Berberine alleviates intestinal barrier dysfunction in glucolipid metabolism disorder hamsters by modulating gut microbiota and gut-microbiota-related tryptophan metabolites.

BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS: The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR. CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiota-related tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs. © 2022 Society of Chemical Industry.

Comparison of the Application of Three Methods for the Determination of Outdoor PM2.5 Design Concentrations for Fresh Air Filtration Systems in China.

With the increasing popularity of fresh-air filtration systems, the methods of determining the outdoor PM2.5 design concentration have become more important. However, the monitoring of atmospheric fine particles in China started relatively late, and there are relatively few cities with complete data, with obvious regional differences, which led to many problems in the selection of air filters for fresh-air filtration systems. In this paper, three methods of determining outdoor PM2.5 design concentration were analyzed using the daily average concentration of PM2.5 in 31 provincial capital cities from 2016 to 2020. Six typical cities in different regions were also taken as examples. The advantages and disadvantages of the three existing statistical methods were compared and analyzed, as well as the corresponding differences in the selection of outdoor PM2.5 concentration value on the filter systems. The results showed that the method of mathematical induction was more accurate and reasonable for the calculation of outdoor PM2.5 design concentrations. The local outdoor PM2.5 design concentration could be quickly calculated using the recommended coefficient K and annual average PM2.5 concentration of the region, especially for small and medium-sized cities without monitoring data. However, the recommended coefficient K should be provided based on the specific region, and should be divided into values for strict conditions and normal conditions during use. This would provide a simple and effective way to select the correct air filters for practical engineering.

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

Green and Scalable Fabrication of High-Performance Biocatalysts Using Covalent Organic Frameworks as Enzyme Carriers.

Enzyme immobilization is essential to the commercial viability of various critical large-scale biocatalytic processes. However, challenges remain for the immobilization systems, such as difficulties in loading large enzymes, enzyme leaching, and limitations for large-scale fabrication. Herein, we describe a green and scalable strategy to prepare high-performance biocatalysts through in situ assembly of enzymes with covalent organic frameworks (COFs) under ambient conditions (aqueous solution and room temperature). The obtained biocatalysts have exceptional reusability and stability and serve as efficient biocatalysts for important industrial reactions that cannot be efficiently catalyzed by free enzymes or traditional enzyme immobilization systems. Notably, this versatile enzyme immobilization platform is applicable to various COFs and enzymes. The reactions in an aqueous solution occurred within a short timeframe (ca. 10-30 min) and could be scaled up readily (ca. 2.3 g per reaction).

Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats.

BACKGROUND: Berberine (BBR) has been found to have antiobesity effects, and obesity can lead to adipose tissue degeneration. As a special adipose tissue, perivascular adipose tissue (PVAT) is closely related to vascular function and affects vasoconstriction and relaxation. What happens to PVAT in the early stages of diet-induced obesity and how BBR affects vascular function is the focus of our experimental study. METHODS: Sprague-Dawley rats were fed a high-fat diet (fat 34% kcal) for 4 weeks to simulate early obesity. Obese rats were treated with BBR (200 mg/kg) or metformin (MET, 100 mg/kg) by gavage for 2 weeks. The mesenteric arterioles were studied by atomic force microscopy (AFM). The force vs. time curves were observed and analysed to indicate vascular function. Nitric oxide (NO) and noradrenaline (NA) release was quantified using an organ bath with fluorescence assays and ELISA, respectively. Network pharmacology was used to analyse the overlapping targets related to BBR and obesity-related diseases, and the expression of NOS in mesenteric PVAT was further analysed with immunohistochemistry and real-time PCR. The serum inflammatory factor levels were tested. RESULTS: BBR significantly reduced the levels of blood glucose, blood lipids and inflammatory factors in serum. It also effectively improved abnormal mesenteric vasoconstriction and relaxation in obese rats. There was no significant change in mesenteric vascular structure, but NO production and eNOS expression were significantly increased in mesenteric PVAT (P < 0.01), and NA was decreased (P < 0.05) in obese rats. All these changes in the mesenteric arterioles and PVAT of obese rats were reversed by treatment with BBR and MET. CONCLUSIONS: In diet-induced obesity in rats, the function of vasoconstriction and relaxation in mesenteric arterioles is altered, NO is increased, and NA is decreased in mesenteric PVAT. All these changes were reversed by BBR, suggesting a novel effect of BBR in ameliorating mesenteric vascular dysfunction by regulating PVAT.

Cell-permeable fluorescent indicator for imaging formaldehyde activity in living systems.

Formaldehyde (FA), as a reactive signaling molecule, plays an important role in living systems through a diverse array of cellular pathways. However, no systematic investigation for detection and imaging of FA by rendering cells transiently permeable has been reported yet. Specifically, we developed a new cell-permeable fluorescence probe functionality that was enhanced cellular entry efficiency and well retained intracellularly after activation for visualizing endogenous FA changes. Moreover, a smart "multi-lock system -key-and-lock" strategy，which have provoked a starting point for the use of probe and related biochemical tools to monitor FA in lysosomes. The versatile "latent" fluorophore that can undergo a subsequent self-immolative spacer for interrogating the roles and functions of FA in living systems as well as related biomedical applications.

Construction of synergistic pH/H2O2-responsive prodrug for prolonging blood circulation and accelerating cellular internalization.

We have developed a real-time and multifunctional doxifluridine-conjugate prodrug (LYX), which involved the preliminary methylfluorescein with 5-fluorouracil linker as protecting group, the targeting biotin unit, and a model therapeutic drug (doxifluridine). The shielding group (5'-DFUR) was found to be effective in prolonging circulation at physiological pH 7.4 and improving accumulation in the acidic microenvironment of the tumor. Based on this strategy, the stability and stimulus responsive properties of prodrug could enhance drug release efficiency and exhibit fewer side effects, thereby providing a unique opportunity for diagnosis and imaging additional analytes or enzymatic activities.

Upregulation of CPNE3 suppresses invasion, migration and proliferation of glioblastoma cells through FAK pathway inactivation.

Glioblastoma (GBM) is a deadly brain tumor with a bleak prognosis. In recent years, the copine III (CPNE3) protein was discovered to be associated to metastasis across various types of malignancies. Nevertheless, its function has not been well documented in glioma. This study characterizes CPNE3 expression in GBM along with its impact and underlying molecular mechanism with regards to cellular migration, invasion and proliferation. Immunohistochemistry was used to characterizes CPNE3 expression in the glioma tissues. Then, knockdown of CPNE3 expression was used to analyze the role of CPNE3 in GBM cell viability, migration, invasion. Western blot analysis was performed to measure the protein levels of FAK signaling pathway. We found that GBM tissues had higher CPNE3 expressions as compared to those in normal brain tissues. CPNE3 silencing in GBM cells impaired the migratory, invasive and proliferative abilities of GBM cells that can be attributed to inactivation of the FAK signaling pathway. Collectively, these findings highlight the role of CPNE3 as a new biomarker, offering deeper insights into its carcinogenic role in GBM.

Compact dual-wavelength blue-green laser for airborne ocean detection lidar.

We have demonstrated a dual-wavelength blue-green laser for airborne ocean lidar based on an all-solid-state master oscillator power amplifier and nonlinear frequency conversion methods. A Q-switched pulsed laser with 10 mJ energy at 1064 nm was amplified to 108 mJ by a Nd:YAG amplifier side pumped by vertical-cavity surface-emitting laser modules. This fundamental laser was then frequency tripled to 355 nm wavelength by lithium triborate (LBO) crystals. With maximum pump energy of 43.5 mJ at 355 nm, 9.6 mJ of blue laser pulse at 486.1 nm was successfully obtained from an optical parametric oscillator unit using two beta-barium borate crystals. The energy of the residual 532 nm laser pulse was 10.6 mJ. Equipped with this laser system, an airborne blue-green lidar was developed, and ocean detection was carried out in the South China Sea, where an optical vertical profile at seawater depth of 94 m was obtained.

Guide Star Selection for the Three-FOV Daytime Star Sensor.

To realize the application of the star sensor in the all-day carrier platform, a three-field-of-view (three-FOV) star sensor in short-wave infrared (SWIR) band is considered. This new prototype employs new techniques that can improve the detection capability of the star sensor, when the huge size of star identification feature database becomes a big obstacle. Hence, a way to thin the guide star catalog for three-FOV daytime star sensor is studied. Firstly, an introduction of three-FOV star sensor and an example of three-FOV daytime star sensor with narrow FOV are presented. According to this model and the requirement of triangular star identification method, two constraints based on the number and the brightness of the stars in FOV are put forward for guide star selection. Then on the basis of these constraints, the improved spherical spiral method (ISSM) is proposed and the optimal number of reference points of ISSM is discussed. Finally, to demonstrate the performance of the ISSM, guide star catalogs are generated by ISSM, magnitude filter method (MFM), 1st order self-organizing guide star selection method (1st-SOPM) and the spherical spiral method (SSM), respectively. The results show that the guide star catalog generated by ISSM has the smallest size and the number and brightness characteristics of its guide stars are better than the other methods. ISSM is effective for the guide star selection in the three-FOV daytime star sensor.

Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

BACKGROUND: This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). METHODS: One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. RESULTS: In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (P< 0.05). The expression of SRSF2 in HCC was not associated with gender (χ2= 0.014, P= 0.906), age (χ2= 0.007, P= 0.931), tumor size (χ2= 3.566, P= 0.059) and T stage (χ2= 2.708, P= 0.100), and was significantly correlated with tumor differentiation (χ2= 9.687, P= 0.007), lymph node metastasis (χ2= 4.827, P= 0.028), distal metastasis (χ2= 9.235, P= 0.002), tumor, node, metastasis (TNM) stage (χ2= 3.978, P= 0.046), portal vein invasion and serum alpha-fetoprotein (χ2= 14.919, P= 0.000). The expression of SRSF2 protein in hepatocellular carcinoma was positively correlated (r = 0.704, P< 0.05) with serum alpha-fetoprotein through Pearson analysis. The survival rates of SRSF2 overexpressing hepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). CONCLUSION: SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients.

[Effect of Rhizoma Coptidis coadministration with Cortex Cinnamomi on tissue distribution of berberine in rats].

OBJECTIVE: To investigate the tissue distribution of berberine in rats after oral administration of Rhizoma Coptidis with Cortex Cinnamomi powder. METHOD: After oral administration of Rhizoma Coptidis powder and Rhizoma Coptidis with Cortex Cinnamomi powder (6:1) at the dosage of 6 g x kg(-1) and 6.6 g x kg(-1) respectively per day for 1 week, the drug concentrations in various tissues were determined by HPLC method. The variations of berberine concentrations in tissues of two treated group of rats were compared by t test using software of SAS. RESULT: With repeated administration of Rhizoma Coptidis powder, berberine distributed widely in tissues of rats and the concentrations of berberine in tissues increased, yet berberine existed mainly in liver. Berberine concentrations in all organs investigated in the group of rats treated with Rhizoma Coptidis and Cortex Cinnamomi powder showed obvious difference with those of the group of rats treated with Rhizoma Coptidis powder (P < 0.01). The berberine concentrations increased in heart, liver and kidney, while decreased in spleen and lung. CONCLUSION: Rhizoma Coptidis coadministration with Cortex Cinnamomi can obviously change the distribution of berberine in rat organs.