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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2021 · IF 3.205

Quantitative analysis of n-3 polyunsaturated fatty acids and their metabolites by chemical isotope labeling coupled with liquid chromatography – mass spectrometry

Rujie Yang,Fangbo Xia,Huanxing Su,Jian-Bo Wan

n-3 polyunsaturated fatty acids (PUFAs) and their metabolites play the crucial role in a wide range of physiologic and pathologic processes, including cardiovascular, neurodegenerative diseases, and inflammation-associated disorders. However, the quantitative analysis of n-3 PUFAs and their metabolites, oxylipins , is obstructed by high structural similarity, poor ionization efficiency and low abundance. In this study, a sensitive method was developed to quantify 28 n-3 PUFAs/oxylipins using chemical isotope labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Standards labeled with cholamine- d 9 were used as one-to-one internal standards to achieve accurate quantification. The cholamine- d 0 -derivatized biological samples were mixed with cholamine d 9 -labeled standards for LC-MS/MS with multiple reaction monitoring. After cholamine derivatization, both MS sensitivity and chromatographic performance of n-3 PUFAs/oxylipins were substantially improved. Furthermore, the relationship between retention time and substituent position of regioisomers, and their fragmentation patterns were investigated, which may facilitate the identification of unknown oxylipins. Additionally, the developed method was applied to quantify the target n-3 PUFAs/oxylipins in serum and brain tissue from fish oil-supplemented mice, which exhibited its great potential and practicability. Collectively, this sensitive and reliable method may facilitate the elucidation of the roles of n-3 PUFAs/oxylipins in the physiological and pathological processes.

CAS / MDL: 75-36-5
研究领域: 生物化学 · 代谢组学 · 医学
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JOURNAL OF MEMBRANE SCIENCE · 2016 · IF 5.557

Novel thin film composite forward osmosis membrane of enhanced water flux and anti-fouling property with N-[3-(trimethoxysilyl) propyl] ethylenediamine incorporated

Shu Xiong,Jian Zuo,Yuan Gui Ma,Lifen Liu,Hao Wu,Yan Wang

In this work, novel thin film composite (TFC) forward osmosis (FO) membranes are developed via interfacial polymerization on the polyacrylonitrile (PAN) substrate, using an organic-inorganic hybrid compound – N-[3-(trimethoxysilyl) propyl] ethylenediamine (NPED) as the amine monomer to mix with m-phenylenediamine (MPD). The PAN substrate was modified with sodium hydroxide and optimized by varying the hydrolyzation time. With the incorporation of NPED in the selective layer, the formed TFC membrane exhibits better hydrophilicity, improved water flux and fouling resistance, and therefore superior membrane performance. By varying the NPED content in the aqueous phase, the surface properties and performance of TFC membranes are investigated with various characterizations. In addition, the anti-fouling properties of the TFC membranes with different NPED content in the aqueous monomer are also studied.

研究领域: 材料科学 · 环境工程 · 膜技术
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY · 2024 · IF 4.8

N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma

Yanqing Wang,Huanying Zhang,Feng Ding,Jianhua Li,Lianyu Li,Zhong Xu,Yan Zhao

Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of β-amyloid (Aβ), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis, and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early-stage AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aβ-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aβ-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aβ in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aβ by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator-activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aβ-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aβ-induced toxicity.

研究领域: 神经生物学 · 分子生物学 · 营养学
✓ 已验证 DOI PubMed 高影响因子
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EXPERIMENTAL PHYSIOLOGY · 2021 ·Vol. 106 ·期 4 ·983-993 · IF 2.969

Endogenous production of n−3 polyunsaturated fatty acids protects mice from carbon tetrachloride-induced liver fibrosis by regulating mTOR and Bcl-2/Bax signalling pathways

Changfeng Shan,Ronghua Wang,Shuai Wang,Zongmeng Zhang,Chaofeng Xing,Wenbin Feng,Zhenggang Zhao,Sujin Zhou,Allan Zijian Zhao,Yunping Mu,Fanghong Li

New Findings What is the central question of this study? What is the protective benefit of n −3 polyunsaturated fatty acids (PUFAs) on liver fibrosis and what are the relevant signalling pathways in a transgenic mouse model overexpressing the mfat-1 enzyme? What is the main finding and its importance? n −3 PUFA elevation strongly prevented carbon tetrachloride (CCl 4 )-induced hepatic damage and inhibited the activation of hepatic stellate cells. n −3 PUFAs suppressed CCl 4 -induced activation of mTOR, elevated Bcl-2 expression, and reduced Bax level, suggesting that n −3 PUFAs can render strong protective effects against liver fibrosis and point to the potential of mfat-1 gene therapy as a treatment modality. Liver fibrosis is a reversible wound healing response with excessive accumulation of extracellular matrix proteins. It is a globally prevalent disease with ultimately severe pathological consequences. However, very few current clinical therapeutic options are available. Nutritional addition of n −3 polyunsaturated fatty acids (PUFAs) can delay and lessen the development of liver fibrosis. Herein, this study examined the protective benefit of n −3 PUFAs on liver fibrosis and the relevant signalling pathways using a transgenic mouse model overexpressing the mfat-1 enzyme that converts n −6 to n −3 PUFAs. Male C57BL/6 wild-type and mfat-1 transgenic mice were administered carbon tetrachloride (CCl 4 ) or control corn oil by intraperitoneal injection. Blood alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were subsequently measured. CCl 4 -induced hepatic damage and fibrosis were assessed using haematoxylin–eosin and Masson's trichrome staining. Western blot assays were used to detect and quantify fibrosis-related proteins and mechanistic target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) signalling components. The direct effect of docosahexaenoic acid (DHA) on primary hepatic stellate cells (HSCs) was also investigated in a co-culture experiment. n −3 PUFAs, as a result of mfat-1 activity, had a strong protective effect on liver fibrosis. The elevation of ALT and AST induced by CCl 4 was significantly lessened in the mfat-1 mice. Histological determination revealed the protective effects of n −3 PUFAs on liver inflammation and collagen deposition. Co-incubation with DHA reduced the expression of profibrogenic factors in the primary HSCs. Moreover, mfat-1 transgenic mice showed significant reduction of proteins that are involved in mTOR and Bcl-2/Bax signalling pathways. Collectively, these results suggest that n −3 PUFA elevation strongly prevents CCl 4 -induced hepatic damage by directly inhibiting the activation of HSCs and regulating the basal activity of the mTOR and Bcl-2/Bax signalling pathways. Gene therapy applying mfat-1 and elevating n −3 PUFAs represents a promising treatment strategy to prevent liver fibrosis.

CAS / MDL: 8001-30-7
研究领域: 肝病学 · 分子生物学 · 药理学 · 营养学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Marine Drugs · 2023 ·Vol. 21 ·期 1 ·39 · IF 5.4

N-3 PUFA Deficiency Aggravates Streptozotocin-Induced Pancreatic Injury in Mice but Dietary Supplementation with DHA/EPA Protects the Pancreas via Suppressing Inflammation, Oxidative Stress and Apoptosis

Hong-Yu Zou,Hui-Juan Zhang,Ying-Cai Zhao,Xiao-Yue Li,Yu-Ming Wang,Tian-Tian Zhang,Chang-Hu Xue

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional β-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA β-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA β-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet β-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.Keywords:streptozotocin;polyunsaturated fatty acid;pancreas injury;oxidative stress;inflammation;apoptosis;mouse

CAS / MDL: 18883-66-4
研究领域: 营养学 · 内分泌学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2021 · IF 7.514

Untargeted lipidomics reveals metabolic responses to different dietary n-3 PUFA in juvenile swimming crab (Portunus trituberculatus)

Ye Yuan,Fangmin Xu,Min Jin,Xuexi Wang,Xiaoying Hu,Mingming Zhao,Xin Cheng,Jiaxiang Luo,Lefei Jiao,Mónica B. Betancor,Douglas R. Tocher,Qicun Zhou

While tissue fatty acid compositions reflect that of the dietary lipid source, little information is available on how dietary oils modify lipid class and molecular species profiles in hepatopancreas of crustacean. Herein, an 8-week nutritional trial and untargeted lipidomic analysis were used to investigate the impacts of dietary n-3 PUFA lipid sources including fish oil, krill oil and linseed oil on the lipidomic characteristics of hepatopancreas of swimming crab ( Portunus trituberculatus ). Dietary krill oil significantly increased distribution of 20:5n-3 and 22:6n-3 at sn-2 in phosphatidylcholine and phosphatidylethanolamine compared to fish oil. Fish oil intake promoted the deposition of 20:5n-3 and 22:6n-3 at sn-1,2,3 in triglyceride compared to linseed oil, which significantly increased the specific accumulation of 18:3n-3 at sn-1,3 in triglyceride and sn-2 in phosphatidylcholine and phosphatidylethanolamine. The study revealed metabolic responses to different dietary n-3 PUFA in swimming crab, which provided novel insight into the lipid nutrition of crustacean.

CAS / MDL: 128-37-0
研究领域: 水产养殖 · 营养学 · 脂质代谢
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE · 2024 · IF 2.6

A low n-6/n-3 PUFA ratio and high level of dietary ɑ-linolenic acid improves sleep behavior in mice with insomnia

Zhu Jie,Zhang Hua-nan,Wu Jia-kai,Li Fei-fei,Liu Yu-qing,Ning Er-juan,Yu Li-qin,Liang Shen

Camelina sativa oil (CSO) and Semen Ziziphi Spinosae oil (SZSO) are functional oils that have beneficial effects on brain health. This study evaluated the sedative and hypnotic effects of vegetable oils with various n − 6/n − 3 polyunsaturated fatty acids (PUFA) ratios and ɑ-linolenic acid (ALA) contents to mice. The n − 6/n − 3 PUFA ratios of CSO (CSO:SZSO = 1:0, 1.8 g/kg), SZSO (CSO:SZSO = 0:1, 1.8 g/kg), CSO-SZSO-L (CSO:SZSO = 1:1, 1.8 g/kg), and CSO-SZSO-H (CSO:SZSO = 1:1, 3.6 g/kg) were 0.51, 140, 1.69, and 1.69, respectively. The doses of ALA administered to mice with p-chlorophenylalanine-induced insomnia were approximately 0.64, 50 × 10 –4 , 0.32, and 0.64 g/kg, respectively. The mice were administered CSO, SZSO, and a low-dose combination of CSO and SZSO for seven days with no obvious hypnotic effects. However, the administration of a high-dose combination of CSO and SZSO significantly prolonged sleep duration in mice with induced insomnia and inhibited the serum levels of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol. Interestingly, there were no significant effects on the structure and function of the hippocampal tissue. The results indicated that the anti-insomnia effects of these vegetable oils were positively correlated with a low n − 6/n − 3 PUFA ratio and the absolute amount of ALA.

CAS / MDL: 7424-00-2
研究领域: 营养学 · 神经科学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AQUACULTURE · 2018 · IF 2.71

n-3 essential fatty acids in Nile tilapia, Oreochromis niloticus: Bioconverting LNA to DHA is relatively efficient and the LC-PUFA biosynthetic pathway is substrate limited in juvenile fish

Cuiying Chen,Wutai Guan,Qingmei Xie,Guoliang Chen,Xiaolei He,Haoliang Zhang,Weiyi Guo,Feng Chen,Yuwen Tan,Qing Pan

This study aimed to gain a better understanding of the long-chain (≥C 20 ) polyunsaturated fatty acid (LC-PUFA) biosynthetic metabolism, with a specific focus on the metabolic fate of linolenic acid (18:3n-3, LNA) and linoleic acid (18:2n-6, LA) and the relationship between these two substrates in the process of LC-PUFA biosynthesis in juvenile Nile tilapia , Oreochromis niloticus . Fish were fed four isoproteic (37.5%) and isolipidic (6.2%) diets formulated with fixed levels of LA (0.60%) and gradual levels of LNA (0.10, 0.63, 1.56 and 2.04% of dry weight, respectively) for 10 weeks. The whole-body fatty acid balance method was used to evaluate fish in vivo fatty acid metabolism . The results showed that most of dietary LNA was bioconverted to LC-PUFA when tilapia receiving not enough LNA for optimal growth. In contrast, when fish receiving sufficient dietary LNA, most of the LNA was β-oxidized, with only <10% LNA being bioconverted. The in vivo apparent △-5/-6 desaturase and elongase activities on n-3 and n-6 PUFA, respectively, exhibited a significant linear increase and decrease with the increasing dietary LNA levels, clearly indicating that for all of the enzyme activities , n-3 PUFA is a preferred substrate and the LC-PUFA biosynthetic pathway is substrate limited in Nile tilapia. Dietary higher inclusion of LNA could block or at least slow down n-6 LC-PUFA biosynthesis from LA, indicating that a direct substrate competition for accessing the Δ-6 desaturase and elongase exists between these two substrates. Furthermore, Nile tilapia were relatively efficient in bioconversion from LNA to DHA, and the DHA biosynthesis from EPA may be more direct or faster than the production of EPA from LNA. Despite of the active bioconversion of LNA up to DHA, this metabolic effort was still insufficient to compensate for the significant reduced dietary intake of n-3 LC-PUFA. No significant difference was observed in the gene expression of fatty acyl desaturase ( fads2 ) and fatty acid elongase ( elovl5 ) among all groups, which suggests that the total in vivo apparent enzyme activities are directly and positively affected by substrate availability rather than the extent of the enzyme gene expression.

CAS / MDL: 1191-41-9 106-33-2
研究领域: 水产养殖 · 营养学 · 生物化学 · 鱼类生理学
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TENSIDE SURFACTANTS DETERGENTS · 2021 ·Vol. 58 ·期 6 ·468-474 · IF 1.049

Preparation and Performance Evaluation of Gemini Sulphobetaine Surfactant Bis{[(N-methyl-N-(3-alkoxy-2-hydroxy) propyl-N-(3-sulfonic) propyl] methylene}

Zhonghua Zuo,Ming Zhou,Mao Liao,Pengao Peng,Jingfeng Zhang

Surfactants are very often used in tertiary oil production. However, the conventional surfactants cannot be used in high salinity reservoirs of tertiary oil production because the high salinity leads to the deactivation of the surfactants. Gemini sulpho-betaine surfactants have been developed to meet the requirements of tertiary oil production in such reservoirs. In this study, the Gemini sulphobetaine surfactant (bis{[(N-methyl-N-(3-alkoxy-2-hydroxy)propyl-N-(3-sulfonate)propyl]methylene}) was prepared by etherification, ring opening reaction and sulfonation reaction with decyl alcohol, epichlorohydrin, N,N’-dimethyl ethylene diamine and 1,3-propanesultone. The experimental conditions obtained are: the ratio of 1,3-propanesulfonic acid lactone to tertiary amine intermediate = 2.3 : 1, reaction temperature = 70°C and reaction time = 11 h. The analysis of the infrared spectrum showed that the structure of the synthesised substance corresponds to that of a Gemini sulphobetaine surfactant. The chemical shifts of the groups were determined by 1 HNMR structural characterisation of the products. The surface tension, emulsifying properties, foaming properties and wetting properties were investigated. The results showed that the surfactant has good foaming properties and good compatibility in a high salt environment.

研究领域: 化学工程 · 石油工程 · 材料科学
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Frontiers in Pharmacology · 2021 · IF 5.811

Piperazine-Derived α1D/1A Antagonist 1- Benzyl-N- (3-(4- (2-Methoxyphenyl) Piperazine-1-yl) Propyl) -1H- Indole-2- Carboxamide Induces Apoptosis in Benign Prostatic Hyperplasia Independently of α1-Adrenoceptor Blocking

Xiao Qing,Liu Qi-Meng,Jiang Ru-Chao,Chen Kai-Feng,Zhu Xiang,Ma Lei,Li Wei-Xi,He Fei,Huang Jun-Jun

Previous studies have indicated that α1D/1A antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α1D- and α1A- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR in vitro. However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. In vivo, HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). In vitro, HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.

CAS / MDL: 8001-25-0 50-50-0
研究领域: 药理学 · 泌尿学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ALLOYS AND COMPOUNDS · 2023 · IF 6.2

Conductivity, thermoelectric, and magnetic properties of pavonite homologue In0.45Mn2.17Bi3.38Se8 with N = 3

Shangqing Qu,Jinhao Chen,Jikun Chen,Guohong Cai,Yonggang Wang,Zhongnan Guo,Jing Zhao,Quanlin Liu

Pavonite homologues are semiconductors that show potential for thermoelectric applications. Herein, we report the synthesis of a quaternary selenide, In 0.5 Mn 2 Bi 3.5 Se 8 , that exhibits good thermal stability below 1032 K. Whereas most pavonite compounds exhibit the metallic properties of degenerate semiconductors, In 0.45 Mn 2.17 Bi 3.38 Se 8 possesses a band gap of 0.85 eV. In addition, its electrical conductivity and Seebeck coefficient exceed 3 S/cm and 300 μV/K at 810 K, respectively, with the compound mainly displaying semiconductor properties . In 0.45 Mn 2.17 Bi 3.38 Se 8 exhibits paramagnetism at room temperature followed by a paramagnetic-to-antiferromagnetic transition at ∼10.2 K. Our findings enrich the current understanding of the pavonite homologous series, providing useful insight for future exploration in related fields.

研究领域: 材料科学 · 凝聚态物理 · 热电材料研究
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-23 · IF 10.6

A multifunctional injectable, self-healing, and adhesive hydrogel-based wound dressing stimulated diabetic wound healing with combined reactive oxygen species scavenging, hyperglycemia reducing, and bacteria-killing abilities

Chen Rong,Wang Pinkai,Xie Jiajun,Tang Zinan,Fu Jinlang,Ning Yanhong,Zhong Qiang,Wang Ding,Lei Mingyuan,Mai Huaming,Li Hao,Shi Zhanjun,Wang Jian,Cheng Hao

The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N 1 -(4-boronobenzyl)-N 3 -(4-boronophenyl)-N 1 , N 1 , N 3 , N 3 -teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation. Graphical Abstract

研究领域: 生物材料 · 伤口愈合 · 糖尿病 · 药学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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