Addition of Ostrea rivularis polysaccharides in microneedle loaded with 3-acetylaconitine liposomes enhance analgesic activities and drug delivery properties.

3-Acetylaconitine (AAC) is a natural compound with strong anti-inflammatory and analgesic properties, but the severely narrow safety range limited its clinical application. Two dissolvable microneedle (MN) systems, AAC-ORP-MN and AAC-MN, loaded with AAC liposomes (AAC-Lips) either mixed with or without Ostrea rivularis polysaccharide (ORP) were developed. The size, zeta potential and encapsulation efficiency of AAC-Lips were 112.9 ±â€¯0.5 nm, -31.3 ±â€¯0.5 mV and 95.7 ±â€¯1.2 %. AAC-ORP-MN demonstrated higher mechanical strength and faster initial drug release rate compared to AAC-MN. The results in the spared nerve injury (SNI) model showed that AAC-ORP-MN and AAC-MN both could significantly increase the mechanical pain threshold on the operated side of the rats, and gradually decrease the difference between the equilibrium pain thresholds of both feet, but AAC-ORP-MN showed a faster onset of action. In addition, AAC-ORP-MN significantly reduced inflammatory factors and improved pathological damage in the spinal cord better than AAC-MN, which might be due to the anti-inflammatory activity of ORP. Overall, the above results supported that AAC-ORP-MN showed promise as a clinical option for analgesia, which had anti-inflammatory and analgesic properties, meanwhile it could effectively deliver poorly water-soluble AAC and improve its safety and availability.

Microneedles containing Cucumaria frondosa polysaccharides and 3-acetylaconitine exert analgesic, anti-inflammatory and chondroprotective activity for knee osteoarthritis.

3-Acetylaconitine (AAC) is a commercially analgesic drug for arthritis, however, due to its narrow safety range, its clinical application is limited. The objective of the study was to investigate the combined effect of Cucumaria frondosa polysaccharide (CFP) and AAC in microneedles on knee osteoarthritis (KOA). The characterization of microneedles was conducted and a rat model of monosodium iodoacetate (MIA)-induced KOA was established to evaluate the anti-inflammatory and analgesic activity in this study. The inhibitory effects on cartilage degradation and synovial inflammation were determined by morphological observation of the knee joint, pathological and imaging results. The von Frey pain threshold and hind limb weight bearing test were used to evaluate the effect of microneedles on pain relief. The results showed that microneedles had the mechanical strength to penetrate the skin and dissolved well in the skin for drug delivery within 30 min after patch administration. Furthermore, AAC-MN and CFP-AAC-MN both played roles in relieving pain, reducing cartilage degeneration and inhibiting synovial inflammation in KOA. In summary, CFP combined with AAC loading into microneedles exhibited higher skin penetration and more advantages in inhibiting cartilage damage and inflammation compared to AAC alone.

Accurate brain pharmacokinetic parametric imaging using the blood input function extracted from the cavernous sinus.

Brain pharmacokinetic parametric imaging based on dynamic positron emission tomography (PET) scan is valuable in the diagnosis of brain tumor and neurodegenerative diseases. For short-axis PET system, standard blood input function (BIF) of the descending aorta is not acquirable during the dynamic brain scan. BIF extracted from the intracerebral vascular is inaccurate, making the brain parametric imaging task challenging. This study introduces a novel technique tailored for brain pharmacokinetic parameter imaging in short-axis PET in which the head BIF (hBIF) is acquired from the cavernous sinus. The proposed method optimizes the hBIF within the Patlak model via data fitting, curve correction and Patlak graphical model rewriting. The proposed method was built and evaluated using dynamic PET datasets of 67 patients acquired by uEXPLORER PET/CT, among which 64 datasets were used for data fitting and model construction, and 3 were used for method testing; using cross-validation, a total of 15 patient datasets were finally used to test the model. The performance of the new method was evaluated via visual inspection, root-mean-square error (RMSE) measurements and VOI-based accuracy analysis using linear regression and Person's correlation coefficients (PCC). Compared to directly using the cavernous sinus BIF directly for parameter imaging, the new method achieves higher accuracy in parametric analysis, including the generation of Patlak plots closer to the standard plots, better visual effects and lower RMSE values in the Ki (P = 0.0012) and V (P = 0.0042) images. VOI-based analysis shows regression lines with slopes closer to 1 (P = 0.0019 for Ki ) and smaller intercepts (P = 0.0085 for V). The proposed method is capable of achieving accurate brain pharmacokinetic parametric imaging using cavernous sinus BIF with short-axis PET scan. This may facilitate the application of this imaging technology in the clinical diagnosis of brain diseases.

Polysaccharides from Ostrea rivularis alleviate type II diabetes induced-retinopathy and VGEF165-induced angiogenesis via PI3K/AKT signaling pathway.

The purpose of this study was to investigate the role of polysaccharides from Ostrea rivularis Gloud (ORPs) in the progression of diabetic retinopathy (DR) and its anti-angiogenic effect on endothelial cell. Transgenic db/db mice with DR model were used to evaluate the protective effect of ORPs on retinal damage. It was found that ORPs could down-regulated levels of random blood glucose and fasting insulin, and further ameliorate retinal structure abnormalities as well as vascular network structure. Moreover, ORPs could reduce the expression of VEGF in retinal tissue and lessen pathological angiogenesis, thus slowing the progression of DR. In vitro, the proliferation, migration and tube formation of VGEF165-induced EA.hy926 cells were inhibited with ORPs administration. Furthermore, the expression of related proteins in the PI3K/AKT pathway and angiogenesis related factors were improved after ORPs intervention. Overall, these findings suggested that ORPs could effectively control the development of DR, and inhibit VGEF165-induced EA.hy926 cells proliferation, migration and tube formation, which effects might work through blocking the activation of PI3K/AKT signaling pathway.

Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout.

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

Advantage effect of Dalbergia pinnata on wound healing and scar formation of burns.

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia pinnata, as a natural and ethnic medicine in China, has been used for burns and wounds with a long history, which has the effect of invigorating blood and astringent sores. However, there were no reports on the advantage activity of burns. AIM OF STUDY: The purpose of this study was to screen out the best active extract part of Dalbergia pinnata and investigate its therapeutic effect on wound healing and scar resolution. MATERIALS AND METHODS: Rat burn model was established and the healing effects of extracts from Dalbergia pinnata on burn wounds were evaluated by the percentage of wound contraction and period of epithelialization. Histological observation, immunohistochemistry, immunofluorescence and ELISA were used for the examination of inflammatory factors, TGF-ß1, neovascularization and collagen fibers through the period of epithelialization. In addition, the effect of the optimal extraction site on fibroblast cells was evaluated by cell proliferation and cell migration assays. The extracts of Dalbergia pinnata were analyzed by UPLC-Q/TOF-MS or GC-MS technique. RESULTS: Compared to the model group, there were better wound healing, suppressed inflammatory factors, more neovascularization as well as newly formed collagen in the ethyl acetate extract (EAE) and petroleum ether extract (PEE) treatment groups. The ratio of Collagen I and Collagen III was lower in the EAE and PEE treatment groups, suggesting a potential for reduced scarring. Furthermore, EAE and PEE could repair wounds by up-regulating TGF-ß1 in the early stage of wound repair and down-regulating TGF-ß1 in the late stage. In vitro studies showed that both EAE and PEE were able to promote NIH/3T3 cells proliferation and migration compared with the control group. CONCLUSIONS: In this study, EAE and PEE were found to significantly accelerate wound repair and might have an inhibitory effect on the generation of scars. It was also hypothesized that the mechanism might be related to the regulation of TGF-ß1 secretion. This study provided an experimental basis for the development of topical drugs for the treatment of burns with Dalbergia pinnata.

Polysaccharides from Ostrea rivularis rebuild the balance of gut microbiota to ameliorate non-alcoholic fatty liver disease in ApoE-/- mice.

The purpose of this study was to investigate the preventive effects of polysaccharide from Ostrea rivularis (ORP) on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in mice and the underlying mechanism. The results showed that NAFLD model group mice had significant fatty liver lesions. ORP could significantly reduce TC, TG and LDL level, and increase HDL level in serum of HFD mice. Besides, it could also reduce the contents of serum AST and ALT and alleviate pathological changes of fatty liver disease. ORP could also enhance the intestinal barrier function. 16sRNA analysis showed that ORP could reduce the abundance of Firmicutes and Proteobacteria and the ratio of Firmicutes/ Bacteroidetes at the phylum level. These results suggested that ORP could regulate the composition of gut microbiota in NAFLD mice, enhance intestinal barrier function, reduce intestinal permeability, and finally delay the progress and reduce the occurrence of NAFLD. In brief, ORP is an ideal polysaccharide for prevention and treatment of NAFLD, which can be developed as functional food or candidate drugs.

DDTC-Cu(I) based metal-organic framework (MOF) for targeted melanoma therapy by inducing SLC7A11/GPX4-mediated ferroptosis.

Disulfiram (DSF), a drug for alcohol withdrawal, has attracted extensive scientific attention due to its potential to treat cancer. The metabolite of DSF, diethyl dithiocarbamate (DDTC), forms a Cu-DDTC complex in vivo with copper ions, which has been shown to be a proteasome inhibitor with high antitumor activity. However, the in vivo stability of Cu-DDTC complexes remains a challenge. In this study, the nanomedicine Cu-BTC@DDTC with high antitumor activity was prepared by using the nanoscale metal-organic framework (MOF) Cu-BTC as a carrier and loading diethyldithiocarbamate (DDTC) through coordination interaction. The results showed that Cu-BTC@DDTC had high drug loading and adequate stability, and exhibited DDTC-Cu(I) chemical valence characteristics and polycrystalline structure features. In vitro cytocompatibility investigation and animal xenograft tumor model evaluation demonstrated the anti-cancer potential of Cu-BTC@DDTC, especially the combination of Cu-BTC@DDTC with low-dose cisplatin showed significant antitumor effect and biosafety. This study provides a feasible protocol for developing antitumor drugs based on the drug repurposing strategy.

Biomimetic modification on the microporous surface of cardiovascular materials to accelerate endothelialization and regulate intimal regeneration.

Vascular stents are widely used in the clinical treatment of coronary heart disease, but the long-term safety still needs to be improved. Surface biological functional modification is an effective way to improve the biocompatibility and clinical performance of cardiovascular materials, but how to achieve long-term effective and precise regulation of in situ vascular intimal repair through the reasonable construction of the surface physical and chemical structure is still an important task in the current surface modification research. In this study, ECM-derived components, including laminin, heparin, and SDF-1, were incorporated into the titanium surface with a microporous structure. It was found that the modified surface could effectively control the continuous release of biomolecules. In vitro biocompatibility evaluation results showed that the constructed functional layer could effectively inhibit the activation of platelet adhesion and excessive proliferation of smooth muscle cells. In addition, the modified surface also showed the potential to induce rapid regeneration of vascular endothelium. In vivo animal tests further proved that the modified sample may contribute to inhibiting vascular intimal hyperplasia. This study provided a new approach for the surface biological function modification of Ti-based vascular stents.

Protective effect of polysaccharides from Ostrea rivularis against reproductive injury via regulating autophagy induced by oxidative stress.

The objective of this study was to investigate the effect of polysaccharides from Ostrea rivularis (ORP) relieving reproductive damage by regulating autophagy. The results showed that ORP intervention could alleviate the pathological changes of the testis and alleviate oxidative stress which were caused by cyclophosphamide (CTX) in vivo, including improve sperm symptoms and rise testosterone level. Reduced level of autophagy after ORP intervention was observed by transmission electron microscopy (TEM), which implied that ORP might regulate cell autophagy. In vitro experiments showed that ORP could alleviate the damage of TM4 cells induced by H2O2, reduce the level of intracellular ROS and the content of MDA. Autophagy-related protein expressions of p62, LC3, Beclin-1 before and after 3-MA inhibitor intervention were also proved that ORP could regulate autophagy. Overall, these results confirmed that ORP could reduce reproductive damage related to autophagy.

Correction: Fucoidans from Cucumaria frondosa ameliorate renal interstitial fibrosis via inhibition of the PI3K/Akt/NF-κB signaling pathway.

Correction for 'Fucoidans from Cucumaria frondosa ameliorate renal interstitial fibrosis via inhibition of the PI3K/Akt/NF-κB signaling pathway' by Zhuoyue Song et al., Food Funct., 2022, 13, 1168-1179, DOI: 10.1039/D1FO03067A.

Exploiting the Twisted Intramolecular Charge Transfer Effect to Construct a Wash-Free Solvatochromic Fluorescent Lipid Droplet Probe for Fatty Liver Disease Diagnosis.

The prominent pathological feature of fatty liver disease lesions is excessive fat accumulation in lipid droplets in hepatocytes. Thus, developing fluorescent lipid droplet-specific probes with high permeability and a high imaging contrast provides a robust tool for diagnosing fatty liver diseases. Herein, we rationally developed a novel donor-acceptor lipophilic fluorescent probe ANI with high photostability for wash-free visualization of lipid droplets and fatty liver disease characteristics. ANI showed a typical twisted intramolecular charge transfer effect with very faint fluorescence in high-polar solvents, but dramatically boosted emissions in low-polar environments. The solvatochromic probe can selectively light up lipid droplets with a high contrast in a wash-free manner. Further use of ANI to reveal the excessive accumulation of lipid droplets with a significantly large size in the liver tissues from the fatty liver disease model mice was successfully demonstrated. The remarkable imaging performances rendered ANI an alternative tool for accurately evaluating fatty liver disease in intraoperative diagnosis.

Fucoidans from Cucumaria frondosa ameliorate renal interstitial fibrosis via inhibition of the PI3K/Akt/NF-κB signaling pathway.

The effects of Cucumaria frondosa polysaccharides (CFPs) on renal interstitial fibrosis by regulating the phosphatidylinositol-3-hydroxykinase/protein kinase-B/nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. The common unilateral urethral obstruction (UUO) model was used to examine the renoprotective effect and its mechanism in vivo. Compared to the UUO group, CFP administration could ameliorate renal function, inhibit inflammation and fibrosis, and reduce the deposition of the extracellular matrix and epithelial-mesenchymal transition. Mechanistic results indicated that CFPs could inhibit the expression of the total protein of PI3K and the conversion of the AKT and NF-κB p65 phosphorylated proteins, thereby inhibiting the transduction of the PI3K/AKT/NF-κB pathway. In addition, CFP treatment could improve inflammation and fibrosis in HK-2 cells induced by TGF-ß1, and its in vitro mechanism was also verified to inhibit the PI3K/Akt/NF-κB signaling pathway. Overall, these results showed that CFP could alleviate renal interstitial fibrosis related to the PI3K/AKT/NF-κB signaling pathway.

Progress on Precise Regulation of Vascular Intimal Repair by a Surface Coating of Vascular Stent.

In the past few decades, drug-eluting stents have made significant contributions to the treatment of coronary heart disease. However, due to the delayed healing of endothelial injuries caused by antiproliferative drugs and insufficient biocompatibility of vascular stent materials, late in-stent thrombosis and restenosis remain major challenges. Surface modification of cardiovascular materials to construct a biological functional layer that can regulate the behavior of blood and vascular cells is an effective way to improve the clinical performance of vascular stents. This paper reviewed the common methods of surface bio-functional modification of cardiovascular materials and especially proposed that take advantage of the new concept of precision medicine, as well as the precise and orderly regulation properties of cardiovascular disease-related gene fragments on vascular biological response behavior, the construction of gene-eluting stents which can in-situ regulate vascular intimal repair at the molecular and genetic level will become an important research direction in the future.

Consumers' attention on identification, nutritional compounds, and safety in heavy metals of Canadian sea cucumber in Chinese food market.

BACKGROUND: Based on the consumers' attention issues of sea cucumbers, we aimed to complete comprehensive information of commercial Canadian sea cucumbers (CCSC), which sprang up extensively in Chinese food market. RESULTS: CCSC were identified as Cucumaria frondosa and characterized based on the characteristics, nutritional compositions, and heavy metals. The abdomen and five internal tendons of Cucumaria frondosa were special orange. The average of soaking degree and water content, which consumers paid great attention to, was 2.8 ± 0.3 and 0.46 ± 0.09%, respectively. Proteins (56.4 ± 9.1%) and polysaccharides (12.2 ± 14.7%) were the principal nutrient component. In addition, there was a variety of free amino acids, in which arginine (70.1 ± 50.0 mg/100 g), glutamate (42.6 ± 23.9 mg/100 g), and alanine (32.2 ± 21.0 mg/100 g) were the main components. Phosphorus (P, 0.26 ± 0.05%), magnesium (Mg, 0.19 ± 0.07%), and kalium (K, 0.17 ± 0.08%) were the major mineral elements. Amount of heavy metal was within the safety limitation (5.5 ± 1.4 mg/kg). Furthermore, the active ingredients were positively correlated with size. CONCLUSION: The overall findings enriched the information of Cucumaria frondosa for consumers and suggested that the quality of Cucumaria frondosa was varied following commercial classification and size.

Extraction, purification and characterization of sulphated polysaccharide from Bellamya quadrata and its stabilization roles on atherosclerotic plaque.

The aim of this paper was to investigate the extraction, purification and characterization of sulphated polysaccharide (BQPS) from Bellamya quadrata and its stabilization roles on atherosclerotic plaque. Firstly, crude polysaccharide (CBQP) from Bellamya quadrata was extracted by protease enzyme assisted extraction. Moreover, its optimal parameters were obtained by the response surface method as follows: the ratio of water to raw material of 24:1, enzyme dosage of 285 U/g, enzymolysis pH value of 4.7 and temperature of 67 °C. Secondly, CBQP was further purified to obtain the target polysaccharide BQPS by Q Sepharose Fast Flow and Sephacryl S-400 gel column chromatography. Then, the characterization of BQPS revealed that it possessed a total polysaccharide content of 91.88 ± 1.23%, sulfuric acid group content of 9.12 ± 1.59% and molecular weight of 91.1 kDa. BQPS was only consisted of glucose without any proteins. Finally, BQPS was confirmed to have a significant stabilizing effect on atherosclerotic plaque and its mechanism was related to the selective promotion of autophagy with the precisely right strength.

Methods of extraction, separation, purification, structural characterization for polysaccharides from aquatic animals and their major pharmacological activities.

The further development of fishery resources is a hotspot in the development of the fishery industry. However, how to develop aquatic animal resources deeply is a key point to be solved in the fishery industry. Over the past decades, numerous aquatic animals have gained great attention in the development and utilization of their bioactive molecules which are of therapeutic applications as nutraceuticals and pharmaceuticals. Recent research revealed that aquatic animals are composed of many vital moieties, such as polysaccharides and proteins, which provide health benefits beyond basic nutrition. In particular, aquatic animal polysaccharides are gaining worldwide popularity owing to their high content, ease of extraction, specific structure, few side effects, prominent therapeutic potential and incorporation in functional foods and dietary supplements. Thus, tremendous research on the isolation, identification and bioactivities of polysaccharides has been carried out. This review presents comprehensive viewpoints on extraction, separation, purification, structural characterization and bioactivity of various polysaccharides from aquatic animals, such as sea cucumber, abalone, oyster and mussels. In addition, this review profiled a brief knowledge on both current challenges and future scope in aquatic animal polysaccharides field. The review will be a direction of deep processing in fishery resources, which is a hotspot, but technical bottleneck. Furthermore, the review could be served as a useful reference material for further investigation, production and application of polysaccharides from aquatic animals in functional foods and therapeutic agents.

Sulfated polysaccharide from Undaria pinnatifida stabilizes the atherosclerotic plaque via enhancing the dominance of the stabilizing components.

The purpose of this study was to investigate the stable effect and mechanism of sulfated polysaccharide from Undaria pinnatifida (SPUP) on atherosclerotic plaque. The results showed that atherosclerotic plaques in the ApoE-/- mice of high-fat diet model group increased significantly without drug intervention. The content of vulnerable components (lipid, inflammatory macrophage) increased significantly, and the content of stability components (smooth muscle cell, collagen) reduced significantly. However, it could find that atherosclerotic plaque areas were decreased in a dose-dependent manner after SPUP intervention. SPUP could enhance the dominance of the stability components in plaque, and reduce the content of vulnerable component. Furthermore, SPUP could significantly reduce the matrix metalloprotein-9 content in atherosclerotic plaque. These results suggested that SPUP could stabilize atherosclerotic plaque by enhancing the dominance of the stability components content, reducing the vulnerability components content, and lowering the vulnerability index value.

An effective and recyclable deproteinization method for polysaccharide from oyster by magnetic chitosan microspheres.

The aim of this study was to synthesize magnetic chitosan microspheres (MCM) for the deproteinization of crude polysaccharides from Ostrea rivularis Gould (ORP), and evaluate their adsorption properties. Firstly, MCM were synthesized by microemulsion process. Then they were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and vibrating-sample magnetometer (VSM). At last, MCM was applied as a magnetic separable adsorbent for deproteinization of ORP. The results showed that MCM had smooth surface with particle diameter of 2-6 µm. The adsorption kinetics and adsorption isotherms were well fitted by the pseudo-second order equation and the Freundlich equation, respectively. Comparing with the Sevag method, MCM exhibited higher deproteinization ratio, higher polysaccharides recovery, and miner pollution. In addition, the deprotenaization capacity can be regenerated. Therefore, MCM would be used as promising adsorbents for the deproteinization of polysaccharides.

Two heteropolysaccharides from Isaria cicadae Miquel differ in composition and potentially immunomodulatory activity.

Two novel heteropolysaccharides (JCH-1 and JCH-2) with molecular weights of 30.9 and 555.3 kDa were first extracted, isolated and purified from Isaria cicadae Miquel (I. Miquel). Monosaccharide analysis showed that JCH-1 and JCH-2 were composed of mannose, glucose and galactose with different monosaccharide ratio. In addition, JCH-1 had higher contents of sulfated and uronic acid compared to JCH-2. Based on MTT assay, JCH-1 and JCH-2 could markedly promote the proliferation of RAW264.7 cells and exhibit no cytotoxicity at a specific concentration range. The immunomodulatory assay exhibited that JCH-1 and JCH-2 could significantly enhance the viability of macrophage cells, and promote the release of NO, IL-6 and TNF-α. Furthermore, the immunomodulatory activity of JCH-1 was significantly better than that of JCH-2. These results proposed that I. Miquel had two polysaccharide fractions with different composition and JCH-1 is better to be developed as a functional food with the better immunomodulator activity.