ABSTRACT
Sweet potatoes are rich in flavonoids and phenolic acids, showing incomparable nutritional and health value. In this investigation, we comprehensively analyzed the secondary metabolite profiles in the flesh of different-colored sweet potato flesh. We determined the metabolomic profiles of white sweet potato flesh (BS), orange sweet potato flesh (CS), and purple sweet potato flesh (ZS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CS vs. BS, ZS vs. BS, and ZS vs. CS comparisons identified a total of 4447 secondary metabolites, including 1540, 1949, and 1931 differentially accumulated metabolites. Among them, there were significant differences in flavonoids and phenolic acids. There were 20 flavonoids and 13 phenolic acids that were common differential metabolites among the three comparison groups. The accumulation of paeoniflorin-like and delphinidin-like compounds may be responsible for the purple coloration of sweet potato flesh. These findings provide new rationale and insights for the development of functional foods for sweet potatoes. List of compounds: Kaempferol (PubChem CID: 5280863); Peonidin 3-(6"-p-coumarylglucoside) (PubChem CID: 44256849); Swerchirin (PubChem CID: 5281660); Trilobatin (PubChem CID: 6451798); 3-Geranyl-4-hydroxybenzoate (PubChem CID: 54730540); Eupatorin (PubChem CID: 97214); Icaritin (PubChem CID: 5318980); Isorhamnetin (PubChem CID: 5281654); Glucoliquiritin apioside (PubChem CID: 74819335); Brazilin (PubChem CID: 73384).
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The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.
Subject(s)
Glutathione , Immunotherapy , Magnetic Resonance Imaging , Ovarian Neoplasms , Paclitaxel , Theranostic Nanomedicine , Female , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Humans , Immunotherapy/methods , Hydrogen-Ion Concentration , Glutathione/chemistry , Paclitaxel/pharmacology , Paclitaxel/chemistry , Paclitaxel/administration & dosage , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Animals , Cell Line, Tumor , Nanoparticles/chemistry , Silicon/chemistry , Particle Size , Surface Properties , B7-H1 Antigen/metabolism , Drug Delivery Systems , Drug Screening Assays, Antitumor , MiceABSTRACT
In this study, five kinds of 1-alkyl-3-methylimidazolium bromide ([CXami]Br) ionic liquids with different alkyl chain lengths (8, 10, 12, 14, and 16) were selected as inhibitors. Then, their corrosion inhibition performances for Q235 steel in 1.0 mol L-1 HCl solution were investigated via a weight loss test, polarization curve method, and surface analysis techniques. The results show that these five imidazolium-based ionic liquids are all mixed-type inhibitors, and they can be spontaneously adsorbed onto the Q235 steel surface. The adsorption process follows the Langmuir model and involves mixed physical-chemical adsorption. Theoretical calculations confirm that the increase in alkyl chain length is conducive to the imidazolium-based ionic liquids exhibiting stronger chemical bonding abilities and forming denser adsorption films. The inhibition efficiency significantly increases below the critical micelle concentration (CMC) with an increase in alkyl chain length, and the highest inhibition efficiency is 95.17% for the [C16ami]Br inhibitor at the concentration of 0.005 mM. However, above the CMC, the inhibition efficiency is minimally affected by the alkyl chain length since all ionic liquid inhibitors have reached adsorption saturation on the steel surface.
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Dental resin composites (DRCs) are commonly used to restore teeth affected by dental caries or defects. These materials must possess excellent properties to withstand the complex oral environment. The objective of this study was to prepare and characterize Boron nitride nanosheets (BNN)/ dimethyl amino hexadecyl methacrylate (DMAHDM) composites (BNN/DMA), and to evaluate them as functional fillers to enhance the mechanical and antimicrobial properties of dental resins. The BNN/DMA composites were successfully prepared under the theoretical guidance of molecular dynamics (MD), and then the physicochemical and morphological characterization of the BNN/DMA composites were carried out by using various test methods, such as FT-IR, XRD, UV-vis spectroscopy, SEM, TEM, and AFM. It was doped into the dental flowable resin in a certain proportion, and the results showed that the flexural strength (FS), elastic modulus (EM), compressive strength (CS), and microhardness (MH) of the modified resin composites were increased by 53.29, 47.8, 97.59, and 37.1%, respectively, with the addition of 0.8 wt % of BNN/DMA composite fillers. It has a good inhibition effect on Streptococcus mutans, with an inhibition rate as high as 90.43%. Furthermore, this effect persists even after one month of aging. In conclusion, the modification of flowable resins with low-concentration BNN/DMA composites favorably integrates the mechanical properties and long-term antimicrobial activity of dental resins. At the same time, they have good biocompatibility and do not affect the aesthetics. The BNN/DMA composite modified flowable resin has the potential to become a new type of antimicrobial dental restorative material.
Subject(s)
Ammonium Compounds , Anti-Infective Agents , Boron Compounds , Dental Caries , Humans , Materials Testing , Spectroscopy, Fourier Transform Infrared , Anti-Infective Agents/pharmacology , Methacrylates/pharmacology , Methacrylates/chemistry , Composite Resins/pharmacology , Composite Resins/chemistryABSTRACT
One of the most common neurodegenerative illnesses is Parkinson's disease (PD). Rotigotine (RTG) is a dopamine agonist that exerts anti-Parkinsonian effects through dopamine receptor agonism to improve motor symptoms and overall performance in PD patients. In this study, an in situ liquid crystal gel called rotigotine-gel (RTG-gel) was developed using soya phosphatidyl choline (SPC) and glycerol dioleate (GDO) to provide long-acting slow-release benefits of rotigotine while minimizing side effects. This study prepared the RTG-gel precursor solution using SPC, GDO, and ethanol (in the ratio of 54:36:10, w/w/w). The internal structures of the gel were confirmed by crossed-polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), and differential scanning calorimetry (DSC). The rheological properties of the RTG-gel precursor solution indicate a favorable combination of low viscosity and excellent flowability. The gel that produced during water absorption was also highly viscous and structurally stable, which helped to maintain the drug delayed release at the injection site. In vitro release assays showed that the in vitro release of RTG-gel followed Ritger-Peppas. The RTG-gel precursor solution was administered by subcutaneous injection, and the results of in vivo pharmacokinetic tests in SD rats showed that the plasma elimination half-life (t1/2) was 59.28 ± 16.08 h; the time to peak blood concentration (Tmax) was 12.00 ± 10.32 h, and the peak concentration (Cmax) was 29.9 ± 10.10 ng/mL. The blood concentration remained above 0.1 ng/mL for 20 days after administration and was still detectable after 31 days of administration, and the bioavailability of RTG can reach 72.59%. The results of in vitro solvent exchange tests showed that the RTG-gel precursor solution undergoes rapid exchange upon contact with PBS, and the diffusion of ethanol can reach 48.1% within 60 min and 80% within 8 h. The results of cytotoxicity test showed 89.27 ± 4.32% cell survival after administration of the drug using RTG-gel. The results of tissue extraction at the administration site showed that healing of the injection site without redness and hemorrhage could be observed after 14 days of injection. The results of tissue section of the administered site showed that the inflammatory cells decreased and granulation tissue appeared after 14 days of administration, and there was basically no inflammatory cell infiltration after 35 days of administration, and the inflammatory reaction was basically eliminated. It shows that RTG-gel has some irritation to the injection site, but it can be recovered by itself in the later stage, and it has good biocompatibility. In summary, RTG-gel might be a potential RTG extended-release formulation for treating PD.
Subject(s)
Liquid Crystals , Parkinson Disease , Tetrahydronaphthalenes , Thiophenes , Humans , Rats , Animals , Parkinson Disease/drug therapy , Liquid Crystals/chemistry , Scattering, Small Angle , Rats, Sprague-Dawley , X-Ray Diffraction , Dopamine Agonists/adverse effects , Injections, Subcutaneous , EthanolABSTRACT
Imaging-guided photodynamic therapy (PDT) has emerged as a promising protocol for cancer theragnostic. However, facile preparation of such a theranostic system for simultaneously achieving tumor location, real-time monitoring, and high-performance reactive oxygen species generation is highly desirable but remains challenging. Herein, we developed a reasonable tumor-targeting strategy based on carbon dots (CDs)-decorated MnO2 nanosheets (HA-MnO2-CDs) with an active magnetic resonance (MR)/fluorescence imaging and enhanced PDT effect. Under light irradiation, the addition of HA-MnO2-CDs increased the production of 1O2 by 2.5 times compared with CDs, providing favorable conditions for the PDT treatment effect on breast cancer. Moreover, HA-MnO2-CDs exhibited excellent performance in producing O2 in the presence of endogenous H2O2, which alleviated hypoxia in tumors and improved the therapeutic effect of PDT. In the presence of glutathione (GSH), the degraded MnO2 nanosheets released CDs and Mn2+ from HA-MnO2-CDs, restoring their fluorescence imaging function and increasing T1 relaxivity (r1) by 23 times. In vivo fluorescence and MR imaging suggested the excellent tumor-targeting property of HA-MnO2-CDs. By combining the complementary properties of nanoprobes and tumor microenvironments, the in vivo PDT therapeutic effect was significantly improved under the action of HA-MnO2-CDs. Overall, our reasonably designed HA-MnO2-CDs may inspire the future development of the next generation of high-performance tumor-responsive diagnostic and therapeutic agents to further enhance the targeted therapy effect of tumors.
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The aim of the present study was to explore the specific pattern of brain deactivation elicited by painful stimuli, in contrast with that elicited by tactile stimuli. Functional magnetic resonance imaging (fMRI) data were collected from 62 healthy subjects under painful and tactile stimuli with varying intensities. The brain deactivations under different conditions were identified using the general linear model. Two-way analysis of variance (ANOVA) was performed to test whether there was a significant interaction between perceived stimulus intensity (factor 1: high intensity, low intensity) and stimulus modality (factor 2: pain, touch) on the brain deactivations. The results showed that there were significant interactions between stimulus intensity and stimulus modality on the deactivations of left medial superior frontal gyrus, left middle occipital gyrus, left superior frontal gyrus and right middle occipital gyrus (P < 0.05, Cluster-level FWE). The deactivations induced by painful stimuli with low perceived intensity (ß = -3.38 ± 0.52) were significantly stronger than those induced by painful stimuli with high perceived intensity (ß = -1.22 ± 0.54) (P < 0.001), whereas the differences between the deactivations induced by tactile stimuli with different perceived intensities were not statistically significant. In addition, there were no significant differences between the deactivations elicited by painful and tactile stimuli with the same stimulus intensities. These results suggest that there is a specific relationship between the deactivations induced by painful stimuli in multiple brain regions (such as the left medial superior frontal gyrus) and the stimulus intensity, providing evidence for a deeper understanding of the brain mechanisms underlying pain perception.
Subject(s)
Pain , Touch , Humans , Touch/physiology , Physical Stimulation/methods , Brain/physiology , Magnetic Resonance Imaging/methods , Brain MappingABSTRACT
OBJECTIVE: To develop a new, alternative sarcopenia risk score to screen for sarcopenia in type 2 diabetes patients in China and to demonstrate its validity. RESEARCH DESIGN AND METHODS: The data for this study came from a multicenter, cross-sectional study that had been designed to estimate the prevalence of sarcopenia among adults with type 2 diabetes and had been conducted in several hospitals in Beijing, China. A total of 1125 participants were randomly divided into two groups: an exploratory population and a validation population. A multivariable logistic regression model using the backward stepwise likelihood ratio method to estimate the probability of sarcopenia was fitted with candidate variables in the exploratory population. A new, alternative sarcopenia risk score was developed based on the multivariable model. The internal and external validations were performed in the exploratory and validation populations. The study was registered at Chinese Clinical Trial Registry (ChiCTR-EOC-15006901). RESULTS: The new, alternative sarcopenia risk score included five variables: age, gender, BMI, total energy intake per day, and the proportion of calories supplied by protein. The score ranged from - 2 to 19. The area under the receiver operating characteristic (ROC) curve of the risk score for the prediction of sarcopenia in type 2 diabetes patients was 0.806 (95% CI 0.741-0.872) and 0.836 (95% CI 0.781-0.892) in the exploratory and validation populations, respectively. At the optimal cutoff value of 12, the sensitivity and specificity of the score for the prediction of sarcopenia were 70.9% and 81.0% in the exploratory population and 53.7% and 88.8% in the validation population, respectively. The Hosmer-Lemeshow goodness-of-fit test showed a good calibration with the risk score in external validation (χ2 = 4.459, P = 0.813). CONCLUSIONS: The new, alternative sarcopenia risk score appears to be an effective screening tool for identification of sarcopenia in Chinese patients with type 2 diabetes in clinical practice. Clinical trial registration Chinese Clinical Trial Registry, ChiCTR-EOC-15006901.
Subject(s)
Diabetes Mellitus, Type 2 , Sarcopenia , Adult , Humans , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , East Asian People , Risk Factors , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Sarcopenia/etiology , Random AllocationABSTRACT
Regeneration is the regrowth of damaged tissues or organs, a vital process in response to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owing to its vast reservoir of adult stem cells, neoblasts, providing an ideal model to delineate the underlying mechanisms for regeneration. RNA N6 -methyladenosine (m6 A) modification participates in many biological processes, including stem cell self-renewal and differentiation, in particular the regeneration of haematopoietic stem cells and axons. However, how m6 A controls regeneration at the whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6 A methyltransferase regulatory subunit wtap abolishes planarian regeneration, potentially through regulating genes related to cell-cell communication and cell cycle. Single-cell RNA-seq (scRNA-seq) analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6 A-modified transcripts grn, cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m6 A modification in regulating whole-organism regeneration.
Subject(s)
Adult Stem Cells , Planarians , Animals , Planarians/genetics , Planarians/metabolism , RNA Interference , Cell Differentiation/genetics , Cell Division , MammalsABSTRACT
In recent years, biodegradable polymers have gained the attention of many researchers for their promising applications, especially in drug delivery, due to their good biocompatibility and designable degradation time. Poly (lactic-co-glycolic acid) (PLGA) is a biodegradable functional polymer made from the polymerization of lactic acid (LA) and glycolic acid (GA) and is widely used in pharmaceuticals and medical engineering materials because of its biocompatibility, non-toxicity, and good plasticity. The aim of this review is to illustrate the progress of research on PLGA in biomedical applications, as well as its shortcomings, to provide some assistance for its future research development.
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The low-voltage droop of high-voltage pulses is required to provide stable pulsed electric fields in many applications. Increasing the capacitance of energy storage capacitors increases both the size and the cost of the system. In this paper, four compensation stages based on the resonant circuit have been inserted into a 16-stage solid-state Marx generator to compensate for the voltage droop in different conditions. The nearly linear part of the sinusoidal voltage is precisely added to the load during discharging as compensation, and the rectangular pulsed voltage with little droop can be realized. Different numbers of compensation stages and different resonant inductances can compensate the droop to different levels, which means the compensation effect is also adjustable. Moreover, these compensation stages can operate as common stages in Marx generators as long as we open-circuit the resonant circuits. Since the capacitors in resonant compensation stages are also charged in parallel with capacitors in common stages, no auxiliary power supply is required. Simulating and experimental results show that the droop of a 9 kV pulse can be ideally compensated over a 500 Ω resistive load at various pulse widths. The pulse width should be shorter than the length of the nearly linear part of the sinusoidal voltage.
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In the context of the era of big data, the management of Alzheimer's patients has aroused widespread concern in the society. What should the elderly and people with dementia do and how the society should accommodate these special groups have aroused heated discussions in the society. The goal of the medical-nursing integration model is to realize the integrated model of medical care-nursing-rehabilitation-old care, and to better satisfy the needs by providing medical services, rehabilitation care, and health management. The medical needs of the elderly can help the elderly maintain a healthy state; the elderly care needs can be better met through elderly care services, and the burden on families and society can be reduced. With the advancement of the medical-care integration model, new solutions have been provided for the management of senile dementia patients. Therefore, under the medical-care integration model, this paper managed Alzheimer's patients based on the big data algorithm based on association rules and compared it with the management of Alzheimer's patients under the traditional model, and drew the following conclusions: compared with the management satisfaction of Alzheimer's patients under the traditional model, family members and patients' total satisfaction with nursing management under the medical-care integration model was greatly improved; compared with the management of Alzheimer's patients under the traditional model, the incidence of adverse events in the management of Alzheimer's patients under the medical-care integration model was greatly reduced, which was reduced to 17.6%; under the medical-care integration model, the anxiety and depression scores of the elderly patients with dementia decreased rapidly; under the medical-care integration model, the living ability of senile dementia patients has been greatly improved; the use of the medical-care integration model to manage senile dementia patients has greatly improved the sleep quality, mental quality, and quality of life of senile dementia patients.
Subject(s)
Alzheimer Disease , Humans , Aged , Alzheimer Disease/epidemiology , Quality of Life , Big Data , Family , AnxietyABSTRACT
Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are the most problematic metabolic diseases in the world. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. T2DM and NAFLD (T2DM-NAFLD) are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively, in Mongolian medicine. Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease. Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD, such as Agriophyllum squarrosum, Haliyasu (dried powder of camel placenta), Digeda-4 (herbs of Lomatogonium carinthiacum, rhizomata of Coptis chinensis, ripe fruits of Gardenia jasminoides, herbs of Dianthus superbus), Guangmingyan Siwei Decoction Powder (Halite, ripe fruits of Terminalia chebula, rhizomata of Zingiber officinale, fruit clusters of Piper longum), Tonglaga-5 (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius), Tegexidegeqi (rhizomata of Inula helenium, ripe fruits of Gardenia jasminoides, rhizomata of Platycodon grandiflorum, rhizomata of Coptis chinensis, heartwood of Caesalpinia sappan), Ligan Shiliu Bawei San (ripe fruits of Punica granatum, barks of Cinnamomum cassia, ripe fruits of Amomum kravanh, fruit clusters of Piper longum, flowers of Carthamus tinctorius, ripe fruits of Amomum tsao-ko, rhizomata of Zingiber officinale), etc. Principles of Mongolian medicine in treating diseases: by balancing "three essences or roots" and "seven elements", strengthening liver and kidney function, transporting nutrients to enhance physical strength and disease resistance, and combined with drugs for comprehensive conditioning treatment. However, their molecular mechanisms remain unclear. In this review, we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB inflammatory pathway via lipid-sensitive nuclear receptors (i.e., FXR and LXR).
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Purpose: To evaluate the resulting level of fiscal medical and health expenditure in China, and to provide the scientific basis for further improving fiscal medical and health service capacity in China. Patients and Methods: The data envelopment method and Gini coefficient method were used to analyze the efficiency and regional fairness of fiscal medical and health expenditure results by using the relevant provincial and municipal data of China from 2007 to 2019. Results: 1.Overall, from 2007 to 2019, the total expenditure continued to increase, the expenditure efficiency increased first and then decreased, and the expenditure fairness continued to improve. 2. From the perspective of subregions, there are apparent differences between regions in terms of total expenditure, expenditure efficiency, and expenditure fairness, showing a better situation in the central, western, northeast and a lower situation in the east. Conclusion: The overall level of fiscal medical and health expenditure in China shows an upward trend, but there is still much room for improvement. At the same time, there are pronounced regional differences, and the problems of efficiency and fairness coexist among regions. Therefore, in the future, we should increase medical and health investment and enhance the government's close attention; Improve the expenditure performance appraisal system; Formulate policies according to local conditions and avoid "one size fits all.".
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Background: Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods: This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased -1.42 ± 1.48 kg/m2(P=0.015) and -0.87 ± 0.93 kg/m2(P=0.003), respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c <9%, the nonatherosclerosis group, and the atherosclerosis group. The decrease in BMI was positively correlated with changes in blood glucose, high-sensitivity C-reactive protein (hsCRP), and systolic blood pressure (SBP). Conclusion: BMI scores improved after exenatide treatment for 52 weeks in T2DM patients. Weight loss was affected by baseline body weight and blood glucose level. In addition, BMI reduction from the baseline to 52 weeks was positively correlated with baseline HbA1c, hsCRP, and SBP. Trial Registration. Chinese Clinical Trial Registry (ChiCTR-1800015658).
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Humans , Exenatide/adverse effects , Diabetes Mellitus, Type 2/complications , Body Mass Index , Hypoglycemic Agents/adverse effects , Blood Glucose/metabolism , Glycated Hemoglobin , Retrospective Studies , C-Reactive Protein , Body Weight , Weight Loss , Cardiovascular Diseases/chemically induced , Venoms/therapeutic useABSTRACT
A new triterpenoid, named nigrumol A (1), along with 5 known triterpenoids were isolated from the aerial parts of Empetrum nigrum subsp. asiaticum (Nakai ex H.Ito) Kuvaev (E. nigrum) . The structure of 1 was elucidated by analysis of its spectroscopic data, including UV, IR, HR-ESI-MS and extensive 1 D and 2 D NMR techniques. Compound 1 showed that it could decrease ethanol-induced or CCl4-induced L02 cell toxicity effectively.[Formula: see text].
Subject(s)
Ericaceae , Triterpenes , Ericaceae/chemistry , Ethanol , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacology , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
5-Methylcytosine (m5C) is one of the most prevalent internal modifications of messenger RNA (mRNA) in higher eukaryotes. Here we report that Y box protein 2 (YBX2) serves as a novel mammalian m5C binding protein to undergo liquid-liquid phase separation (LLPS) both in vivo and in vitro, and this YBX2-dependent LLPS is enhanced by m5C marked RNA. Furthermore, the crystal structure assay revealed that W100, as a distinct m5C binding site of YBX2, is critical in mediating YBX2 phase separation. Our study resolved the relationship between RNA m5C and phase separation, providing a clue for a new regulatory layer of epigenetics.
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We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.
ABSTRACT
Sarcopenia is considered to be a new complication of type 2 diabetes (T2DM) leading to increased risk of adverse outcome. We performed a survey to evaluate glucose metabolism and nutritional status in sarcopenia patients with T2DM. Diabetic participants aged ≥50 years were grouped into a probable sarcopenia group with low muscle strength (n = 405) and a nonsarcopenia group with normal muscle strength (n = 720) according to the revised recommendations from EWGSOP2 (2018). Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, longer diabetes duration, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate and lower bone mineral content, lower fatless upper arm circumference, lower appendicular skeletal muscle mass index (ASMI), and muscle quality in both genders. Multivariable logistic regression analysis showed increased age, male, low BMI, and increased HbA1c, combined with diabetic nephropathy and decreased serum albumin levels, were risk factors associated with low muscle strength in diabetes patients. In conclusion, diabetic patients with sarcopenia had worse glucose metabolism and nutritional status, decreased renal function and reduced muscle quality ,and muscle mass with a greater likelihood of osteoporosis, who need an overall health management to improve outcomes. This clinical trial registration is registered with the Chinese Clinical Trial Registry, ChiCTR-EOC-15006901.