XENOBIOTICA
·
2024
·
IF 1.3
Li Shao,Jiajia Mo,Qinlong Xu,Guangwei He,Chunyu Xing,Zhaoxing Chu
HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC–MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1–7.6% after transdermal application of 1–4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.
研究领域:
药理学
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皮肤病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Trauma and Acute Care Surgery
·
2023
·Vol. 94
·期 4
·608
·
IF 3.4
Wang Wei,Han Peng,Yang Lei,Meng Zhiyun,Gan Hui,Wu Zhuona,Zhu Xiaoxia,Sun Wenzhong,Gu Ruolan,Dou Guifang
BACKGROUND Control of massive hemorrhage from penetrating wound sites is difficult in both combat and civilian settings. A new hemostatic dressing, sodium polyacrylate (PAAs)–based bag (PB), based on PAAs is designed for the first aid of massive penetrating hemorrhage. This study aimed to investigate the efficacy of PB in a penetrating trauma model in swine. METHODS A complex groin penetrating injury was produced in swine by completely excising the femoral vessels and surrounding muscles. After 15-second free bleeding, 18 healthy Guizhou female swine were administered PB (n = 6), CELOX-A (n = 6; Medtrade Products, Crewe, United Kingdom), or standard gauze (n = 6) for hemostatic intervention, followed by 3-minute compression if the bleeding persisted, with subsequent observation continuing for 1 hour. The primary outcomes included initial hemostasis, the incidence of applying manual pressure, and application time. RESULTS Sodium polyacrylate could rapidly absorb the liquid to expand, crosslink with a large number of red blood cells, induce cellular morphological alteration, and promote blood coagulation. Sodium polyacrylate–based bag and CELOX-A initiated and sustained hemostasis for 60 minutes, whereas 0% of the standard gauze achieved initial hemostasis. Maximum number of manual compressions were applied in standard gauze (6 of 6 [100%]), followed by CELOX-A (5 of 6 [80%]), while no manual pressure was required in the case of PB (0 of 6 [0%]). Application time for PB (19.0 ± 4.6 seconds) was significantly less than CELOX-A (169.0 ± 73.5 seconds) and standard gauze (187.8 ± 1.7 seconds). CONCLUSION We prepared a type of superabsorbent PAAs and made an original hemostatic dressing, PB. It can rapidly achieve durable hemostasis in the groin-penetrating trauma hemorrhage swine model without any external compression. The packet form makes PB easy to deploy and remove from wounds. Therefore, PB could be a promising hemostatic candidate for controlling penetrating hemorrhage. Export We designed and prepared an original sodium polyacrylate (PAAs)-based stasis dressing, PB, for the first aid of massive penetrating hemorrhage. It allows durable hemostasis in the groin-penetrating trauma hemorrhage swine model without any external compression.
研究领域:
医学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Wang Yue,Zhang Ziting,Du Min,Ji Xu,Liu Xiaodan,Zhao Chunfang,Pang Xunsheng,Jin Erhui,Wen Aiyou,Li Shenghe,Zhang Feng
Introduction: Enterotoxigenic Escherichia coli (ETEC) is the main diarrhea-causing pathogen in children and young animals and has become a global health concern. Berberine is a type of “medicine and food homology” and has a long history of use in China, particularly in treating gastrointestinal disorders and bacterial diarrhea.Methods: In this study, we explored the effects of berberine on growth performance, intestinal inflammation, oxidative damage, and intestinal microbiota in a weaned piglet model of ETEC infection. Twenty-four piglets were randomly divided into four groups—a control group (fed a basal diet [BD] and infused with saline), a BD+ETEC group (fed a basal diet and infused with ETEC), a LB+ETEC group (fed a basal diet with 0.05% berberine and infused with ETEC infection), and a HB+ETEC group (fed a basal diet with 0.1% berberine and infused with ETEC).Results: Berberine significantly improved the final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) (P<0.05) of piglets, and effectively decreased the incidence of diarrhea among the animals (P<0.05). Additionally, berberine significantly downregulated the expression levels of the genes encoding TNF-α, IL-1β, IL-6, IL-8, TLR4, MyD88, NF-κB, IKKα, and IKKβ in the small intestine of piglets (P<0.05). ETEC infection significantly upregulated the expression of genes coding for Nrf2, CAT, SOD1, GPX1, GST, NQO1, HO-1, GCLC, and GCLM in the small intestine of the animals (P<0.05). Berberine significantly upregulated 12 functional COG categories and 7 KEGG signaling pathways. A correlation analysis showed that berberine significantly increased the relative abundance of beneficial bacteria (Gemmiger, Pediococcus, Levilactobacillus, Clostridium, Lactiplantibacillus, Weissella, Enterococcus, Blautia, and Butyricicoccus) and decreased that of pathogenic bacteria (Prevotella, Streptococcus, Parabacteroides, Flavonifractor, Alloprevotella) known to be closely related to intestinal inflammation and oxidative stress in piglets. In conclusion, ETEC infection disrupted the intestinal microbiota in weaned piglets, upregulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, and consequently leading to intestinal inflammation and oxidative stress-induced damage.Discussion: Our data indicated that berberine can optimize intestinal microbiota balance and modulate the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, thus helping to alleviate intestinal inflammation and oxidative damage caused by ETEC infection in weaned piglets.
研究领域:
兽医学
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微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC BIOTECHNOLOGY
·
2023
·Vol. 23
·期 1
·1-9
·
IF 3.5
Jiang Huiming,Lu Jun,Li Jiawei,Liu Zizheng,Chen Fufei,Wu Rui,Xu Xingquan,Liu Yuan,Jiang Yiqiu,Shi Dongquan
Background Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. Methods Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25–40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (micro-CT), and histologic and immunohistochemistry tests. Results At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. Conclusions ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.
研究领域:
骨科
·
组织工程
·
再生医学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
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
·
药理学
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 8
·2924-2934
·
IF 6.6
Zhaoyi Wang,Wangbei Cao,Fanghui Wu,Xiurong Ke,Xinyu Wu,Tong Zhou,Jun Yang,Guojing Yang,Cheng Zhong,Zhongru Gou,Changyou Gao
Osteochondral tissue involves cartilage, calcified cartilage and subchondral bone. These tissues differ significantly in chemical compositions, structures, mechanical properties and cellular compositions. Therefore, the repairing materials face different osteochondral tissue regeneration needs and rates. In this study, we fabricated an osteochondral tissue-inspired triphasic material, which was composed of a poly(lactide-co-glycolide) (PLGA) scaffold loaded with fibrin hydrogel, bone marrow stromal cells (BMSCs) and transforming growth factor-β1 (TGF-β1) for cartilage tissue, a bilayer poly(L-lactide-co-caprolactone) (PLCL)-fibrous membrane loaded with chondroitin sulfate and bioactive glass, respectively, for calcified cartilage, and a 3D-printed calcium silicate ceramic scaffold for subchondral bone. The triphasic scaffold was press-fitted into the osteochondral defects in rabbit (cylindrical defects with a diameter of 4 mm and a depth of 4 mm) and minipig knee joints (cylindrical defects with a diameter of 10 mm and a depth of 6 mm). The μ-CT and histological analysis showed that the triphasic scaffold was partly degraded, and significantly promoted the regeneration of hyaline cartilage after they were implanted in vivo. The superficial cartilage showed good recovery and uniformity. The calcified cartilage layer (CCL) fibrous membrane was in favor of a better cartilage regeneration morphology, a continuous cartilage structure and less fibrocartilage tissue formation. The bone tissue grew into the material, while the CCL membrane limited bone overgrowth. The newly generated osteochondral tissues were well integrated with the surrounding tissues too.
研究领域:
组织工程学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Wei Wei,Yuanzhu Ma,Xianzhu Zhang,Wenyan Zhou,Hongwei Wu,Jingwei Zhang,Junxin Lin,Chenqi Tang,Youguo Liao,Chenglin Li,Xiaozhao Wang,Xudong Yao,Yi Wen Koh,Wenwen Huang,Hongwei Ouyang
Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.
研究领域:
组织工程
·
骨科
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
·
2023
·Vol. 120
·期 6
·e2219024120
·
IF 11.1
Yuanbo Jia,Jinteng Feng,Zhe Feng,Jingyi Liu,Yanshen Yang,Xiaokang Li,Meng Lei,Hui Guo,Zhao Wei,Yi Lv,Feng Xu
Postoperative adhesions occur widely in various tissues, bringing the risk of secondary surgery and increased medical burden. Hydrogel barriers with Janus-adhesive ability can achieve physical isolation of adjacent tissues and are therefore considered an ideal solution. However, integrating endoscopic delivery convenience and viscoelastic Janus hydrogel formation remains a great challenge. Here, we present a report of the in situ formation of Janus-adhesive hydrogel barrier using a sprayable fast-Janus-gelation (FJG) powder. We first methacrylate the polysaccharide macromolecules to break the intermolecular hydrogen bonds and impart the ability of rapid hydration. FJG powder can rapidly absorb interfacial water and crosslink through borate ester bonds, forming a toughly adhesive viscoelastic hydrogel. The Janus barrier can be simply formed by further hydrating the upper powder with cationic solution. We construct rat models to demonstrate the antiadhesions efficiency of viscoelastic FJG hydrogels in organs with different motion modalities (e.g., intestine, heart, liver). We also developed a low-cost delivery device with a standardized surgical procedure and further validated the feasibility and effectiveness of FJG powder in minimally invasive surgery using a preclinical translational porcine model. Considering the advantages in terms of therapeutic efficacy, clinical convenience, and commercialization, our results reveal the great potential of Janus-gelation powder materials as a next-generation antiadhesions barrier.
研究领域:
生物医学工程
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外科研究
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材料科学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 18
·2203236
·
IF 10
Guocheng Ding,Yangyang He,Yuanyuan Shi,Maihemuti Maimaitimin,Xin Zhang,Hongjie Huang,Wei Huang,Ran Yu,Jianquan Wang
Osteoarthritis is a serious disease affecting joint cartilage. Owing to poor blood supply, the meniscus and acetabular labrum of joints heal poorly after injury. However, the development of artificial alternatives to these components that have similar mechanical properties and cartilage-protection ability is challenging. In this study, a strong hydrogel with a biomimetic microstructure is prepared with an emulsion-type photosensitive resin, where both hydrophilic and hydrophobic monomers, photo-initiator, and drugs can be adopted. In this system, the hydrophobic monomer forms uniformly dispersed aggregates after curing, improving the mechanical properties of the hydrogel significantly. Furthermore, the coordination bonds between nontoxic Zr 4+ cations and sulfonic acid groups prevent hydrogel swelling. In addition, the water–oil biphasic hydrogel ink enables the loading of water- and lipid-soluble drugs, yielding hydrogel scaffolds with sustained dual-drug release ability. Crucially, hydrogel scaffolds having excellent mechanical properties, low swelling, and sustained biphasic drug release ability can be prepared using digital light processing 3D printing technology, owing to the high curing rate of the hydrophobic photo-initiator. These hydrogel scaffolds are applied as meniscal and labral replacements in a porcine model and show great promise for the prevention of secondary osteoarthritis, demonstrating the broad potential clinical applications of this material.
研究领域:
生物医学工程
·
组织工程
·
骨科
·
材料科学
·
3D打印
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2020
·Vol. 4
·期 9
·853-862
·
IF 18.952
Zheng Di-Wei,Pan Pei,Chen Ke-Wei,Fan Jin-Xuan,Li Chu-Xin,Cheng Han,Zhang Xian-Zheng
Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.
研究领域:
医学
·
生物技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-12
·
IF 14.7
Cui Zhanding,Liu Jinlong,Xie Chong,Wang Tao,Sun Pu,Wang Jinlong,Li Jiaoyang,Li Guoxiu,Qiu Jicheng,Zhang Ying,Li Dengliang,Sun Ying,Yin Juanbin,Li Kun,Zhao Zhixun,Yuan Hong,Bai Xingwen,Ma Xueqing,Li Pinghua,Fu Yuanfang,Bao Huifang,Li Dong,Zhang Qiang,Liu Zaixin,Cao Yimei,Zhang Jing,Lu Zengjun
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.
研究领域:
兽医学
·
分子生物学
·
药理学
·
病毒学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Military Medical Research
·
2023
·Vol. 10
·期 1
·1-15
·
IF 21.1
Xue Yao-Ting,Chen Ming-Yu,Cao Jia-Sheng,Wang Lei,Hu Jia-Hao,Li Si-Yang,Shen Ji-Liang,Li Xin-Ge,Zhang Kai-Hang,Hao Shu-Qiang,Juengpanich Sarun,Cheng Si-Bo,Wong Tuck-Whye,Yang Xu-Xu,Li Tie-Feng,Cai Xiu-Jun,Yang Wei
Background Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging.Methods This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery.Results ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface.Conclusion sACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.
研究领域:
生物医学工程
·
组织工程
·
外科材料
·
伤口愈合
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
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