Hyperoside prevents doxorubicin-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway.

Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 µM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.

Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study.

BACKGROUND: Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens. METHODS: Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy. RESULTS: A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95-0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97-0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11-0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial. CONCLUSIONS: For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.

Aroma characterisation of Liu-pao tea based on volatile fingerprint and aroma wheel using SBSE-GC-MS.

Liu-pao tea (LPT) has unique aroma characteristics, and is a special microbial fermented tea produced using dark raw tea (LPM) as its raw material. In this study, stir bar sorptive extraction (SBSE) combined with gas chromatography-mass spectrometry (GC-MS) was applied to investigate the volatiles of 16 LPTs and 6 LPMs. Moreover, variations in volatile profiles between LPTs and LPMs were explored. Results showed that a total of 132 volatile compounds were identified from LPTs. The volatile fingerprint was constructed with a similarity ranged from 0.85 to 0.99. Furthermore, twenty-six aroma compounds were selected to depict the molecular aroma wheel of LPT. Multivariate statistical analysis revealed that the contents of 24 aroma compounds changed significantly (P < 0.05) when LPMs were processed into LPTs. These results reveal the volatile profiles of LPTs and aroma composition changes during microbial fermentation process, which might provide chemical basis of the aroma quality of LPT.

Comprehensive investigation on non-volatile and volatile metabolites in four types of green teas obtained from the same tea cultivar of Longjing 43 (Camellia sinensis var. sinensis) using the widely targeted metabolomics.

In this study, we produced roasted, baked, steamed, and sun-dried green tea products using the same batch of fresh tea leaves (FTL) of Longjing 43 (Camellia sinensis var. sinensis), and explored processing effects on the metabolic profiles of four types of green teas (FGTs) using the widely targeted metabolomics. Results showed that 146 differential metabolites including flavonoids, amino acids, lipids, and phenolic acids were screened among 1034 non-volatiles. In addition, nineteen differential metabolites were screened among 79 volatiles. Most of non-volatiles and volatiles metabolites changed notably in different manufacturing processes, whereas there were no significant differences (p＞0.05) in the levels of total catechins between FGTs and FTL. The transformation of metabolites was the dominant trend during green tea processing. The results contribute to a better understanding of how the manufacturing process influences green tea quality, and provide useful information for the enrichment of tea biochemistry theory.

Insights into crucial odourants dominating the characteristic flavour of citrus-white teas prepared from citrus reticulata Blanco 'Chachiensis' and Camellia sinensis 'Fudingdabai'.

Citrus-white teas (CWs), which possess a balanced flavour of tea and citrus, are becoming more popular worldwide; however, their characteristic flavour and odourants received limited research. Volatile components of two types of CWs prepared from Citrus reticulata Blanco 'Chachiensis' and Camellia sinensis 'Fudingdabai' were comprehensively investigated using a combination of stir bar sorptive extraction and gas chromatography-mass spectrometry (GC-MS). Ninety-nine crucial odourants in the CWs were quantified by applying GC-olfactometry/MS, significant differences were compared, and their odour activity values (OAVs) were calculated. Twenty-two odourants (in total 2628.09 and 1131.18 mg/kg respectively) were further confirmed as traditional CW (CW-A) and innovated CW (CW-B) characteristic flavour crucial contributors which all possessed > 1 OAVs, particularly limonene (72919 in CW-A) and trans-ß-ionone (138953 in CW-B). The unravelling of CWs aroma composition will greatly expanding our understanding of tea aroma chemistry and the potential aroma interactions will offer insights into tea blending technologies.

Hypolipidaemic and antioxidant effects of various Chinese dark tea extracts obtained from the same raw material and their main chemical components.

In order to investigate the hypolipidaemic and antioxidant effects of various dark teas produced from different post-fermentation using the same raw material, a hyperlipidaemia zebrafish model combined with binding bile salts assay and antioxidant assays were performed in this study. Results showed that the hypolipidaemic effect of dark tea extracts increased significantly (p < 0.05) while the antioxidant ability decreased sharply compared with raw material. Particularly, Liupao tea (50%) and Pu-erh tea (48%) showed promising hypolipidaemic potential; however, the antioxidant capacity of Pu-erh tea decreased (31-49%) most dramatically. Besides, the levels of total polyphenols and catechins decreased sharply, but theabrownin, gallic acid, and caffeine increased significantly after post-fermentation. Moreover, the potential mechanisms of regulating hyperlipidaemia by dark tea extracts were discussed. These results suggest that microbial fermentation significantly affects the bioactivity of dark teas, and provide theoretical basis for processing and improving of dark tea products for hyperlipidaemia therapy.

Assessment of the contribution of chiral odorants to aroma property of baked green teas using an efficient sequential stir bar sorptive extraction approach.

Chiral volatile compounds are known to be distributed in teas at various enantiomeric ratios. However, the performance of each enantiomer, including aroma characteristics, aroma intensities, and contribution to the overall flavor of tea, is still unclear. In this study, aroma characteristics and intensities of 38 volatile enantiomers in standards and baked green teas with chestnut-like aroma and clean aroma were evaluated by an efficient sequential headspace-stir bar sorptive extraction (seq-HS-SBSE) approach combined with the enantioselective gas chromatography-olfactometry/mass spectrometry (Es-GC-O/MS) technique. Moreover, aroma recombination results for the two types of baked green teas using 14 chiral odorants and four achiral odorants indicated that the combinations of the detected odorants mainly contributed to the "floral", "sweet", and "chestnut-like" aromas. R-Linalool simultaneously enhanced the "floral", "sweet", and "chestnut-like" aromas; R-limonene mainly contributed to the "sweet" and "clean" aromas; and S-α-terpineol promoted the "sweet" and "floral" aromas of baked green tea.

Insight into the pigmented anthocyanins and the major potential co-pigmented flavonoids in purple-coloured leaf teas.

Tea cultivars possessing purple shoots have attracted global interest. In order to gain a better understanding of the major chemical constituents responsible for the purple colouration, we applied widely targeted metabolomics to investigate the pigmented flavonoids of freeze-dried purple-coloured tea leaves (PTLs) in comparison with green-coloured tea leaves (GTLs). Thirty-three anthocyanins were identified, and delphinidin 3-O-galactoside and cyanidin 3-O-galactoside were found to be the most abundant in PTLs. A total of 226 metabolites including 193 flavonoids and 33 tannins were identified, and the methylated, acylated, and glycosylated flavonoids differed significantly between PTLs and GTLs. Moreover, significant differences (p < 0.01) in the average anthocyanin, flavonoid, chlorophyll and catechin contents were also observed. Four PTLs were found to contain high levels of (-)-epigallocatechin-3-(3″-O-methyl) gallate (>10 mg/g). These results suggest that structurally modified anthocyanins and major potential co-pigmented flavonoids are the chemicals primarily responsible for the purple colouration of the tea leaves.

Impact of Various Microbial-Fermented Methods on the Chemical Profile of Dark Tea Using a Single Raw Tea Material.

In the present study, we produced Pu-erh, Liubao, Qingzhuan, and Fuzhuan teas using a single raw tea material and applied widely targeted metabolomics to study the impact of various microbial-fermented methods on the chemical profile of dark tea. The contents of catechins and free amino acids decreased drastically, whereas the contents of gallic acid and theabrownins increased significantly during microbial fermentation. Pu-erh tea had the highest content of theabrownins (11.82 ± 0.49%). Moreover, MS-based metabolomics analysis revealed that the different types of dark teas were significantly different from their raw material. A total of 85 differential metabolites were screened among 569 metabolites identified referring to self-compiled database. Glycosylated, hydroxylated, methylated, and condensed and oxidated products originating from microbial bioconversion of their corresponding primitive forms were significantly increased in dark teas. These results suggest that various microbial-fermented methods greatly affect the metabolic profile of dark tea, which can provide useful information for dark tea biochemistry research.

Antioxidant Effect of Polygonatum sibiricum Polysaccharides in D-Galactose-Induced Heart Aging Mice.

Polygonatum sibiricum polysaccharides (PSP), the extract of Polygonatum sibiricum, are demonstrated to exhibit a wide range of pharmacological activities. A recent study reported that PSP alleviated the aging of the kidney and meninges. However, the effect of PSP on heart aging remains unclear. The present study is aimed at investigating the protection of PSP on D-galactose- (D-gal-) induced heart aging. Results showed that irregularly arranged cardiac muscle fibers were observed in heart tissues of D-gal-treated mice, and the levels of cardiac troponin T (cTnT), creatine kinase (CK), p21, and p53 were increased after D-gal treatment. D-gal-induced heart aging and injury can be attenuated by oral administration of PSP. Moreover, PSP also decreased reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the level of superoxide dismutase (SOD) in the hearts of D-gal-treated mice. DNA damages and lipid peroxidation induced by oxidative stress were also inhibited by PSP as indicated by reduced levels of 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE). Collectively, PSP attenuated D-gal-induced heart aging via inhibiting oxidative stress, suggesting that PSP might serve as a potential effective Chinese herbal active constituent for antiaging therapy.

Insight into the volatile profiles of four types of dark teas obtained from the same dark raw tea material.

Various dark teas are quite different in their volatile profiles, mainly due to the huge differences in the phytochemical profiles of dark raw tea and the diverse post-fermentation processing technologies. In this study, gas chromatography-mass spectrometry (GC-MS), qualitative GC-olfactometry (GC-O), and enantioselective GC-MS coupled with multivariate analysis were applied to characterise the volatile profiles of various dark teas obtained from the same dark raw tea material. A total of 159 volatile compounds were identified by stir bar sorptive extraction (SBSE) combined with GC-MS, and 49 odour-active compounds were identified. Moreover, microbial fermentation could greatly influence the distribution of volatile enantiomers in tea, and six pairs of enantiomers showed great diversity of enantiomeric ratios among various dark teas. These results suggest that post-fermentation processing technologies significantly affect the volatile profiles of various dark teas and provide a theoretical basis for the processing and quality control of dark tea products.

Discrimination and Identification of Aroma Profiles and Characterized Odorants in Citrus Blend Black Tea with Different Citrus Species.

Citrus blend black teas are popular worldwide, due to its unique flavor and remarkable health benefits. However, the aroma characteristics, aroma profiles and key odorants of it remain to be distinguished and cognized. In this study, the aroma profiles of 12 representative samples with three different cultivars including citrus (Citrus reticulata), bergamot (Citrus bergamia), and lemon (Citrus limon) were determined by a novel approach combined head space-solid phase microextraction (HS-SPME) with comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS). A total of 348 volatile compounds, among which comprised esters (60), alkenes (55), aldehydes (45), ketones (45), alcohols (37), aromatic hydrocarbons (20), and some others were ultimately identified. The further partial least squares discrimination analysis (PLS-DA) certified obvious differences existed among the three groups with a screening result of 30 significant differential key volatile compounds. A total of 61 aroma-active compounds that mostly presented green, fresh, fruity, and sweet odors were determined in three groups with gas chromatography-olfactometry/mass spectrometry (GC-O/MS) assisted analysis. Heptanal, limonene, linalool, and trans-ß-ionone were considered the fundamental odorants associated with the flavors of these teas. Comprehensive analysis showed that limonene, ethyl octanoate, copaene, ethyl butyrate (citrus), benzyl acetate, nerol (bergamot) and furfural (lemon) were determined as the characterized odorants for each type.

[Assessment of efficacy of acupuncture combined with hyperbaric oxygen therapy for patients with delayed encephalopathy of CO intoxication by magnetic resonance voxel incoherent motion imaging].

OBJECTIVE: To observe the effect of acupuncture plus hyperbaric oxygen (HBO) on cerebral blood perfusion in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP). METHODS: Twenty-eight patients with DEACMP were randomly divided into acupuncture group (n=14 cases) and control group (n=14 cases). Patients of the acupuncture group were treated by using "Xingnao Kaiqiao" needling technique (specific set of acupuncture points as Yintang ï¼»EX-HN3ï¼½, Shangxing ï¼»GV23ï¼½, Baihui ï¼»GV20ï¼½, Sishenchong ï¼»EX-HN1ï¼½, Fengchi ï¼»GB20ï¼½, Taichong ï¼»LR3ï¼½, etc., and strong stimulation) combined with HBO in an air pressurized tank, and those of the control group treated by simple HBO. The treatment was conducted once a day, 5 days a week for 6 weeks. All the patients underwent head routine magnetic resonance imaging (MRI) and intravoxel incoherent motion imaging(IVIM) scan before and after the treatment. The values of pseudo-diffusion coefficient D (D*) and perfusion fraction (f) of the bilateral semi-oval centers were measured by using MITK software package to calculate the ave-rage fD* value (f×D*). The Barthel index (BI) score was used to assess the patients' daily living ability, and the correlation between parameter values was evaluated by Pearson method. RESULTS: After the treatment, the values of f, fD* and BI scores were significantly increased in both acupuncture group and control groups (P<0.05). The values of the 3 indexes were significantly higher in the acupuncture group than those in the control group (P<0.05). The values of f and fD* were positively correlated with BI score (P<0.05), with the correlation coefficients being 0.822, 0.636 and 0.601, respectively between the fD* and f, BI and f, and BI and fD*. CONCLUSION: Acupuncture combined with HBO can significantly improve the low-perfusion of bilate-ral semi-oval center and daily living ability in patients with DEACMP, being significantly superior to simple HBO therapy in the curative effect.

Characterization of the key aroma compounds in Longjing tea using stir bar sorptive extraction (SBSE) combined with gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), odor activity value (OAV), and aroma recombination.

Longjing tea is the most famous premium green tea, and is regarded as the national tea in China, with its attractive aroma contributing as a prime factor for its general acceptability; however, its key aroma compounds are essentially unknown. In the present study, volatile compounds from Longjing tea were extracted and examined using stir bar sorptive extraction (SBSE) combined with gas chromatography-mass spectrometry (GC-MS). Data obtained from the present study revealed that 151 volatile compounds from 16 different chemical classes were identified by GC-MS analysis. Enols (8096 µg/kg), alkanes (6744 µg/kg), aldehydes (6442 µg/kg), and esters (6161 µg/kg) were the four major chemical classes and accounted for 54% of the total content of volatile compounds. Geraniol (6736 µg/kg) was the most abundant volatile compound in Longjing tea, followed by hexanal (1876 µg/kg) and ß-ionone (1837 µg/kg). Moreover, 14 volatile compounds were distinguished as the key aroma compounds of Longjing tea based on gas chromatography-olfactometry (GC-O) analysis, odor activity value (OAV) calculations, and a preliminary aroma recombination experiment, including 2-methyl butyraldehyde, dimethyl sulfoxide, heptanal, benzaldehyde, 1-octen-3-ol, (E, E)-2,4-heptadienal, benzeneacetaldehyde, linalool oxide I, (E, E)-3,5-octadien-2-one, linalool, nonanal, methyl salicylate, geraniol, and ß-ionone. This is the first comprehensive report describing the aroma characterizations and the key aroma compounds in Longjing tea using SBSE/GC-MS. The findings from this study contribute to the scientific elucidation of the chemical basis for the aromatic qualities of Longjing tea.

[Current state of researches on mechanisms of acupuncture in improvement of hypoxia-ischemic diseases of the central nervous system].

Acupuncture is widely used in the treatment of ischemic diseases of the central nervous system in different clinical stages and has achieved a good clinical effect. The current research showed that acupuncture can improve cerebral blood flow perfusion via increasing blood flow volume, blood flow velocity, the levels of vasomotor substances and reduction of blood viscosity and erythrocyte aggregation index. In recent years, many studies focused on the pathophysiological mechanism of acupuncture in improving cerebral ischemia via triggering the cholinergic vasodilatation, up-regulation of expression of vascular-related proteins and genes，attenuation of inflammatory reaction, etc. Currently, the methods for evaluating the effect of acupuncture are mostly noninvasive functional magnetic resonance imaging in healthy subjects. Future studies should include united selection of acupoints and acupuncture needle manipulations, more reasonable combination of different acupoints, united outcome evaluative standards, better repeatability, employment of big data, etc.

Magnetic liposomes for light-sensitive drug delivery and combined photothermal-chemotherapy of tumors.

The targeted delivery of anticancer drugs for improving the therapeutic efficacy and reducing the side effects has attracted great attention in cancer therapy. In this study, multifunctional magnetic nanoparticles-loaded thermosensitive liposomes (Fe3O4-TSL) were developed for the near-infrared (NIR) laser-triggered release and combined photothermal-chemotherapy of tumors. Doxorubicin (DOX) was encapsulated into the Fe3O4-TSL (DOX-Fe3O4-TSL) via an ammonium sulfate gradient, with an encapsulation efficiency of up to 90.9%. Once treated with NIR laser irradiation, significantly improved drug release was observed in the DOX-Fe3O4-TSL compared to that of DOX-TSL. After an intravenous injection, Fe3O4-TSL tended to enrich in the tumor over time and showed remarkable magnetic resonance imaging (MRI) and photothermal effects. The combined chemo-photothermal therapy study demonstrated that DOX-Fe3O4-TSL could significantly inhibit the tumor growth without causing any significant damage to normal tissues under NIR laser irradiation. These results revealed a great potential for DOX-Fe3O4-TSL for the diagnosis and synergistic therapy of tumors.

Effect of magnetic nanoparticles size on rheumatoid arthritis targeting and photothermal therapy.

Nanoparticles based multifunctional system exhibits great potential in diagnosis and therapy of rheumatoid arthritis (RA). The size of nanoparticles plays an essential role in biodistribution and cellular uptake, in turn affects the drug delivery efficiency and therapeutic effect. To investigate the optimal size for RA targeting, Fe3O4 nanoparticles with well-defined particle sizes (70-350 nm) and identical surface properties were developed as model nanoparticles. The synthesized Fe3O4 nanoparticles exhibited excellent biocompatibility and showed higher temperature response under irradiation of near infrared light. Size-dependent internalization was observed when incubated with inflammatory cells. Compared with large ones, small nanoparticles were more readily be phagocytized, leading to higher cytotoxicity in vitro. However, the in vivo experiment in CIA mice demonstrated a quite different result that nanoparticles with size of 220 nm exerted better accessibility to inflamed joint and resulted in higher temperature and better therapeutic effect under laser irradiation. This study not only offered a novel method for RA therapy but also a guideline for RA targeted drug carrier design.