MATERIALS & DESIGN
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2022
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IF 9.417
Zhenyu Yang,Xueqiao Yu,Pengfei Wei,Yiqian Huang,Shuai Zhou,Wei Jing,Yan Zhang,Liya Sun,Guoqiang Bao,Xianli He,Bo Zhao
Pancreatic leakage is severe and life-threatening when happening pancreatitis or conducting pancreatectomy on patients, which easily induces bleeding, infection and even death. Commercial tissue adhesives cannot meet the demands for pancreatic leakage sealing due to the weak adhesiveness, potential toxicity and inability to degrade. Few reports have been feasibly paid attention to pancreas sealants due to the complicated conditions such as enzymatic microenvironments, mechanical dynamics and pre-infections. Herein, we prepared a rapid high-adhesion, antibacterial, biodegradable and injectable bioadhesive based on the FDA-approved polyethylene glycol to seal the pancreatic leakage for clinical translations and commercial applications. The tetra-armed poly(ethylene glycol) succinimidyl glutarate (PEG-SG), tetra-armed poly(ethylene glycol) amine (PEG-NH 2 ) and tannic acid (TA) were integrated to rapidly form the adhesive hydrogel (gelling time < 5 seconds) for convenient operations, while this bioadhesive achieved tough tissue adhesion (∼ 30 kPa), robust antibacterial activity (∼ 95% efficiency) and biocompatibility, revealing the excellent performances for pancreatic wound closure. In the established pre-clinical pancreatectomy using Bama miniature pig model, the bioadhesive presented efficient outcomes on pancreatic leakage, and this indicated the promising feasibility of the bioadhesive for clinical trials and translations.
研究领域:
生物医学工程
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材料科学
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外科手术
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药理学
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DOI
高影响因子
Animals
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2024
·Vol. 14
·期 7
·999
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IF 2.7
Xiangyun Zhai,Liping Dang,Shiyu Wang,Wenyuan Li,Chao Sun
Simple SummarySuccinate is an important product of the fermentative metabolism of dietary fiber, and similar to propionate, high levels of succinate in the gut modulate the body’s inflammatory response, glucose tolerance, and lipid metabolism. Our study showed that the addition of 1% succinate to pig diets promoted growth and fat deposition capacity without affecting feed intake, remodeled the fatty acid content of the longissimus dorsi muscle, and consequently improved meat quality. Further, we isolated and cultured primary porcine preadipocytes. The results showed that succinate increased the expression of genes related to adipogenic differentiation while decreasing the levels of genes related to lipolysis and promoting the formation of cellular lipid droplets. Mechanistically, dietary supplementation with succinate increases succinylation modification in adipose tissue to promote facilitated lipogenesis. This suggests that it is feasible and important to improve fatty acids and meat quality in porcine muscle through dietary succinate supplementation.AbstractSuccinate, one of the intermediates of the tricarboxylic acid cycle, is now recognized to play a role in a broad range of physiological and pathophysiological settings, but its role in adipogenesis is unclear. Our study used Bama miniature pigs as a model to explore the effects of succinate on performance, meat quality, and fat formation. The results showed that adding 1% succinate significantly increased the average daily gain, feed/gain ratio, eye muscle area, and body fat content (p< 0.05), but had no effect on feed intake. Further meat quality analysis showed that succinate increased the marbling score and intramuscular fat content of longissimus dorsi muscle (LM), while decreasing the shear force and the cross-sectional area of LM (p< 0.05). Metabolomics analysis of LM revealed that succinate reshaped levels of fatty acids, triglycerides, glycerophospholipids, and sphingolipids in LM. Succinate promotes adipogenic differentiation in porcine primary preadipocytes. Finally, dietary succinate supplementation increased succinylation modification rather than acetylation modification in the adipose tissue pool. This study elucidated the effects of succinate on the growth and meat quality of pigs and its mechanism of action and provided a reference for the role of succinate in the nutrition and metabolism of pigs.
研究领域:
动物营养
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代谢
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分子生物学
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食品科学
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产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
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2023
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IF 28.1
Zhang Juan,Wei Xiangqian,Liu Wei,Wang Yanfang,Kahkoska Anna R.,Zhou Xianchi,Zheng Huimin,Zhang Wentao,Sheng Tao,Zhang Yang,Liu Yun,Ji Kangfan,Xu Yichen,Zhang Peng,Xu Jianchang,Buse John. B.,Wang Jinqiang,Gu Zhen
Glucose-responsive formulations of insulin can increase its therapeutic index and reduce the burden of its administration. However, it has been difficult to develop single-dosage formulations that can release insulin in both a sustained and glucose-responsive manner. Here we report the development of a subcutaneously injected glucose-responsive formulation that nearly does not trigger the formation of a fibrous capsule and that leads to week-long normoglycaemia and negligible hypoglycaemia in mice and minipigs with type 1 diabetes. The formulation consists of gluconic acid-modified recombinant human insulin binding tightly to poly- l -lysine modified by 4-carboxy-3-fluorophenylboronic acid via glucose-responsive phenylboronic acid–diol complexation and electrostatic attraction. When the insulin complex is exposed to high glucose concentrations, the phenylboronic acid moieties of the polymers bind rapidly to glucose, breaking the complexation and reducing the polymers’ positive charge density, which promotes the release of insulin. The therapeutic performance of this long-acting single-dose formulation supports its further evaluation and clinical translational studies.
研究领域:
药理学
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糖尿病研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
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2024
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IF 5.7
Lin Hongbing,Liu Jinbin,Hou Yulin,Yu Zhiyan,Hong Juan,Yu Jianghong,Chen Yu,Hu Jingwen,Xia Dengning
Transdermal delivery of peptide drugs is almost impossible with conventional penetration enhancers because of epidermal barrier function. Microneedle (MN) patches can bypass the epidermal barrier and have been developed for trans- and intradermal delivery of peptide drugs and vaccines. However, dissolving MN patches are limited by low drug loading capacities due to their small size and admixture of drug and water-soluble excipients. Furthermore, few in vivo pharmacokinetic studies, especially in large animals such as pigs, have been performed to assess post-application systemic drug exposure. Here, we developed a dissolving MN patch with pure liraglutide at the needle tips. The MN patch could load up to 2.21 ± 0.14 mg of liraglutide in a patch size of 0.9 cm 2 , which was nearly two orders of magnitude higher than that obtained with conventional MN patches of the same size. Raman imaging confirmed that liraglutide was localized at the MN tips. The MN had sufficient mechanical strength to penetrate the epidermis and could deliver up to 0.93 ± 0.04 mg of liraglutide into skin with a dosing variability of less than 6.8%. The MN patch delivery enabled faster absorption of liraglutide than that provided by subcutaneous (S.C.) injection, and achieved relative bioavailability of 69.8% and 46.3% compared to S.C. injection in rats and minipigs, respectively. The MN patch also exhibited similar patterns of anti-hyperglycemic effect in diabetic rats and individual variability in pharmacokinetic parameters as S.C. injection. The liraglutide MN application was well tolerated; no skin irritation was observed in minipigs except for mild erythema occurring within 4 h after once daily administration for 7 days at the same site. Our preclinical study suggests that MN patch with pure drug needle tips might offer a safe and effective alternative to S.C. injection for administration of liraglutide. Graphical abstract
研究领域:
药学
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药物递送系统
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药代动力学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Mengmeng Feng,Yize Li,Yanfei Jiang,Chunyue Zhao
There has been a growing interest in hydroxytyrosol (HT) due to its powerful antioxidant and free-radical scavenging properties when added to formulations such as pharmaceuticals and cosmetics. To study the stability and transdermal properties of hydrogels and creams (HT-based formulations), a high-performance liquid chromatography method was developed for determining HT. In the Franz diffusion cell system, both hydrogel and cream show a rapid and similar penetration profile through the Bama miniature pig skin. However, the Strat-M® membrane exhibits slightly lower permeability and is selective to different formulations; that is, the cream has a permeability value of 10.69%, while the hydrogel has a value of 5.27%. The dynamics parameters from the permeation assays indicate that the model using the Strat-M® membrane can be used as a screening tool to evaluate the skin uptake and permeation efficacy of different formulations. Adding 3- O -ethyl-L-ascorbic acid to HT-based formulations can effectively prevent discoloration under prolonged high-temperature storage, while combining multiple antioxidants delays degradation most effectively. This study provides novel ideas for functional formulation optimization to enhance the realism and reproducibility of cosmetic products containing HT and provides scientific evidence for the production, packaging, shelf life, storage, and transportation of products.
研究领域:
药学
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化妆品科学
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分析化学
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制剂科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
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2025
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IF 26.8
Yajun Shuai,Tao Yang,Meidan Zheng,Li Zheng,Jie Wang,Chuanbin Mao,Mingying Yang
Assembling natural proteins into large, strong, bone-mimetic scaffolds for repairing bone defects in large-animal load-bearing sites remain elusive. Here this challenge is tackled by assembling pure silk fibroin (SF) into 3D scaffolds with cortical-bone-like lamellae, superior strength, and biodegradability through freeze-casting. The unique lamellae promote the attachment, migration, and proliferation of tissue-regenerative cells (e.g., mesenchymal stem cells [MSCs] and human umbilical vein endothelial cells) around them, and are capable of developing in vitro into cortical-bone organoids with a high number of MSC-derived osteoblasts. High-SF-content lamellar scaffolds, regardless of MSC inoculation, regenerated more bone than non-lamellar or low-SF-content lamellar scaffolds. They accelerated neovascularization by transforming macrophages from M1 to M2 phenotype, promoting bone regeneration to repair large segmental bone defects (LSBD) in minipigs within three months, even without growth factor supplements. The bone regeneration can be further enhanced by controlling the orientation of the lamella to be parallel to the long axis of bone during implantation. This work demonstrates the power of oriented lamellar bone-like protein scaffolds in repairing LSBD in large animal models.
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2019
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IF 3.845
Zhang Wei-jian,Su Wei-wei,Li Pei-bo,Rao Hong-yu,Lin Qing-wei,Zeng Xuan,Chen Tao-bin,Yan Zeng-hao,Liu Hong,Yao Hong-liang
Naoxintong capsule (NXT), a Chinese medicine, has performed excellent effects on the prevention and treatment against cardiovascular diseases. NXT is a fine powder mixture without any herb extraction, and there must be lots of ingredients hard to be absorbed. However, little is known about the correlation between the NXT’s cardioprotective effects and gut microbiota. Herein, we report the effect of NXT on the development of cardiovascular diseases and clarify the correlation between NXT’s cardioprotective effects and gut microbiota. In the current study, minipigs were selected and fed with high-fat diet and NXT daily for successive 8 months. During the process, up to 18 biomedical parameters were monthly determined to observe the dynamic changes after NXT treatment. At the end of experimental process, pathological examinations of heart, coronary artery, carotid artery, thoracic aorta, and abdominal aorta were conducted by HE staining and 16SrDNA sequencing, and analyzing of gut microbiota were conducted. Our results showed that NXT’s effects against cardiovascular diseases were through regulating blood lipid profiles, inhibiting vascular inflammation, enhancing antioxidant capacity, and alleviating myocardial injury, without damages on liver and kidney particularly. Concurrently, we also found that long-term administration of NXT increased the diversity of gut microbiota, influenced the microbiome structure and composition stably, and revered the increase of the ratio of the Firmicutes to Bacteroidetes (F/B ratio) in relative abundance. Specifically, our results revealed some key bacterium of Caproiciproducens (enhanced), Sutterella (enhanced), Erysipelotrichaceae (enhanced), and Romboutsia (decreased) that were closely involved in NXT’s effects. Taken together, our study demonstrates that NXT can inhibit the development of cardiovascular diseases by ameliorating high-fat diet–induced metabolic disorders and partly through improving gut microbiota.
研究领域:
心血管医学
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微生物学
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药理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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