Angelica sinensis polysaccharide ameliorates nonalcoholic fatty liver disease via restoring estrogen-related receptor α expression in liver.

Angelica sinensis polysaccharide (ASP) showed increasingly recognized hepatoprotective effects and lipid regulation. Because polysaccharides are typically degraded into fragments or short-chain fatty acids in the gut, rather than being absorbed in their intact form, it is worth pondering why ASP can regulate hepatic lipid metabolism and protect the liver from damage caused by lipid accumulation. In vivo and in vitro nonalcoholic fatty liver disease (NAFLD) models with lipid accumulation were established to investigate the effect and potential mechanisms of ASP on hepatic fat accumulation. Our results showed that ASP remodeled the composition and abundance of the gut microbiota in high-fat diet-fed mice and increased their levels of propionate (0.92 ± 0.30 × 107 vs. 2.13 ± 0.52 × 107 ) and butyrate (1.83 ± 1.31 × 107 vs. 6.39 ± 1.44 × 107 ). Sodium propionate significantly increased the expression of estrogen-related receptor α (ERRα) in liver cells (400 mM sodium propionate for 2.19-fold increase) and alleviated the progress of NAFLD in methionine-choline-deficient diet model. Taken together, our study demonstrated that ASP can regulate hepatic lipid metabolism via propionate/ERRα pathway and ultimately relieving NAFLD. Our findings demonstrate that ASP can be used as a health care product or food supplement to prevent NAFLD.

Gastrointestinal metabolism characteristics and mechanism of a polysaccharide from Grifola frondosa.

Grifola frondosa polysaccharide (GFP) is mainly composed of α-1,4 glycosidic bonds and possesses multiple pharmacological activities. However, the absence of pharmacokinetic studies has limited its further development and utilization. Herein, GFP was labeled with 5-DTAF (FGFP) and cyanine 5.5 amine (GFP-Cy5.5) to investigate its gastrointestinal metabolism characteristics and mechanism. Significant distributions of the polysaccharide in the liver and kidneys were observed by near infrared imaging. To investigate the specific distribution form of the polysaccharide, in vitro digestion models were constructed and revealed that FGFP was degraded in saliva and rat small intestine extract. The metabolites were detected in the stomach and small intestine, followed by further degradation in the distal intestine in the in vivo experiment. Subsequent investigations showed that α-amylase was involved in the gastrointestinal degradation of GFP, and its metabolite finally entered the kidneys, where it was excreted directly with urine.

Metabolic degradation of polysaccharides from Lentinus edodes by Kupffer cells via the Dectin-1/Syk signaling pathway.

It had been shown that lentinan (LNT) was mainly distributed in the liver after intravenous administration. The study aimed to investigate the integrated metabolic processes and mechanisms of LNT in the liver, as these have not been thoroughly explored. In current work, 5-([4,6-dichlorotriazin-2-yl] amino) fluorescein and cyanine 7 were used to label LNT for tracking its metabolic behavior and mechanisms. Near-infrared imaging demonstrated that LNT was captured mainly by the liver. Kupffer cell (KC) depletion reduced LNT liver localization and degradation in BALB/c mice. Moreover, experiments with Dectin-1 siRNA and Dectin-1/Syk signaling pathway inhibitors showed that LNT was mainly taken up by KCs via the Dectin-1/Syk pathway and promoted lysosomal maturation in KCs via this same pathway, which in turn promoted LNT degradation. These empirical findings offer novel insights into the metabolism of LNT in vivo and in vitro, which will facilitate the further application of LNT and other ß-glucans.

Structural characterisation and structure-antioxidant activity relationship of polysaccharides from Dendrobium catenatum Lindl.

Dendrobium catenatum Lindl. has been long used in China as a functional food and traditional Chinese medicine and polysaccharides from Dendrobium catenatum Lindl. (DOP) exhibited extensive bioactivities. However, studies on the structure-activity relationship of DOP are rarely reported. Here, two polysaccharides named DOP-1 and DOP-2 were obtained, which differed in the ratio of monosaccharide composition and molecular weight. Structural characteristics were elucidated by spectral and chemical analysis. The main structures of DOPs were the linkage of ß-(1→4)-D-Manp, with some attached 2-O- or 3-O-acetylated groups. Additionally, the DPPH, hydroxyl and superoxide radicals scavenging assays of DOP-1 and DOP-2 showed that DOP-2 exhibited the higher antioxidant activity, which might be related to its lower molecular weight, higher mannose proportion and lower degree of acetylation, and higher phenolic content. Our results provide a more accurate basis for the application of DOPs in the pharmaceutical and food industries.

Application Analysis of Multidisciplinary Diagnosis and Treatment Nursing Mode Based on Doctor-Nurse-Integration for Stroke Patients Undergoing Emergency Intervention Surgery.

Purpose: To analyze the application value of multidisciplinary diagnosis and treatment (MDT) nursing mode based on doctor-nurse-integration for stroke patients undergoing emergency intervention surgery. Methods: In this study, a historical comparative study method was adopted. 118 stroke patients and medical staff (9 doctors and 11 nurses) who met the diagnosis and inclusion criteria of emergency intervention surgery admitted from July 2021 to February 2022 were treated clinically according to the traditional medical care mode (TMC group), 87 stroke patients and medical staff (9 doctors and 11 nurses) who met the diagnosis and inclusion criteria of emergency intervention surgery admitted from February 2022 to June 2022 were treated and cared according to the MDT nursing mode based on medical integration (MDT group). Comparison of perioperative time indicators, postoperative outcome indicators, treatment compliance, secondary complications and visit satisfaction between the two groups of patients, and comparison of cooperation satisfaction between the two groups of medical staff. Results: The MDT group had shorter onset-emergency physician's reception time, arrival at CT room-completion time of CT/MR, notify intervention chamber-arrival time at catheter chamber, admission-femoral artery puncture time, admission-first vessel recanalization time, mean postural restraint time than the TMC group (P < 0.05). The postoperative mortality rate in the MDT group (5.75%) was comparable to that in the TMC group (8.47%) (P > 0.05); the postoperative disability rate in the MDT group (28.74%) was less than that in the TMC group (45.76%) (P < 0.05); the NIHSS score in the MDT group was lower than that in the TMC group, and the FMA score and BI score were both higher than those in the TMC group (P < 0.05). The MDT group had higher treatment compliance than the TMC group, fewer secondary complications than the TMC group, and higher patient visit satisfaction and medical staff cooperation satisfaction than the TMC group (P < 0.05). Conclusion: The implementation of the MDT nursing mode based on the doctor-nurse-integration for stroke patients undergoing emergency intervention surgery can improve the work efficiency of rescuing patients, improve the clinical treatment outcome of patients, and improve the satisfaction of doctors, nurses, and patients.

Synthesis of CdSe and CdSe/ZnS Quantum Dots with Tunable Crystal Structure and Photoluminescent Properties.

Mastery over the structure of nanocrystals is a powerful tool for the control of their fluorescence properties and to broaden the range of their applications. In this work, the crystalline structure of CdSe can be tuned by the precursor concentration and the dosage of tributyl phosphine, which is verified by XRD, photoluminescence and UV-vis spectra, TEM observations, and time-correlated single photon counting (TCSPC) technology. Using a TBP-assisted thermal-cycling technique coupled with the single precursor method, core-shell QDs with different shell thicknesses were then prepared. The addition of TBP improves the isotropic growth of the shell, resulting in a high QY value, up to 91.4%, and a single-channel decay characteristic of CdSe/ZnS quantum dots. This work not only provides a facile synthesis route to precisely control the core-shell structures and fluorescence properties of CdSe nanocrystals but also builds a link between ligand chemistry and crystal growth theory.

Predictive Model of Chemotherapy-Induced Myelosuppression for Patients with Esophageal Cancer.

BACKGROUND: The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to develop a model for prediction of incidence of myelosuppression during chemotherapy among patients with esophageal cancer. METHODS: In this retrospective study, a total of 1446 patients with esophageal cancer who underwent five different chemotherapy regimens between 2013 and 2020 at our institute were randomly assigned in a 7:3 ratio to training and validation data sets. Clinical and drug-related variables were used to develop the prediction model from the training data set by the machine learning method of random forest. Finally, this model were tested in the validation data set. RESULTS: The prediction model were established with 16 indispensable variables selected from 46 variables. The model obtained an area under the receiver-operating characteristic curve of .883 and accompanied by prediction accuracy of 80.0%, sensitivity of 77.8% and specificity of 81.8%. CONCLUSION: This new prediction model showed excellent predictive ability of incidence of myelosuppression in turn providing preventative measures for patients with esophageal cancer during chemotherapy.

Chemotherapy-Induced Myelosuppression in Esophageal Cancer Patients: Risks and Suggestions for Its Management.

OBJECTIVE: The influential factors of chemotherapy-induced myelosuppression in esophageal cancer in central China are unclear. This study aimed to investigate the effect of commonly used chemotherapy regimens on the incidence of myelosuppression in clinical treatment of esophageal cancer. METHODS: In this retrospective study, 624 patients with esophageal cancer who received six different chemotherapy regimens between 2013 and 2020 at our institute were included. Chemotherapy consisted of lobaplatin, 5-fluorouracil (5-F), lobaplatin and 5-F, nedaplatin, nedaplatin and paclitaxel (PTX), cisplatin and PTX. Multivariable logistic regression analysis was used to explore the risk of myelosuppression among the six different chemotherapy regimens. RESULTS: Compared with lobaplatin group, the incidence of myelosuppression in patients treated with chemotherapy regimens of lobaplatin and 5-F, nedaplatin, nedaplatin and PTX and cisplatin and PTX were significantly ameliorated. The dose of lobaplatin was significantly reduced (P=0.007) when lobaplatin was combined with 5-F, and the combination could significantly reduce the risk of myelosuppression (P=0.022). Furthermore, chemotherapeutic regimens, the dose of platinum, hemoglobin and uric acid levels, age, sex, total bilirubin and immune-enhancing drugs were found to be strong predictors of developing myelosuppression. CONCLUSION: Targeted preventive interventions that enhance immune function, reduce uric acid levels and choose combined medication during chemotherapy should be implemented for high-risk patients to reduce the occurrence of myelosuppression. In addition, the dose of lobaplatin should be adjusted when combined with other chemotherapy drugs to reduce the incidence of myelosuppression.

Metabolism and Biodegradation of ß-Glucan in vivo.

The ß-Glucans widely exist in plants and edible fungi, and their diverse bioactivities and good physicochemical properties have been widely reported. In addition, ß-glucan intravenous injections (such as lentinan and schizophyllan) have been clinically used as immunomodulators and antitumor polysaccharides. However, the pharmacokinetic studies of ß-glucans only stay on the level of plasma concentration and biodistribution in vivo, and little is known about their metabolism and degradation in vivo, which severely limits the further application of ß-glucans in the field of medicine and biomaterials. The aim of this paper is to explore the metabolism and degradation process of lentinan (as a representative of ß-glucans) in vivo by labeling it with water-soluble fluorescein 5-([4, 6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF). Fluorescently labeled lentinan (FLNT) was intravenously administered to rats at a single dose of 8 mg/kg. The degradation of LNT in blood, liver, kidney, and urine was evaluated by the gel permeation chromatography. Our results showed that although LNT could be degraded in blood, liver, kidney, and urine, there were still some prototypes until excreted in urine due to the incomplete degradation of LNT in each step. To the best of our knowledge, this is the first report to comprehensively study LNT metabolic degradation in rats. These results provide an important reference for further exploration and application of LNT and other ß-glucans.

Advances in oral absorption of polysaccharides: Mechanism, affecting factors, and improvement strategies.

Polysaccharides have been widely used as biomaterials and drugs after oral administration due to their suitable physicochemical properties, good bioactivities and low toxicities. However, studies on their pharmacokinetics and absorption mechanism after oral administration are significantly restricted by the lack of polysaccharide detection methods. With the advancement of polysaccharide detection technologies such as immunoassays, fluorescent and isotopic labelling, the oral pharmacokinetics of polysaccharides have gradually been revealed. Here, paracellular pathway, transcellular pathways and M cell-mediated transport were analysed as mechanisms for oral absorption. The potential factors affecting the oral absorption of polysaccharides, including their charge, molecular weight, spatial structure and dose, as well as the species and physiological state of organisms, were analysed. Based on the absorption mechanism and influencing factors, we look forward to further investigating possible strategies for improving the oral absorption of polysaccharides.

Pectic polysaccharide from Smilax china L. ameliorated ulcerative colitis by inhibiting the galectin-3/NLRP3 inflammasome pathway.

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum. Although galectin-3 (Gal-3) has been reported to play a proinflammatory role in UC, it is unknown whether pectic polysaccharide, a Gal-3 inhibitor in tumor metastasis, can alleviate UC by inhibiting Gal-3. The aim of this study was to investigate the anti-inflammatory effects and underlying mechanisms of SCLP, a pectic polysaccharide purified from Smilax china L. in our previous work, on dextran sulfate sodium-induced UC in BALB/c mice. The results showed that SCLP could significantly improve symptoms, alleviate histopathological damage and reduce the secretion of inflammatory mediators in mice with UC. Analysis of the anti-colitis mechanisms indicated that SCLP could inhibit the Gal-3/NLRP3 inflammasome/IL-1ß pathway by suppressing the expression of Gal-3 and the interaction of Gal-3 and NLRP3. Our results suggested that SCLP could be a promising candidate for prevention and treatment of UC.

Association of Myocardial Enzyme Abnormality with Clinical Outcomes of Patients with COVID-19: A Retrospective Study.

BACKGROUND: It has been observed that COVID-19 may cause myocardial damage, but there are few detailed reports on myocardial enzyme abnormalities. METHODS: In this retrospective study, we analyzed data from 157 consecutive laboratory-confirmed and hospitalized COVID-19 patients from Wuhan. We collected information on demographic and clinical characteristics, laboratory findings, and clinical outcomes. Logistic regression analysis was used to explore the risk factors associated with the severity of COVID-19. The association between myocardial enzyme abnormalities and the mortality was also investigated. RESULTS: The mortality in abnormal myocardial enzyme group was obviously higher than the normal group (P < 0.001). The majority of patients (n = 72, 97.3%) with normal cardiac enzyme group were of the common novel coronavirus pneumonia (NCP) type, whereas half of the patients with cardiac enzyme abnormalities (n = 40, 48.2%) developed critical and severe NCP type. The multivariable logistic regression analysis indicated that COVID-19 patients with increasing age (P = 0.035), higher levels of CRP (P = 0.038), and TNI (P = 0.036) were associated with increased death than other patients. CONCLUSIONS: Myocardial enzyme abnormality and myocardial injury were associated with the severity and fatal outcomes of COVID-19. Clinicians should pay attention to the markers of myocardial injury in COVID-19 patients, especially those with older age, comorbidities, and inflammation.

Oral absorption characteristics and mechanisms of a pectin-type polysaccharide from Smilax china L. across the intestinal epithelium.

The elucidation of the oral absorption of natural polysaccharides contributes to their further research and utilization. Herein, to explore the absorption of a pectin-type polysaccharide from Smilax china L. (SCLP), SCLP was respectively fluorescently labeled with fluorescein-5-thioicarbazide (FSCLP) and Cyanine7 amine (Cy7-SCLP) for in vitro and in vivo tracking. The near-infrared imaging demonstrated that Cy7-SCLP was absorbable in the small intestine and distributed in the liver and kidney after oral administration. Subsequently, in vitro intestinal epithelial tissue experiments showed that the jejunum was the dominant site of FSCLP transport. Further transport studies in the Caco-2 cell monolayer illustrated that FSCLP was delivered across the monolayer via transcellular transport by caveolae-mediated endocytosis and macropinocytosis together with paracellular transport by reversibly affecting tight junctions. In summary, this work presents the oral absorption characteristics and mechanisms of SCLP through the intestinal epithelium, which will facilitate the further development of SCLP and pectin polysaccharides.

Mechanism of Lentinan Intestinal Absorption: Clathrin-Mediated Endocytosis and Macropinocytosis.

Lentinan (LNT), a typical triple helix ß-glucan extracted from Lentinus edodes, has been widely used as a functional food and an orally administered drug. However, its oral pharmacokinetics has been rarely reported. The aim of this work is to systematically study the pharmacokinetics and intestinal absorption mechanism of LNT after oral administration. Radioactive 99m-technetium (99mTc) was introduced to label LNT to determine the plasma concentration, tissue distribution, and excretion of the ß-glucan in rats after oral administration. The results confirmed the absorption of LNT, with the maximal plasma concentration reached at 1 h. 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF) was used to label LNT to explore the absorption mechanism of LNT, utilizing both a Ussing chamber and a monolayer of Caco-2 cells. These transport assays showed that LNT could penetrate through the intestine and epithelial monolayer, which was mediated by macropinocytosis and clathrin-mediated endocytosis. These findings provide a pharmacokinetic reference for LNT and help provide a greater understanding of the absorption of ß-glucans in general.

Lentinan inhibited colon cancer growth by inducing endoplasmic reticulum stress-mediated autophagic cell death and apoptosis.

Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro. SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca2+concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.

Construction of Ultrasonic Tactile Force Feedback Model in Teleoperation Robot System.

The ultrasonic phased array as an emerging interactive tool is increasingly used for aerial tactile interaction. However, there is almost no method to achieve remote variable force feedback through the ultrasonic phased array as far as we know. This article presents a force tactile feedback method for teleoperating robot systems that tracks the five fingers and forms a focus on the fingertips. First, the perceived size of the focus depends on the input parameters. The influence of the parameters on the physical output pressure intensity was obtained through physical test experiments. Then, the absolute threshold and difference threshold of human perception were studied through psychophysical experimental methods. Finally, the input parameters were selected according to the experimental results. According to the collected data, the construction of the force regression model was completed, and different parameters were mapped to the perceived intensity. The contact force generated in the actual operation is fed back to the haptic system, and the constructed model automatically adjusts the control parameters to ensure that the user's hand presents a sensory output corresponding to the intensity change. The entire force feedback system is evaluated, and results show that the system shows good perceptual quality.

The Effects of a Passive Exoskeleton on Human Thermal Responses in Temperate and Cold Environments.

The exoskeleton as functional wearable equipment has been increasingly used in working environments. However, the effects of wearing an exoskeleton on human thermal responses are still unknown. In this study, 10 male package handlers were exposed to 10 °C (COLD) and 25 °C (TEMP) ambient temperatures while performing a 10 kg lifting task (LIFTING) and sedentary (REST) both with (EXO) and without the exoskeleton (WEXO). Thermal responses, including the metabolic rate and mean skin temperature (MST), were continuously measured. Thermal comfort, thermal sensation and sweat feeling were also recorded. For LIFTING, metabolic heat production is significant decrease with the exoskeleton support. The MST and thermal sensation significantly increase when wearing the exoskeleton, but thermal discomfort and sweating are only aggravated in TEMP. For REST, MST and thermal sensation are also increased by the exoskeleton, and there is no significant difference in the metabolic rate between EXO and WEXO. The thermal comfort is significantly improved by wearing the exoskeleton only in COLD. The results suggest that the passive exoskeleton increases the local clothing insulation, and the way of wearing reduces the "pumping effect", which makes a difference in the thermal response between COLD and TEMP. Designers need to develop appropriate usage strategies according to the operative temperature.

Molecular dynamics simulation of lentinan and its interaction with the innate receptor dectin-1.

Lentinan, a ß-1,3-D-glucan, is clinically used as an immune enhancement drug for tumor therapy. Dectin-1 is a cell-surface immune receptor, which plays an important role in immunological defense against fungal pathogens and ß-glucan-mediated immune modulation. Herein we attempted to study the advanced structure of lentinan and how lentinan interacts with dectin-1 for its immune enhancement effect. We firstly used MD simulation and rigid macromolecule docking, combining some spectral techniques, to uncover the complex 3D conformation of a typical polysaccharide - lentinan, and the detailed interaction mode of lentinan with dectin-1. We proved by computational simulation that lentinan can maintain its triple-helix through hydrogen network and disclosed some structural properties of lentinan. We also characterized the affinity of lentinan to dectin-1 by LSPR and binding free energy calculation, and we found out that hydrogen bonds and CH-π interaction are the major contributors for lentinan's binding to dectin-1. Besides, after bound with lentinan, dectin-1 might surprisingly go through a conformational change. In summary, our work provided insights into lentinan's advanced structure and ß-glucan recognition by dectin-1.

Metabolic degradation of lentinan in liver mediated by CYP450 enzymes and epoxide hydrolase.

Lentinan (LNT), a typical triple helix ß-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other ß-glucans.

Apoptosis induction activity of polysaccharide from Lentinus edodes in H22-bearing mice through ROS-mediated mitochondrial pathway and inhibition of tubulin polymerization.

BACKGROUND: Lentinus edodes is a medicinal mushroom widely used in Asian countries for protecting people against some types of cancer and other diseases. OBJECTIVE: The objective of the present study was to investigate the direct antiproliferation activity and the antitumor mechanisms of water-extracted polysaccharide (WEP1) purified from L. edodes in H22 cells and H22-bearing mice. DESIGN: The extraction, isolation, purification, and structure determination of the water-soluted L. edodes polysaccharide WEP1 were performed. The growth inhibitory effects of WEP1 on H22 cells and H22-bearing mice were determined by 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) method and animal studies. Flow cytometry, scanning electron microscopy, and laser scanning confocal microscopy were used to observe the morphological characteristics of apoptotic cells. The levels of intracellular reactive oxygen species (ROS) were detected by flow cytometry using 2',7'-dichlorofluorescein-3',6'-diacetate (DCFH-DA). Western blot was used to determine the expressions of cell cycle proteins and apoptosis-related proteins. RESULTS: Results showed that WEP1 with a molecular weight of 662.1 kDa exhibited direct antiproliferation activity on H22 cells in a dose-dependent manner. In vivo, WEP1 significantly inhibited the growth of tumor at different doses (50, 100, and 200 mg/kg) and the inhibition rates were 28.27, 35.17, and 51.72%, respectively. Furthermore, morphological changes of apoptosis and ROS overproduction were observed in H22 cells by WEP1 treatment. Cell cycle assay and western blot analyses indicated that the apoptosis induction activity of WEP1 was associated with arresting cell cycle at G2/M phase and activating mitochondrial-apoptotic pathway. Besides, WEP1 disrupted the microtubule network accompanied by alteration of cellular morphology. CONCLUSION: Results suggested that the antitumor mechanisms of WEP1 might be related to arresting cell cycle at G2/M phase, inhibiting tubulin polymerization and inducing mitochondrial apoptosis. Therefore, WEP1 possibly could be used as a promising functional food for preventing or treating liver cancer.