Differentiation of isomeric chalcone and dihydroflavone using liquid chromatography coupled with hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS): An application for flavonoids-focused characterization of Snow chrysanthemum.

Although the co-occurrences of isomeric chalcones and dihydroflavones widely appear in medicinal plants, the differentiation of such isomerism seldom succeeds using MS/MS, attributing to totally identical MS/MS spectra. Here, efforts were paid to pursue an eligible tool allowing to address the technical challenge. Being inspired by that one more proton signal is observed in 1H NMR spectrum of isoliquiritigenin than liquiritigenin when employing DMSO­d6 as solvent, hydrogen-deuterium exchange (HDX)-MS/MS was evaluated towards differentiating isomeric chalcones and dihydroflavones through replacing H2O with D2O to prepare the mobile phase. As a result, differences were observed for either MS1 or MS2 spectrum when comparing two pairs of isomers, such as liquiritigenin vs. isoliquiritigenin and liquiritin vs. isoliquiritin, because the isomeric precursor and fragment ion species owned different amounts of hydroxyl protons and those reactive protons could be partially or completely substituted by deuterium protons at the exposure in D2O to result in n × 1.006 mass increments. Moreover, utmost four hydrogen/deuterium exchanges occurred for a single glucosyl moiety. Thereafter, HDX-MS/MS was applied to characterize the flavonoids of Snow chrysanthemum, a precious edible herbal medicine that is rich in isomeric chalcones and dihydroflavones. Through paying special attention to the deuterium labeling styles of (de)protonated molecules as well as those featured fragment ions, five pairs of isomeric chalcones and dihydroflavones were confirmatively differentiated, in addition to that 28 flavonoids were structurally annotated by applying those well-defined mass fragmentation rules. Hence, this study offered an in-depth insight towards the flavonoids-focused characterization of Snow chrysanthemum, and more importantly, HDX-MS/MS is a superior tool to differentiate, but not limited to, isomeric chalcones and dihydroflavones.

Dahuang zhechong pill ameliorates hepatic fibrosis by regulating gut microbiota and metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: DHZCP is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber" that has been often used in the treatment of hepatic disorders, gynecopathy and atherosclerosis. However, its underlying mechanisms in preventing hepatic fibrosis remain incompletely understood. AIM OF THE STUDY: This study aims to explore the therapeutic efficacy and potential mechanism of DHZCP in a CCL4-induced experimental hepatic fibrosis rat model. MATERIALS AND METHODS: DHZCP was orally administered at doses of 0.168, 0.084 and 0.042 g⋅kg-1⋅d-1 in a CCL4-induced hepatic fibrosis model using SD rats. Histopathology, immunohistochemistry and biochemical analysis, ELISA, Flow cytometry, WB, RT-PCR, 16 S rRNA, and untargeted metabolomic analysis were used to determine the therapeutic effects and mechanisms of DHZCP in the treatment of CCL4-induced hepatic fibrosis. RESULTS: Pharmacodynamically, DHZCP inhibited ALT and AST, improved liver function, decreased NF-κB, TNF-α and IL-6 in liver tissue, indicating its role in inhibiting CCL4-induced liver inflammation. Most importantly, it reduces the level of fibrosis in serum and liver tissue. Histological analysis also showed that DHZCP could effectively inhibit inflammatory cytokine infiltration and excessive collagen deposition. Mechanistically, DHZCP regulates gut microbiota, improves the proportion of firmicutes and bacteroidota at the phylum level, and increases the abundance of beneficial bacteria at the genus level, such as muribagulaceae unclassified, prevotella, alloprevotella, closteriales unclassified, lachnospiraceae unclassified and phascolarctobacterium. Instead, it reduced the abundance of two harmful bacteria, desulfovibrio and colidextribacter. Four types of metabolites such as hydrocarbons, organic nitrogen compounds, organic oxygen compounds, and organosulfur compounds were added. Furthermore, DHZCP was found to reduce the damage of intestinal barrier caused by changes in gut microbiota and metabolites. CONCLUSION: DHZCP is an effective inhibitor of hepatic fibrosis by regulating gut microbiota and metabolites, improving the integrity of the intestinal barrier.

Bavachinin Ameliorates Rheumatoid Arthritis Inflammation via PPARG/PI3K/AKT Signaling Pathway.

Bavachinin (BVC) is a natural small molecule from the Chinese herb Fructus Psoraleae. It exhibits numerous pharmacological effects, including anti-cancer, anti-inflammation, anti-oxidation, anti-bacterial, anti-viral, and immunomodulatory properties. BVC may serve as a novel drug candidate for the treatment of rheumatoid arthritis (RA). Nevertheless, the effects and mechanisms of BVC against RA are still unknown. BVC targets were selected by Swiss Target Prediction and the PharmMapper database. RA-related targets were collected from the GeneCards, OMIM, DrugBank, TTD, and DisGeNET databases. PPI network construction and enrichment analysis were conducted by taking the intersection target of BVC targets and RA-related targets. Hub targets were further screened using Cytoscape and molecular docking. MH7A cell lines and collagen-induced arthritis (CIA) mice were used to confirm the preventive effect of BVC on RA and its potential mechanism. Fifty-six RA-related targets of BVC were identified through databases. These genes were primarily enriched in PI3K/AKT signaling pathway according to KEGG enrichment analysis. Molecular docking analysis suggested that BVC had the highest binding energy with PPARG. The qPCR and western blotting results showed that BVC promoted the expression of PPARG at both the mRNA level and protein level. Western blotting indicated that BVC might affect MH7A cell functions through the PI3K/AKT pathway. Furthermore, treatment with BVC inhibited the proliferation, migration, and production of inflammatory cytokines in MH7A cells and induced cell apoptosis to a certain extent. In vivo, BVC alleviated joint injury and inflammatory response in CIA mice. This study revealed that BVC may inhibit the proliferation, migration, and production of inflammatory cytokines in MH7A cells, as well as cell apoptosis through the PPARG/PI3K/AKT signaling pathway. These findings provide a theoretical foundation for RA therapy.

PTT/ PDT-induced microbial apoptosis and wound healing depend on immune activation and macrophage phenotype transformation.

Antibiotics show unsuccessful application in biofilm destruction, which induce chronic infections and emergence of antibiotic resistant bacteria. Photodynamic therapy (PDT) and photothermal therapy (PTT), as widely accepted antimicrobial tools of phototherapy, could effectively activate the immune system and promote the proliferation of wound tissue, thus becoming the most promising therapeutic strategy to replace antibiotics and avoid drug-resistant strains. However, there is no consensus on whether antibacterial and wound healing achieved by PDT/PTT depend not only on the cytotoxic effect of the treatment itself, but also on the activation of host immune system. In this study, CaSiO3-ClO2@PDA-ICG nanoparticles (CCPI NPs) were designed as PDT/PTT antimicrobial model material. With the comparison of healing effect between wide-type mice and severely immunodeficient (C-NKG) mice, the dependence of PDT/PTT-induced microbial apoptosis and wound healing on immune activation and macrophage phenotype transformation was explored and verified. Furthermore, the induced phenotypic transformation of macrophages during PDT/PTT treatment was demonstrated to play crucial role in the improvement of epithelial-mesenchymal transformation (EMT). In summary, this study represents great significance for further identifying the role of immune system activation in antibacterial phototherapy and developing new treatment strategies for biofilm-infected wound healing. STATEMENT OF SIGNIFICANCE: A PDT/PTT combination therapy model nanoparticle was established for biofilm-infected wounds. Both microbial apoptosis and wound healing achieved by PDT/PTT combination therapy were highly dependent on the activated immune system, especially the M2 macrophage phenotype. PDT/PTT could promote the polarization of monocytes to the phenotype of M2 macrophages, which promotes EMT behavior of the tissue at the edge of the wound through the secretion of TGF-ß1, thus accelerating wound healing.

Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease that may lead to joint damage, deformity, and disability, if not treated effectively. Hedyotis diffusa Willd (HDW) and its main components have been widely used to treat a variety of tumors and inflammatory diseases. The present study utilized a network pharmacology approach, microarray data analysis and molecular docking to predict the key active ingredients and mechanisms of HDW against RA. Eleven active ingredients in HDW and 180 potential anti-RA targets were identified. The ingredients-targets-RA network showed that stigmasterol, beta-sitosterol, quercetin, kaempferol, and 2-methoxy-3-methyl-9,10-anthraquinone were key components for RA treatment. KEGG pathway results revealed that the 180 potential targets were inflammatory-related pathways with predominant enrichment of the AGE-RAGE, TNF, IL17, and PI3K-Akt signaling pathways. Screened through the PPI network and with Cytoscape software, RELA, TNF, IL6, TP53, MAPK1, AKT1, IL10, and ESR1 were identified as the hub targets in the HDW for RA treatment. Molecular docking was used to identify the binding of 5 key components and the 8 related-RA hub targets. Moreover, the results of network pharmacology were verified by vitro experiments. HDW inhibits cell proliferation in MH7A cells in a dose and time-dependent manner. RT-qPCR and WB results suggest that HDW may affect hub targets through PI3K/AKT signaling pathway, thereby exerting anti-RA effect. This study provides evidence for a clinical effect of HDW on RA and a research basis for further investigation into the active ingredients and mechanisms of HDW against RA.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Outcome of Santulli enterostomy in patients with immaturity of ganglia: single institutional experience from a case series.

BACKGROUND: Immaturity of ganglia (IG) is an extremely rare disease and always requires surgical intervention in the neonatal period, but without guidelines to choose the ideal enterostomy procedure, the timing of stoma closure remains controversial. The aim of this study was to report our experience using Santulli enterostomy for the treatment of nine infants diagnosed with IG. METHODS: Patients who underwent Santulli enterostomy and were diagnosed with IG in our center between 2016 and 2021 were retrospectively studied. Temporary stoma occlusion and a 24-h delayed film of barium enema (BE) were performed to evaluate intestinal peristalsis function to determine the timing of stoma closure. The demographic data, clinical and radiological findings, stoma occlusion and stoma closure results were explored. RESULTS: A total of 9 infants underwent Santulli enterostomy and were diagnosed with IG postoperatively. Their median gestational age at birth was 36 weeks (range 31-42), and their median birth weight was 2765 g (range 1300-3400). All patients had symptom onset in the neonatal period, including abdominal distension and biliary vomiting. Eight patients showed obvious small bowel dilatation in the plain films, except for one patient's films that suggested gastrointestinal perforation with free gas downstream of the diaphragm. BE was performed in 6 patients, all of which had microcolons. The median age at operation was 3 days (range 1-23). Seven patients had an obvious transitional zone (TZ) during laparotomy, and the position of the TZ was 25-100 cm proximal above the ileocecal (IC) valve. Immature ganglion cells were present in the colon in 7 patients and the terminal ileum in 6 patients. The median age of successful stoma occlusion was 5 M (range 2-17) and 8 M (range 4-22) at ostomy closure. There was little or no barium residue in the 24-h delayed film of BE before stoma closure, and all patients were free of constipation symptoms during the follow-up. CONCLUSION: Santulli enterostomy appears to be a suitable and efficient procedure for IG, combined with temporary stoma occlusion and 24-h delayed film of BE to evaluate the recovery of intestinal peristalsis function.

Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies.

Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking.

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.

Efficacy and Safety of Dahuang Zhechong Pill in Silicosis: A Randomized Controlled Trial.

BACKGROUND: There is no effective therapy for silicosis, and Dahuang Zhechong pill (DHZCP), an ancient Chinese medicine prescription, may have a therapeutic effect on silicosis. This study aims to verify the efficacy and safety of DHZCP in silicosis. METHODS: This is a randomized controlled clinical trial done at Panzhihua Second People's Hospital (Panzhihua City, Sichuan Province, China). Participants diagnosed with silicosis were recruited and randomized to the conventional treatment group (CG) or DHZCP combined with the conventional treatment group (DG). Forced vital capacity % predicted (FVC%), diffusing capacity of the lung for carbon monoxide % predicted (DLCO%), six-minute walk distance (6MWD), peripheral oxygen (SpO2), King's Brief Interstitial Lung Disease Questionnaire (K-BILD), and safety outcomes were measured at baseline and 9 weeks. RESULTS: Fifty-six participants (28 in each group) completed the study, and 53 of them (26 in DG and 27 in CG) completed pulmonary function. At 9 weeks, compared with no DHZCP, DHZCP treatment was associated with significant improvements in FVC% (mean ± SD, 95%CI) (8.2 ± 3.9, 0.3 to 16.0), DLCO% (8.6 ± 3.5, 1.5 to 15.7), SpO2 (3.8 ± 0.7, 2.3 to 5.2), and K-BILD total score (6.0 ± 2.3, 1.4 to 10.7). And, there were no statistical differences of safety outcomes between the two groups. Eight patients accepting DHZCP developed mild diarrhea during the first week, which subsequently resolved on its own. CONCLUSION: DHZCP could improve the pulmonary function, the quality of life, and the exercise capacity of silicosis patients.

[Meta analysis on the treatment of coronavirus disease 2019 by traditional Chinese and Western medicine].

OBJECTIVE: To evaluate the clinical efficacy and safety of combination of traditional Chinese and Western medicine in the treatment of coronavirus disease 2019 (COVID-19) by Meta analysis. METHODS: The clinical randomized controlled trials (RCT) and cohort studies on the treatment of COVID-19 with combination of Chinese traditional and Western medicine published on CNKI, Wanfang database, VIP database and PubMed were searched by computer from January 2020 to June 2020. Patients in the simple Western medicine treatment group were treated with routine treatment of Western medicine, and the patients in integrated traditional Chinese and Western medicine treatment group were treated with traditional Chinese medicine on the basis of routine treatment of Western medicine. The main outcome was the total effective rate of treatment. The secondary outcome were the antipyretic rate, chest CT recovery rate, lymphocyte count (LYM), C-reactive protein (CRP) level and safety. The Cochrane manual and the Newcastle Ottawa Scale (NOS) were used to evaluate the quality of the literature; the RevMan5.3 software was used to analyze the articles that meets the quality standards, and a funnel chart was drawn to evaluate the total effective publication bias. RESULTS: Thirteen articles were analyzed, including 1 039 COVID-19 patients, 559 in integrated traditional Chinese and Western medicine treatment group and 480 in simple Western medicine treatment group. The results of Meta- analysis showed that compared with the simple Western medicine treatment group, the combination of routine treatment of Western medicine and traditional Chinese medicine Qingfei Paidu decoction, Lianhua Qingwen granule, Shufeng jiedu capsule, Xuebijing injection or Reyanning mixture could significantly improve the total effective rate, antipyretic rate and chest CT recovery rate [total effective rate: odds ratio (OR) = 2.95, 95% confidence interval (95%CI) was 2.10-4.14, P < 0.000 01; antipyretic rate: OR =3.01, 95%CI was 1.64-5.53, P = 0.000 4; chest CT recovery rate: OR = 2.53, 95%CI was 1.83-3.51, P = 0.000 1], increase LYM levels [mean difference (MD) = 0.26, 95%CI was 0.02-0.50, P = 0.03], and reduce of CRP content (MD = -17.68, 95%CI was -33.14 to -2.22, P = 0.02). Based on the funnel chart analysis of 12 articles with total efficiency, the result showed that the funnel chart distribution was not completely symmetrical, indicating that there might be publication bias. CONCLUSIONS: On the basis of routine treatment with Western medicine, combined with traditional Chinese medicine can significantly improve the total effective rate of COVID-19 and improve the laboratory results and clinical symptoms of patients. Compared with the routine treatment of Western medicine alone, the combination of traditional Chinese and Western medicine has better clinical efficacy and safety.

Ferroptosis as a New Mechanism in Parkinson's Disease Therapy Using Traditional Chinese Medicine.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. To date, among medications used to treat PD, only levodopa exhibits a limited disease-modifying effect on early-onset PD, but it cannot delay the progression of the disease. In 2018, for the first time, the World Health Organization included traditional Chinese medicine (TCM) in its influential global medical compendium. The use of TCM in the treatment of PD has a long history. At present, TCM can help treat and prevent PD. Iron metabolism is closely associated with PD. Ferroptosis, which is characterized by the accumulation of lipid peroxides, is a recently discovered form of iron-dependent cell death. The research literature indicates that ferroptosis in dopaminergic neurons is an important pathogenetic mechanism of PD. TCM may thus play unique roles in the treatment of PD and provide new ideas for the treatment of PD by regulating pathways associated with ferroptosis.

Dahuang Zhechong Pills Suppress Silicosis Fibrosis Progression via p38 MAPK/TGF-ß1/Smad Pathway In Vitro.

BACKGROUND: Dahuang Zhechong pills (DHZCP) is a classic Chinese medicinal prescription in "Treatise on Cold Pathogenic and Miscellaneous Diseases (Shanghan Zabing Lun)," and it has the function of tonifying blood, nourishing Yin, and removing blood stasis. Previous studies have shown that DHZCP could alleviate SiO2 induced pulmonary fibrosis in mice. This study aims to further explore the preventive and therapeutic effects of DHZCP against silicosis fibrosis and the underlying mechanisms in vitro. METHODS: We used the experimental model of SiO2-induced MH-S cells to evaluate the therapeutic potential of DHZCP. MH-S cells induced by SiO2 were intervened with the drug-containing serum of DHZCP, and the effects of drug-containing serum of DHZCP on the MH-S cells were detected by CCK8, ELISA, flow cytometry, western blot, and immunofluorescence. RESULTS: DHZCP improved cell viability by reducing apoptosis. It also decreased the levels of TNF-α, IL-1ß, IL-6 in the supernatant of MH-S cells induced by SiO2, inhibited the expression of p38 MAPK, blocked the activation of NF-κB, and controlled the upstream inflammatory response by multiple targeting. Concomitantly, we observed upregulation of Smad7 and a marked decline in TGF-ß1, α-SMA, Smad2, Smad3 expression in MH-S cells treated with DHZCP. CONCLUSION: To sum up, we conclude that DHZCP protects against SiO2-induced silicosis by reducing the persistent irritation of inflammation, regulating the p38 MAPK/TGF-ß1/Smad pathway.

[Visual analysis of influenza treated by traditional Chinese medicine based on CiteSpace].

OBJECTIVE: To analyze the research status, research hotspots and frontier trends of traditional Chinese medicine (TCM) in the treatment of influenza in the past 20 years through the knowledge graph, so as to provide reference basis for further research. METHODS: The related literatures of TCM in the treatment of influenza were collected in China National Knowledge Infrastructure (CNKI) from 2000 to 2019. The relevant graphs of authors, research institutions and key words were drawn by CiteSpace 5.6, the distribution and cooperation of main research forces in this field were analyzed, and the research frontiers and hot spot information in this field were discussed. RESULTS: A total of 3 048 related literatures were obtained, involving 949 authors and 242 research institutions. The analysis of the number of articles showed that the volume of articles related to the treatment of influenza with TCM fluctuated greatly in the past 20 years, which was obviously affected by the sudden hot spots around 2010, but showed an overall upward trend, with an average annual volume of about 152 articles. The analysis of the author's cooperation map showed that a total of 77 core authors had published more than 5 articles, accounting for only 8.1% of all authors, and 5 authors had published more than 30 articles. Five major teams had been formed with Gu Ligang, Liu Qingquan, Lu Fangguo, Cui Xiaolan and Zhang Fengxue as the core. The analysis of the cooperation map of research institutions showed that the cooperation among institutions was not good, and only the scientific research institutes in Beijing and Guangzhou had formed a closely related cooperation network. The keyword co-occurrence map showed that 8 keywords appeared more than 100 times, especially ultra-high-frequency keywords, influenza virus ranked first (n = 518). There were 14 key nodes, such as influenza virus, TCM treatment, viral pneumonia and so on, which supported the current research field of TCM in the treatment of influenza. Fourteen clusters were formed to classify the current research hotspots, including the nomenclature of influenza, virus type, TCM treatment, western medicine knowledge, etc., and the map showed that the clustering was reasonable and the structure was significant. Timeline graph showed that parainfluenza virus, virus disease, pharmacodynamics, heat-clearing and detoxifying drugs, bacteriostasis and experimental research had all been studied for more than 8 years, revealing the research hotspots and trends of TCM in the treatment of influenza. CONCLUSIONS: The overall research related to the treatment of influenza with TCM is relatively perfect. In the future, the close cooperation among authors and institutions should be strengthened. The molecular mechanism research, clinical and animal trials of TCM should be further studied, so as to improve the research system of TCM treatment of influenza.

Natural product-based semisynthesis and biological evaluation of thiol/amino-Michael adducts of xanthatin derived from Xanthium strumarium as potential pesticidal agents.

Xanthatin, a natural sesquiterpene lactone, occurs as one of the major constituents of Xanthium plants (Compositae) and exhibits many important biological properties. To discover natural products-based pesticides, forty-nine Michael-type thiol/amino adducts of xanthatin were synthesized and characterized, while their pesticidal activities were investigated. Among them, compounds 2c, 2h, 2i, and 2t exhibited more potent antifungal activity against Botrytis cinerea (IC50 = 0.96, 0.38, 6.33, and 7.21 µg/mL, respectively) than xanthatin and the two commercial fungicides. Compounds 2t and 2u displayed broad-spectrum and excellent antifungal effects against all tested phytopathogenic fungi, while their IC50 values ranged from 7.21 to 75.88 µg/mL. Compounds 2a, 2f, 2l, 2m, 2v, 7c, 7e, 7h, 7i, and 7j showed moderate larvicidal activity against Plutella xylostella Linnaeus. Furthermore, compounds 2b, 7g, and 7h demonstrated significant ovicidal activity against P. xylostella with the LC50 values of 14.04, 10.00, and 11.95 mg/L, respectively. These findings suggest that thiol/amino appended in the C-13 position of xanthatin may improve antifungal and ovicidal activities for the derivatives. It was also noticed that the exocyclic double bond of xanthatin is crucial for its larvicidal activity. This work also provides some important hints for further design, synthesis, and structural modification of the xanthanolides sesquiterpene lactones toward development of the new environmentally friendly pesticides for sustainable agricultural production.

Amygdalin - A pharmacological and toxicological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Amygdalin is commonly distributed in plants of the Rosaceae, such as peach, plum, loquat, apple and bayberry, but most notably in the seeds (kernels) of apricot almonds. As a naturally aromatic cyanogenic compound, it has long been used in Asia, Europe and other regions for the treatment of various diseases including cough, asthma, nausea, leprosy and leukoderma. Importantly, in recent years, an increasing attention has been paid to its antitumor effect. AIM OF THE STUDY: The paper aims to review the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation. METHODS: Electronic databases including the Web of Science, Cochrane Library, PubMed, EMBASE, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database and VIP information database were searched up to November 2019 to identify eligible studies. A meticulous review was performed, an in-depth analysis on the pharmacological activity and toxicology of amygdalin was conducted, and perspectives for future research were also discussed. RESULTS: A total of 110 papers about in vitro/in vivo studies on amygdalin have been reviewed. Analysis on the data suggested that this compound presented pharmacological activities of anti-tumor, anti-fibrotic, anti-inflammatory, analgesic, immunomodulatory, anti-atherosclerosis, ameliorating digestive system and reproductive system, improving neurodegeneration and myocardial hypertrophy, as well as reducing blood glucose. In addition, studies revealed that amygdalin's toxicity was caused by its poisonous decomposite product of benzaldehyde and hydrogen cyanide after oral ingestion, toxicity of intravenous administration route was far less than the oral route, and it can be avoidable with an oral dose ranging from 0.6 to 1 g per day. CONCLUSION: This paper has systematically reviewed the pharmacology and toxicology of amygdalin and provided comprehensive information on this compound. We hope this review highlights some perspectives for the future research and development of amygdalin.

Effects and Mechanisms of Traditional Chinese Herbal Medicine in the Treatment of Ischemic Cardiomyopathy.

The incidence of ischemic cardiomyopathy (ICM) is increasing yearly, which seriously endangers human health. There is rarely any remarkable progress in the treatment of ICM from the available drugs. Recent research shows that natural herbal medicine may have beneficial effects in the prevention and treatment of cardiovascular diseases. The effective extracts of the herbs may improve myocardial ischemia through various actions, such as hemodynamic, hemorheological, and vascular actions, and on various cell biology aspects, such as intracellular calcium balance, mitochondria function, cell apoptosis, and scavenging free radicals. Here, we review the animal research progress and potential mechanisms in the treatment of ICM using extracts of well-known traditional Chinese herbal medicines.

BH3 mimetics derived from Bim-BH3 domain core region show PTP1B inhibitory activity.

A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD = 8.38 nmol/L), inhibitory activity (IC50 = 1.20 µmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model. These results may indicate a new direction for the application of BH3 peptide mimetics and promising PTP1B peptide inhibitors could be designed and developed based on SM-6.

Using sludge fermentation liquid to reduce the inhibitory effect of copper oxide nanoparticles on municipal wastewater biological nutrient removal.

The deterioration of biological nutrient removal (BNR) can occur with the release of engineering nanomaterials into wastewater treatment plants (WWTPs). Also, large amounts of waste sludge are generated in WWTPs, which can be reutilized as a useful resource. In this study, the use of sludge fermentation liquid to reduce CuO nanoparticles (NPs) toxicity to municipal wastewater BNR was reported. In the BNR system supplemented with sodium acetate, which was widely used as additional carbon source of municipal wastewater in literatures, the appearance of 2.5 mg/L CuO NPs for 5.5 h decreased the total nitrogen (TN) removal efficiency from 81.4% to 59.0%, but the TN removal was recovered to 78.7% after sodium acetate was replaced by sludge fermentation liquid. It was found that CuO NPs induced excessive generation of reactive nitrogen species (RNS), which led to the disorder of redox status, low levels of energy and reduction equivalents generations, and deterioration of denitrification. Further investigation revealed that cysteine in fermentation liquid played a vital biological role in reducing nanotoxicity by facilitating the synthesis of glutathione, which reduced excessive RNS generation, increased key proteins expression, guaranteed the metabolisms of intracellular energy and substrate smoothly, and finally recovered the BNR performance.

Systematic review of ß-elemene injection as adjunctive treatment for lung cancer.

OBJECTIVE: To evaluate the effectiveness and safety of ß-elemene Injection as an adjunctive treatment for lung cancer by systematic review. METHODS: We retrieved randomized controlled clinical trials related to the use of ß-elemene Injection as an adjunctive treatment for lung cancer from Chinese Biomedical (CBMweb), Chinese Medical Current Content (CMCC), China National Knowledge Infrastructure (CNKI), ChinaInfo, Cochrane Central Register of Controlled Trials; MEDLINE, EMBASE, OVID and TCMLARS. We also referred to an unpublished conference proceeding titled Clinical Use and Basic: Elemene Injection. We then divided the studies into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) subgroups by RevMan 5.1 software. RESULTS: A total of 21 source documents (1,467 patients) matched pre-specified criteria for determining the effectiveness and safety of ß-elemene Injection as an adjunctive treatment for lung cancer. Five studies involving 285 NSCLC patients reported a higher 24-month survival rate (39.09%) with the adjunctive treatment than with chemotherapy alone (26.17%; RR, 1.51; 95% CI, 1.03 to 2.21). Four studies involving 445 patients reported that the increased probability for improved performance status for patients treated with elemene-based combinations was higher than that of patients treated with chemotherapy alone (RR, 1.82; 95% CI, 1.45 to 2.29). The results from a subgroup analysis on 12 studies involving 974 NSCLC patients and 9 studies involving 593 patients with both SCLC and NSCLC showed that the tumor control rate for NSCLC improved more in the elemene-based combinations treatment group (78.70%) than in the chemotherapy alone control group (71.31%; RR, 1.06; 95% CI, 1.00 to 1.12). The tumor response rate for NSCLC also improved more among patients treated with elemenebased combinations (50.71%) than among patients treated with chemotherapy alone (38.04%; RR, 1.34; 95%CI, 1.17 to 1.54). In addition, the main adverse reaction to ß-elemene Injection was phlebitis, but usually only to a mild degree. An Egger's test showed no publication bias in our study (P=0.7030). CONCLUSIONS: The effectiveness of chemotherapy for the treatment of lung cancer may improve when combined with ß-elemene injection as an adjunctive treatment. The combined treatment can result in an improved quality of life and prolonged survival. However, these results require confirmation by rigorously controlled trials.