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Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with deleterious maternal and fetal outcomes. Angelica sinensis polysaccharide (ASP) has been shown to reduce hepcidin expression in IDA rats. However, the role of ASP in the treatment of IDA during pregnancy and its potential mechanisms have not been investigated. Moreover, the effect of ASP on duodenal iron absorption is not clear. The aim of this study was to investigate the preventive efficacy of ASP against IDA during pregnancy and clarify the underlying mechanisms. Our results showed that ASP improved maternal hematological parameters, increased serum iron, maternal tissue iron, and fetal liver iron content, and improved pregnancy outcomes. Additionally, ASP combated oxidative stress caused by iron deficiency by improving the body's antioxidant capacity. Western blot results demonstrated that ASP downregulated hepcidin expression by blocking the BMP6/SMAD4, JAK2/STAT3 and TfR2/HFE signaling pathways, which in turn increased the expression of FPN1 in the liver, spleen, and duodenum and promoted iron cycling in the body. Furthermore, ASP increased the expression of DMT1 and Dcytb in the duodenum, thereby facilitating duodenal iron uptake. Our results suggest that ASP is a potential agent for the prevention and treatment of IDA during pregnancy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

In this study, a porous sponge material was formed by physically mixing chitosan (CS) and Angelica sinensis polysaccharide (ASP). After removing the water by freeze-drying, the CS/ASP sponge was obtained. The prepared sponges exhibited excellent swelling properties, thermal stability and biocompatibility as well as improvements over the insufficient mechanical properties of pure chitosan sponges. Notably, the ASP released from the CS/ASP sponge could be effectively absorbed by the liver, which endowed the CS/ASP sponge with effective liver-protective effects against CCl 4 -induced acute liver injury; these protective effects surpassed those of both blank CS and CS/Dextran sponges. The underlying protective mechanism may involve the activation of the Nrf2-mediated antioxidant signaling pathway and the inhibition of hepatocyte apoptosis. Understanding CS/ASP sponges may provide new insights and inspire new methods for the clinical application of ASP. At the same time, we hope to suggest future directions for the development of polysaccharide preparations., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Anal fistula is a common benign anorectal disease that often requires surgical intervention for effective treatment. In recent years, preoperative colonoscopy as a diagnostic tool in patients with anal fistula has garnered increasing attention due to its potential clinical application value. By investigating underlying inflammatory bowel disease (IBD), polyps, and other abnormalities, preoperative colonoscopy can offer insights to refine surgical strategies and improve patient outcomes., Methods: This retrospective study focused on 1796 patients with various benign anorectal diseases who underwent preoperative intestinal endoscopy and met surgical criteria within the preceding three years at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. Among these patients, 949 diagnosed with anal fistula comprised group A, while 847 patients without anal fistula were assigned to group B for comparison. The investigation encompassed an analysis of general patient information, endoscopic findings, polyp histopathology, distribution of bowel inflammation sites, and results of inflammatory bowel disease assessments between the two patient cohorts. A subgroup analysis was also conducted on 2275 anal fistula patients with no surgical contraindications. This subgroup was categorized into Group A (949 patients who underwent preoperative intestinal endoscopy) and Group C (1326 patients who did not undergo preoperative colonoscopy). The study compared the rates of detecting endoscopic lesions and IBD-related findings between the two subgroups., Results: The study initially confirmed the comparability of general patient information between groups A and B. Notably, the abnormal detection rate in group A was significantly higher than in group B (P < 0.01). In terms of endoscopic findings, the anal fistula group (group A) exhibited higher rates of detecting bowel inflammation, inflammatory bowel disease, and polyps compared to the non-anal fistula group (group B) (P < 0.05). The distribution of inflammation locations indicated higher detection rates in the terminal ileum, ileocecal region, and ascending colon for group A compared to group B (P < 0.05). Although the incidence of IBD in group A was higher than in group B, this difference did not reach statistical significance (P > 0.05). Subsequently, the analysis of the subgroup (groups A and C) revealed a significant disparity in intestinal endoscopic detection rates (P < 0.01) and statistically significant differences in detecting IBD (P < 0.05) and Crohn's disease (P < 0.05) between the two anal fistula subgroups., Conclusions: The findings of this study underscore the substantial clinical value of preoperative colonoscopy in the comprehensive evaluation of patients with anal fistula. Preoperative colonoscopy aids in ruling out localized perianal lesions caused by underlying inflammatory bowel disease, thereby mitigating the likelihood of missed diagnoses and enhancing treatment outcomes. This research highlights the importance of incorporating preoperative colonoscopy as a valuable diagnostic tool in managing anal fistula patients., (© 2023. The Author(s).)

Herein we present a visible-light-facilitated transition-metal-free allylic silylation reaction under mild conditions. This protocol is enabled by an inexpensive organophotocatalyst and provides efficient and concise synthetic routes to substituted allylsilanes, particularly from readily available allyl sulfones and stable silanecarboxylic acids as silyl radical precursors. Further investigations reveal that this strategy is also generally compatible with vinyl sulfones to access vinylsilanes. The silver catalytic system opens up an alternative entry to realize the decarboxylative allylation of silanecarboxylic acids.

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 β-glucans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

As typical acetylated glucomannans, Dendrobium officinale polysaccharides (DOPs) from different origins differ in their structural characteristics and some of their physicochemical properties. To rapidly select D. officinale plants, we systematically investigate the differences among DOPs from different origins and analyzed the structural characteristics, such as the degree of acetylation and monosaccharide composition; the physicochemical properties, such as solubility, water absorption and apparent viscosity; and the lipid-lowering activity of the obtained DOPs. Principal component analysis (PCA), a method for analyzing multiple variables, was used to analyze the relationship between the physicochemical and structural properties, and lipid-lowering activity. It was found that the structural and physicochemical characteristics had significant effects on lipid-lowering activity, and DOPs with a high degree of acetylation, high apparent viscosity and large D-mannose-to-d-glucose ratio were associated with greater lipid-lowering activity. Therefore, this study provides a reference for the selection and application of D. officinale., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not published previously, and not under consideration for publication elsewhere, in whole or in part., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: To explore the clinical significance of 18 F-FDG metabolic imaging in the diagnosis and biological risk assessment of gastrointestinal stromal tumors (GIST)., Methods: This study is a clinical retrospective study. The research subjects were patients with GIST who were admitted to our hospital from January 2014 to December 2019 and underwent 18 F-FDG metabolic imaging, and the relationship between biological risk and FDG metabolism was analyzed retrospectively., Results: A total of 32 patients with GIST were included in this study, of which 17 patients had very low and low-risk lesions, and the FDG metabolism level did not increase; five patients had moderate-risk gastric lesions, and the FDG metabolism level was abnormally increased; 10 patients had high-risk lesions, and except for one patient with multiple lesions, the FDG metabolism level of these patients was increased., Conclusions: The level of glucose metabolism is abnormally increased in tumor cells with vigorous mitosis and has higher biological risk. The 18 F-FDG metabolism level can determine the biological risk of GIST and whether high-risk lesions involve other tissues and organs, as it more comprehensively reflects the distribution of lesions, the activity of tumor cells and the stage of the disease., (© 2022. The Author(s).)

Angelica sinensis polysaccharide (ASP) has presented increasingly recognized lipid regulation and antioxidant abilities. However, there is little direct evidence to explain why ASP possesses the observed lipid-lowering and anti-oxidation effects. In vivo and in vitro models of alcoholic fatty liver disease (AFLD) were established to examine the direct effect of ASP on hepatic fat accumulation. Our results showed that the lipid-lowering effect of ASP might result from the dual inhibition of lipid synthesis and CD36-mediated lipid uptake. The antioxidation of ASP might be attributed to the reversal of alcohol metabolic pathways from CYP2E1 catalysis to ADH catalysis. Taken together, the study demonstrated the direct role of ASP in lipid metabolism for the first time and revealed the underlying mechanism of reducing ROS, providing an available strategy for ASP as a potential agent to treat AFLD., (Copyright © 2022. Published by Elsevier B.V.)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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-1β 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., (Copyright © 2021. Published by Elsevier Ltd.)

Aim: To prepare the hyaluronic acid-coated Olaparib-loaded PEI - PLGA nanoparticles (HA-Ola-PPNPs) and investigate their tumour-targeted anticancer effect., Methods: The synthesis of HA-Ola-PPNPs was verified by DLS, TEM and SEM, followed was measured its cytotoxicity using CCK-8 assay. Confocal microscopy was used to observe the cellular uptake. Cell apoptosis was analysed by flow cytometry, biological SEM, and TEM. The expression of related proteins within the tumour site was investigated by immunostaining., Results: The prepared HA-Ola-PPNPs showed a diameter of ∼160 nm with a negatively charged surface (-16.9 ± 2.7 mV) and sustained drug release behaviour. And the encapsulation efficiency of HA-Ola-PPNPs was 78.63 ± 5.29%. HA-Ola-PPNPs exhibited efficient in vitro and in vivo antitumor activities. HA-Ola-PPNPs induced cell apoptosis by upregulating Bax, Cytochrome C, and Caspase 3, downregulating Bcl-2 in breast cancer-bearing mice., Conclusions: According to the results, the Ola-loaded and HA-coated PEI - PLGA nanoparticles could be considered as a powerful tumour-targeted drug delivery system for TNBC treatment.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acute alcoholic liver injury (AALI) is a threat to human health. Dendrobium officinale polysaccharide (DOP) has the potential to protect the liver by enhancing the anti-oxidative system to maintain the relative balance of ROS (active oxygen species) and antioxidants in AALI mice. However, the dynamic improvement effect of DOP on AALI is still not clear and accurate medication guidance is not available, which limits the clinical application of DOP. Because of the advantages of high sensitivity, noninvasiveness, and visualization, near-infrared (NIR) fluorescence imaging has been widely studied in biochemistry and biomedicine. As the glutathione (GSH) level in the liver is closely related to the progression of AALI, herein, an NIR fluorescent probe for GSH, HCG was used to dynamically evaluate the effect of DOP on AALI mice. In this study, DOP was proven to maintain the relative balance of GSH content in the liver to protect it from damage. To the best of our knowledge, it is the first time to assess the effect of DOP on AALI mice through a NIR fluorescence imaging technique. This study may also provide a potential NIR imaging agent for the clinical research to improve the management of liver injury-related diseases., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

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 Ca 2+ 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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Silkworm faeces are the dry faeces of the insect Bombyx mori (Linnaeus) and have historically been used in traditional Chinese medicine to treat blood deficiency and rheumatic pain. Silkworm faeces extract (SFE) is derived from silkworm faeces., Aim of the Study: Clinical observations of patients in the Department of Nephrology have shown that SFE effectively improves renal anaemia. However, the molecular mechanism remains unclear. This article mainly explores the regulatory effects of SFE on erythropoietin (EPO) and hepcidin to identify the molecular mechanism of SFE., Materials and Methods: A rat model of renal anaemia was established by feeding rats food containing 0.75% adenine. SFE was orally administered to the rats, while recombinant human erythropoietin (rhEPO) was used as a positive control drug. Haematological parameters and inflammation levels were compared between rats from each group, and pathological kidney sections from each rat were observed. The serum EPO and hepcidin levels were detected using enzyme-linked immunosorbent assay (ELISA) kits, while Western blot analyses were performed to detect the levels of proteins involved in the EPO-related hypoxia-inducible factor 2α (HIF-2α)/prolyl hydroxylase 2 (PHD2) signalling pathway and hepcidin-related BMP6/SMAD4 and interleukin-6 (IL-6)/STAT3 signalling pathways., Results: SFE significantly ameliorated haematological parameters, renal function, and inflammation levels in the rats. A mechanistic study showed that SFE promoted EPO expression by upregulating HIF-2α expression and inhibiting the expression of NF-κB and GATA2 both in vivo and in vitro. In particular, SFE inhibited PHD2 expression, resulting in a decrease in the enzymatic reaction of HIF-2α to increase EPO expression. Furthermore, SFE inhibited hepcidin expression by blocking the BMP6/SMAD4 and IL-6/STAT3 pathways., Conclusions: SFE regulated iron metabolism by inhibiting hepcidin and simultaneously promoted EPO synthesis to improve renal anaemia in rats., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lentinan (LNT), a typical triple helix β-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 β-glucans., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Angelica sinensis polysaccharide (ASP) has hepatoprotective effects in liver injury models. However, its role and mechanism in chronic liver fibrosis have not been fully elucidated. In this study, a carbon tetrachloride (CCl 4 )-induced chronic liver fibrosis mouse model was established. The results showed that ASP treatment reduced serum alanine aminotransferase by approximately 50% and liver fibrosis areas by approximately 70%. Hepatic stellate cell (HSC) activation was inhibited in ASP-treated mice. Furthermore, the mechanism was studied in-depth, focusing on the interleukin 22/signal transducer and activator of transcription 3 (IL-22/STAT3) axis. Concentrations of 50 μg/ml and 100 μg/ml ASP induced the secretion of IL-22 in vitro, which further increased at a concentration of 200 μg/ml. Moreover, in vivo data showed that ASP significantly promoted IL-22 production in splenocytes and liver tissues. The antifibrotic effects of ASP were abolished after IL-22 neutralization. In addition, ASP activated the STAT3 pathway in the liver, as demonstrated by a 2-fold increase compared to that of the CCl 4 group, which was abrogated by the IL-22 antibody. Subsequently, we showed that the antifibrotic effects of ASP were abrogated by blocking STAT3 with S3I-201. In conclusion, ASP effectively alleviates chronic liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway., Competing Interests: Declaration of competing interest All the authors declared no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Glycogen is a branched glucose polymer involved in sustaining blood glucose homeostasis. Liver glycogen comprises α particles (up to 300 nm in diameter) made of joined β particles (∼20 nm in diameter). Glycogen α particles in a mouse model for diabetes are molecularly fragile, breaking down into smaller β particles more readily than in healthy mice. Glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen degradation, is overexpressed in diabetic mice. This study shows that Metformin and Berberine, two common drugs, two common drugs used to treat diabetes, are able to revert the liver glycogen of diabetic mice to the stable structure seen in non-diabetic mice. It is also shown that these drugs reduce the GP level via the cAMP/PKA signaling pathway in diabetic livers and decrease the affinity of GP with the glycogen of db/db mice. These effects of these drugs may slow down the degradation of liver glycogen and improve glucose homeostasis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Large-area horizontal-aligned ZnO nanotubes (ZNTs), TiO 2 nanotubes (TNTs), TiO 2 -ZnO core-shell nanotubes (TZNTs) and ZnO-TiO 2 core-shell nanotubes (ZTNTs) were successfully synthesized by electrospinning combined with pulsed-laser deposition. The morphology, structure, and composition of the samples were characterized by scanning electron microscopy, high-resolution transmission electron microscopy, and Raman spectroscopy. The photoluminescence (PL) spectra of these samples indicate that the addition of a TiO 2 layer greatly decreases the recombination of photogenerated carriers in the heterojunction nanotubes. The photodetectors (PDs) were fabricated by assembling horizontally ordered nanotubes on the gold interdigital electrode, and their ultraviolet (UV) detection performances were compared. The test results at room temperature show that the PD with aligned ZTNTs have the best UV response and a short response recovery time. In addition, the performance of ZTNT PDs and TZNT PDs are further improved under heating. The photo/dark current ratio, responsivity ( R λ ), detectivity ( D *), and external quantum efficiency (EQE) of ZTNTs increased to 388, 450 uA·W -1 , 1.1 × 10 10 cm·Hz 1/2 ·W -1 , and 0.15%, respectively, under the condition of 365 nm UV radiation with a power density of 4.9 mW·cm -2 and a 1 V bias at 90 °C. The UV response mechanism and structural superiority of the horizontally ordered coaxial heteronanotube were also discussed. In addition, this work provides an important method for the design of other ordered nanomaterials and structures, which have a wide range of applications in the fields of sensors, transistors, transparent flexible electrodes, and other multifunctional devices.

The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Multifunctional magnetic nanoparticles (MNPs) were widely used for ablation of cancer cells because of their potential on physical treatment. Herein, we developed the "cell targeting destructive" multifunctional polymeric nanoparticles (named as HA-Olb-PPMNPs) based on PEI-PLGA co-loaded with the anticancer drug Olaparib (Olb) and superparamagnetic iron oxide nanoparticles (Fe 3 O 4 NPs), and further coated with a low molecular weight hyaluronic acid (HA) on its surface. Due to the high affinity between HA and CD44-receptor on cell surface of triple negative breast cancer (TNBC), an active targeting can be achieved. Under a rotating magnetic field (RMF), HA-Olb-PPMNPs produced a physical transfer of mechanical force by incomplete rotation. This mechanical force could cause the "two strikes" effect on the cells, in which "First-strike" was to damage the cell membrane structure (magneto-cell-lysis), another "Second-strike" could activate the lysosome-mitochondrial pathway by injuring lysosomes to induce cell apoptosis (magneto-cell-apoptosis). Therefore, the mechanical force and Olb exert dual anti-tumor effect to achieve synergistic therapeutic in the presence of RMF. This study proposes a novel multi-therapeutic concept for TNBC, as well as provided evidences of new anti-tumor therapeutic effects induced by the magnetic nanoparticles drug system., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We explored the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on CCl 4 -induced liver fibrosis with respect to the intestinal hepatic axis using a rat model. Histopathological staining results showed that DOP alleviated extensive fibrous tissue proliferation in interstitium and lessened intestinal mucosal damage. Western blot and PCR results showed that DOP maintained intestinal balance by upregulating the expression of tight junction proteins such as occludin, claudin-1, ZO-1, and Bcl-2 proteins while downregulating the expression of Bax and caspase-3 proteins in the intestine. The transepithelial electrical resistance (TEER) value of the LPS-induced Caco-2 monolayer cell model was increased after DOP administration. These illustrated that DOP can protect the intestinal mucosal barrier function. DOP also inhibited activation of the LPS-TLR4-NF-κB signaling pathway to reduce the contents of inflammatory factors TGF-β and TNF-α, increased the expression of anti-inflammatory factor IL-10, and significantly decreased α-SMA and collagen I expression. These results indicated that DOP maintained intestinal homeostasis by enhancing tight junctions between intestinal cells and reducing apoptosis, thereby inhibiting activation of the LPS-TLR4-NF-κB signaling pathway to protect against liver fibrosis., (Copyright © 2020 Wang, Yang, Wu, Wang, Li, Mei, You and Zhang.)

Ethnopharmacological Relevance: Dendrobium officinale polysaccharide (DOP) is the main active ingredient of Dendrobium officinale Kimura & Migo, which is a precious traditional Chinese medicine and often used in treatment of hepatitis, diabetes, obesity and rheumatoid arthritis., Aim of the Study: DOP exhibits significant hypoglycemic activity, while its mechanism remains unclear. The present study aims to investigate the hypoglycemic mechanisms of DOP based on the glucagon-mediated signaling pathways and the liver glycogen structure, which catalyze hepatic glucose metabolism, and provide new knowledge about the antidiabetic mechanism of DOP and further evidence for its clinical use for diabetes., Materials and Methods: DOP were obtained from the dry stems of Dendrobium officinale by water extraction and alcohol precipitation method. T2DM mice model was established by high-fat diet combined with streptozotocin. Liver histopathological changes were observed by H&E and PAS straining. Pancreatic histology was studied by H&E staining and immunofluorescence analysis. The levels of glucagon and insulin were detected by Elisa Kit and the hepatic glycogen content was detected by GOPOD. The expressions of the hepatic glycogen-related metabolism enzymes, hepatic gluconeogenesis enzymes, and the related protein in cAMP-PKA and Akt/FoxO1 signaling pathways were detected by western blots. Liver glycogen was extracted from the liver tissues by sucrose density gradient centrifugation, and size exclusion chromatography (SEC) was used to analyze the structure of liver glycogen., Results: DOP could significantly affect the glucagon-mediated signaling pathways, cAMP-PKA and Akt/FoxO1, to further promote hepatic glycogen synthesis, inhibit hepatic glycogen degradation and hepatic gluconeogenesis. Moreover, DOP could reverse the instability of the liver glycogen structure and thus probably suppressed glycogen degradation. Thus, DOP finally would ameliorate hepatic glucose metabolism via glucagon-mediated signaling pathways and modifying liver-glycogen structure in diabetic mice., Conclusions: The hypoglycemic mechanism of DOP might be associated with the regulation of glucagon-mediated hepatic glycogen metabolism and gluconeogenesis, and of liver glycogen structure, contributing to improved hepatic glucose metabolism in diabetic mice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Wound healing is a complex process involving diverse changes in multiple cell types where the application of electric fields has been shown to accelerate wound closure. To define the efficacy of therapies based on electric fields, it would be valuable to have a platform to systematically study the effects of electrical stimulation (ES) upon the inflammation phase and the activation of signaling mediators. Here, an in vivo ES model in which flexible electrodes are applied to an animal model for monitoring inflammation in a wound is reported on. Subcutaneous implants of polyvinyl alcohol sponges elicit inflammation response as defined by the infiltration of leukocytes. The wound site is subjected to electric fields using two types of additively fabricated flexible electrode arrays. The sponges are then harvested for flow cytometry analysis to identify changes in the phosphorylation state of intracellular targets. This platform enables studies of molecular mechanisms, as it shows that an application of low-frequency ES ≤0.5 Hz increases phosphorylation of Erk proteins in recruited leukocytes, identifying a signaling pathway that is activated during the healing process., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In recent years, the utilization of polysaccharides as targeted drug carriers has attracted considerable attention. Herein, Angelica sinensis polysaccharide (ASP), a plant polysaccharide with good biocompatibility, excellent aqueous solubility and intrinsic liver-targeted capability, was modified with hydrophobic group (deoxycholic acid) to fabricate amphiphilic conjugate (ASP-DOCA). Self-assembled nanoparticles were successfully developed for hepatoma-targeted delivery of therapeutic drug doxorubicin (DOX). The DOX loaded nanoparticles (DOX/ASP-DOCA NPs) were spherical in shape with a particle size of 228 nm and negatively charged around -17 mV. DOX was released from nanoparticles in a sustainable and pH-dependent manner. In vitro cellular uptake revealed that DOX/ASP-DOCA NPs were internalized into HepG2 cells through asialoglycoprotein receptor (ASGPR)-mediated endocytosis, resulting in a higher anti-proliferation effect than DOX-loaded dextran derivative DOX/DEX-DOCA NPs. Additionally, DOX/ASP-DOCA NPs showed higher inhibition on the growth of HepG2 multicellular spheroids (MCs) than DOX/DEX-DOCA NPs. In vivo imaging demonstrated that ASP-DOCA NPs specifically targeted HepG2 tumors via ASGPR, improving the accumulation of DOX/ASP-DOCA NPs in tumors and generating superior antitumor activity compared with free DOX and DOX/DEX-DOCA NPs. Taken together, ASP-DOCA NPs possess potential applications in drug delivery systems targeting liver cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Here, we have successfully synthesised and purified multifunctional PLGA-based nanoparticles by the co-encapsulation of an anticancer drug (tetrandrine) and a magnetic material (Fe 3 O 4 ). The obtained Tet-Fe 3 O 4 -PLGA NPs had a uniform spherical shape with a particle size of approximately 199 nm and a negative surface charge of -18.0 mV, displaying a high encapsulation efficiency. Furthermore, TEM studies provided representative images of the purification process of the magnetic nanoparticles with MACS ® technology. The MFM and VSM results indicated that both the Fe 3 O 4 NPs and Tet-Fe 3 O 4 -PLGA NPs were superparamagnetic. The DSC spectrum demonstrated that Tet was successfully encapsulated within the PLGA-based nanoparticles. Significantly, the release studies revealed NPs had a relatively slower release rate than free Tet after 8 h's initial burst release, which had decreased from 98% to 65% after 24 h. In vitro cellular studies revealed that NPs could effectively penetrate into A549 cells and A549 multicellular spheroids to exert cytotoxicity, displaying a significantly high anti-proliferation effect. Moreover, western blot demonstrated that the co-loaded NPs had a higher anticancer activity by injuring lysosomes to activate the mitochondria pathway and induce A549 cell apoptosis. The magnetic characteristics and high anticancer activity support the use of Tet/Fe 3 O 4 co-loaded PLGA-based nanoparticles as a promising strategy in the treatment of lung cancer.

The multichannel concentric-ring electrodes are stencil printed on stretchable elastomers modified to improve adhesion to skin and minimize motion artifacts for electrophysiological recordings of electroencephalography, electromyography, and electrocardiography. These dry electrodes with a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate interface layer are optimized to show lower noise level than that of commercial gel disc electrodes. The concentric ring geometry enables Laplacian filtering to pinpoint the bioelectric potential source with spatial resolution determined by the ring distance. This work shows a new fabrication approach to integrate and create designs that enhance spatial resolution for high-quality electrophysiology monitoring devices., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The antitumor effect of Lentinan is thought rely on the activation of immune responses; however, little is known about whether Lentinan also directly attacks cancer cells. We therefore investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from Lentinus edodes) and its probable mechanism. We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic and extrinsic pathways, which presented as the activation of Caspases-9 and -8, upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF-κB, and overproduction of ROS and TNF-α in vitro and in vivo. Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-α-mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon cancer prevention and treatment.

Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia. Furthermore, ASP inhibited NF- κ B p65 activation via the I κ B kinases- (IKKs-) I κ B α pathway, thereby reducing the secretion of interleukin-6 (IL-6) and TNF- α , which is known to inhibit erythropoiesis. Our findings indicate that ASP is a potential treatment option for patients suffering from ACD.