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1.
Food Chem ; 444: 138642, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38325088

ABSTRACT

Chinese quince (Chaenomeles sinensis) fruit is an underutilized resource, rich in proanthocyanidins with antioxidant ability but poor lipid solubility. In this study, a novel modified oligomeric proanthocyanidin (MOPA) was prepared, which exhibited favorable lipid solubility (354.52 mg/100 g). It showed higher radical scavenging abilities than commercial antioxidant-BHA (butylated hydroxyanisole), both at 0.4-0.5 mg/mL. The addition of MOPA (0.04 %wt.) significantly increased the oxidative stability index of the soybean oil from 5.52 to 8.03 h, which was slightly lower than that of BHA (8.35 h). Analysis of the physicochemical properties and composition of oil during deep-frying showed that MOPA demonstrated significant antioxidant effects and effectively restricted the oil oxidation. This inhibition also delays the formation of heterocyclic amines (HAs) in fried food, thereby reducing the migration of HAs from food to deep-frying oil. Therefore, MOPA is a promising novel liposoluble antioxidant for protecting the quality of deep-frying oil.


Subject(s)
Phenylacetates , Proanthocyanidins , Rosaceae , Antioxidants/chemistry , Soybean Oil/chemistry , China
2.
Zhen Ci Yan Jiu ; 49(1): 71-78, 2024 Jan 25.
Article in English, Chinese | MEDLINE | ID: mdl-38239141

ABSTRACT

Acupuncture has a positive effect in the treatment of ischemic stroke (IS). A number of studies have confirmed that the role of acupuncture in the treatment of IS, which is closely related to its functions of regulating mitochondrial functions. In the present article, we review the mechanisms of acupuncture underlying improvement of mitochondria in the treatment of IS from 4 aspects: 1) protecting mitochondrial structure integrity, 2) regulative effect on mitochondrial functional activities, including regulating energy metabolism, reducing oxidative stress, suppressing calcium overload, and regulating mitochondrial membrane potential changes, 3) regulating mitochondrial quality control system, including promoting mitochondrial biosynthesis, regulating mitochondrial dynamics and apoptosis, and 4) regula-ting mitochondria-related apoptosis pathways. All of these may provide a theoretical basis for acupuncture in the treatment of IS and a reference for further research.


Subject(s)
Acupuncture Therapy , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Neurons/metabolism , Oxidative Stress , Stroke/genetics , Stroke/therapy
3.
Phytomedicine ; 123: 155169, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37992493

ABSTRACT

BACKGROUND: Huachansu (HCS), a known Chinese patent drug extracted from the Chinese toad skin, is frequently used for the treatment of various advanced cancers, especially gastric cancer, due to the good therapeutic effect. However, it is rather difficult to clarify the active substances and molecular mechanisms involved owing to the lack of appropriate research strategies. We recently proposed the concept and research ideas of compound-composed Chinese medicine formula. PURPOSE: To discover compound-composed Chinese medicine from Huachansu and to explore its mechanism of action in inducing apoptosis of gastric cancer cells. METHOD: Network pharmacology combined with serum pharmacochemistry was utilized to screen the predominant active constituents from HCS against gastric cancer. Then, the compound-composed Chinese medicine of HCS (CCMH) was prepared according to their relative contents in serum. The pharmacological effects and potential mechanisms for CCMH were investigated by assays for cell viability, cell cycle, apoptosis, mitochondrial membrane potential (MMP), proteomics, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, proteasome activity, and western blot. RESULTS: CCMH was comprised of arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%). CCMH evidently induced proliferation inhibition, cell cycle arrest, apoptosis, and MMP collapse in gastric cancer cells, possessing the better activities than HCS. Proteomic analysis showed that CCMH influenced ROS pathway, ubiquitin proteasome system, and PI3K/Akt and MAPK signaling pathways. CCMH markedly enhanced intracellular ROS levels in gastric cancer cells, which was reversed by NAC. Accordingly, NAC antagonized the apoptosis-inducing effect of CCMH. Significantly decreased proteasome 20S activity by CCMH was observed in gastric cancer cells. CCMH also regulated the expression of key proteins in PI3K/Akt and MAPK signaling pathways. CONCLUSION: CCMH possesses more significant apoptotic induction effects on gastric cancer cells than HCS, which is achieved primarily through suppression of proteasome activities and increase of ROS levels, followed by regulating PI3K/Akt and MAPK signaling pathways. Network pharmacology combined with serum pharmacochemistry is an effective strategy for discovering compound-composed Chinese medicine from traditional Chinese medicine, which can help clarify the pharmacological substances and mechanisms of action for traditional Chinese medicine.


Subject(s)
Amphibian Venoms , Stomach Neoplasms , Humans , Reactive Oxygen Species/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Proteasome Endopeptidase Complex , Proto-Oncogene Proteins c-akt/metabolism , Medicine, Chinese Traditional , Phosphatidylinositol 3-Kinases/metabolism , Proteomics , Cell Line, Tumor , Apoptosis
4.
Comput Biol Med ; 165: 107405, 2023 10.
Article in English | MEDLINE | ID: mdl-37678137

ABSTRACT

OBJECTIVE: Time-consuming data labeling in brain-computer interfaces (BCIs) raises many problems such as mental fatigue and is one key factor that hinders the real-world adoption of motor imagery (MI)-based BCIs. An alternative approach is to integrate readily available, as well as informative, unlabeled data online, whereas this approach is less investigated. APPROACH: We proposed an online semi-supervised learning scheme to improve the classification performance of MI-based BCI. This scheme uses regularized weighted online sequential extreme learning machine (RWOS-ELM) as the base classifier and updates its model parameters with incoming balanced data chunk-by-chunk. In the initial stage, we designed a technique that combines the synthetic minority oversampling with the edited nearest neighbor rule for data augmentation to construct more discriminative initial classifiers. When used online, the incoming chunk of data is first pseudo-labeled by RWOS-ELM as well as an auxiliary classifier, and then balanced again by the above-mentioned technique. Initial classifiers are further updated based on these class-balanced data. MAIN RESULTS: Offline experimental results on two publicly available MI datasets demonstrate the superiority of the proposed scheme over its counterparts. Further online experiments on six subjects show that their BCI performance gradually improved by learning from incoming unlabeled data. SIGNIFICANCE: Our proposed online semi-supervised learning scheme has higher computation and memory usage efficiency, which is promising for online MI-based BCIs, especially in the case of insufficient labeled training data.


Subject(s)
Algorithms , Brain-Computer Interfaces , Humans , Electroencephalography/methods , Supervised Machine Learning , Software , Imagination
5.
J Pharm Pharmacol ; 75(9): 1141-1153, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37390473

ABSTRACT

OBJECTIVES: Cinobufagin is a natural active ingredient isolated from the traditional Chinese medicine Venenum Bufonis (Chinese: Chansu), which is the dried secretion of the postauricular gland or skin gland of the Bufo gargarizans Cantor or Bufo melanostictus Schneider. There is increasing evidence indicating that cinobufagin plays an important role in the treatment of cancer. This article is to review and discuss the antitumor pharmacological effects and mechanisms of cinobufagin, along with a description of its toxicity and pharmacokinetics. METHODS: The public databases including PubMed, China National Knowledge Infrastructure and Elsevier were referenced, and 'cinobufagin', 'Chansu', 'Venenum Bufonis', 'anticancer', 'cancer', 'carcinoma', and 'apoptosis' were used as keywords to summarize the comprehensive research and applications of cinobufagin published up to date. KEY FINDINGS: Cinobufagin can induce tumour cell apoptosis and cycle arrest, inhibit tumour cell proliferation, migration, invasion and autophagy, reduce angiogenesis and reverse tumour cell multidrug resistance, through triggering DNA damage and activating the mitochondrial pathway and the death receptor pathway. CONCLUSIONS: Cinobufagin has the potential to be further developed as a new drug against cancer.


Subject(s)
Neoplasms , Animals , Humans , Apoptosis , Bufonidae , Cell Proliferation , China , Neoplasms/drug therapy
6.
Sci Rep ; 13(1): 6888, 2023 04 27.
Article in English | MEDLINE | ID: mdl-37106016

ABSTRACT

Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 µg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 µg/g, 207.32 µg/g, 56.76 µg/g, 2331.46 µg/g, 788.31 µg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali.


Subject(s)
Drugs, Chinese Herbal , Wolfiporia , Antioxidants , Fermentation , Drugs, Chinese Herbal/chemistry , Biotransformation , Digestion , Chromatography, High Pressure Liquid/methods
7.
Molecules ; 28(5)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36903317

ABSTRACT

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.


Subject(s)
Ginsenosides , Panax , Rhizome/chemistry , Ginsenosides/pharmacology , Glycoside Hydrolase Inhibitors , Chromatography, High Pressure Liquid/methods , Ultrafiltration , alpha-Glucosidases , Plant Roots/chemistry
8.
Zhongguo Zhong Yao Za Zhi ; 48(2): 329-335, 2023 Jan.
Article in Chinese | MEDLINE | ID: mdl-36725222

ABSTRACT

Rheumatoid arthritis(RA) is an autoimmune disease that seriously affects the physical and mental health of patients, but its pathogenesis is still unclear. At present, clinical treatment drugs include conventional synthetic disease modifing anti-rheumatic drugs(csDMARDs), nonsteroid anti-inflammtory drugs(NSAIDs), hormones, small molecule targeted drugs, biological agents, etc. These drugs can relieve the clinical symptoms of most patients with RA to a certain extent, but there are still many limitations, such as drug adverse reactions and individual differences in drug efficacy. Therefore, the research on drug treatment targets and the development of low-toxicity drugs helps further improve the precise prevention, diagnosis, and treatment of RA. There is an urgent need for efficient and low-toxic treatments to delay the clinical progress of RA. As a treasure of Chinese culture, traditional Chinese medicine(TCM) is widely used as an alternative therapy in the treatment of various diseases, and has a significant clinical efficacy. TCM therapy(including monomer traditional Chinese medicine, classical compounds, and non-drug therapies) has a significant curative effect on RA. Based on the literature research in recent years, this paper reviewed the clinical and mechanism research of TCM therapy in the treatment of RA, and provided more in-depth thinking for the wide application of TCM therapy in clinical practice.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Drugs, Chinese Herbal , Humans , Medicine, Chinese Traditional , Drugs, Chinese Herbal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Antirheumatic Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
9.
Molecules ; 28(3)2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36770610

ABSTRACT

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.


Subject(s)
Ginsenosides , Panax , Humans , Tandem Mass Spectrometry/methods , Rhizome/chemistry , Ginsenosides/chemistry , Panax/chemistry , Chromatography, High Pressure Liquid/methods , Plant Roots/chemistry , Ions/analysis
10.
Chin J Integr Med ; 29(5): 441-447, 2023 May.
Article in English | MEDLINE | ID: mdl-35723812

ABSTRACT

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.


Subject(s)
Ischemic Stroke , Humans , Syndrome , Medicine, Chinese Traditional , Liver , Phenotype
11.
Food Res Int ; 162(Pt A): 111946, 2022 12.
Article in English | MEDLINE | ID: mdl-36461202

ABSTRACT

The quality of pork, such as intramuscular fat (IMF) content and flavor, can affect the acceptance of the consumer. Many studies have reported on the pork quality of Chinese local and commercial pigs (for example Large White (LW) pigs). The Jianhe White Xiang (JWX) pig, one of the Chinese Xiang pigs, is known for its high IMF and pork flavor. However, studies investigating the characterization and difference of lipids and metabolites between the JWX and LW pork are limited. Herein, we performed metabolomic and lipidomic profiling of JWX and LW pork by high-performance liquid chromatography-tandem mass spectrometry. The IMF and meat redness (a*) of the JWX pork were significantly higher than those of the LW pork. Metabolomic profiling revealed that 118 out of 501 polar metabolites, such as carnitine, amino acids, sugar, and dipeptide, were significantly different between the two types of pork. Additionally, the screened metabolites were mainly related to carnitine synthesis, phospholipid metabolism, sugar metabolism, and amino acid metabolism. Lipidomic profiling identified 100 of 376 lipids, which contained carnitine, diglyceride, triglyceride (TG), sphingomyelin, cardiolipin, fatty acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which were significantly different between the two types of pork under the positive and negative ion modes (variable importance in projection (VIP) > 1, p < 0.05, and fold change (FC) > 2 or FC < 0.5). All of the different TG substances were up-regulated in the JWX pork, and their carbon chain length was longer than that of the residual TGs. In addition, the JWX pork had more double bonds of PC and PE substances than LW pork. Thus, our findings provide comprehensive metabolomic and lipidomic profiles between the JWX and LW pork and a basic understanding on increasing the pork quality.


Subject(s)
Pork Meat , Red Meat , Swine , Animals , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Carnitine , Lecithins , Triglycerides , Sugars
12.
RSC Adv ; 12(51): 33340-33347, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36425164

ABSTRACT

Chemical substance identification is an indispensable step in research on therapeutic materials based on traditional Chinese medicine and its formulas. The successful characterization of chemical substances mainly relies on high-quality MS/MS spectra. However, to date, relatively few studies have specifically addressed the issues of improving the acquisition of MS/MS spectra of compounds for characterization. The current auto-MS/MS mode, where the precursor ions are selected depending on their signal intensity, encounters a drawback when the sample contains many overlapping signals, leading to compounds with a lower or much lower abundance missing identification. To solve this problem, a strategy in which molecular features oriented precursor ion selection was followed by targeted MS/MS analysis for structure elucidation was proposed. The precursor ions were selected according to their first and second molecular features, namely m/z and retention time, irrespective of their intensities. By performing targeted MS/MS analysis, the MS/MS spectra of many more compounds of interest can be obtained, leading to an improvement in natural product identification. As an example, the chemical substances in the Zhi-Ke-Yang-Yin extract were analyzed using this strategy, and as a result, 431 ingredients were tentatively characterized, including both known and unknown or new compounds.

13.
Neurosci Lett ; 788: 136860, 2022 09 25.
Article in English | MEDLINE | ID: mdl-36041546

ABSTRACT

There are negative correlations between indices of heart rate variability (HRV) and markers of inflammation. The inflammation plays an important role in myocardial damages after myocardial infarction (MI). Our previous study found that fastigial nucleus electrostimulation (FNS) improved abnormal HRV in a rat model of MI. Whether it can reduce inflammation and improve cardiac function after MI and the underlying mechanisms remain unknown. 66 Sprague Dawley rats were randomly divided into 4 groups as follows: i) Sham group (sham operation); ii) MI group (left anterior descending coronary artery ligation); iii) FNS + MI group (left fastigial nucleus electrostimulation plus MI); iv) FNL + FNS + MI group (left fastigial nucleus lesion plus FNS plus MI). The serum expressions of acetylcholine (ACh), pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and anti-inflammatory cytokines IL-10 were measured by ELISA. Subsequently, the infarct size, the infiltration of inflammatory cells, the fibrotic area, and cardiac function were also evaluated. Additionally, the expressions of the cholinergic anti-inflammatory pathway (CAP)-related proteins in infarct tissue, such as nuclear factor kappa B (NF-κB) and singal transducers and activators of transcription 3 (STAT3), were determined by Western blot. We found that FNS significantly increased ACh and IL-10 levels in serum, and decreased TNF-α and IL-6 levels. FNS significantly attenuated inflammatory cell infiltration, reduced infarct size, decreased fibrosis, increased left ventricular ejection fraction, and reduced mortality. Besides, the ratios of phosphorylated-STAT3/STAT3 and phosphorylated-NF-κB/NF-κB in infarct tissue significantly elevated after MI. FNS reduced the ratios of p-STAT3/STAT3 and p-NF-κB/NF-κB in infarct tissue. The protective effects of FNS were partially reversed by the fastigial nucleus lesion. Our data suggested that FNS can alleviate the inflammation after MI, and its cardiac neuroprotective mechanism may be achieved by increasing vagal tone, releasing ACh, and further activating the CAP via α7 nicotinic acetylcholine receptor. The precise mechanism remains to be elucidated.


Subject(s)
Electric Stimulation Therapy , Myocardial Infarction , Animals , Rats , Acetylcholine , Cerebellar Nuclei/physiology , Disease Models, Animal , Inflammation/metabolism , Inflammation/therapy , Interleukin-10/metabolism , Interleukin-6/metabolism , Myocardial Infarction/complications , Myocardial Infarction/metabolism , Myocardial Infarction/therapy , Neuroimmunomodulation , NF-kappa B/metabolism , Rats, Sprague-Dawley , Stroke Volume , Tumor Necrosis Factor-alpha/metabolism , Ventricular Function, Left
14.
Int J Biol Sci ; 18(13): 5168-5184, 2022.
Article in English | MEDLINE | ID: mdl-35982894

ABSTRACT

High-dose ascorbate confers tubular mitophagy responsible for septic acute kidney injury (AKI) amelioration, yet its biological roles in immune regulation remain poorly understood. Methods: The role of tubular mitophagy in macrophage polarization upon high-dose ascorbate treatment was assessed by fluorescence-activated cell sorter analysis (FACS) in vitro and by immunofluorescence in AKI models of LPS-induced endotoxemia (LIE) from Pax8-cre; Atg7 flox/flox mice. The underlying mechanisms were revealed by RNA-sequencing, gene set enrichment analysis (GSEA), luciferase reporter, chromatin immunoprecipitation (ChIP) and adeno-associated viral vector serotype 9 (AAV9) delivery assays. Results: High-dose ascorbate enables conversion of macrophages from a pro-inflammatory M1 subtype to an anti-inflammatory M2 subtype in murine AKI models of LIE, leading to decreased renal IL-1ß and IL-18 production, reduced mortality and alleviated tubulotoxicity. Blockade of tubular mitophagy abrogates anti-inflammatory macrophages polarization under the high-dose ascorbate-exposed coculture systems. Similar abrogations are verified in LIE mice with tubular epithelium-specific ablation of Atg7, where the high-dose ascorbate-inducible renal protection and survival improvement are substantially weaker than their control littermates. Mechanistically, high-dose ascorbate stimulates tubular secretion of serpin family G member 1 (SerpinG1) through maintenance of mitophagy, for which nuclear factor-erythroid 2 related factor 2 (NRF2) transactivation is required. SerpinG1 perpetuates anti-inflammatory macrophages to prevent septic AKI, while kidney-specific disruption of SerpinG1 by adeno-associated viral vector serotype 9 (AAV9)-short hairpin RNA (shRNA) delivery thwarts the anti-inflammatory macrophages polarization and anti-septic AKI efficacy of high-dose ascorbate. Conclusion: Our study identifies SerpinG1 as an intermediate of tubular mitophagy-orchestrated myeloid function during septic AKI and reveals a novel rationale for ascorbate-based therapy.


Subject(s)
Acute Kidney Injury , Ascorbic Acid , Complement C1 Inhibitor Protein , Macrophages , NF-E2-Related Factor 2 , Acute Kidney Injury/drug therapy , Animals , Ascorbic Acid/pharmacology , Complement C1 Inhibitor Protein/genetics , Kidney , Kidney Tubules/metabolism , Macrophages/drug effects , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/genetics , Transcriptional Activation
15.
Front Neurol ; 13: 911668, 2022.
Article in English | MEDLINE | ID: mdl-35873761

ABSTRACT

Background: Acute sleep deprivation (ASD) can effect mood, attention, memory, alertness and metabolism. Especially, it is often accompanied by cognitive impairment of the brain. Acupuncture is safe and effective for improving cognitive function, but its underlying mechanism is not fully understood. In this study, an event-related potential (ERP) technique will be employed to measure the behavioral, cognitive, and physiological changes produced by electroacupuncture intervention after ASD. Methods: We will recruit 60 healthy subjects. The participants will be randomly divided into a treatment group, a control group, a sham electroacupuncture group and a blank group, at a 1:1:1:1 ratio. The primary outcome will be determined by the change from baseline to 36 h in the MoCA score. The secondary results include the amplitude and latency of ERP N2 and P3, Go-hit rates, Go-RTs, No-Go-FA rates, the WCST, the Digit Span Subtest of the WAIS, the ESS score and FS-14. The 15 healthy subjects will not receive acupuncture treatment and ASD, but will receive EEG records and cognition functions test at the beginning and end of the experiment. Electroacupuncture intervention will be performed for 30 min once every 12 h, a total of three times. ERP measurements and other tests will be performed after baseline and ASD, and the statistician and outcome evaluator will be blinded to treatment allocation. Discussion: This study is expected to investigate the effectiveness of electroacupuncture in improving cognition for ASD. Trial Registration: ChiCTR2200055999.

16.
J Colloid Interface Sci ; 623: 124-134, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35569221

ABSTRACT

Targeting excess H2O2 in the tumor microenvironment, nanotheranostic agents for catalytic therapy are designed based on Fenton reaction, catalyzing H2O2 into oxygen and hydroxyl radical (OH). But the catalytic efficiency in tumor microenvironment is not satisfactory. In order to solve the problem, a series of bimetallic-dual ligands metal-organic frameworks Fe/Tm-MOFs were designed, that Fe3+ and Tm3+ as metalions, 2-methylimidazole and trimesic acid as ligands. Due to the doped Tm3+ in Fe/Tm-MOFs and the conjugated structures formed by two ligands, the rate of electron transfer was improved, thus promoting the generation of OH at some extent. In addition, the photothermal effect of Fe/Tm-MOFs further promotes the generation of OH, which was evidenced by the 3,3',5,5'-tetramethylbenzidine(TMB). Combining the drug loading and release capabilities of Fe/Tm-MOFs, synergetic therapy of photothermal/chemo-/catalytic therapy can be achieved. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive. In vivo anti-cancer results show that the tumors of mice almost disappeared within 10 days, which were injected with Fe/Tm-MOFs/DOX and irradiated with 808 nm for 10 min. Thus, an excellent therapeutic performance has been achieved. Besides, Fe/Tm-MOFs can serve as a multimodality bioimaging contrast agent, covering fluorescence imaging, photothermal imaging and magnetic resonance imaging. Thus, an all-in-one nanotheranostic agent is constructed, improving the catalytic efficiency and providing a novel method to design an efficient nanotheranostic agent.


Subject(s)
Hyperthermia, Induced , Metal-Organic Frameworks , Nanoparticles , Neoplasms , Animals , Cell Line, Tumor , Hydrogen Peroxide , Hyperthermia, Induced/methods , Ligands , Metal-Organic Frameworks/chemistry , Mice , Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Phototherapy/methods , Tumor Microenvironment
17.
Colloids Surf B Biointerfaces ; 215: 112490, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35405536

ABSTRACT

Theranostic nanoplatforms with accurate diagnosis and effective therapy show a bright prospect for tumor treatments. Herein, a novel boracic acid-modified graphite carbon nitride and Prussian blue nanohybrid (PB@B-g-C3N4) was developed, which provides sialic acid-targeted Raman recognition and synergistic photothermal/photodynamic therapy in the near-infrared region. Owing to the specific interaction between boracic acid and sialic acid and Raman response at 2157 cm-1 of PB, the nanohybrids exhibit high specificity and Raman sensitivity for detection of the overexpressed sialic acid on tumor cells. Moreover, the photothermal conversion efficiency of PB@B-g-C3N4 is as high as 47.0% with 808 nm laser irradiation due to the enhanced absorbance of PB@B-g-C3N4. PB@B-g-C3N4 also possesses excellent photodynamic activity, which is attributed to the energy transfer of PB (type I) and electron transfer between PB and B-g-C3N4 (type II). This nanotheranostic agent for Raman recognition of cancer markers and synergistic photothermal/photodynamic therapy holds great potential for the development of efficient theranostic nanoplatforms.


Subject(s)
Neoplasms , Photochemotherapy , Ferrocyanides , Humans , N-Acetylneuraminic Acid , Neoplasms/therapy , Phototherapy/methods
18.
Anal Chim Acta ; 1189: 339224, 2022 Jan 02.
Article in English | MEDLINE | ID: mdl-34815036

ABSTRACT

Psoralen ultraviolet A (PUVA) therapy has thrived as a promising treatment for psoriasis. However, overdose of PUVA treatment will cause side-effects, such as melanoma formation. And these side-effects are often ignored during PUVA therapy. Hence, in situ monitoring therapeutic response of PUVA therapy is important to minimize side-effects. Aberrant expression of tyrosinase (TYR) has been proved to be associated with melanoma, indicating that TYR is a potential target for evaluation of PUVA therapy. Herein, we reported a strategy for in situ monitoring TYR activity during PUVA therapy by using a cell-array chip-based SERS platform. The cell-array chip was used to simulate cell survival environment for cell culture. Capture of single cells and living cell analysis were realized in the isolated microchambers. An enzyme-induced core-shell self-assembly substrate was used to evaluate TYR activity in living cells during PUVA therapy. The gold nanoparticle modified with a SERS reporter, 4-mercaptobenzonitrile (4-MBN), was used as the core. In the presence of oxygen and TYR, hydroxylation of l-tyrosine occurred, leading to the reduction of silver ion on the surface of gold cores. The growth of silver shells was accompanied by the increased SERS intensity of the reporter, which is related directly to TYR activity. The detection limit for TYR activity is 0.45 U/mL. Upregulation of TYR activity was successfully monitored after PUVA therapy. Notably, real-time and in situ information of therapeutic response can be obtained through monitoring PUVA therapy by using a cell-array chip-based SERS platform, which has great potential to guide the clinical application of PUVA therapy.


Subject(s)
Gold , Metal Nanoparticles , PUVA Therapy , Animals , Cell Line , Mice , Silver , Spectrum Analysis, Raman
19.
Chemosphere ; 291(Pt 3): 133044, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34826450

ABSTRACT

Nutrients in centralized discharge area of treated sewage can cause high ecological risks to aquatic systems, thus a deep-level nutrient removal is necessary. Recently, periphyton has attracted increasing interests for its excellent performance in nutrient removal. In this study, the suitability and durability of basalt fiber (BF) as a new green carrier of periphyton was evaluated, and development process of basalt fiber-periphtyon (BFP) was tracked with bacterial community succession and physiological indicators. Then, well-developed BFP was applied to deeply purify water containing the same concentration of nutrient as the treated sewage. Results showed the periphyton could adapt to BF and formed in large quantities. In addition, the tensile strength of BF after being used as a carrier was still strong. Bacterial community and physiological indicators indicated that BFP was well developed in 40-50 days. LEfSE and random forest analysis revealed that Deinococcus-Deinococci, Spartobacteria and Chlamydiia at class-level, Rhizobiales and Rhodobacterales at order-level were the biomarkers for development of BFP. Moreover, application results showed BFP efficiently removed nitrogen and phosphorus from water and promoted the transformation of ammonia to nitrate. The concentration of ammonia and phosphorus severely decreased from 4.90 ± 0.11 mg/L to 0.51 ± 0.20 mg/L, from 0.66 ± 0.016 mg/L to 0.023 ± 0.013 mg/L, respectively. The efficient nutrient removal was attributed to accumulation of nitrogen and phosphorus metabolism related organisms in BFP as well as favorable water physic-chemical conditions created by BFP. These results suggest that BF is a suitable and durable green carrier of periphyton, and BFP could efficiently reduce ecological risk to aquatic systems receiving treated sewage.


Subject(s)
Periphyton , Nitrogen , Nutrients , Phosphorus , Silicates
20.
Polymers (Basel) ; 15(1)2022 Dec 30.
Article in English | MEDLINE | ID: mdl-36616543

ABSTRACT

In this study, a rubber-composite-nanoparticle-modified epoxy powder composite coating with low curing temperature and high toughness was successfully fabricated. The effects of N,N-dimethylhexadecylamine (DMA) carboxy-terminated nitrile rubber (CNBR) composite nanoparticles on the microstructure, curing behavior, and mechanical properties of epoxy-powder coating were systematically investigated. SEM and TEM analysis revealed a uniform dispersion of DMA-CNBR in the epoxy-powder coating, with average diameter of 100 nm. The curing temperature of the epoxy-composite coatings had reduced almost 19.1% with the addition of 1phr DMA-4CNBR into the coating. Impact strength tests confirmed that DMA-CNBR-modified epoxy-composite coatings showed significant improvements compared with the neat EP coating, which was potentially attributed to the nanoscale dispersion of DMA-CNBR particles in epoxy coatings and their role in triggering microcracks. Other mechanical properties, including adhesion and cupping values, were improved in the same manner. In addition, thermal and surface properties were also studied. The prepared epoxy composite powder coating with the combination of low curing temperature and high toughness broadened the application range of the epoxy coatings.

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