pharmacology evaluation method guidance].

Traditional Chinese medicine(TCM) has unique advantages in the prevention and treatment of diseases owing to its holistic view and more than 2 000 years of experience in the clinical use of natural medicine. The "holistic" characteristic of TCM gives birth to a new generation of research paradigm featuring "network" and "system", which has been developing rapidly in the era of biomedical big data and artificial intelligence. Network pharmacology, a representative research field, provides new ideas and methods for the research of the interdiscipline of artificial intelligence and medicine, the analysis of massive biomedical data, and the transformation from data to knowledge. TCM plays an important role in proposing the core theory of "network target" and promoting the establishment and development of network pharmacology, and has taken the lead in formulating the first international standard of network pharmacology--Network Pharmacology Evaluation Method Guidance. In terms of theory, network target can systematically link drugs and diseases and quantitatively interpret the overall regulatory mechanism of drugs. In the aspect of method, network pharmacology is developing towards a research model that combines computational, experimental, and clinical approaches. This review introduces the resent important progress of TCM network pharmacology in predicting drug targets, understanding the biological basis of drugs and diseases, and searching for disease and syndrome biomarkers. Under the guidance of Network Pharmacology Evaluation Method Guidance, the development of network pharmacology is expected to become more and more standardized and healthy. Network target will help produce more high-quality research outcomes in TCM and effectively boost the modernization and internationalization of TCM.

Feasibility and mechanism analysis of Reduning in the prevention of sepsis-induced pulmonary fibrosis.

Introduction: The increasing mortality in patients with sepsis-induced pulmonary fibrosis owes to a lack of effective treatment options. This study aims to explore the possibility and possible targets of Reduning in the prevention of sepsis-related pulmonary fibrosis. Methods: The active components and targets of Reduning were searched and screened from the database and analysis platform of traditional Chinese medicine (TCM) system pharmacology. GeneCards, human genome database, DisGeNET database, and the OMIM database were checked to determine the targets associated with sepsis-induced pulmonary fibrosis. DAVID Bioinformatics Resources 6.8 was used for GO and KEGG enrichment analysis to predict its possible signaling pathways and explore its molecular mechanism. The protein-protein interaction (PPI) network was used to identify key active components and core targets. Molecular docking technology was applied to screen the complexes with stable binding of key active components and core targets. Molecular dynamics simulations were used to verify the binding stability and molecular dynamics characteristics of the complexes. The protective effect of RDN on sepsis-induced pulmonary fibrosis was verified by in vitro and in vivo experiments. Results: There were 319 shared targets between sepsis-induced pulmonary fibrosis and RDN. GO enrichment analysis showed that they mainly regulated and participated in the positive regulation of kinase activity, mitogen-activated protein kinase (MAPK) cascade, and protein phosphorylation. KEGG enrichment analysis showed that they were mainly enriched in the mitogen-activated protein kinase cascade signaling pathway, the calcium signaling pathway, the apoptosis pathway, and other signaling pathways. The results of molecular docking and molecular dynamics simulations showed that the active components, stigmasterol, beta-sitosterol, and quercetin, had good binding activities with ERBB2, and they exhibited good stability. Molecular validation experiments confirmed RDN could alleviate lung fibrosis induced by cecum ligation and puncture (CLP), in parallel with the inhibition of the ERBB2-p38 MAPK pathway in mouse alveolar macrophages (AMs). Discussion: Reduning may prevent sepsis-induced pulmonary fibrosis by regulating the ERBB2-p38 MAPK signaling pathway, which provides a possibility for the prevention of sepsis-induced pulmonary fibrosis with traditional Chinese medicine.

Pyrolysis characteristics and products distribution of petroleum sludges.

Pyrolysis can realise the harmlessness, reduction and resource utilisation of petroleum sludge in a short period. In the present work, a tank bottom sludge (SSOS) and a landing sludge (SLOS) from Shengli Oilfield were used for experimental research. Thermogravimetric testing is used to initially determine the optimal range of pyrolysis temperature. Pyrolysis experiments were performed in a tube furnace reactor. Pyrolysis products were collected and analysed separately. The char yield of SSOS and SLOS were 50% and 70%, respectively. Although there are differences in the oil content of the two types of petroleum sludge, the oil yield remained nearly the same, which were both between 7% and 8%. As the pyrolysis temperature was raised to 500°C, the yield of each product did not change greatly while their composition had obvious changes. High temperature is more conducive to the production of small molecule products. Result showed that pyrolysis treatment of petroleum sludge can effectively recover energy materials in the form of pyrolysis gas and oil. The heating value of char is lower than that of petroleum sludge, which means that char is not suitable for direct use as fuel. Pyrolysis treatment also showed good curing effect on Cr, which reached 85%. However, the solidification effect decreased as pyrolysis temperature increasing. It is necessary to pay attention to the heavy metal contained in char as soil improver. The rich surface structure of char provides evidence to produce high value-added carbon materials.

UPLC-Q-TOF-MS based metabolomics study of hawthorn leaves in different geographical regions.

The quality evaluation of hawthorn leaves in different geographical regions derived from the dried leaves of Crataegus pinnatifida Bge. Var. Major N.E.Br. or Crataegus pinnatifida Bge., a common blood-activating and stasis-eliminating traditional Chinese medicine, has hardly been reported. In this study, the chemical comparison of 40 batches of hawthorn leaf samples collected from Hebei, Liaoning, Shandong and Shanxi Provinces was performed using an ultra-high performance liquid chromatography with electrospray ionization-tandem mass spectrometry-based metabolic profile and pattern recognition analysis approach. A total of 233 compounds were determined. Among them, 40 compounds were selected as potential metabolites responsible for the differential clustering, and the differential metabolite-based evaluation model was applied to well distinguish the origin of seven batches of hawthorn leaves sold on the market. Further analysis of the KEGG pathway showed that five core metabolites containing flavonoids and lignins were mainly involved in flavonoid biosynthesis, flavone and flavonol biosynthesis, and stilbenoid, diarylheptanoid and gingerol biosynthesis. Taking the content of flavonoids, core markers, as the evaluation basis, it was found that the quality of hawthorn leaves in Hebei and Liaoning was better. The study provides a reference for the rational utilization of hawthorn leaves, and highlights that the metabolomics-driven analysis method is more suitable for the quality evaluation of traditional Chinese medicine.