Camel milk Polar Lipids ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by modulating the gut microbiota.

Milk contains abundant polar lipids, which are vital constituents of biological membranes. These polar lipids are present in the human diet as phospholipids (PL) and sphingolipids (SL). Nevertheless, the limited focus has been on the attributes and role of camel milk polar lipids (MPLs). In this study, camel MPLs were isolated, and the composition of their lipidome was determined using Ultra Performance Liquid Chromatography-tandem mass spectrometry. This study characterized a total of 333 polar lipids, which encompassed glycerophospholipids and sphingolipids. Camel milk is rich in polar lipids, mainly phosphatidylethanolamine (PE), sphingomyelin (SM), and phosphatidylcholine (PC). The results indicated that MPLs intervention relieved the clinical symptoms and colon tissue damage in mice with DSS-induced colitis, while also suppressing the expression of pro-inflammatory cytokines. Moreover, administration of MPLs partially alleviated mouse gut microbiota dysbiosis by increasing the abundance of probiotics (such as Lachnospiraceae_NK4A136_group, Muribaculaceae) and decreasing the number of harmful bacteria (such as Bacteroides, Parabacteroides). This study was conducted to investigate the potent protective effects of MPLs in camel milk treatments on a mouse model of colitis and provided new ideas for the application of camel milk.

Fat storage-inducing transmembrane proteins: beyond mediating lipid droplet formation.

Fat storage-inducing transmembrane proteins (FITMs) were initially identified in 2007 as members of a conserved endoplasmic reticulum (ER) resident transmembrane protein gene family, and were found to be involved in lipid droplet (LD) formation. Recently, several studies have further demonstrated that the ability of FITMs to directly bind to triglyceride and diacylglycerol, and the diphosphatase activity of hydrolyzing fatty acyl-CoA, might enable FITMs to maintain the formation of lipid droplets, engage in lipid metabolism, and protect against cellular stress. Based on the distribution of FITMs in tissues and their important roles in lipid droplet biology and lipid metabolism, it was discovered that FITMs were closely related to muscle development, adipocyte differentiation, and energy metabolism. Accordingly, the abnormal expression of FITMs was not only associated with type 2 diabetes and lipodystrophy, but also with cardiac disease and several types of cancer. This study reviews the structure, distribution, expression regulation, and functionality of FITMs and their potential relationships with various metabolic diseases, hoping to provide inspiration for fruitful research directions and applications of FITM proteins. Moreover, this review will provide an important theoretical basis for the application of FITMs in the diagnosis and treatment of related diseases.

The orphan GPR50 receptor interacting with TßRI induces G1/S-phase cell cycle arrest via Smad3-p27/p21 in BRL-3A cells.

The liver has the powerful capacity to regenerate after injury or resection. In one of our previous studies, GPR50 was observed to be significantly upregulated at 6 h, following a partial hepatectomy (PH) in rat liver regeneration (LR) via gene expression profile. However, little research has been done on the regulation and mechanism of GPR50 in the liver. Herein, we observed that the overexpression of GPR50 inhibited the proliferation of BRL-3A cells. To further explore the molecular mechanisms of GPR50 in the regulation of BRL-3A cell proliferation, interaction between GPR50 and transforming growth factor-beta I (TßRI) and iTRAQTM differential proteomic analysis were elucidated, which suggested that GPR50 may interact with TßRI to activate the TGF-ß signaling pathway and arrest BRL-3A cell cycle G1/S transition. Subsequently, the potential mechanism underlying the role of GPR50 in hepatocyte growth was also explored through the addition of a signaling pathway inhibitor. These data suggested that interaction between the orphan GPR50 receptor and TßRI induced the G1/S-phase cell cycle arrest of BRL-3A cells via the Smad3-p27/p21 pathway.

Stereoselective protein binding studies of 2-(2-hydroxypropanamido) benzoic acid enantiomers in rat, beagle dog and human plasma.

As the stereoselective plasma protein binding is an important factor for the differences in pharmacokinetic or pharmacodynamic properties of chiral drugs, we elucidated the binding of (R)-/(S)-HPABA to plasma protein. A UHPLC-MS/MS method was developed and validated to the quantitation and equilibrium dialysis method was applied to the separation of bound and unbound drugs. Protein binding reached equilibrium within 12h of incubation at 37°C. Liquid-liquid extraction with ethyl acetate was used for sample preparation. The separation was achieved through a Thermo Syncronis C18 column (50mm×2.1mm, 1.7µm; Thermo, USA) using gradient elution at a flow rate of 0.4ml/min. All of the recovery and matrix effect of the method met the requirements of analytical method validation. The plasma protein binding of (R)-/(S)-HPABA show significant species dependence in enantioselectivity. In addition, the results of molecular docking showed that the combining capacity of (R)-HPABA with HSA was higher than that of (S)-HPABA.

Simultaneous identification and quantification of the common compounds of Viscum coloratum and its corresponding host plants by ultra-high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry and triple quadrupole mass spectrometry.

Viscum coloratum is a perennial evergreen, semi-parasitic plant. It is generally used for treating cardiovascular diseases, cancer, hepatitis and hemorrhage. In this study, reliable methods were developed for the qualitative and quantitative analysis of the common constituents in Viscum coloratum and its corresponding host. In the rapid qualitative analysis, a method of ultra-high performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry was established for identification of the same compounds. Based on the retention times, accurate mass measurement and previous literatures, 23 components were clearly identified by comparison with reference substances. In the quantitative analysis, a method for Viscum coloratum and its corresponding host was developed by ultra-high performance liquid chromatography with triple quadrupole mass spectrometry. 13 common compounds of viscum coloratum and host plants from 19 batches were analyzed with a good linearity (r2≥0.9991), intra-day precision (RSD≤3.24%), inter-day precision (RSD≤3.31%), repeatability (RSD≤2.43%), stability (RSD≤2.63%), and recovery (98.2-102.4%). The overall limits of quantification were less than 5.0ng/mL. The results indicated that these effective and comprehensive methods can be applicable to simultaneous qualitative and quantitative analysis of these common compounds presented in Viscum coloratum and corresponding host plants.

Studies on New Activities of Enantiomers of 2-(2-Hydroxypropanamido) Benzoic Acid: Antiplatelet Aggregation and Antithrombosis.

R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent.

The determination of 2-(2-hydroxypropanamido) benzoic acid enantiomers and their corresponding prodrugs in rat plasma by UHPLC-MS/MS and application to comparative pharmacokinetic study after a single oral dose.

A simple and sensitive UHPLC-MS/MS method was developed and validated to determine the pharmacokinetic profile of 2-(2-hydroxypropanamido) benzoic acid (HPABA) enantiomers and their prodrugs in rat plasma. Separation was performed on a Thermo Syncronis C18 column (50mm×2.1mm, 1.7µm; Thermo, USA), which was protected by a high pressure column prefilter (2µm) at a flow rate of 0.4ml/min. Liquid-liquid extraction with ethyl acetate was used to process plasma samples. The separation of two enantiomers, prodrugs of (R)-/(S)-HPABA and internal standard was obtained within a cycle time of 4.5min. The lower limit of quantification of (R)-/(S)-HPABA and prodrugs of (R)-/(S)-HPABA in plasma were 0.01µg/ml and 0.2µg/ml, respectively. (S)-HPABA showed significantly higher AUC, Cmax and a longer t1/2 than (R)-HPABA, indicating higher bioavailability of the (S)-HPABA. Additionally, inversion between HPABA enantiomers was not observed in rats. (R)-/(S)-HPABA showed higher Cmax and AUC than those of their prodrugs. However, the values of t1/2 of prodrugs were higher than those of (R)-/(S)-HPABA. Furthermore, the higher Vz values of prodrugs might improve the targeting of (R)-/(S)-HPABA in rat tissues.

Comparison of intestinal permeability and p-glycoprotein effects on the intestinal absorption of enantiomers of 2-(2-hydroxypropanamido) benzoic acid in rats.

The purpose of this study was to compare intestinal permeability between enantiomers of 2-(2-hydroxypropanamido) benzoic acid ((R)-/(S)-HPABA), a marine-derived antiinflammatory drug, using an in situ single-pass intestinal perfusion (SPIP) model in rats. Concentrations, isolated regions of small intestine, and p-glycoprotein (P-gp) inhibitor were performed to investigate their influences on the intestinal absorption of (R)-/(S)-HPABA. In addition, a molecular docking method was performed to illustrate our prediction. The absorption rate coefficients (Ka ) and permeability values (Peff ) of (R)-/(S)-HPABA were calculated. The permeability of (S)-HPABA was significantly (P < 0.01) higher than that of (R)-HPABA in jejunum, and ileum permeability of (R)-/(S)-HPABA appeared best in ileum; the investigated concentrations ranged from 20 to 80 µg/mL, Ka and Peff values of (R)-/(S)-HPABA increased linearly; in the presence of P-gp inhibitor (verapamil), Peff values of two enantiomers were increased significantly; and the effect of P-gp on absorption of (R)-HPABA is stronger than that of (S)-HPABA in ileum segment. Based on these results, carrier-mediated transport or passive transport combined with carrier-mediated transport seems to be the mechanism for intestinal absorption of (R)-/(S)-HPABA, and (R)-/(S)-HPABA may be recognized as the P-gp substrate. In addition, the intestinal permeability of (S)-HPABA is higher than that of (R)-HPABA.

The needle-rolling therapy for treatment of non-organic chronic insomnia in 90 cases.

OBJECTIVE: To evaluate the therapeutic effects of needle-rolling therapy for chronic insomnia. METHODS: In the present multi-central randomly controlled clinical study, 180 cases of chronic insomnia were randomly divided into the following two groups, a treatment group (90 cases) treated by the needle-rolling therapy and a control group (90 cases) treated with clonopin. The treatment course for both the two groups was 4 weeks. The therapeutic effects were evaluated based on improvement of the TCM symptoms and the Pittsburgs's sleep-quality index (PSQI). RESULTS: After treatment, there were significant differences between the two groups in the effective rate (P<0.05), and in the total score of PSQI and in the scores of the 4 sub-items, i.e. sleep-quality, sleep-efficiency, hypnotic and daytime function (P<0.05). Although there was no significant difference between the two groups in the effective rate after a 3-month follow-up period, significant differences still existed in the 3 sub-items of sleep-efficiency, hypnotic, and daytime function of the PSQI (P<0.05). CONCLUSION: As compared with hypnotics of the second generation, the needle-rolling therapy may show better therapeutic effects for chronic insomnia patients.

Effect of silicon dioxide on expression of poly (ADP-ribose) polymerase mRNA and protein.

Silicon dioxide induces acute injury and chronic pulmonary fibrosis. International Agency for Research on Cancer (IARC) listed it as a human carcinogen in 1996. However, the molecular mechanisms to induce cancer are not understood yet. The content of poly (ADP-ribose) polymerases (PARP) mRNA and protein in Hela cells treated with concentrations of silicon dioxide up to 400microg/ml was determined by real-time fluorogenetic quantitative PCR (RQ-PCR) and immunofluorescence assay, respectively. MTT assay was used to determine cell viability. The results showed that viability at 400microg/ml silica was significantly decreased but not at lower concentrations. The protein content of gamma-H2AX in silica-treated group was significantly higher than the controls. The PARP mRNA and protein levels were significantly reduced with a dose response manner from the lowest silicon dioxide level. Our findings suggested that silicon dioxide increased the expression of gamma-H2AX and inhibited the expression of PARP mRNA and protein in Hela cells.

[Clinical and qualitative research on acu-moxibustion: considerations on acupuncture clinical trail methods].

Qualitative research refers to a generic name of research methods corresponding to the quantitative research. It is different from quantitative research not only in methods, properties of the collected data, but also and particularly in philosophy, ideology and epistemology. In the present paper, the authors make a brief introduction about the background and methodology of qualitative research, and forecast the future possible tendency of the combined clinical trails of acu-moxibustion. Hopefully, it may provide a possible model for acupuncture clinical research methods and make the acupuncture researchers understand the qualitative research methods in clinical practice so as to promote the further development of acupuncture clinical trails, improve the level of acupuncture theory and provide substantial acupuncture clinical evidence.

[Discussion on randomized controlled trials about clinical researches of acupuncture and moxibustion medicine].

The characteristics of clinical tests of acupuncture and moxibustion were analyzed by studies of the literature about clinical evidence-based trials of acupuncture and moxibustion medicine at present and on the basis of full analysis on the cause of insufficient evidence of clinical researches of acupuncture and moxibustion, in combination with the authors' experiences of clinical studies, and it is put forward that future clinical researches of acupuncture and moxibustion medicine should actively search for new research methods, insist evidence-based acupuncture and moxibustion medical researches, pay attention to retaining own researching characteristics of the acupuncture and moxibustion medicine, accumulate experiences, gradually establish and perfect the assessment system conforming with clinical research methods of acupuncture and moxibustion medicine, elevate the position of acupuncture and moxibustion medicine and develop the acupuncture and moxibustion medicine.

[Preliminary study on training of resident physicians and special physicians of acupuncture-moxibustion].

By using principles and methods of evidence-based medicine in a broad sense to systematically look up clinical acupuncture and moxibustion literatures issued in Chinese Acupuncture and Moxibustion, Journal of Clinical Acupuncture and Moxibustion, and Shanghai Journal of Acupuncture and Moxibustion from January, 2003 to June 2005, and relative official internet station of the departments responsible for health, to stipulate common criteria and select literatures. Preliminarily selected clinical acupuncture and moxibustion study literatures of 1 637 papers, and comprehensive synthesizing the message from the official internet station of The Ministry of Health and The State Administration of Chinese Medicine and Pharmacy etc., indicates that although acupuncture and moxibustion have been widely applied in clinical treatment of 327 diseases, at present there is no systematic training system for resident physicians and special physicians of acupuncture and moxibustion, which is unfavourable for development of sciences and internationalization. On the basis of comprehensively considering the tendency of medical development at home and abroad and characteristics of training of talented persons and subject development of acupuncture and moxibustion, the training system of resident physicians and special physicians of acupuncture and moxibustion should be founded as soon as possible.