Mussel-Inspired Calcium Alginate/Polyacrylamide Dual Network Hydrogel: A Physical Barrier to Prevent Postoperative Re-Adhesion.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility. How to effectively prevent postoperative re-adhesion has become a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for the postoperative anti-adhesion of IUA. First, a calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared via covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it showed excellent adhesion (more than 6 kPa). Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.

Network Pharmacology Combined with Molecular Docking and Experimental Verification Reveals the Bioactive Components and Potential Targets of Danlong Dingchuan Decoction against Asthma.

BACKGROUND: Danlong Dingchuan Decoction has a definite effect in the clinical treatment of asthma. This study aimed to explore the material and molecular biological basis of Danlong Dingchuan Decoction in treating asthma through network pharmacology combined with animal experiments. MATERIALS AND METHODS: First, the chemical constituents of Danlong Dingchuan Decoction were screened from the Traditional Chinese Medicine Systematic Pharmacology Analysis Platform (TCMSP) and the Traditional Chinese Medicine and Chemical Composition Database. Literature reports on asthma targets were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic Targets Database (TTD), and other databases. Then, the protein-protein interaction network was constructed according to the matching results of Danlong Dingchuan Decoction and asthma targets. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, the interaction between the active compounds of Danlong Dingchuan Decoction and key targets was simulated using molecular docking. In animal experiments, ovalbumin was used to induce asthma in mice. After treating the mice by oral gavage administration of Danlong Dingchuan Decoction, the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in the lung tissue of the mice by enzyme-linked immunosorbent assay kit, whereas TLR4 mRNA expression was detected by quantitative reverse transcription-polymerase chain reaction. RESULTS: A total of 247 active compounds and 155 potential targets were obtained. Enrichment analysis showed that quercetin, xanthine, lysine, kaempferol, ß-sitosterol, and four other active compounds were the main components of Danlong Dingchuan Decoction; IL-6, TNF, CXCL8, VEGFA, MAPK3, IL-10, PTGS2, IL-1ß, IL-4, and TLR4 were the potential targets for therapy. KEGG analysis showed that the cAMP signaling pathway, cGMP-PKG signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway might play an important role in treating asthma. Molecular docking analysis showed that quercetin combined well with TNF, CXCL8, and TLR4. Animal experiments showed that Danlong Dingchuan Decoction effectively reduced the expression levels of TNF-α, IL-4, TGF-ß1, IL-6, IL-8, and IL-1ß in the lung tissue of asthmatic mice and inhibited TLR4 mRNA expression. CONCLUSIONS: Danlong Dingchuan Decoction may act on key targets (such as IL-6, TNF, CXCL8, VEGFA, and MAPK3) with key active ingredients (such as quercetin, xanthine, lysine, kaempferol, and ß-sitosterol) to reduce the expression levels of IL-4, IL-6, IL-8, and other Th2 cytokines. This may be the mechanism by which Danlong Dingchuan Decoction reduces airway inflammation and treats asthma mediated by Th2 cytokines.

Application of multivariate statistical analysis and network pharmacology to explore the mechanism of Danggui Liuhuang Tang in treating perimenopausal syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Liuhuang Tang (DGLHT), first recorded in "Lan-Shi-Mi-Cang" (written in 1276 AD), is a famous classical formula. In 2018, it was listed in the Catalogue of Ancient Classic and Famous Prescriptions (First Batch) formulated by the National Administration of Traditional Chinese Medicine and the National Medical Products Administration. Perimenopausal syndrome (PMS) refers to a series of syndromes with autonomic nervous system dysfunction and neuropsychological symptoms. The treatment of PMS demands non-hormonal drugs. Natural products are considered to be effective substitutes for the treatment of PMS. It is reported that DGLHT has not only good therapeutic effects but also higher safety and fewer side effects in the treatment of PMS. However, the mechanism of DGLHT in treating PMS is not clear. AIM OF THE STUDY: To explore the chemical basis and the mechanism of DGLHT in treating PMS. MATERIALS AND METHODS: Multivariate statistical analysis was used to analyze the difference of components in supernatant before and after compatibility of DGLHT based on LC-MS data. The qualitative analysis was performed on the precipitate formed in the decocting process using LC-MS while the quantitative analysis on the potential markers using LC-UV. Then, the potential markers were analyzed by network pharmacology. The regulatory effect of DGLHT on FSH, P and E2 were carried out in PMS rats. RESULTS: Five potential markers, epiberberine, coptisine, palmatine, berberine and baicalin, were screened from the analysis of compounds in the supernatant. Four complexes, composed of potential marker monomers, were identified in the sediment, including two that have not been reported. The key targets of potential markers include TNF, NOS3, EGFR, ESR1, PTGS2, AR, CDC42 and RPS6KB1. The top signaling pathways include the cGMP-PKG signaling pathway, PI3K-Akt signaling pathway and estrogen signaling pathway. DGLHT could call back the hormone levels of P and E2 in PMS rats. CONCLUSION: DGLHT active ingredients, epiberberine, coptisine, palmatine, berberine and baicalin contribute a lot to the therapeutic effect. And DGLHT takes effect by regulating hormones secreted by the ovary.

Pharmacokinetic study of Tangwang Mingmu granule for the management of diabetic retinopathy based on network pharmacology.

CONTEXT: Tangwang Mingmu granule (TWMM), a traditional Chinese medicine, has been widely used in the treatment of diabetic retinopathy (DR), the most common microvascular complication in diabetes mellitus. OBJECTIVE: To establish a method to select target compounds from herbs for a pharmacokinetic study using network pharmacology, which could be applied in clinical settings. MATERIALS AND METHODS: First, UPLC/Q Exactive Q-Orbitrap and GCMS 2010 were used to determine the non-volatile and volatile ingredients of TWMM. Based on the identified compounds, network pharmacology was used to screen the key compounds and targets of TWMM in the treatment of DR. Based on the compound-target-pathway network and identification of components emigrant into blood, the potential compound markers in vivo were chosen. Then, Sprague-Dawley (SD) rats were administrated of TWMM at a 9.6 g/kg dose to investigating pharmacokinetic parameters using the UPLC-QQQ-MS. RESULTS: Ninety and forty-five compounds were identified by UPLC-MS and GC-MS, respectively. Based on the network pharmacology, nine compounds with a degree value above 15 were screened and implied that these compounds are the most active in DR treatment. Moreover, criteria of degree value greater than 7 were applied, and PTGS2, NOS2, AKT1, ESR1, TNF, and MAPK14 were inferred as the core targets in treating DR. After identification of components absorbed into blood, luteolin and formononetin were selected and used to investigate the pharmacokinetic parameters of TWMM after its oral administration. CONCLUSIONS: The reported strategy provides a method that combines ingredient profiling, network pharmacology, and pharmacokinetics to determine luteolin and formononetin as the pharmacokinetic markers of TWMM. This strategy provides a clinically relevant methodology that allows for the screening of pharmacokinetic markers in Chinese medicines.

[Predictive analysis of quality markers of Coptidis Rhizoma based on network pharmacology and multivariate statistical analysis].

Coptidis Rhizoma, as a bulk medicinal material, is in great demand in clinical practice. Its quality is uneven in the market due to the mixture of genuine, counterfeit and adulterants. Therefore, it is particularly important to establish a quality control system for Coptidis Rhizoma. Based on the concept of Chinese medicine quality marker(Q-marker), the potential quality markers of Coptidis Rhizoma were analyzed and predicted from the perspective of chemistry and pharmacology. The sources of the Q-markers of Coptidis Rhizoma were identified by literature retrieval. The potential Q-markers were then screened through the visualization of the "components-targets-pathways" network. High performance liquid chromatography(HPLC) was used to establish a multi-indicator qualitative and quantitative control method featuring fingerprints for 10 batches of Coptidis Rhizoma. A supervised mode of orthogonality partial least squares method-discriminant analysis(OPLS-DA) was used to screen the main marker components that caused differences between groups. The literature review results showed that the alkaloids were the main source of Coptidis Rhizoma Q-markers.The fingerprints of 13 common peaks were successfully established, and berberine, palmatine, berberine and epiberberine were selected as Q-markers of Coptidis Rhizoma, and their contents were determined.Based on the concept of the Q-marker of traditional Chinese medicine, the four components can be selected as the Q-marker of Coptidis Rhizoma after comprehensive consideration. The results of this study are not only conducive to the quality evaluation of Coptidis Rhizoma on the market, but also provide a reference for the overall quality control of Coptidis Rhizoma and lay foundation for the future exploration of the mechanism of Coptidis Rhizoma.

Network pharmacology combined with metabolomics to study the mechanism of Shenyan Kangfu Tablets in the treatment of diabetic nephropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenyan Kangfu Tablets (SYKFT) is a traditional prescription evolved from Shenqi Pills. It has been included in the Synopsis of the Golden Chamber for more than 2000 years. SYKFT was listed as a national Chinese medicine protected class by the China Food and Drug Administration. Diabetic nephropathy (DN) is one of the serious microvascular diseases caused by diabetes and is also one of the important factors leading to the death of patients. The pathogenesis of DN is diverse and complex, and there is no particularly effective drug treatment. There is clinical evidence that SYKFT has a good therapeutic effect on DN with no obvious adverse effects, but the mechanism of treatment is not clear. AIM OF THE STUDY: In this study, network pharmacology was combined with metabolomics technology to explore the mechanism of SYKFT in the treatment of DN. MATERIALS AND METHODS: First, the research team conducted a qualitative study of the chemical components contained in SYKFT, and carried out network pharmacology to search for potential targets based on the characterized chemical components. Second, we analysed the metabolic profile of db/db mouse urine based on UHPLC-QTOF-MS technology, and biomarkers were identified by multivariate statistical analysis. Then, we performed further pathway enrichment analysis. Finally, the results of metabolomics and network pharmacology were conjointly analysed. RESULTS: Seventy-five chemical components of SYKFT were identified. According to the TCMSP database, the corresponding targets of the qualitatively identified components were searched, and a total of 36 potentially active components and 160 targets related to DN were obtained. A total of 38 biomarkers were found in metabolomics based on UHPLC-QTOF-MS technology. Biosynthesis of unsaturated fatty acids and starch and sucrose metabolism are the most related pathways, the former of which has been rarely reported concerning DN. Finally, the results of the joint analysis show that two targets, hexokinase 2 (HK2) and maltase glucoamylase (MGAM), are the overlapping targets. It means they are not only the related targets of pathways involved in potential biomarkers in metabolomics but also the intersection targets of diseases and drugs identified by network pharmacology. CONCLUSIONS: The study reveals that the potential mechanism of SYKFT is most related to insulin resistance (IR) in the treatment of DN. It also proves that network pharmacology combined with metabolomics to find the mechanisms by which herbs treat complex diseases is a feasible tool.

Screening a strain of Aspergillus niger and optimization of fermentation conditions for degradation of aflatoxin B1.

Aflatoxin B1, a type of highly toxic mycotoxin produced by some species belonging to the Aspergillus genus, such as Aspergillus flavus and Aspergillus parasiticus, is widely distributed in feed matrices. Here, coumarin was used as the sole carbon source to screen microorganism strains that were isolated from types of feed ingredients. Only one isolate (ND-1) was able to degrade aflatoxin B1 after screening. ND-1 isolate, identified as a strain of Aspergillus niger using phylogenetic analysis on the basis of 18S rDNA, could remove 26.3% of aflatoxin B1 after 48 h of fermentation in nutrient broth (NB). Optimization of fermentation conditions for aflatoxin B1 degradation by selected Aspergillus niger was also performed. These results showed that 58.2% of aflatoxin B1 was degraded after 24 h of culture under the optimal fermentation conditions. The aflatoxin B1 degradation activity of Aspergillus niger supernatant was significantly stronger than cells and cell extracts. Furthermore, effects of temperature, heat treatment, pH, and metal ions on aflatoxin B1 degradation by the supernatant were examined. Results indicated that aflatoxin B1 degradation of Aspergillus niger is enzymatic and this process occurs in the extracellular environment.

Involvement of polyamine oxidase in abscisic acid-induced cytosolic antioxidant defense in leaves of maize.

Using pharmacological and biochemical approaches, the role of maize polyamine oxidase (MPAO) in abscisic acid (ABA)-induced antioxidant defense in leaves of maize (Zea mays L.) plants was investigated. Exogenous ABA treatment enhanced the expression of the MPAO gene and the activities of apoplastic MPAO. Pretreatment with two different inhibitors for apoplastic MPAO partly reduced hydrogen peroxide (H2O2) accumulation induced by ABA and blocked the ABA-induced expression of the antioxidant genes superoxide dismutase 4 and cytosolic ascorbate peroxidase and the activities of the cytosolic antioxidant enzymes. Treatment with spermidine, the optimum substrate of MPAO, also induced the expression and the activities of the antioxidant enzymes, and the upregulation of the antioxidant enzymes was prevented by two inhibitors of MPAO and two scavengers of H2O2. These results suggest that MPAO contributes to ABA-induced cytosolic antioxidant defense through H2O2, a Spd catabolic product.

Biodegradation and detoxification of endosulfan in aqueous medium and soil by Achromobacter xylosoxidans strain CS5.

Achromobacter xylosoxidans CS5, capable of utilizing endosulfan as the sole carbon, sulfur and energy source, was isolated from the activated sludge. Degradation of endosulfan by strain CS5 was examined by HPLC. Analysis of culture pH, cells growth, and residual endosulfan demonstrated that CS5 could degrade more than 24.8 mg/l alpha-endosulfan and 10.5mg/l beta-endosulfan after 8 days in aqueous medium, with the formation of endosulfan diol and endosulfan ether as the major metabolites. Cell-free extract of strain CS5 was able to metabolize endosulfan rapidly, and the degradative enzymes were constitutively expressed. Inoculation of strain CS5 was found to promote the removal of endosulfan in soil. Our results suggested that A. xylosoxidans CS5 might degrade endosulfan by a non-oxidative pathway. In addition, detoxification of endosulfan was evaluated using a Salmonella typhimurium TA1535/pSK1002 (umu-test). These finding suggested that the metabolism of endosulfan by strain CS5 was accompanied by significant reduction in the toxicity.