Probable targets and mechanism of ginsenoside Rg1 for non-alcoholic fatty liver disease: a study integrating network pharmacology, molecular docking, and molecular dynamics simulation.

Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.

Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation.

Apolipoprotein E (ApoE) is a member of apolipoprotein (apo) family and plays critical role in lipid metabolism. In this study, the relationship between abnormal lipid metabolism caused by ApoE-deficient and male reproduction was investigated. The effect of hyperbaric oxygen (HBO) therapy on 7-month-old ApoE-knockout male mice was assessed subsequently. Mice were randomly divided into 3 groups: control group (WT), ApoE (- / -) group (AP-CON), and ApoE (- / -) plus HBO group (AP-HBO), which received HBO treatment. We found that ApoE knockout caused a decrease in male reproductive capacity due to the reduced total sperm motility, progressive motility (PR), and lower blastocyst formation rate. HBO treatment could accelerate serum lipoprotein metabolism including LDL, T-CHO, and TG and semen quality. As a result, fertilization and blastocyst formation of AP-HBO group were higher than that of AP-CON, proving positive therapeutic effect. Mechanism exploration found that HBO treatment ameliorated the testicular microenvironment by attenuating inflammatory factor production and oxidative stress, eventually improved the sperm motility. Collectively, our study provided more evidences of HBO treatment for improving the semen quality of patients with abnormal lipid metabolism caused by ApoE-deficient.

Identification of Q-Markers from Hedan Tablet by employing "spider-web" mode and taking compounds' hepatotoxicity into account.

Objective: Due to the complicated compounds and the synergistic effect of multi-compounds, the quality control and assessment of Chinese materia medica (CMM) encounters a great challenge about how to identify the key compounds, which are directly correlated with its efficacy and safety. On the guidance of study on quality marker (Q-Marker), identification of Q-Markers was performed from Hedan Tablet (HDT) by the aid of the "spider-web" mode and hepatotoxicity evaluation derived from our previous researches and literatures. Methods: By the established ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method, online UPLC-DPPH· and offline antioxidant assay, 21 candidate compounds of HDT were systematically investigated and comprehensively evaluated by the "spider-web" mode for them properties of Q-Marker based on "content-stability-activity". In addition, the Q-Markers related with hepatotoxicity based on our previous researches and literatures were identified. Results: Salvianolic acid B (SaB), quercetin-3-O-glucuronide (Qug), isoquercitrin (IQ) and hyperoside (Hyp) were adopted as the preferable Q-Markers of HDT according to the shaded area (A) of tested compounds in "spider-web" mode. Psoralen (Ps), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) were also strongly recommended as Q-Markers closely related with safety by considering hepatotoxicity of the accumulated Ps and IP and conversion between glycoside (PO and IPO) and aglycone (Ps and IP). Conclusion: This study provided scientific evidence for quality control and assessment of HDT, and also provided a meaningful reference for application of Q-Markers in CMM.

[Quality evaluation of Psoraleae Fructus based on QAMS method and TLC identification].

The present study established a determination method of Psoraleae Fructus by quantitative analysis of multi-components by the single marker(QAMS) and further improved the thin-layer chromatography(TLC) method. The QAMS method was established by UPLC with psoralen as the internal marker, and the content of psoralenoside, isopsoralenoside, psoralen, and isopsoralen was simultaneously determined. As revealed by the comparison with results of the external standard method, the QAMS method was accurate and feasible. According to the current quality standards of Psoraleae Fructus, the TLC method was further optimized and improved, and bakuchiol was added for identification based on the original TLC method with psoralen and isopsoralen as indicators. This study provides a reference for improving the quality control method of Psoraleae Fructus.

Advances in Chemical Composition, Extraction Techniques, Analytical Methods, and Biological Activity of Astragali Radix.

Astragali Radix (AR) is one of the well-known traditional Chinese medicines with a long history of medical use and a wide range of clinical applications. AR contains a variety of chemical constituents which can be classified into the following categories: polysaccharides, saponins, flavonoids, amino acids, and trace elements. There are several techniques to extract these constituents, of which microwave-assisted, enzymatic, aqueous, ultrasonic and reflux extraction are the most used. Several methods such as spectroscopy, capillary electrophoresis and various chromatographic methods have been developed to identify and analyze AR. Meanwhile, this paper also summarizes the biological activities of AR, such as anti-inflammatory, antioxidant, antitumor and antiviral activities. It is expected to provide theoretical support for the better development and utilization of AR.

Optimization of extraction and bioactivity detection of celery leaf flavonoids using BP neural network combined with genetic algorithm and response.

In the present study, ultrasound-assisted extraction was employed to extract the general flavone from celery leaves using response surface methodology and BP neural network model with a genetic algorithm (GA). The effects of temperature, time, solid-liquid ratio, and ethanol concentration on the extraction results were assessed by Box-Behnken design. Further optimization of the process was performed by GA-BP. Our results showed that the optimal conditions were an ethanol concentration of 70.31%, a temperature of 67.2 °C and an extraction time of 26.6 min. In addition, significant antioxidant activity and in vitro bacteriostasis were observed. We found that the total flavonoids of the celery leaves exerted a strong inhibitory effect on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Additionally, considerable DPPH· and ·OH scavenging effects were exerted by flavonoids. Therefore, flavonoids from celery leaves can be considered natural antioxidants and bacterial inhibitors.

Mindfulness-based intervention in Chinese pregnant women with recurrent miscarriage: A non-randomized controlled study.

OBJECTIVE: Pregnant women with recurrent miscarriage have high rates of anxiety and depression. Mindfulness-based interventions have shown benefits in improving mental health in diverse populations; however, few studies have explored their efficacy in pregnant women with recurrent miscarriage, which was investigated in the present study. DESIGN: A nonrandomized controlled study was carried out from August 2019 to November 2020. SETTING: The study was conducted at a regional teaching hospital in Guangzhou, China that provides leading care for recurrent miscarriage. PARTICIPANTS: A total of 158 pregnant women with recurrent miscarriage were recruited and allocated to the intervention group (n = 79) or the control group (n = 79); 131 women completed the study. INTERVENTION: The mindfulness-based intervention consisted of a 1-h education session and daily mindfulness exercises guided by audio recordings during hospitalization. MEASUREMENTS AND FINDINGS: Study outcomes included perceived stress measured with the Perceived Stress Scale; symptoms of anxiety and depression measured with the Self-rating Anxiety Scale and Edinburgh Postnatal Depression Scale, respectively; and positive and negative affect measured with the Positive Affect and Negative Affect Scale - Revised, respectively. Compared to the control group, participants in the intervention group showed significant decreases in perceived stress, depression symptoms, and negative affect and an increase in positive affect after the intervention. Anxiety increased significantly in the control group during the study but remained unchanged in the intervention group. KEY CONCLUSIONS: A mindfulness-based intervention can reduce psychological symptoms and improve mental health in pregnant women with recurrent miscarriage. IMPLICATIONS FOR PRACTICE: A mindfulness-based intervention should be incorporated into routine care to help improve the mental health of pregnant women with recurrent miscarriage.

Anti-aging function and molecular mechanism of Radix Astragali and Radix Astragali preparata via network pharmacology and PI3K/Akt signaling pathway.

BACKGROUND: Radix Astragali (RA) consists of the dried root of Astragalus membranaceus Bunge and is one of the most frequently used dietetic Chinese herbs to treat inflammation and neurodegenerative disease among other conditions. Radix Astragali preparata (RAP) is a medicinal form of RA. RA and RAP have been used as anti-aging agent, however, the mechanisms underlying their effects are still unclear. PURPOSE: Considering the wide application of RA and RAP in clinical practice, it is necessary to identify the better product between the two and elucidate the molecular mechanism responsible for their anti-aging effects. STUDY DESIGN: In this study, network pharmacology integrated with molecular biology techniques were employed to explore the possible mechanism of RA and RAP against aging. METHODS: Aging animal models were constructed by exposure to D-galactose (D-gal), and the anti-aging effect of RA and RAP were determined based on behavior tests and histomorphological observation. Network pharmacology was performed to construct the "compound-target-pathway" network. Gene and protein expression of possible targets were validated and analyzed using qRT-PCR and Western blotting. RESULTS: Treatment by RA and RAP could alleviate the symptoms of aging such as a decrease in body weight and organ indices, behavioral impairment, increased oxidative stress, weaken histopathological evaluation. The effect of RAP was more pronounced than that of RA in preventing aging process in a mouse model. The anti-aging effect of RA and RAP is associated with the balance of oxidative stress and activation of PI3K/Akt signaling pathway. CONCLUSION: Using an integrated strategy of network pharmacology and molecular biology we attempted to elucidate the mechanisms of action of RA and RAP.

Evaluation of the chemical qualities and microstructural changes of Lentinula edodes caused by airborne ultrasonic treatment combined with microwave vacuum drying.

This study analyzed a new drying method using airborne ultrasound combined with microwave vacuum to study its effect on the quality characteristics and microstructure of dehydrated L. edodes. Ultrasonic treatment resulted in many micropores in the product, forming the sponge effect caused by ultrasonic waves, which can promote the rapid evaporation of water in the product. Samples of Lentinula edodes individuals were dried using four methods: hot air drying (HAD), microwave vacuum drying (MVD), microwave vacuum drying after ultrasonic pretreatment (US+MVD) and airborne ultrasonic treatment combined with microwave vacuum drying (USMVD). The results showed that USMVD can reduced the loss of total sugar, total phenol, and total antioxidants in L. edodes, and increased the relative content of ergosterol, sulfur compounds, and free amino acids (p < 0.05). Scanning electron microscope observation revealed that USMVD resulted in a uniform reticular porous structure, which could better maintain desirable levels of nutrients. Therefore, USMVD can produce high quality products. PRACTICAL APPLICATION: Airborne ultrasonic waves combined with MVD provides an innovative drying method for mushrooms, which has not been studied at present. The mixed drying method has great potential in maintaining product quality. It provides a theoretical basis for studying drying technology in the future.

Application of "spider-web" mode in discovery and identification of Q-markers from Xuefu Zhuyu capsule.

BACKGROUND: The selection of quality control indicators in a complex system is a key scientific issue for the study of Chinese materia medica (CMM), which is directly related to its safety and efficacy. In order to scientifically understand and control the quality of CMM, quality marker (Q-marker) has been recently raised as a new concept, which provided a novel research idea for the quality control and evaluation of CMM. PURPOSE: By a new and integrated "spider-web" mode, Q-markers of Xuefu Zhuyu capsule (XZC) were comprehensively uncovered, conducing to great improvement of quality control of XZC. METHODS: Mainly established by three dimensions derived from six variables including content, stability and activity, "spider-web" mode was constructed to evaluate Q-marker property of candidate compounds by taking regression area of the tested compounds into account. RESULTS: The candidate compounds with larger regression area were preferentially adopted as Q-markers, which should possess the satisfactorily integrated properties of content, stability and activity. Six compounds, naringin, isoliquiritin, paeoniflorin, protocatechuic acid, neohesperidin and ferulic acid, were identified and preferred as Q-markers of XZC. CONCLUSION: Based on "spider-web" mode, Q-markers from Xuefu Zhuyu capsule were successfully screened, which would substantially perform quality control of XZC and prove the feasibility of "spider-web" mode in solving the selection of quality control indicators from compound formulae.

Natural Chalcones in Chinese Materia Medica: Licorice.

Licorice is an important Chinese materia medica frequently used in clinical practice, which contains more than 20 triterpenoids and 300 flavonoids. Chalcone, one of the major classes of flavonoid, has a variety of biological activities and is widely distributed in nature. To date, about 42 chalcones have been isolated and identified from licorice. These chalcones play a pivotal role when licorice exerts its pharmacological effects. According to the research reports, these compounds have a wide range of biological activities, containing anticancer, anti-inflammatory, antimicrobial, antioxidative, antiviral, antidiabetic, antidepressive, hepatoprotective activities, and so on. This review aims to summarize structures and biological activities of chalcones from licorice. We hope that this work can provide a theoretical basis for the further studies of chalcones from licorice.

Molecular Mechanisms That Define Redox Balance Function in Pathogen-Host Interactions-Is There a Role for Dietary Bioactive Polyphenols?

To ensure a functional immune system, the mammalian host must detect and respond to the presence of pathogenic bacteria during infection. This is accomplished in part by generating reactive oxygen species (ROS) that target invading bacteria; a process that is facilitated by NADPH oxidase upregulation. Thus, bacterial pathogens must overcome the oxidative burst produced by the host innate immune cells in order to survive and proliferate. In this way, pathogenic bacteria develop virulence, which is related to the affinity to secrete effector proteins against host ROS in order to facilitate microbial survival in the host cell. These effectors scavenge the host generated ROS directly, or alternatively, manipulate host cell signaling mechanisms designed to benefit pathogen survival. The redox-balance of the host is important for the regulation of cell signaling activities that include mitogen-activated protein kinase (MAPK), p21-activated kinase (PAK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor κB (NF-κB) pathways. An understanding of the function of pathogenic effectors to divert host cell signaling is important to ascertain the mechanisms underlying pathogen virulence and the eventual host-pathogen relationship. Herein, we examine the effectors produced by the microbial secretion system, placing emphasis on how they target molecular signaling mechanisms involved in a host immune response. Moreover, we discuss the potential impact of bioactive polyphenols in modulating these molecular interactions that will ultimately influence pathogen virulence.

Multicolor and photothermal dual-readout biosensor for visual detection of prostate specific antigen.

Developing a facile and reliable approach for tumor marker detection is crucial in early diagnosis of cancer. Here, a multicolor and photothermal dual signal readout immunosensor was proposed based on a nanoparticle-mediated transformation strategy and used for sensitive detection of prostate specific antigen (PSA). To construct such a platform, Fe3O4 nanoparticles (NPs) -functionalized graphene oxide was modified with partially complementary DNA and served as the signal probes. In the absence of PSA, the signal probes were captured via hybridization reaction between DNA and PSA aptamer. Subsequently, Fe3O4 NPs anchored on the probes were transformed into a photothermal agent, Prussian blue NPs, which converted biological signal into heat via the near-infrared laser irradiation, and thus sensitive quantitative detection of PSA was realized by using a thermometer with a lower detection limit of 0.31 ng/mL. Meanwhile, Prussian blue NPs displayed multiply colors by mixing with potassium ferricyanide, and rapid qualitative detection by naked eyes was realized. The two sets of data mutually validate each other, which greatly improved the accuracy and reliability of PSA detection. More strikingly, graphene oxide as the enrichment carrier of Fe3O4 NPs significantly enhanced the accumulation of Prussian blue NPs in situ, and thus the signal amplification was effectively accomplished. Besides, the sensing strategy avoided the use of enzyme and simplified analysis process. Such a cost-effective and sensitive dual-readout visual protocol opens up new perspectives for personalized diagnosis and on-site detection.

Berberine suppresses mast cell-mediated allergic responses via regulating FcɛRI-mediated and MAPK signaling.

The anti-allergic effect of berberine was evaluated in cellular and animal models of allergic responses. In this study, the results of the in vitro model of immunoglobulin (Ig) E-mediated mast cell degranulation showed that berberine significantly inhibited the release of ß-hexosaminidase (ß-HEX), histamine, IL-4 and TNF-α in rat basophilic leukemia cells (RBL-2H3 cells). Pretreatment with berberine prevented morphological changes in IgE-stimulated RBL-2H3 cells such as the recovery of an elongated shape. Pretreatment with berberine also suppressed the phosphorylation of antigen-induced Lyn, Syk, and Gab2, thus suppressing the downstream MAPK pathways. In the in vivo model of allergic responses, administration of berberine inhibited passive cutaneous anaphylaxis (PCA) in mice. The above results indicate berberine could suppress mast cell activation and allergic responses.

Pd nanoparticle-decorated hydroxy boron nitride nanosheets as a novel drug carrier for chemo-photothermal therapy.

A multi-stimuli responsive nanoagent, hydroxy boron nitride nanosheets and Pd nanohybrids (Pd@OH-BNNS), was studied. The well-dispersed hydroxy boron nitride nanosheets were prepared via a facile thermal substitution approach. Pd@OH-BNNS was endowed with a photothermal property after in situ formation of Pd nanoparticles on the surface of the nanosheets. Pd@OH-BNNS as a drug delivery carrier exhibited high loading capability for the anticancer drug doxorubicin. The release of doxorubicin from the nanohybrids was triggered by a decrease in pH, and increases in glutathione concentration and near-infrared irradiation. The faster release behavior of the nanohybrids under near-infrared irradiation was confirmed by a cellular uptake study. In addition, local hyperthermia was verified using an imaging test and an infrared thermal camera. Tumor growth was remarkably inhibited in mice after two weeks of treatment with Pd@OH-BNNS/doxorubicin injection, demonstrating the high efficacy of combining chemotherapy and photothermal therapy. The Pd@OH-BNNS as a drug delivery system exhibited good stability, low cytotoxicity and multi-stimuli responsiveness.

Governor vessel moxibustion: Ancient Chinese medical technology with new vitality.

Moxibustion is an ancient therapeutic technique used in Chinese medicine. Governor Vessel moxibustion (GVM) was developed from long snake moxibustion, a popular technique used in China's Jiangsu and Zhejiang Provinces, and is significantly more effective than general moxibustion. We aimed to review GVM, including its theoretical basis, choices of moxibustion points and materials, operation procedures, clinical applications, and contraindications. This information could increase the appropriate use of GVM and support further in-depth research.

A Historical Cohort Study on the Efficacy of Glucocorticoids and Riboflavin Among Patients with Late-onset Multiple Acyl-CoA Dehydrogenase Deficiency.

BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown. METHODS: We performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected. RESULTS: After 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time. CONCLUSIONS: Our results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

RNAi targeting putative genes in phosphatidylcholine turnover results in significant change in fatty acid composition in Crambe abyssinica seed oil.

The aim of this study was to evaluate the importance of three enzymes, LPCAT, PDCT and PDAT, involved in acyl turnover in phosphatidylcholine in order to explore the possibility of further increasing erucic acid (22:1) content in Crambe seed oil. The complete coding sequences of LPCAT1-1 and LPCAT1-2 encoding lysophosphatidylcholine acyltransferase (LPCAT), PDCT1 and PDCT2 encoding phosphatidylcholine:diacylglycerol cholinephosphotransferase (PDCT), and PDAT encoding phospholipid:diacylglycerol acyltransferase (PDAT) were cloned from developing Crambe seeds. The alignment of deduced amino acid sequences displayed a high similarity to the Arabidopsis homologs. Transgenic lines expressing RNA interference (RNAi) targeting either single or double genes showed significant changes in the fatty acid composition of seed oil. An increase in oleic acid (18:1) was observed, to varying degrees, in all of the transgenic lines, and a cumulative effect of increased 18:1 was shown in the LPCAT-PDCT double-gene RNAi. However, LPCAT single-gene RNAi led to a decrease in 22:1 accumulation, while PDCT or PDAT single-gene RNAi had no obvious effect on the level of 22:1. In agreement with the abovementioned oil phenotypes, the transcript levels of the target genes in these transgenic lines were generally reduced compared to wild-type levels. In this paper, we discuss the potential to further increase the 22:1 content in Crambe seed oil through downregulation of these genes in combination with fatty acid elongase and desaturases.

[Data mining analysis of professor Li Fa-zhi AIDS itchy skin medical record].

OBJECTIVE: Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of itchy skin, provide the corresponding drug reference basis for Chinese medicine treatment of AIDS, skin itching. METHOD: By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS patients with skin pruritus, etiology and pathogenesis analysis, skin itching AIDS syndrome differentiation of old Chinese medicine treatment and medication rule. RESULT: The use of multi-dimensional query analysis, core drug skin itching AIDS treatment in this study as a windbreak, cicada slough, bupleurum, Qufeng solution table drug, licorice detoxification efficacy of drugs, Radix Scutellariae, Kochia scoparia, clearing away heat and promoting diuresis medicine; core prescription for Jingfang San streak virus. CONCLUSION: Professor Li Fa-zhi treatment of AIDS in the skin itching Qufeng solution table dehumidification antipruritic treatment.

[Data mining analysis of professor Li Fa-zhi AIDS herpes zoster medical record].

OBJECTIVE: Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of herpes zoster and postherpetic neuralgia, provide reference for the use of Chinese medicine treatment of AIDS, herpes zoster and postherpetic neuralgia. METHOD: By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS of herpes zoster and postherpetic neuralgia patients, patients are input structured clinical information collection system, into the analysis of the data, carries on the research analysis theory of traditional Chinese medicine compatibility system algorithm and complex network analysis the use of complex networks. RESULT: The use of multi-dimensional query analysis of AIDS drugs, the core of herpes zoster and postherpetic neuralgia treated in this study are Scutellariae Radix, Glucyrrhizae Radix, Carthame Flos, Plantaginis Semen, Trichosamthis Fructus, Angelicae Sinensis Radix, Gentianae Radix; core prescription for Longdan Xiegan decoction and Trichosanthes red liquorice decoction. CONCLUSION: Professor Li Fa-zhi treatment of AIDS, herpes zoster and postherpetic neuralgia by clearing heat and removing dampness and activating blood circulation to.