Antioxidant mechanisms of mesenchymal stem cells and their therapeutic potential in vitiligo.

Vitiligo is a skin pigmentation disorder caused by melanocyte damage or abnormal function. Reac-tive oxygen species Reactive oxygen species can cause oxidative stress damage to melanocytes, which in turn induces vitiligo. Traditional treatments such as phototherapy, drugs, and other methods of treatment are long and result in frequent recurrences. Currently, mesenchymal stem cells (MSCs) are widely used in the research of various disease treatments due to their excellent paracrine effects, making them a promising immunoregulatory and tissue repair strategy. Furthermore, an increasing body of evi-dence suggests that utilizing the paracrine functions of MSCs can downregulate oxidative stress in the testes, liver, kidneys, and other affected organs in animal models of certain diseases. Addition-ally, MSCs can help create a microenvironment that promotes tissue repair and regeneration in are-as with oxidative stress damage, improving the disordered state of the injured site. In this article, we review the pathogenesis of oxidative stress in vitiligo and promising strategies for its treatment.

Effects of immersing treatment of curcumin and piperine combined with vacuum packaging on the quality of salmon (Salmo salar) during cold chain logistics.

In order to study the effects of the compound preservatives (curcumin and piperine (CP)) and vacuum packaging (VP) on the quality of salmon during cold chain logistics suffered from temperature abuse, the physiochemical indexes (texture, water holding capacity (WHC), total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS), free amino acids (FAA) contents), microbial indicators (total mesophilic bacteria count (MBC), total psychrotrophic bacteria count (PBC), H2S-producing bacteria count (HSBC)) were determined, and the moisture changes were explored by near-infrared (NIR) spectroscopy and low-field nuclear magnetic resonance (LF-NMR). The results showed that the treatment of curcumin and piperine in combination with vacuum packaging could maintain the quality of salmon suffered from temperature abuse most effectively. At the end of storage, the MBC of VP+CP was only 4.95 log CFU/g, which was about 1 log CFU/g lower than the control sample stored at the same condition. The combined treatment also retarded the increase of TVB-N, TBARS, and the decrease of hardness, springiness, and a* value, as well as water migration in salmon, contributing to higher water holding capacity and better appearance. Besides, VP+CP retarded the decrease of free glutamate, which contributed to umami taste. Due to the biological activity and safety of the preserves, the combined treatment could be a promising method for preservation of seafood.

Cardioprotective Effects of Tetrahydropalmatine on Acute Myocardial Infarction in Rats.

Tetrahydropalmatine (THP) is an active component of Corydalis yanhusuo W. T. Wang. The current study investigates the possible cardioprotective effects of tetrahydropalmatine in acute myocardial ischemia (AMI) rats. The anterior descending coronary artery of SD rats was ligated to establish an AMI model. After two weeks of gavage of THP, cardiac function was determined by echocardiography. The organ index and the infarct size were assessed after the experiment, and the histopathological myocardial tissue changes were observed. In addition, the apoptosis index of myocardial cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of SOD, MDA, CAT, GSH-Px, BNP, and cTn-I were measured by enzyme-linked immunosorbent assay. To determine relevant proteins, the Western blot and molecular docking were applied. Compared with the model group, THP could enhance rat cardiac ejection function to improve cardiac function, drastically lessen the infarct size, reduce myocardial cell damage and inflammatory cell infiltration. THP might also prevent ischemic myocardial damage by inhibiting myocardial cell apoptosis and efficiently reducing oxidative stress. Specifically, THP could decrease MDA, BNP, c-TnI activities, as well as the expression of Bax and Caspase-3 protein, while increasing SOD, GSH-Px, CAT activities, and Bcl-2 level. Furthermore, THP could significantly promote the phosphorylation of PI3K and Akt proteins. The involved pathways and proteins have also been verified through molecular docking. According to these findings, THP may preserve the myocardium due to its anti-oxidant and anti-apoptotic properties.

Japonisine A, a fawcettimine-type Lycopodium alkaloid with an unusual skeleton from Lycopodium japonicum Thunb.

Japonisine A, a novel fawcettimine-type Lycopodium alkaloid with an unusual skeleton and two new fawcettimine-type ones, along with 20 known Lycopodium alkaloids, were isolated from the whole plants of Lycopodium japonicum Thunb. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR, and HR-ESIMS, as well as by comparison with the literature data. Notably, japonisine A (1) was the first example of fawcettimine-related Lycopodium alkaloid with a 2-oxopropyl attached at C-6. All the isolates were evaluated for their inhibitory effects on acetylcholinesterase (AChE) and α-glucosidase. Unfortunately, the results indicated that all the compounds were inactive against the acetylcholinesterase (AChE) and α-glucosidase.

[Study on residues of heavy metals and harmful elements in Qingqiao and Laoqiao based on chemometrics].

Forsythiae Fructus is divided into Qingqiao and Laoqiao due to different harvesting periods. So far, the accumulation of heavy metals in the two types of Forsythiae Fructus has not been reported. In this study, the residual levels of copper(Cu), lead(Pb), chromium(Cr), arsenic(As), cadmium(Cd) and mercury(Hg) in 29 batches of Laoqiao and 60 batches of Qingqiao were determined by inductively coupled plasma mass spectrometry(ICP-MS). The samples were collected from Shanxi, Shaanxi, Henan, and Hebei Provinces. In addition, the diversity and correlation of harmful elements in Qingqiao and Laoqiao were analyzed by multivariate statistical method. Furthermore, principal component analysis(PCA) was used to analyze the harmful elements concentrations of Qingqiao and Laoqiao. The results showed that there was a significant difference on the residual levels of heavy metals and harmful elements between Qingqiao and Laoqiao. Among them, the content of Pb in Laoqiao is significantly higher than that in Qingqiao(P<0.01), while the content of Cu is significantly lower than that in Qingqiao. However, the difference in harmful elements among different producing areas of Forsythiae Fructus is not significant. PCA analysis showed that Qingqiao and Laoqiao were successfully grouped into two categories. This study suggests significant difference in the residual levels of heavy metals and harmful elements between Qingqiao and Laoqiao. Besides, Forsythiae Fructus has a certain enrichment of Pb in the fruit ripening stage(Laoqiao). This study provides a reference for the quality classification and safety of Forsythiae Fructus.

Incidence of Cellulitis Following Acupuncture Treatments in Taiwan.

Background: Cellulitis is a complication of acupuncture, but the risk factors and annualized incidence remain unclear. Objective: This study analyzed the incidence and risk factors of cellulitis related to acupuncture in a cohort of one million participants derived from Taiwan's Longitudinal Health Insurance Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all outpatient medical information including diagnosis and treatment. Patients were categorized according to age, gender, comorbidities, residential area, and number of acupuncture treatments. We compared the incidence and risk of cellulitis between different demographics and comorbidities by logistic regression analysis and adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: We included 407,802 patients and 6,207,378 acupuncture treatments. The incidence of cellulitis after acupuncture was 64.4 per 100,000 courses of acupuncture treatment. The most common sites of cellulitis after acupuncture were the legs, feet, and face. Comorbidity was associated with post-acupuncture cellulitis; a multivariate logistic regression analysis showed that chronic kidney disease (aOR, 1.71; 95% CI, 1.55-1.88), rheumatoid arthritis (aOR, 1.86; 95% CI, 1.21-3.60), liver cirrhosis (aOR, 1.23; 95% CI, 1.15-1.32), diabetes mellitus (aOR, 1.69; 95% CI, 1.57-1.82), stroke (aOR, 1.44; 95% CI, 1.31-1.58), varicose veins (aOR, 2.38; 95% CI, 2.17-2.84), or heart failure (aOR, 1.81; 95% CI, 1.65-1.98) significantly increased cellulitis. Repeated exposure to acupuncture treatment was associated with an increased risk of cellulitis. Conclusions: A variety of chronic diseases may increase the risk of cellulitis after acupuncture. Physicians asked about past medical history before acupuncture might help to reduce cellulitis.

[Effect of Ferula ferulaeoides on growth and apoptosis of human gastric cancer MGC-803 transplantation tumor in nude mice].

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-ß1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.

[Analysis of arsenic speciation in Sepiae Endoconcha and research on its limit standard].

Sepiae Endoconcha is a common marine animal medicine,which generally contains high concentration of arsenic( As).The Chinese Pharmacopoeia( 2010 edition,part I) stipulated that the total As content of Sepiae Endoconcha should not exceed 2 mg·kg~(-1),while this limit was revised to 10 mg·kg~(-1) in the 2015 edition. So far,there is no research on the speciation of As in Sepiae Endoconcha,which made it hard to accurately evaluate its security risk. In this study,32 batches of Sepiae Endoconcha from different sources were collected. The safety risk assessment was carried out by determining the total As content and As speciation,inorganic As[As( Ⅲ),As( Ⅴ) ]and organic As( MMA,DMA,As C,As B) by HPLC-ICP-MS,and then the limit standard was discussed. The results showed that As B was the main form of As in Sepiae Endoconcha,followed by DMA and As( Ⅴ) ． Of the 32 batches of Sepiae Endoconcha,9 batches( accounting for 28%) were detected possessing i As. The maximum concentration of As( Ⅲ) was 103. 3 µg·kg~(-1),and the maximum concentration of As( Ⅴ) was 222. 4 µg·kg~(-1). According to the limit of i As in food,18. 75% of the samples exceeded the standard. The results indicate that there is no simple positive correlation between total As and As morphology in Sepiae Endoconcha. Besides,there is a risk in the total As limit,especially after the relaxation of the total As limit. The problem of high i As content caused by pollution and other factors is difficult to regulate. Since the toxicity of inorganic As is much higher than that of organic As,it is of great practical significance to establish inorganic As form limits in Sepiae Endoconcha.

[Feasibility study of preoperative percutaneous catheter drainage in the treatment of lumbar tuberculosis with psoas abscess].

OBJECTIVE: To investigate the effect of preoperative percutaneous drainage in lumbar tuberculosis with psoas abscess, through compare the clinical efficacy of two different methods. METHODS: Thirty-six patients with lumbar tuberculosis complicated with psoas abscess in corresponding with the inclusion criteria were admitted in Zhejiang Province Traditional Chinese Medicine Hospital from January 2015 to January 2017. The patients were divided into group A and group B according to the different therapeutic methods. All patients were given the standard anti tuberculosis treatment, and percutaneous catheter drainage was used in group A after admission immediately for psoas abscess before operation, while group B with no special treatment. At 3 weeks after anti tuberculosis treatment, 2 patients were excluded in group B, which had to postpone operation because of no reduction in erythrocyte sedimentation rate(ESR) and C reactive protein(CRP). Finally 34 patients were enrolled in this study. There were 18 cases in group A, including 10 males and 8 females, aged from 24 to 73 years old with an average of(42.5±10.2) years. There were 16 cases in group B, including 9 males and 7 females, aged from 23 to 75 years old with an average of(42.3±9.8) years. All patients were treated with posterior pedicle screw fixation, anterior debridement and bone graft fusion. Anterior surgery bleeding volume, operation time, anterior incision length, postoperative anus exhaust time, VAS score, Cobb angle, ESR, CRP changes and postoperative sinus formation were compared between two groups. RESULTS: All patients were followed up for 6 to 21 months with an average of 13 months. At the last follow-up, no mixed infection, tuberculosis recurrence, pedicle screw loosening and nail withdrawal were found. The average operative time, anterior surgery bleeding volume and anterior incision length of group A were less than that of group B(P<0.05). Postoperative anal exhaust time of group A was lower than that of group B(P<0.05). Improvement degree of ESR, CRP at 3 weeks after anti tuberculosis and 1 week after operation, group A was better than group B(P<0.05), and there was no significant difference between two groups in 1 month and 6 months after operation(P>0.05). There was 1 case sinus formation in group A and 5 cases in group B, there was significant difference in sinus formation rate between two groups (P<0.05). VAS score and Cobb angle at 1 month after operation was obvious improved(P<0.05), but there was no significant difference between two groups (P>0.05). Spinal cord nerve injury was obvious improved after operation, but there was no significant difference between two groups. CONCLUSIONS: Preoperative percutaneous catheter drainage is a safe and feasible method for the treatment of lumbar tuberculosis with psoas abscess. It can increase the effect of anti tuberculosis before operation, reduce the surgical trauma and reduce the incidence of postoperative complications. It can be recommended in clinical application.

[Estimation of bioaccessibility and risk assessment of heavy metals in decoction pieces of Bupleuri Radix].

This project was launched to study on the overall residual status of heavy metals of comprehensive understanding in decoction pieces of Bupleuri Radix (DPBR) from different habitats and risk assessment. In this study, inductively coupled plasma mass spectrometry was used to determine the heavy metals of 30 batches of Bupleuri Radix in different producing areas. Simulated gastrointestinal fluid method was used to determine the dissolution rate of heavy metals in the simulated gastrointestinal fluid and the average daily intake Average Daily Dose (ADD) and Hazard Quotient (HQ) index were used to assess the risk of heavy metals in DPBR. The results showed that the contents of copper (Cu), lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg) in the 30 batches of DPBR didn't exceed the limit of Chinese Pharmacopeia, however, the chromium (Cr) in DPBR exeeded the limit set by NSF in USA and the limit for herbal ingredients in Canada. The mean bioaccessible heavy metal concentrations decreased from Cu (5.27 mg·kg⁻¹)>Cr (4.67 mg·kg⁻¹)>As (0.18 mg·kg⁻¹)>Pb (0.12 mg·kg⁻¹)>Cd (0.06 mg·kg⁻¹), and Hg was not detected in this test. In addition, cumulative non-carcinogenic health risks (HI) for adults and children were 0.799 and 0.714, respectively. Both HI values in adults and children for combined trace element and heavy metal element exposures were below the value of 1 (HI<1), indicating very low carcinogenic health risk. Heavy metals toxicity in herbal medicines and its health risk to humans would be overestimated when assessed only by the total concentrations without considering the bioaccessibility. Therefore, bioaccessibility has great significance for evaluating the human health risks induced by heavy metals.

The efficacy of combination of induction chemotherapy and irreversible electroporation ablation for patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND AND OBJECTIVES: Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). METHODS: From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. RESULTS: No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. CONCLUSIONS: Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

Three New Cytotoxic Monoterpenoid Bisindole Alkaloids from Tabernaemontana bufalina.

Three new bisindole alkaloids, 3'-(2-oxopropyl)-19,20-dihydrotabernamine (1: ), 3'-(2-oxopropyl)-ervahanine B (2: ), 19,20-dihydrovobparicine (3: ), and 20 known compounds were isolated from the aerial parts of Tabernaemontana bufalina. The structures of these alkaloids were elucidated using spectroscopic methods. The absolute configurations of 1: -3: were determined by the circular dichroic exciton chirality method. Compounds 1: -23: were screened for their cytotoxicity against two human cancer cell lines, A-549 and MCF-7. Ten compounds (1: -3, 10, 14, 16, 17, 19, 22: , and 23: ) exhibited inhibitory effects against the two human cancer cells with IC50 values of 1.19 ~ 6.13 µM.

Feasibility study of preoperative percutaneous catheter drainage in the treatment of lumbar tuberculosis with psoas abscess / 中国骨伤

OBJECTIVE@#To investigate the effect of preoperative percutaneous drainage in lumbar tuberculosis with psoas abscess, through compare the clinical efficacy of two different methods.@*METHODS@#Thirty-six patients with lumbar tuberculosis complicated with psoas abscess in corresponding with the inclusion criteria were admitted in Zhejiang Province Traditional Chinese Medicine Hospital from January 2015 to January 2017. The patients were divided into group A and group B according to the different therapeutic methods. All patients were given the standard anti tuberculosis treatment, and percutaneous catheter drainage was used in group A after admission immediately for psoas abscess before operation, while group B with no special treatment. At 3 weeks after anti tuberculosis treatment, 2 patients were excluded in group B, which had to postpone operation because of no reduction in erythrocyte sedimentation rate(ESR) and C reactive protein(CRP). Finally 34 patients were enrolled in this study. There were 18 cases in group A, including 10 males and 8 females, aged from 24 to 73 years old with an average of(42.5±10.2) years. There were 16 cases in group B, including 9 males and 7 females, aged from 23 to 75 years old with an average of(42.3±9.8) years. All patients were treated with posterior pedicle screw fixation, anterior debridement and bone graft fusion. Anterior surgery bleeding volume, operation time, anterior incision length, postoperative anus exhaust time, VAS score, Cobb angle, ESR, CRP changes and postoperative sinus formation were compared between two groups.@*RESULTS@#All patients were followed up for 6 to 21 months with an average of 13 months. At the last follow-up, no mixed infection, tuberculosis recurrence, pedicle screw loosening and nail withdrawal were found. The average operative time, anterior surgery bleeding volume and anterior incision length of group A were less than that of group B(0.05). There was 1 case sinus formation in group A and 5 cases in group B, there was significant difference in sinus formation rate between two groups (0.05). Spinal cord nerve injury was obvious improved after operation, but there was no significant difference between two groups.@*CONCLUSIONS@#Preoperative percutaneous catheter drainage is a safe and feasible method for the treatment of lumbar tuberculosis with psoas abscess. It can increase the effect of anti tuberculosis before operation, reduce the surgical trauma and reduce the incidence of postoperative complications. It can be recommended in clinical application.

Chemical Components, Biological Activities, and Toxicological Evaluation of the Fruit (Aril) of Two Precious Plant Species from Genus Taxus.

The fruit (aril) of the endangered genus Taxus plants is an abandoned herbal resource. Traditionally, people enthusiastically focus on its bark, its renewable, tremendous arils fall into the soil with seeds after they are mature. The present research investigated the fruit of two species from the genus Taxus, Taxus chinensis var. mairei, and Taxus media, with regards to their antioxidant and antihyperglycaemic activities, safety, and bioactive constituents. Results showed that T. chinensis var. mairei and T. media both had certain biological activities with T. chinensis var. mairei better in antioxidant activity and T. media better in antihyperglycaemic activity. Correlation analysis revealed that the differences in bioactivities depended on content of their mainly chemical components. The mice acute oral toxicity test indicated that the methanol extracts of the two biotypes of Taxus were safe. And nineteen compounds were tentatively assigned from the two varieties, via tandem mass spectrometry using a LC-ESI-Q-TOF-MS instrument, which included phenols, flavonoids, and terpenes. These results indicate a possible application of Taxus fruit extracts in various fields like in food industry, however, this still needs further investigations.

[Total flavonoids in Scutellaria barbata prevents NLRP3 inflammasome expression in tumor cells by affecting autologous pathway].

This paper was aimed to investigate the relationship between autophagy and NLRP3 inflammasome activation by studying the effect oftotal flavonoids in Scutellaria barbata (TF-SB) on autophagy in tumor cells and NLRP3 inflammasome, and to provide experimental evidence for further study of the anti-tumor mechanism of TF-SB. Mielanoma models were established by inoculating B16-F1 cell line to mice, and then were randomly divided into 5 groups (n=10 in each group): model control, positive control control(Rap, 1.5 mg•kg⁻¹), and TF-SB low, middle and high groups (50, 100 and 200 mg•kg⁻¹). Meanwhile, healthy C57BL/6J mice were used as normal control group (n=10). The drugs were given once daily for 2 weeks consecutively. Thirty minutes after last treatment, the determinations at endpoint were performed; pathological changes of tumor tissue were evaluated by using HE staining; protein expressions of LC3-II/LC3-I or NLRP3inflammasome/caspase-1/IL-1ß and IL-18 in tumor tissues were detected by using Western-blot; and serum levels of IL-1ß and IL-18 were detected by using Elisa kit. The results showed that the tumor cells in model group showed obvious atypia and malignant proliferation; the invasion of tumor tissue was significantly reduced, the tumor necrosis area was significantly increased, and the inflammatory reaction was significantly alleviated in positive control group and various TF-SB groups. As compared with model control group, LC3-II/LC3-I was significantly increased, while NLRP3/caspase-1/IL-1ßand IL-18 protein expressions were significantly decreased in positive control group and TF-SB groups. Serum IL-1ß and IL-18 levels in model control group were found higher than those in control group (P<0.001), but they were significantly lowered in positive control group and TF-SB groups (P<0.05, P<0.01 or P<0.001). Taken together, total flavonoids in S. barbata could effectively alter the tumor growth micro-environment by inhibiting the expression of NLRP3 inflammasome, and its anti-tumor effect may be associated with the induction of tumor cell autophagy.

Analysis of aflatoxins in traditional Chinese medicines: Classification of analytical method on the basis of matrix variations.

A classification system for analytical methods was developed for the first time to determine the presence of aflatoxins B1, B2, G1 and G2 in traditional Chinese medicines (TCMs) based on different matrix types using ultra-performance liquid chromatography-tandem mass spectrometry. A useful characteristic of the approach was that the TCMs could be systematically divided into four categories (i.e., volatile oils, proteins, polysaccharides and fatty oils) depending on the matrix types. The approach concluded that different types of TCMs required different optimal sample preparation procedures. Based on the optimized analytical conditions, the limits of detection and quantification, average recoveries and linearity of four aflatoxins were determined and conformed to research limits. Of 22 TCMs samples, 14 samples were contaminated with at least one type aflatoxin at concentrations ranging from 0.2 to 7.5 µg/kg, and the average contents of aflatoxins were significantly different for the different matrix types. Moreover, we found a potential link between the contamination levels of aflatoxins and matrix types. TCMs containing fatty oils were the most susceptible to contamination by aflatoxins and followed by TCMs containing polysaccharides and proteins; TCMs containing abundant amounts of volatile oils were less prone to contamination.

Comparative Evaluation of the Chemical Composition, Antioxidant and Antimicrobial Activities of the Volatile Oils of Hawk Tea from Six Botanical Origins.

In this study, volatile oils of six Hawk tea varieties were studied for their chemical composition, antioxidant and antimicrobial activities to screen the most suitable botanical origins of Hawk tea. A total of 72 components were separated and identified from the six oils. The major constituents of the volatile oils were: α-pinene, camphene, limonene, 1,8-cineole, linalool, cis-nerolidol, and germacrene B. Moreover, the volatile oils were evaluated for antioxidant potential and antimicrobial activities. The results showed that all volatile oils exhibited acceptable antioxidant and antimicrobial activities, which suggested that these volatile oils may serve as natural alternatives to synthetic antioxidants and preservatives to be applied in food and pharmaceutical industries. Principal component analysis results denoted that some major compounds may be closely related to the antioxidant and antimicrobial activities. It also showed that the volatile oils from Litsea coreana var. lanuginosa and Litsea pungens Hemsl. were characterized by positive values of first two principal components, indicating higher active chemical compounds and antioxidant and antimicrobial activities compared with other species. Thus, they were temporarily considered as good sources of Hawk tea.

Eucarobustols A-I, Conjugates of Sesquiterpenoids and Acylphloroglucinols from Eucalyptus robusta.

Nine new conjugates of sesquiterpenoids and acylphloroglucinols, named eucarobustols A-I (1-9), as well as 11 known analogues were isolated from the leaves of Eucalyptus robusta. The sesquiterpenoid motifs furnishing the new conjugates included four structural types of aristolane (1 and 2), guaiane (3), eudesmane (4), and aromadendrane (5-9) moieties. Compounds 1 and 2 were found to represent the first examples of conjugates of aristolane and acylphloroglucinol units. In turn, compound 3 features a new coupling model of guaiane and acylphloroglucinol via the C-4-C-7' bond. Compounds 1, 7, and 9 showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 1.3, 1.8, and 1.6 µM, respectively.

Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits.

Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

Glucagon receptor antagonism induces increased cholesterol absorption.

Glucagon and insulin have opposing action in governing glucose homeostasis. In type 2 diabetes mellitus (T2DM), plasma glucagon is characteristically elevated, contributing to increased gluconeogenesis and hyperglycemia. Therefore, glucagon receptor (GCGR) antagonism has been proposed as a pharmacologic approach to treat T2DM. In support of this concept, a potent small-molecule GCGR antagonist (GRA), MK-0893, demonstrated dose-dependent efficacy to reduce hyperglycemia, with an HbA1c reduction of 1.5% at the 80 mg dose for 12 weeks in T2DM. However, GRA treatment was associated with dose-dependent elevation of plasma LDL-cholesterol (LDL-c). The current studies investigated the cause for increased LDL-c. We report findings that link MK-0893 with increased glucagon-like peptide 2 and cholesterol absorption. There was not, however, a GRA-related modulation of cholesterol synthesis. These findings were replicated using structurally diverse GRAs. To examine potential pharmacologic mitigation, coadministration of ezetimibe (a potent inhibitor of cholesterol absorption) in mice abrogated the GRA-associated increase of LDL-c. Although the molecular mechanism is unknown, our results provide a novel finding by which glucagon and, hence, GCGR antagonism govern cholesterol metabolism.