Malus toringoides (Rehd.) Hughes decoction alleviates isoproterenol-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3 signaling pathway.

Malus toringoides (Rehd.) Hughes, called "Eseye (Ese)," is a traditional medicinal plant from the Tibet province of China that has proven effective in treating cardiac conditions due to its anti-inflammatory, antioxidative, and antiapoptotic properties. In this study, we explored the underlying protective mechanisms of Ese decoction in isoproterenol (ISO)-induced cardiac fibrosis (CF) and established the fact that treatment with an Ese decoction attenuated tissue injury, decreased the release of IL-1ß, IL-18, TNF-α, and caspase-3, and elevated the Bax/Bcl-2 ratio in CF mice. We also found that with Ese treatment damage to the mitochondrial ultrastructure of myocardium was alleviated, and the level of reactive oxygen species was markedly diminished. Ese inhibited the expression of proteins associated with pyroptosis by the HK1/NLRP3 signaling pathway and also improved CF. Due to the anti-inflammatory, antioxidative, and antiapoptotic characteristics of Ese decoction, we found that Ese protected against ISO-induced CF, by inhibiting inflammation and pyroptosis as mediated by the HK1/NLRP3 signaling pathway.

Unraveling the Positive Effect of Soil Moisture on the Bioaugmentation of Petroleum-Contaminated Soil Using Bioinformatics.

Petroleum contamination is a severe threat to the soil environment. Previous studies have demonstrated that petroleum degradation efficiency is promoted by enhancing soil moisture content (MC). However, the effects of MC on soil microbial ecological functions during bioremediation remain unclear. Here, we investigated the impacts of 5% and 15% of moisture contents on petroleum degradation, soil microbial structures and functions, and the related genes using high-throughput sequencing and gene function prediction. Results indicated that petroleum biodegradation efficiency was increased by 8.06% in the soils with 15% MC when compared to that with 5% of MC. The complexity and stability of soil microbial community structures with 15% MC were higher than those in the soils with 5% MC when hydrocarbon-degrading bacterial flora (HDBF) were inoculated into the soils. Fifteen percent of moisture content strengthened the interaction of the bacterial community network and reduced the loss of some key bacteria species including Mycobacterium, Sphingomonas, and Gemmatimonas. Some downregulated gene pathways relating to bioaugmentation were enhanced in the soils with 15% MC. The results suggested that the dynamic balances of microbial communities and the metabolic interactions by 15% MC treatment are the driving forces for the enhancement of bioremediation in petroleum-contaminated soil.

Influence of CYP2D6 and ß2-adrenergic receptor gene polymorphisms on the hemodynamic response to propranolol in Chinese Han patients with cirrhosis.

BACKGROUND AND AIM: Propranolol is widely used to prevent gastroesophageal variceal bleeding; however, some patients could not benefit from propranolol. This study is to evaluate the relationship between CYP2D6 and ß2-adrenergic receptor (ß2-AR) gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients. METHODS: The clinical data of patients with gastroesophageal varices undergoing hepatic venous pressure gradient (HVPG) measurement before and 7 days after oral propranolol administration in our department were collected. Four single nucleotide polymorphisms of CYP2D6 and ß2-AR genes were detected. The relationship was identified by logistic regression model. RESULTS: Thirty patients were involved in the analysis. Sixty milligram propranolol twice each day was well tolerated by all the patients. The initial and secondary average of HVPG was 17.4 ± 5.8 mmHg vs. 13.2 ± 4.8 mmHg, respectively (t = 5.726, P < 0.001). Twenty patients responded to propranolol. The mean reduction value of HVPG was 6.6 ± 3.6 mmHg (range from 3 to 19). Genotype analysis showed: 20 homozygotes for C/C188 and 10 for heterozygous C/T188, 8 homozygotes for G/G4268 and 22 heterozygotes for G/C4268, 14 homozygotes for Gly16 and 10 heterozygotes, and 6 homozygotes for Arg16, 27 homozygotes for Gln27 and 3 heterozygotes. The multivariate logistic regression analysis indicated that CYP2D6 (188C>T) genotype was an independent predicting factor for HVPG response to propranolol (P = 0.033). CONCLUSIONS: CYP2D6 (188C>T) gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices. However, HVPG response cannot be completely predicted from CYP2D6 and ß2-AR gene polymorphisms.

[Studies on coumarins from fruit of Cnidium monnieri and their cytotoxic activities].

This study is to study is to investigate the coumarins from Fruit of Cnidium monnieri and their cytotoxic activities. The constituents were separated by column chromatography, and their structures were elucidated by spectroscopic data analyses. The isolated compounds were evaluated for their cytoxic activities by MTT method. Eleven compounds were isolated and identified as osthole (1), bergaptan (2), xanthotoxol (3), xanthotoxin (4), imperatorin (5), isopimpinellin (6), osthenol (7), psoralen (8), 5,7-dimethoxycoumarin (9), oxypeucedaninhydrate (10), and swietenocoumarin F (11). Compounds 7, 9-11 were isolated from the Cnidium genus for the first time. Compounds 1,5,10 and 11 showed significant cytotoxic activities against L1210 cell lines at a concentration of 1 x 10(-5) mol x L(-1) with inhibitory rates of were 70.13, 63.10, 55.77, and 75.08% respectively.

[Studies on flavonoids from stems of Nelumbo nucifera Gaertn and their cytotoxic activities].

This research is to investigate study the flavonoids from stems of Nelumbo nucifera and the cytotoxic activities of iso- lated compounds. The constituents were separated by column chromatography,and their structures were elucidated by spectroscopic data analyses. The isolated compounds were evaluated for cytoxic activities by MTT method. Twelve compounds were isolated and identified as rhamnazin-3-O-beta-D-glucopyranoside (1), luteolin-3', 4'-dimethylether-7-O-beta-D-glucoside (2), kaempferol-3-O-beta-D-xylopyranosyl-(1-->2)-O-beta-D-glucopyranoside (3), quercetin-3,3'-di-O-beta-D-glucopyranoside (4), 1, 8-dihydroxy-3,7-dimethoxyxanthone (5), isorhamnetin-3-O-beta-D-glucopyranoside(6) , kaempferol(7), isorhamnetin (8), quercetin(9), astragalin(10), hyperoside (11) and 1-hy- droxy-3,7,8-trimethoxyxanthone(12). All compounds were isolated from stems of this plant for the first time, and compounds 1-5 were firstly isolated from the family nelumbonaceae. Compounds 24 and 6 showed significant cytotoxic activities against BEL-7402 carcinoma cell lines at a concentration of 1 x 10(-5) mol x L(-1) with the inhibitory rate of 67.36%, 53.25%, 57.78%, 60.13% and 52.11%, respectively.

[Cytotoxic alkaloids from stems of Nelumbo nucifera].

Chemical investigation was carried out to study the alkaloids from stems of Nelumbo nucifera and their cytotoxic activities. The constituents were separated by column chromatography, and their structures were elucidated by spectroscopic data analyses. The isolated compounds were evaluated for their cytotoxic activities by MTr method. Fifteen compounds were isolated from the total alkaloids extract and identified as asimilobine (1), isococlaurine (2), N-acetylnorarmepavine (3), crykonisine (4), velucryptine (5), pycnarrhine (6), liriodenine (7), nuciferine (8), nornuciferine (9), armepavine (10), N-methylasimilobine (11), coclaurine (12), N-norarmepavine (13), N-methylcoclaurine (14) and lysicamine (15). Compounds 1-7 and 12-15 were isolated from stems of this plant for the first time, and compounds 2-6 were firstly isolated from the family Nelumbonaceae. Compounds 7-10, 13 and 14 showed significant cytotoxic activities against HL-60 carcinoma cell line with inhibitory ratios of 51.36%, 59.09%, 52.51%, 53.93%, 51.43%, and 64.31% at concentration of 1 x 10(-5) mol x L(-1), respectively.

Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer.

AIMS: Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor properties, as well as its activities against kidney deficiency and impotence. In this study, we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF via network pharmacology and in vitro antitumor experiments. METHODS: Network pharmacology was used to investigate the anti-CRC mechanism of CF. First, a series of databases was used to screen the active phytochemical targets and anti-CRC core targets. Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments were carried on verifying anti-CRC mechanism of CF. RESULTS: In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals were screened for molecular docking to show protein-ligand interactions. According to the results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti- CRC functional verification in vitro. MTT assay showed that O-acetylcolumbianetin significantly inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner. O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells apoptosis, thus exert anti-CRC effect. CONCLUSION: This study preliminarily verified the anti-CRC effect and molecular mechanism of CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.

Study of Active Phytochemicals and Mechanisms of Cnidii Fructus in Treating Osteoporosis Based on HPLC-Q-TOF-MS/MS and Network Pharmacology.

INTRODUCTION: This study aimed to clarify the anti-osteoporosis mechanism of Cnidii Fructus (CF) via network pharmacology and experimental verification.\ Methods: HPLC fingerprints combined with HPLC-Q-TOF-MS/MS analysis confirmed common components (CCS) of CF. Then, network pharmacology was used to investigate the anti-OP mechanism of CF, including potential anti-OP phytochemicals, potential targets, and related signalling pathway. Molecular docking analysis was carried on investigating the protein-ligand interactions. Finally, in vitro experiments were performed to verify anti-OP mechanism of CF. RESULTS: In this study, 17 compounds from CF were identified by HPLC-Q-TOF-MS/MS and HPLC fingerprints and then were further screened key compounds and potential targets by PPI analysis, ingredient-target network and hub network. The key compounds were SCZ10 (Diosmin), SCZ16 (Pabulenol), SCZ6 (Osthenol), SCZ8 (Bergaptol) and SCZ4 (Xanthotoxol). The potential targets were SRC, MAPK1, PIK3CA, AKT1 and HSP90AA1. Molecular docking further analysis indicated that the five key compounds have a good binding affinity with related proteins. CCK8 assays, TRAP staining experiments, and ALP activity assays concluded that osthenol and bergaptol inhibited osteoclast formation and promoted osteoblast bone formation to improve osteoporosis. CONCLUSION: Based on network pharmacology and in vitro experiments analysis, this study revealed that CF possessed an anti-OP effect, and its potential therapeutic effect may be involved with osthenol and bergaptol from CF.

Two new benzophenones from the moss Pogonatum spinulosum.

Two new benzophenone derivatives (1 and 2), named Pogonatone C and pogonatone D, were isolated from the moss Pogonatum spinulosum. Their structures were elucidated by spectroscopic data analyses. The cytotoxicity of compounds for HepG2, HCT-116, A-549 and PANC-1 cells line was also evaluated by using the MTT method. Pogonatone C (1) displays high cytotoxicity on PANC-1 cell with IC50 value of 9.2 µM.

In situ detection and mass spectrometry imaging of protein-related metabolites in Bombyx batryticatus before and after frying with wheat bran.

Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology.

[Chemical constituents from Corydalis yanhusuo].

OBJECTIVE: To investigate the chemical constituents of Corydalis yanhusuo. METHOD: The compounds were isolated and purified by column chromatography over macroporous absorption resin, silica gel, and Sephadex LH-20. Their structures were elucidated on the basis of physicochemical properties and spectral data. RESULT: 22 compounds were isolated and identified as corydaline (1), tetrahydropalmatine (2), protopine (3), tetrahydrocorysamine (4), tetrahydrocoptisine (5) , tetrahydroberberine (6), tetrahydrocolumbamine (7), noroxyhydrastine (8), dehydrocorydaline (9), glaucine (10), columbamine (11), 8-oxocoptisine (12), 13-methyl-columbamine (13), coptisine (14), palmatine (15), herberine (16), oxoglaucine (17), 13-methyl-palmatrubine (18), dehydrocorybulbine (19), stepharanine (20), adenosine (21), and N5 -acetylornithine (22). CONCLUSION: Compounds 13, 20, 21, and 22 were isolated from this plant for the first time.

Feasibility of laparoscopic enucleation for hemangioma in special hepatic segments.

Background and aim: This study aims to evaluate the safety and efficacy of laparoscopic enucleation for liver hemangioma in special hepatic segments. Methods: We retrospectively reviewed 58 patients who underwent laparoscopic surgery for hepatic hemangioma at a single center from January 2016 to January 2022. Segments I, IVa, VII, and VIII are defined as special hepatic segments, attributing to the bad visualization and adjacent to important vessels such as hepatic veins and inferior vena cava that lead to a high risk in laparoscopic surgery. Patients were categorized into a special location group (SLG) and a normal location group (NLG) according to the location of hemangioma. General data, intraoperative and postoperative outcomes, and postoperative complications of the two groups were compared and analyzed. Results: There were no significant differences in age (p = 0.288), gender (p = 0.331), body mass index (p = 0.168), the maximum diameter of hemangioma (p = 0.330), ASA risk grading (p = 0.615), and comorbidities (p > 0.05) between the two groups. The operation time (p < 0.001), intraoperative blood loss (p < 0.001), and intraoperative blood transfusion rate (p = 0.047) were significantly higher in the SLG. The rate of conversion to laparotomy was higher in the SLG, but there was no significant difference (p = 0.089). In addition, the exhaust time (p = 0.03) and postoperative hospital stay (p < 0.01) were significantly shorter in the NLG. The postoperative complications were comparable between the two groups, and there were no perioperative deaths. Conclusion: Laparoscopic enucleation of hemangioma in special hepatic segments is difficult and has a critical risk of massive bleeding during surgery. Meanwhile, it is also safe, feasible, and effective.

Hydrocarbon transformation pathways and soil organic carbon stability in the biostimulation of oil-contaminated soil: Implications of 13C natural abundance.

Mineralization, assimilation, and humification are key processes to detoxify oil-contaminated soil by biostimulation remediation strategies, and these processes are affected by stimulants. In this study, we investigated the effects of either inorganic salts or organic stimulants (organic compost and sawdust) on hydrocarbon transformation. Total petroleum hydrocarbons (TPH) and hydrocarbon components were determined by gravimetry and gas chromatography, and the 13C of CO2, microbial biomass carbon (MBC), and humus were measured by stable isotope mass spectrometry. The results showed that organic compost was the most beneficial for the dissipation of hydrocarbons. After 60 days of remediation, the removal rates of TPH, saturates, aromatics, C7-C30 n-alkanes, and 16 PAHs were 35.7%, 39.6%, 15.9%, 80.5%, and 8.8%, respectively. A total of 84.7%-88.5% of the removed hydrocarbons were mineralized in all the treatments. The hydrocarbon degradation pathway in the control soil (without stimulant addition) was "assimilation → humification → mineralization". The hydrocarbon transformation pathways in the biostimulation treatments were "assimilation → mineralization → humification". The soil organic carbon (SOC) stability decreased during remediation, which was attributed to the enhanced microbial activity and the removal of recalcitrant hydrocarbons.

Two new benzophenones from endohydric moss Polytrichum Commune.

Two new benzophenones (1 and 2), were isolated from the endohydric moss Polytrichum commune. Their structures were elucidated by spectroscopic methods including extensive 2 D NMR techniques. Compound 2 is the first example of benzophenone with a rare cyclopropylacetamide from the natural resources. Compounds 1 and 2 were screened their cytotoxicity against five cancer cell lines (HCT-116, A-549, MCF-7, HepG2, A-375,), and no cytotoxic activities were observed (IC50 > 100 µM).

S-Adenosylmethionine suppresses the expression of Smad3/4 in activated human hepatic stellate cells via Rac1 promoter methylation.

The aim of the present study was to investigate whether S-adenosylmethionine (SAM) was able to suppress activated human hepatic stellate cells (HSCs). Human LX-2 HSCs were cultured with SAM or NSC23766, and were transfected with plasmids encoding ras-related C3 botulinum toxin substrate 1 (Rac1) protein or an empty expression vector. Cell proliferation was detected by Cell Counting Kit-8. Cell migration and invasion were determined using the Transwell assay. The expression levels of Rac1 and Smad3/4 were detected by reverse transcription­quantitative polymerase chain reaction (PCR) or western blotting. The methylation status of Rac1 promoters was measured by methylation­specific PCR. The results demonstrated that SAM and NSC23766 suppressed the expression of Smad3/4 in LX­2 cells. The overexpression of Rac1 enhanced the proliferation, migration and invasion of LX­2 cells. In addition, compared with the control groups, a marked increase was observed in the protein expression levels of Smad3/4 in the LX­2 cells transfected with Rac1 plasmids. The methylation-specific PCR findings showed that SAM increased the methylation of Rac1 promoters. The results of the present study suggested that Rac1 enhanced the expression of Smad3/4 in activated HSCs; however, this increase may be suppressed by SAM-induced methylation of Rac1 promoters.