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2.
J Clin Med ; 10(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34575275

RESUMO

Hepatocellular carcinoma (HCC) is the second common cause of cancer-related death in Taiwan. Tumor recurrence is frequently observed in HCC patients receiving surgical resection, resulting in unsatisfactory overall survival (OS). Therefore, it is pivotal to identify effective prognostic makers, so that intensive surveillance or adjuvant treatments can be applied to predictively unfavorable patients. Previous studies indicated that Annexin A2 (ANXA2) was an effective prognostic marker in several cancers, including HCC. However, the prognostic value of ANXA2 in Taiwanese HCC patients remains unclear, where a great proportion of patients had chronic hepatitis B with liver cirrhosis. Here, ANXA2 was highly expressed in HCC tissues compared with para-neoplastic noncancerous tissues. Furthermore, high ANXA2 expression in HCC tissues independently predicted shorter OS. In subgroup analysis, however, ANXA2 expression could not effectively predict OS in the following subgroups: female, age > 65 years old, Child-Pugh classification B, hepatitis B virus surface antigen negative or anti-hepatitis C antibody positive, alcoholism, tumor number >1, presence of micro- or macrovascular invasion, absence of capsule, non-cirrhosis and high alpha-fetoprotein. In conclusion, ANXA2 expression in HCC tissues could predict postoperative OS. However, the predictive value was limited in patients with specific clinical conditions.

3.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

4.
Drug Deliv Transl Res ; 11(4): 1532-1544, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34125402

RESUMO

There is an urgent need for treatments for hydrofluoric acid (HF) burns and their derivative problems that prevent hydrogen ion dissociation and fluoride ion binding to tissues. This study evaluated the ability of chitosan-based hydrogels combined with a buffer solution containing either boric acid or Tris and calcium gluconate (CHS-BA-CG and CHS-Tris-CG) to repair HF burn wounds and prevent wound infections. We assessed calcium release rates and biocompatability and constructed a mouse HF burn model to assess the tissue repair effects of the hydrogels. Finally, we performed disc diffusion tests from burn tissue and quantified the bacterial counts to assess the anti-infection properties of the hydrogels. Calcium was gradually released in the CHS-BA-CG and CHS-Tris-CG groups (73% and 43%, respectively, after 48 h). The cell viabilities at 48 h after HF burn in these groups were significantly higher than those in the phosphate-buffered saline (PBS) and CG-treated groups. Histopathological evaluation showed a clear boundary between the epidermal and dermal layers in both CHS-BA-CG and CHS-Tris-CG-treated groups, indicating their effectiveness in tissue repair. In the disc diffusion test, CHS-BA-CG and CHS-Tris-CG exhibited larger inhibition zones against Acinetobacter baumannii than those for PBS and CG. The bacterial counts on HF burn wounds were significantly lower in the CHS-BA-CG and CHS-Tris-CG-treated groups than those in the PBS and CG-treated groups. The in vitro studies demonstrated the biocompatibility and antimicrobial effects of the CHS-BA-CG and CHS-Tris-CG hydrogels. Both gels also demonstrated tissue repair and anti-infection effects. Thus, chitosan-based hydrogels may be candidates for HF burn therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33610508

RESUMO

BACKGROUND: Tigecycline is an antibiotic that well tolerated for treating complicated infections. It has received attention as an anti-cancer agent and expected to solve two major obstacles, sides effects that accompany chemotherapy and drug resistance, in the breast cancer treatment. However, previous studies reported that the levels in the blood are typically low of tigecycline, so higher doses are needed to treat cancer, that may increase the risk of side effects. To achieve better anti-cancer effects for tigecycline, we need to find a novel adjunct agent. METHODS: In this study, we used different concentration of pyrvinium pamoate combined with tigecycline to treat cell. And assess the effect of two drugs in inhibit cell proliferation, induce cell autophagy, or increase cell apoptosis to evaluate the consequent of combined therapy. RESULTS: We observed that after the combined therapy, the cell cycle arrest at G1/s phase, the level of p21 increased, but decreased the levels of CDK2. Others, two drugs via different mechanisms to inhibit cancer cell proliferation and with selective cytotoxic to different cell lines. That could enhance the effect of breast cancer treatment. CONCLUSION: Combining low dose of tigecycline use with pyrvinium pamoate is a novel approach for breast cancer treatment. Appropriate combined therapy in breast cancer is recommended to improve outcomes. Other problems like drug resistance occur in patients or the microbes surrounding breast tissues would confer susceptibility to cancers then influence the effectiveness of treatment, which could be improved through combined therapy.

6.
Biomed Pharmacother ; 136: 111260, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33465676

RESUMO

OBJECTIVE: Cryptotanshinone (CPT) and dihydrotanshinone (DHT) are diterpenoid anthraquinone compounds extracted from traditional Chinese herbal medicine (TCM). Recent studies have shown that CPT regulates the signal transduction pathways via microRNA (miRNA) alterations. However, few studies have investigated the role of DHT in miRNA alterations affecting cell-signaling pathways. This study aimed to investigate the miRNA alterations and post-transcriptional regulation activities of DHT in comparison to CPT. METHODS: HepG2 and HT-29 cells were treated with DHT or CPT for 72 h. MiRNA, transcription factor encoding mRNA, and downstream gene expression were determined using real-time quantitative PCR. Protein expression was analyzed using western blotting. RESULTS: The results revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via miR-15a-5p, miR-27a-5p, miR-100-5p, and miR-200a-5p alterations.In silico target predictions showed that downregulation of epidermal growth factor receptor (EGFR) mRNA expression by DHT might also suppress the expression of STAT family proteins and lead to anti-proliferation effects. We also found that, compared to CPT, DHT might possess higher potency in cell growth regulation via multi-miRNA and transcription factor alterations. CONCLUSION: This study revealed that CPT and DHT targeted cell proliferation and apoptosis signaling pathways via alterations in miRNAs and transcription factors. In addition, the findings of this study suggest that DHT is more potent than CPT in cancer chemopreventive activities. Therefore, DHT at a low dose is a TCM compound with less toxic side effects and may contribute to the development of natural medicine as a potential cancer chemopreventive agent.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Furanos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/metabolismo , Fenantrenos/farmacologia , Quinonas/farmacologia , Transcriptoma/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Células HT29 , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
J Antimicrob Chemother ; 76(2): 451-459, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33057603

RESUMO

BACKGROUND: According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like ß-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). OBJECTIVES: In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D ß-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. METHODS: A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time-kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. RESULTS: Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time-kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. CONCLUSIONS: Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

9.
Phys Rev Lett ; 125(14): 143902, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33064523

RESUMO

We demonstrate the first compact photonic flywheel with sub-fs time jitter (averaging times up to 10 µs) at the quantum-noise limit of a monolithic fiber resonator. Such quantum-limited performance is accessed through novel two-step pumping scheme for dissipative Kerr soliton generation. Controllable interaction between stimulated Brillouin lasing and Kerr nonlinearity enhances the DKS coherence and mitigates the thermal instability challenge, achieving a remarkable 22-Hz intrinsic comb linewidth and an unprecedented phase noise of -180 dBc/Hz at 945-MHz carrier at free running. The scheme can be generalized to various device platforms for field-deployable precision metrology.

10.
Opt Lett ; 45(15): 4184-4187, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735254

RESUMO

We analytically and numerically unveil the existence condition of symbiotic solitons in doubly resonant non-degenerate optical parametric oscillators. Resonant signal and idler with terahertz comb bandwidth and femtosecond pulse duration in the mid-infrared are attainable through this symbiotic soliton mode-locking technique. The group velocity mismatches between the three interacting waves are the dominant cause of the symbiotic soliton perturbation, and their effects are numerically investigated in detail. The principle can be applied to commonly used mid-infrared material platforms, making it a competitive ultrashort pulse and broadband comb source architecture.

11.
Front Pharmacol ; 11: 892, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32625091

RESUMO

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription-syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.

12.
Int J Mol Sci ; 21(12)2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32560269

RESUMO

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.


Assuntos
Técnicas de Cultura de Células/instrumentação , Células-Tronco Mesenquimais/citologia , Técnicas Analíticas Microfluídicas/instrumentação , Materiais Biomiméticos/química , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Meios de Cultura/química , Humanos , Fenótipo
13.
Int J Mol Sci ; 21(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455543

RESUMO

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Assuntos
Parafusos Ósseos/normas , Osseointegração , Impressão Tridimensional , Tendões/cirurgia , Tíbia/cirurgia , Ligas/química , Animais , Parafusos Ósseos/efeitos adversos , Interface Osso-Implante/cirurgia , Fosfatos de Cálcio/química , Porosidade , Coelhos
14.
Opt Lett ; 45(8): 2311-2314, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32287221

RESUMO

We examine the existence condition of the quadratic soliton mode-locked degenerate optical parametric oscillator in the previously unexplored parameter space. We study the nature of the quadratic solitons and divide their dynamics into two distinctive branches, depending on the system parameters. Origin of the quadratic soliton perturbation is identified, and strategy to mitigate its detrimental effect is developed. Frequency comb with terahertz bandwidth and femtosecond pulse duration are attainable in an example periodically poled lithium niobate waveguide resonator. Design rules of the quadratic soliton mode-locking are summarized. The principle can be further extended to other material platforms, making it a competitive ultrashort pulse and broadband comb source architecture at the mid-infrared.

15.
Light Sci Appl ; 9: 52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284854

RESUMO

Femtosecond mode-locked laser frequency combs have served as the cornerstone in precision spectroscopy, all-optical atomic clocks, and measurements of ultrafast dynamics. Recently frequency microcombs based on nonlinear microresonators have been examined, exhibiting remarkable precision approaching that of laser frequency combs, on a solid-state chip-scale platform and from a fundamentally different physical origin. Despite recent successes, to date, the real-time dynamical origins and high-power stabilities of such frequency microcombs have not been fully addressed. Here, we unravel the transitional dynamics of frequency microcombs from chaotic background routes to femtosecond mode-locking in real time, enabled by our ultrafast temporal magnifier metrology and improved stability of dispersion-managed dissipative solitons. Through our dispersion-managed oscillator, we further report a stability zone that is more than an order-of-magnitude larger than its prior static homogeneous counterparts, providing a novel platform for understanding ultrafast dissipative dynamics and offering a new path towards high-power frequency microcombs.

16.
Polymers (Basel) ; 12(2)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069799

RESUMO

Healing of an anterior cruciate ligament graft in bone tunnel yields weaker fibrous scar tissue, which may prolong an already prolonged healing process within the tendon-bone interface. In this study, gelatin molecules were added to thermosensitive chitosan/ß-glycerol phosphate disodium salt hydrogels to form chitosan/gelatin/ß-glycerol phosphate (C/G/GP) hydrogels, which were applied to 0.1 mg/mL collagenase carrier in the tendon-bone junction. New Zealand white rabbit's long digital extensor tendon was detached and translated into a 2.5-mm diameter tibial plateau tunnel. Thirty-six rabbits underwent bilateral surgery and hydrogel injection treatment with and without collagenase. Histological analyses revealed early healing and more bone formation at the tendon-bone interface after collagenase partial digestion. The area of metachromasia significantly increased in both 4-week and 8-week groups after collagenase treatment (p < 0.01). Micro computed tomography showed a significant increase in total bone volume and bone volume/tissue volume in the 8 weeks after collagenase treatment, compared with the control group. Load-to-failure was significantly higher in the treated group at 8 weeks (23.8 ± 8.13 N vs 14.3 ± 3.9 N; p = 0.008). Treatment with collagenase digestion resulted in a 66% increase in pull-out strength. In conclusion, injection of C/G/GP hydrogel with collagenase improves tendon-to-bone healing in a rabbit model.

17.
Light Sci Appl ; 8: 107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798846

RESUMO

Photonic sensors that are able to detect and track biochemical molecules offer powerful tools for information acquisition in applications ranging from environmental analysis to medical diagnosis. The ultimate aim of biochemical sensing is to achieve both quantitative sensitivity and selectivity. As atomically thick films with remarkable optoelectronic tunability, graphene and its derived materials have shown unique potential as a chemically tunable platform for sensing, thus enabling significant performance enhancement, versatile functionalization and flexible device integration. Here, we demonstrate a partially reduced graphene oxide (prGO) inner-coated and fiber-calibrated Fabry-Perot dye resonator for biochemical detection. Versatile functionalization in the prGO film enables the intracavity fluorescent resonance energy transfer (FRET) to be chemically selective in the visible band. Moreover, by measuring the intermode interference via noise canceled beat notes and locked-in heterodyne detection with Hz-level precision, we achieved individual molecule sensitivity for dopamine, nicotine and single-strand DNA detection. This work combines atomic-layer nanoscience and high-resolution optoelectronics, providing a way toward high-performance biochemical sensors and systems.

18.
J Clin Med ; 8(10)2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31635078

RESUMO

INTRODUCTION: serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. METHODS: between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ≥15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan-Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. RESULTS: a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. CONCLUSION: N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

19.
J Agric Food Chem ; 67(35): 9812-9819, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31392887

RESUMO

We investigated the absorption and metabolic behavior of hesperidin (hesperetin-7-O-rutinoside) in the blood system of Sprague-Dawley rats by liquid chromatography- and matrix-assisted laser desorption ionization mass spectrometries (LC-MS and MALDI-MS). After a single oral administration of hesperidin (10 mg/kg), which was expected to be absorbed in its degraded hesperetin form, we detected intact hesperidin in the portal vein blood (tmax, 2 h) for the first time. We successfully detected glucuronized hesperidin in the circulating bloodstream, while intact hesperidin had disappeared. Further MS analyses revealed that homoeriodictyol and eriodictyol conjugates were detected in both portal and circulating blood systems. This indicated that hesperidin and/or hesperetin are susceptible to methylation and demethylation during the intestinal membrane transport process. Sulfated and glucuronized metabolites were also detected in both blood systems. In conclusion, hesperidin can enter into the circulating bloodstream in its conjugated forms, together with the conjugated forms of hesperetin, homoeriodictyol, and/or eriodictyol.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Hesperidina/farmacocinética , Administração Oral , Animais , Cromatografia Líquida , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Hesperidina/administração & dosagem , Hesperidina/sangue , Hesperidina/química , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
20.
Light Sci Appl ; 8: 50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31149335

RESUMO

Dissipative Kerr solitons in resonant frequency combs offer a promising route for ultrafast mode-locking, precision spectroscopy and time-frequency standards. The dynamics for the dissipative soliton generation, however, are intrinsically intertwined with thermal nonlinearities, limiting the soliton generation parameter map and statistical success probabilities of the solitary state. Here, via use of an auxiliary laser heating approach to suppress thermal dragging dynamics in dissipative soliton comb formation, we demonstrate stable Kerr soliton singlet formation and soliton bursts. First, we access a new soliton existence range with an inverse-sloped Kerr soliton evolution-diminishing soliton energy with increasing pump detuning. Second, we achieve deterministic transitions from Turing-like comb patterns directly into the dissipative Kerr soliton singlet pulse bypassing the chaotic states. This is achieved by avoiding subcomb overlaps at lower pump power, with near-identical singlet soliton comb generation over twenty instances. Third, with the red-detuned pump entrance route enabled, we uncover unique spontaneous soliton bursts in the direct formation of low-noise optical frequency combs from continuum background noise. The burst dynamics are due to the rapid entry and mutual attraction of the pump laser into the cavity mode, aided by the auxiliary laser and matching well with our numerical simulations. Enabled by the auxiliary-assisted frequency comb dynamics, we demonstrate an application of automatic soliton comb recovery and long-term stabilization against strong external perturbations. Our findings hold potential to expand the parameter space for ultrafast nonlinear dynamics and precision optical frequency comb stabilization.

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