Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Effects of non-pharmacological interventions on pain in wound patients during dressing change: A systematic review.

BACKGROUND: Changes to the wound dressing frequently cause pain. Some adverse side effects of pharmacologic pain management may cause problems or even impede wound healing. There is no systematic study of non-pharmacologic therapies for pain during wound dressing changes, despite the gradual promotion of non-pharmacologic pain reduction methods. OBJECTIVES: To give clinical wound pain management a new direction, locating and assessing non-pharmacological interventions regarding pain brought on by wound dressing changes are necessary. METHOD: The researchers conducted a comprehensive literature review on non-pharmacological interventions for pain during wound dressing changes across five databases: PubMed, Web of Science, Medline, Embase, and the Cochrane Library spanning the period from January 2010 to September 2022. The evaluation of literature and data extraction was carried out independently by two researchers, and in cases of disagreement, a third researcher participated in the deliberation. To assess the risk of bias in the literature, the researchers utilised the Cochrane Handbook for Reviews of Interventions, version 5.1.0. RESULTS: In total, 951 people were involved in 11 investigations covering seven non-pharmacological therapies. For pain triggered by dressing changes, virtual reality (VR) distraction, auditory and visual distractions, foot reflexology, religious and spiritual care, and guided imaging demonstrated partially positive effects, with hypnosis therapy and jaw relaxation perhaps having a weak effect. CONCLUSION: The key to managing wounds is pain management. According to our review, there is some indication that non-pharmacologic interventions can help patients feel less discomfort when having their wound dressings changed. However, the evidence supporting this view is weak. It needs to be corroborated by future research studies with multicentre and large samples. To promote and use various non-pharmacologic interventions in the future, it is also necessary to build standardised and homogenised paths for their implementation.

Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives.

Cancer is a leading cause of death worldwide. The burden of cancer incidence and mortality is increasing rapidly. New approaches to cancer prevention and treatment are urgently needed. Natural products are reliable and powerful sources for anticancer drug discovery. Baicalin and baicalein, two major flavones isolated from Scutellaria baicalensis Georgi, a multi-purpose traditional medicinal plant in China, exhibit anticancer activities against multiple cancers. Of note, these phytochemicals exhibit extremely low toxicity to normal cells. Besides their cytotoxic and cytostatic activities toward diverse tumor cells, recent studies demonstrated that baicalin and baicalein modulate a variety of tumor stromal cells and extracellular matrix (ECM) in the tumor microenvironment (TME), which is essential for tumorigenesis, cancer progression and metastasis. In this review, we summarize the therapeutic potential and the mechanism of action of baicalin and baicalein in the regulation of tumor microenvironmental immune cells, endothelial cells, fibroblasts, and ECM that reshape the TME and cancer signaling, leading to inhibition of tumor angiogenesis, progression, and metastasis. In addition, we discuss the biotransformation pathways of baicalin and baicalein, related therapeutic challenges and the future research directions to improve their bioavailability and clinical anticancer applications. Recent advances of baicalin and baicalein warrant their continued study as important natural ways for cancer interception and therapy.

Enhanced treatment of landfill leachate by biochar-based aerobic denitrifying bacteria functional microbial materials: Preparation and performance.

Objective: In this work, polyvinyl alcohol (PVA) and sodium alginate (SA) were used as entrapped carriers and Artemisia argyi stem biochar (ABC) was used as an absorption carrier to immobilize aerobic denitrifying bacteria screened from landfill leachate, thus a new carbon-based functional microbial material (PVA/SA/ABC@BS) was successfully prepared. Methods: The structure and characteristics of the new material were revealed by using a scanning electron microscope and Fourier transform infrared spectroscopy, and the performance of the material for treating landfill leachate under different working conditions was studied. Results: ABC had abundant pore structures and that the surface contained many oxygen-containing functional groups, carboxyl groups, and amide groups, etc. and it had good absorbing performance and strong acid and alkali buffering capacity, which was beneficial to the adhesion and proliferation of microorganisms. After adding ABC as a composite carrier, the damage rate of immobilized particles was decreased by 1.2%, and the acid stability, alkaline stability, and mass transfer performance were increased by 9.00, 7.00, and 56%, respectively. When the dosage of PVA/SA/ABC@BS was 0.017g/ml, the removal rates of nitrate nitrogen (NO3 --N) and ammonia nitrogen (NH4 +-N) were the highest, which were 98.7 and 59.4%, respectively. When the pH values were 11, 7, 1, and 9, the removal rates of chemical oxygen demand (COD), NO3 --N, nitrite nitrogen (NO2 --N) and NH4 +-N reached the maximum values, which were 14.39, 98.38, 75.87, and 79.31%, respectively. After PVA/SA/ABC@BS was reused in 5 batches, the removal rates of NO3 --N all reached 95.50%. Conclusion: PVA, SA and ABC have excellent reusability for immobilization of microorganisms and degradation of nitrate nitrogen. This study can provide some guidance for the great application potential of immobilized gel spheres in the treatment of high concentration organic wastewater.

Zhen Wu decoction represses renal fibrosis by invigorating tubular NRF2 and TFAM to fuel mitochondrial bioenergetics.

BACKGROUND: Zhen Wu Decoction (ZWD) is a prescription from the classical text "Treatise on Exogenous Febrile Disease" and has been extensively used to control kidney diseases since the time of the Eastern Han Dynasty. HYPOTHESIS: We hypothesized that ZWD limits tubular fibrogenesis by reinvigorating tubular bio-energetic capacity. STUDY DESIGN / METHODS: A mouse model of chronic kidney disease (CKD) was established using unilateral ureteral obstruction (UUO). Three concentrations of ZWD, namely 25.2 g/kg (high dosage), 12.6 g/kg (middle dosage), and 6.3 g/kg (low dosage), were included to study the dose-effect relationship. Real-time qPCR was used to observe gene transcription in blood samples from patients with CKD. Different siRNAs were designed to study the role of mitochondrial transcription factor A (TFAM) and nuclear factor (erythroid-derived 2)-related factor 2 (NRF2) in transforming growth factor (TGF)-ß1 induced fibrogenesis and mitochondrial damage. RESULTS: We showed that ZWD efficiently attenuates renal function impairment and reduces renal interstitial fibrosis. TFAM and NRF2 were repressed, and the stimulator of interferon genes (STING) was activated in CKD patient blood sample. We further confirmed that ZWD activated TFAM depended on NRF2 as an important negative regulator of STING in mouse kidneys. Treatment with ZWD significantly reduced oxidative stress and inflammation by regulating the levels of oxidative phosphorylation (OXPHOS) and pro-inflammatory factors, such as interleukin-6, interleukin-1ß, tumor necrosis factor receptor 1, and mitochondrial respiratory chain subunits. NRF2 inhibitors can weaken the ability of ZWD to increase TFAM expression and heal injured mitochondria, playing a similar role to that of STING inhibitors. Our study showed that ZWD elevates the expression of TFAM and mitochondrial respiratory chain subunits by promoting NRF2 activation, after suppressing mitochondrial membrane damage and cristae breakdown and restricting mitochondrial DNA (mtDNA) leakage into the cytoplasm to reduce STING activation. CONCLUSION: ZWD maintains mitochondrial integrity and improves OXPHOS which represents an innovative insight into "strengthening Yang-Qi" theory. ZWD limits tubular fibrogenesis by reinvigorating tubular bioenergetic capacity.

Modified biochar/humic substance/fertiliser compound soil conditioner for highly efficient improvement of soil fertility and heavy metals remediation in acidic soils.

Fertile and uncontaminated soil with appropriate pH is crucial in terms of the agricultural sustainable development. Herein, a compound soil conditioner containing chitosan modified straw biochar (CBC), kitchen waste compost product-derived humic substance (HS), NPK compound fertiliser (NPK-CF) was prepared to simultaneously adjust acidic soil pH, improve fertility, and immobilize heavy metal. The results exhibited that the best Pb and NH4+ adsorption performance was obtained in CBC with chitosan:biochar of 1:5. Then, the acid soil pH was improved from 5.03 to 6.66 in the presence of CBC/HS (5:5) with 3% addition weight (the mass ratio of conditioner to soil). Meanwhile, compared with the control, the contents of organic matter, available nitrogen, and available phosphorus significantly increased by 52.4%, 92.6%, and 136.3%, respectively. Moreover, Pb was highly efficient immobilised by CBC, and the concentration of Pb in the soil was decreased by 55.2%. The optimal growth trend of ryegrass was obtained in the presence of 3% addition weight (the mass ratio of conditioner to soil) CBC/HS (CBC:HS = 5:5) combined with 60% of the recommended NPK-CF application weight, which was mainly contributed by the improvement of the soil microbial abundance and community structure diversity. The addition of CBC/HS could effectively reduce the addition of NPK-CF and contribute to simultaneous controlling nitrogen loss, releasing phosphorus, immobilising Pb, adjusting pH, improving soil quality and controlling nonpoint pollution.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

A Novel Hybrid Brain-Computer Interface Combining Motor Imagery and Intermodulation Steady-State Visual Evoked Potential.

The hybrid brain-computer interface (hBCI) combining motor imagery (MI) and steady-state visual evoked potential (SSVEP) has been proven to have better performance than a pure MI- or SSVEP-based brain-computer interface (BCI). In most studies on hBCIs, subjects have been required to focus their attention on flickering light-emitting diodes (LEDs) or blocks while imagining body movements. However, these two classical tasks performed concurrently have a poor correlation. Therefore, it is necessary to reduce the task complexity of such a system and improve its user-friendliness. Aiming to achieve this goal, this study proposes a novel hybrid BCI that combines MI and intermodulation SSVEPs. In the proposed system, images of both hands flicker at the same frequency (i.e., 30 Hz) but at different grasp frequencies (i.e., 1 Hz for the left hand, and 1.5 Hz for the right hand), resulting in different intermodulation frequencies for encoding targets. Additionally, movement observation for subjects can help to perform the MI task better. In this study, two types of brain signals are classified independently and then fused by a scoring mechanism based on the probability distribution of relevant parameters. The online verification results showed that the average accuracies of 12 healthy subjects and 11 stroke patients were 92.40 ± 7.45% and 73.07 ± 9.07%, respectively. The average accuracies of 10 healthy subjects in the MI, SSVEP, and hybrid tasks were 84.00 ± 12.81%, 80.75 ± 8.08%, and 89.00 ± 9.94%, respectively. The high recognition accuracy verifies the feasibility and robustness of the proposed system. This study provides a novel and natural paradigm for a hybrid BCI based on MI and SSVEP.

Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice.

Alzheimer's disease (AD) is an age-related neurological disorder. Currently, there is no effective cure for AD due to its complexity in pathogenesis. In light of the complex pathogenesis of AD, the traditional Chinese medicine (TCM) formula Kai-Xin-San (KXS), which was used for amnesia treatment, has been proved to improve cognitive function in AD animal models. However, the active ingredients and the mechanism of KXS have not yet been clearly elucidated. In this study, network pharmacology analysis predicts that KXS yields 168 candidate compounds acting on 863 potential targets, 30 of which are associated with AD. Enrichment analysis revealed that the therapeutic mechanisms of KXS for AD are associated with the inhibition of Tau protein hyperphosphorylation, inflammation, and apoptosis. Therefore, we chose 7-month-old senescence-accelerated mouse prone 8 (SAMP8) mice as AD mouse model, which harbors the behavioral and pathological hallmarks of AD. Subsequently, the potential underlying action mechanisms of KXS on AD predicted by the network pharmacology analyses were experimentally validated in SAMP8 mice after intragastric administration of KXS for 3 months. We observed that KXS upregulated AKT phosphorylation, suppressed GSK3ß and CDK5 activation, and inhibited the TLR4/MyD88/NF-κB signaling pathway to attenuate Tau hyperphosphorylation and neuroinflammation, thus suppressing neuronal apoptosis and improving the cognitive impairment of aged SAMP8 mice. Taken together, our findings reveal a multi-component and multi-target therapeutic mechanism of KXS for attenuating the progression of AD, contributing to the future development of TCM modernization, including KXS, and broader clinical application.

Effectiveness of online mindfulness-based interventions for improving mental health in patients with physical health conditions: Systematic review and meta-analysis.

We aimed to determine the effectiveness of online mindfulness-based interventions (MBIs) for improving mental health in patients with physical health conditions. Randomized controlled trials (RCTs) in PubMed, Cochrane Library, Web of Science, Elsevier, and CINAHL published through September 2019 were searched. Two reviewers selected trials, conducted a critical appraisal, and extracted the data. Meta-analyses were performed. A total of nine RCTs were included. Analyses revealed that online MBIs was effective in improving depression [standardized mean difference (SMD) = -0.22, 95% confidence interval (CI) (-0.37, -0.07), p = 0.004], anxiety [SMD = -0.19, 95% CI (-0.33, -0.04), p = 0.01], and stress [SMD = -0.32, 95% CI (-0.52, -0.13), p = 0.001], and mindfulness [SMD = 1.67, 95% CI (0.14, 3.20), p = 0.03] in patients with physical conditions. We did not find any obvious effects on well-being [SMD = 1.12, 95% CI (-0.11, 2.36), p = 0.08]. Nevertheless, additional well-designed randomized clinical trials are further needed.

Metabolomics reveals the role of PPARα in Tripterygium Wilfordii-induced liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) have been used to treat autoimmune diseases clinically, however, the side effects of TWT are higher than TGT, especially for hepatotoxicity. THE AIM OF THE STUDY: This study aims to determine the mechanism of TWT-induced liver injury. MATERIALS AND METHODS: We performed metabolomic analysis of samples from mice with liver injury induced by TGT and TWT. Ppara-null mice were used to determine the role of PPARα in TWT-induced liver injury. RESULTS: The results indicated that TWT induced the accumulation of medium- and long-chain carnitines metabolism, which was associated with the disruption of PPARα-IL6-STAT3 axis. PPARα agonists fenofibrate could reverse the liver injury from TWT and TP/Cel, and its protective role could be attenuated in Ppara-null mice. The toxicity difference of TWT and TGT was due to the different ratio of triptolide (TP) and celastrol (Cel) in the tablet in which TP/Cel was lower in TWT than TGT. The hepatotoxicity induced by TP and Cel also inhibited PPARα and upregulated IL6-STAT3 axis, which could be alleviated following by PPARα activation. CONCLUSIONS: These results indicated that PPARα plays an important role in the hepatotoxicity of Tripterygium wilfordii, and PPARα activation may offer a promising approach to prevent hepatotoxicity induced by the preparations of Tripterygium wilfordii.

Early stem growth mutation alters metabolic flux changes enhance sesquiterpenoids biosynthesis in Atractylodes lancea (Thunb.) DC.

Atractylodes lancea (Thunb.) DC. is a well-known medicinal herb in China, containing abundant active components, including a variety of sesquiterpenoids. Owing to a shortage of wild resources, artificial cultivation has become the main breeding mode, leading to the germplasm degradation. In preliminary research, our research group found that a mutant tissue culture seedling of A. lancea is an excellent germplasm resource, characterized by early stem growth and higher sesquiterpenoid content than that of the wild type. In this study, the physiological and biochemical mechanisms underlying efficient sesquiterpenoids synthesis by this mutant A. lancea were systematically evaluated. The results showed that the photosynthetic efficiency, central carbon metabolism efficiency, and energy metabolism efficiency were significantly improved in mutant A. lancea compared with the wild type, and the content of endogenous hormones, such as gibberellin and jasmonic acid, changed significantly. In addition, levels of key metabolites and the expression level of key genes in the mevalonate and 2-C-methyl-d-erythritol-4-phosphate pathways were significantly higher in mutant type than in wild type, resulting in elevated sesquiterpenoid synthesis in the mutant. These physiological and biochemical properties explain the rapid growth and high sesquiterpenoid content of mutant A. lancea. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-022-02240-5.

25-hydroxyvitamin D levels are inversely related to metabolic syndrome risk profile in northern Chinese subjects without vitamin D supplementation.

BACKGROUND: The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. METHODS: A cohort of 211 participants including 151 MetS patients and 60 controls at 20-69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. RESULTS: Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P < 0.05). Participants in the lowest tertile of 25(OH)D levels had increased odds for MetS (P = 0.045), elevated FBG (P = 0.004) in all subjects, and one MetS score gain in MetS patients (P = 0.005). Longitudinally, the metabolic statuses as well as 25(OH)D levels of MetS patients were significantly improved (all P < 0.05), and the increase of 25(OH)D levels were inversely related to MetS scores, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), FBG, and TyG, while positively related to high-density lipoprotein cholesterol (HDL-C) after adjusting for confounders. CONCLUSIONS: 25(OH)D levels were significantly decreased in MetS patients, and it was negatively associated with metabolic dysfunctions at baseline and 1-year after. Metabolic aberrations of MetS patients were significantly ameliorated with 1-year follow-up counselling accompanying by notably elevated 25(OH)D levels.

Microscopic investigations and pharmacognostic techniques for the standardization of the fruits of Rosa laxa Retz.

Rosa laxa Retz., a shrub belonging to the family Rosaceae, is widely distributed in the northern foothills of the Tianshan Mountains in Xinjiang, China. The fruits of R. laxa (FRL) has antibacterial, hypolipidemic, and antioxidant effects. In this study, FRL was subjected to pharmacognostic identification of its source, morphology, microscopic characteristics, and physicochemical properties. The microscope showed that the cross-sectional features of FRL were obvious, and the FRL powder contained vessel, parenchyma cells, exocarp cells, pollen grains, and cluster crystals. Scanning electron microscopy (SEM) analysis results show that numerous villi and many small particles (particle size of 5-50 µm) were observed in the FRL powder, and there are many gullies on the surface of the particles. In addition, the secondary metabolites of FRL were characterized via ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and thin-layer chromatography (TLC). Results showed that FRL contains various secondary metabolites, including flavonoids, phenolic acids, glycosides, and tannins. Water as the extraction solvent had the highest extraction rate and the contented of total flavonoids was 2.88 mg/g, and the contented of total polyphenols was 54.89 mg/g. Moreover, TLC identification revealed that it contains catechin and tiliroside. These parameters of FRL, which are reported herein, are important to the development of the pharmacognostic standards, as well as in the identification and quality control of FRL.

Metabolic Profile of C-Prenyl Coumarins Using Mass Spectrometry-Based Metabolomics.

C-prenyl coumarins (C-PYCs) are compounds with similar structures and various bioactivities, which are widely distributed in medicinal plants. Until now, the metabolic characterizations of C-PYCs and the relationship between metabolism and bioactivities remain unclear. In this study, ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics (UPLC-ESI-QTOF-MS) was firstly used to determine the metabolic characterizations of three C-PYCs, including meranzin hydrate (MH), isomeranzin (ISM), and meranzin (MER). In total, 52 metabolites were identified, and all of them were found to be novel metabolites. Among these metabolites, 10 were from MH, 22 were from ISM, and 20 were from MER. The major metabolic pathways of these C-PYCs were hydroxylation, dehydrogenation, demethylation, and conjugation with cysteine, N-acetylcysteine, and glucuronide. The metabolic rate of MH was much lower than ISM and MER, which was only 27.1% in MLM and 8.7% in HLM, respectively. Additionally, recombinant cytochrome P450 (CYP) screening showed that CYP1A1, 2B6, 3A4, and 3A5 were the major metabolic enzymes involved in the formation of metabolites. Further bioactivity assays indicated that all of these three C-PYCs exhibited anti-inflammatory activity, but the effects of ISM and MER were slightly higher than MH, accompanied by a significant decrease in inflammatory cytokines transcription induced by lipopolysaccharide (LPS) in macrophages RAW 264.7. Taken together, the metabolic characterizations of the three C-PYCs suggested that the side chain of the prenyl group may impact the metabolism and biological activity of C-PYCs.

Calycosin Alleviates Injury in Airway Epithelial Cells Caused by PM 2.5 Exposure via Activation of AMPK Signalling.

METHODS: Phospho-AMP-activated protein kinase (p-AMPK) and AMP-activated protein kinase (AMPK) were detected by western blot. Immunofluorescence staining was used to validate changes in the levels of nuclear factor kappa B (NF-кB) p65 nuclear translocation. Mice were administered intraperitoneally with calycosin one hour before anaesthesia and endotracheal instillation of PM 2.5. The extent of lung injury was evaluated in the H&E-stained lung sections. Apoptotic cells were detected by TUNEL staining. RESULTS: Administration of calycosin was increased in PM 2.5-treated B2B cells in a dose-dependent manner in vitro. Fluorescence signals from anti-NF-кB p65 were increased in nuclei of cells pretreated with calycosin. The level of p-AMPK was increased by calycosin in vitro and in vivo. After pretreatment with compound C, the inhibitory effects of calycosin on cytotoxicity, levels of inflammatory cytokines and p-AMPK, and levels of NF-кB p65 nuclear translocation were not significantly decreased in vitro or in vivo. CONCLUSIONS: Calycosin effectively decreased the release of inflammatory cytokines and alleviated injury caused by PM 2.5. These effects were mediated through activation of AMPK to suppress NF-κB signalling.

Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

The protective role of Zingerone in a murine asthma model via activation of the AMPK/Nrf2/HO-1 pathway.

Asthma is one of the most common illnesses associated with chronic airway inflammation; however, there are currently no effective therapies apart from glucocorticoids. Zingerone (ZIN), an active compound isolated from ginger, has been reported to have a broad spectrum of pharmacological properties. In this study, Zingerone was administrated to H2O2-stimulated mouse airway epithelial cell line MLE12 cells and asthmatic mice. The concentration of cytokines was evaluated using enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE), Periodic Acid-Schiff (PAS) and Masson staining were used for histological analyses. Protein levels in cells or lung tissues were determined using western blot, immunohistochemistry staining. The results showed that treatment with Zingerone dramatically inhibited oxidative stress and the inflammatory response in MLE12 cells stimulated with H2O2 and asthmatic mice. Furthermore, Zingerone treatment could decrease the expression of phosphorylated (p)-IκBα and p65 (nuclear) and increase the expression of phosphorylation of AMP-activated protein kinase (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) to alleviate oxidative damage and inflammation both in vivo and in vitro. In addition, Zingerone treatment reduced the exudation and infiltration of inflammatory cells and suppressed goblet cell hyperplasia in a murine asthma model. Treatment with Zingerone also decreased the level of interleukin (IL)-4, IL-5, IL-13, and increased the level of interferon gamma (IFN-γ) in the BALF and attenuated airway hyperresponsiveness (AHR). However, inhibition of AMPK or Nrf2 suppressed the cellular protective, antioxidative, and anti-inflammatory properties of Zingerone. Taken together, these results demonstrate that Zingerone possesses the potential to relieve asthma via upregulating the AMPK/Nrf2/HO-1 signaling pathway.

Synergistic effects of UVA irradiation and phlorotannin extracts of Laminaria japonica on properties of grass carp myofibrillar protein gel.

BACKGROUND: Oxidized phlorotannin can be used as a protein crosslinking agent to produce high-quality fish gel products. Phlorotannin can be easily induced to form quinone compounds in an oxidizing environment, while o-quinone has been proven to be a reactive, electrophilic intermediate that easily reacts with proteins to form rigid molecular crosslinking networks. The objective of this study was to investigate the synergistic effects of ultraviolet A (UVA) irradiation (1 h, 15 W m-2 ) and various concentrations of Laminaria japonica phlorotannin extracts (PTE) on the gel properties of grass carp myofibrillar protein (MP). RESULTS: UVA treatment and PTE could synergistically improve the MP gel properties more than PTE alone (P < 0.05). At 625 mmol kg-1 MP PTE alone, the gel strength and cooking yield reached 3.10 ± 0.16 g cm and 47.45 ± 0.35%, respectively, while with the same level of PTE plus UVA they became 4.26 ± 0.19 g cm and 53.89 ± 1.54%, respectively. The three-dimensional network structure of the gel (with PTE + UVA) showed higher connectivity and tightness than that of the control group (no treatment). CONCLUSIONS: The synergistic effects of PTE and UVA could effectively induce crosslinking of grass carp MP, which could lead to an improvement of MP gel quality. These findings would provide a new technical approach to produce high-quality protein gel products in the fish processing industry. © 2020 Society of Chemical Industry.

Rapid fingerprinting technology of heavy oil spill by mid-infrared spectroscopy.

With the increase of unconventional oil production and transportation, the detection methods of light crude oil have been challenged. Mid-Infrared spectroscopy can reflect the functional group of the oil related samples, which has strong absorption signals with distinguishable peaks featured as a fast, economy, and robust technique. Nevertheless, the previous study and application of oil relevant samples, such as petroleum chemical industry online monitoring, are mainly based on Near-infrared spectroscopy. Recently, the rapid development of the spectral instrument manufacturing and the data analysis methods provides a more comprehensive technical support for the rapid and accurate identification of marine oil spill by Mid-infrared spectroscopy. In this paper, 10 crude oil samples were selected for infrared spectroscopy detection, and the results were analysed and compared with those of gas chromatography flame ionization detection method. The character information of the IR spectra and GC/FID chromatograms were extracted and classified both by principal component analysis and partial least squares regression. Under the condition of small sample size, the recognition accuracy was up to 100%. The results show that the mid-infrared method combined with chemometrics can be expected to achieve rapid, accurate and economical identification of heavy oil species.