Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Yongnian Zeng,Chenyuan Wang,Jiapeng Lei,Xue Jiang,Kai Lei,Yinli Jin,Tianshu Hao,Wen Zhang,Jianying Huang,Wei Li
High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating L-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H 2 O 2 ), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H 2 O 2 with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.
研究领域:
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Ying-kun Zhi,Jing Li,Lang Yi,Rui-li Zhu,Jin-fang Luo,Qing-ping Shi,Sha-sha Bai,Yan-wu Li,Qun Du,Jia-zhong Cai,Liang Liu,Pei-xun Wang,Hua Zhou,Yan Dong
Background Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis . In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. Purpose To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. Methods The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro , α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. Results SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. Conclusions SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro . The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.
研究领域:
免疫学
·
药理学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2021
·
IF 6.165
Yushan Li,Na Li,Fengping Chen,Xi Yang,Yating Lei,Yijing Liu,Xun Tuo
Mono-benzyl phthalate (MBZP) is the metabolite of benzyl-butyl phthalate (BBP), and it plays a significant role in the toxicity of BBP. In current work, the interaction between MBZP and human serum albumin (HSA) was investigated using solution experiments and computer simulations. The results obtained from experiments illustrated that the intrinsic fluorescence of HSA was quenched because of the formation of HSA–MBZP complex. The K a value was (8.67 ± 0.34) × 10 4 M −1 (298 K) and the n value was approximately 1. The formation of HSA–MBZP complex was dominated by H-bonds and van der Waals force. Meanwhile, MBZP was inserted into site I of HSA and enclosed to some amino acid residues. The interaction of Trp-214 with MBZP is an important reason for the fluorescence quenching phenomenon of HSA. The combination of HSA with MBZP could cause the structure of HSA to be more compact and it led to a simultaneous decrease and increase in the α-helix and β-sheet contents, respectively. Additionally, Trp-214 and Arg-218 contributed to stabilising the HSA–MBZP complex, according to the analysis of data from molecular dynamics simulation. In summary, the results could provide new insight into the toxicological study of MBZP.
研究领域:
化学
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生物化学
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药理学
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毒理学
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分子生物学
✓ 已验证
DOI
高影响因子
BIORESOURCE TECHNOLOGY
·
2021
·
IF 9.642
Yu-Xi Gao,Xing Li,Jun-Ru Zhao,Zhong-Xing Zhang,Xiao-Yan Fan
The responses of microbial communities and antibiotic resistance genes (ARGs) to azithromycin and copper combined pollution under gradient increasing (from 0.5 to 10 mg/L) and decreasing exposure (from 10 to 0.5 mg/L) modes were investigated. Nitrification was inhibited more obviously under gradient increasing exposure mode. Responses of archaeal community and function structure were more obvious than bacteria under both exposure modes. The dominant bacterial and archaeal compositions ( Hyphomicrobium , Euryarchaeota , etc.) were affected by two exposure modes, except some rare archaea ( Methanoregula and Methanosarcina ). There were more positive correlations between bacteria and archaea, and Nitrospira was keystone genus. Ammonia-oxidizing archaea (0.37–3.06%) and complete ammonia oxidizers ( Nitrospira_ENR4 ) were enriched, and Nitrososphaera_viennensis was closely related to denitrifying genes ( napA/B , nosZ , etc.). 50 ARG subtypes were detected and specific ARG subtypes ( aac , ImrA , etc.) proliferated in two exposure modes. Bacteria and archaea were common hosts for 24 ARGs and contributed to their shifts.
研究领域:
环境科学
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微生物学
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废水处理
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生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 12
·1-11
·
IF 5.3
Tan Suhui,Tan Mengyuan,Zhang Tao,Gao Lu,Li Yi,Xu Xuechao,Yang Zhen-quan
A multienzyme-like L-argininemodified CeO 2 (Arg-CeO 2 ) nanozyme was prepared for accurate total antioxidant capacity (TAC) determination of Ganoderma sichuanense ( G. sichuanense ). It exhibits oxidase-like and peroxidase-like activities catalyzing the generation of superoxide anion free radicals and hydroxyl radicals, accelerating 3, 3′, 5, 5′-tetramethylbenzidine (TMB) chromogenic reaction. Antioxidants can effectively eliminate the generated free radicals, inhibiting the TMB chromogenic reaction. Hence, TAC can be assessed by Arg-CeO 2 catalyzed TMB chromogenic reaction using ascorbic acid (AA) as a reference substance. TAC of G. sichuanense extracted using different solvents was determined, indicating the highest TAC observed in the G. sichuanense extracted by the mixture solvent (deionized water/ethanol/ethyl acetate = 1 : 1 : 1). A visual assessment platform based on Arg-CeO 2 hydrogel nanozyme utilizing a self-programmed smartphone app and a self-designed 3D printed device is established. TAC using AA as a reference substance (3.33 ~ 83.33 µM) can be detected with a detection limit as low as 0.58 µM. The platform can realize one-step quantitative determination of TAC in G. sichuanens e within 40 min. The proposed visual assessment platform presented exhibits promising application prospects in the field of TAC assessment in food. Graphical
研究领域:
食品科学
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生物化学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
研究领域:
药理学
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免疫学
·
心脏病学
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病理生理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2018
·
IF 7.297
Dong Wu,Ruoqi Ma,Huawei Wei,Kai Yang,Bing Xie
Around 350 million tons of solid waste is disposed of in landfills every year globally, with millions of cubic meters of landfill leachates released into neighboring environment. However, to date, little is known about the variations of antimicrobial resistance (AMR) in on-site leachate treatment systems and its development in leachate-receiving water environment. Here, we quantified 7 subtypes of antibiotic resistance genes (ARGs), 3 types of culturable antibiotic resistant bacteria (ARB) and 6 subtypes of mobile genetic elements (MGEs) in the effluents from a combined leachate treatment process, including biological treatment (MBR), physical separation (UF), ultraviolet (UV) disinfection and advanced oxidation process (AOP). The contents of ARGs, ARB and MGEs were generally enriched by the MBR , but then decreased significantly along with the tertiary treatment process. However, in the effluent-receiving water samples, the abundance of dominant ARGs (i.e. ermB , sul1 , bla TEM ) increased by 1.5 orders of magnitude within 96 h, alongside a general increase of MGEs (~10.0 log 10 (copies/mL) and total ARB (~1100 CFU/mL). Structural correlation analyses reveal that target ARGs were closely associated with MGEs, particularly in effluent-receiving samples (Procrustes test; M 2 = 0.49, R = 0.71, P = 0.001); and occurrences of ARB were majorly affected by ARG's distribution and environmental conditions (e.g. nitrogen speciation) in effluent and recipient groups, respectively. This study indicates that current treatment technologies and operation protocols are not feasible in countering the development of AMR in effluent-receiving water environment, particularly in tidal rivers that are capable of retaining contaminants for a long residence time.
研究领域:
环境科学
·
微生物学
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水处理工程
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生态毒理学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Waimei Si,Xin Li,Bei Jing,Shiquan Chang,Yachun Zheng,Zhenni Chen,Guoping Zhao,Di Zhang
(Switching from the microglial M1 phenotype to the M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). This study aimed to investigate the potential use of stigmasterol for treating NP. In animal experiments, 32 male Sprague–Dawley rats were randomly divided into the sham operation group, chronic constriction injury (CCI) group, CCI + ibuprofen group, and CCI + stigmasterol group. We performed behavioral tests, enzyme-linked immunosorbent assay, hematoxylin-esoin staining (H&E) staining and immunohistochemistry, immunofluorescence, and Western blotting. In cell experiments, we performed flow cytometry, immunofluorescence, Western blotting, and qRT-PCR. Stigmasterol reduced thermal and mechanical hyperalgesia and serum IL-1β and IL-8 levels and increased serum IL-4 and TGF-β levels in CCI rats. Stigmasterol reduced IL-1β, COX-2, and TLR4 expression in the right sciatic nerve and IL-1β expression in the spinal cord. Stigmasterol reduced the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, COX-2, IL-1β, and CD32 in the spinal cord of CCI rats while increasing the expression of IL-10 and CD206. Stigmasterol decreased M1 polarization markers and increased M2 polarization markers in lipopolysaccharide (LPS)-induced microglia and decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, pERK, iNOS, COX-2, and IL-1β in LPS-treated microglia while increasing the expression of Arg-1 and IL-10. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF-κB pathway to alleviate NP.
研究领域:
药理学
·
神经科学
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免疫学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2023
·
IF 8.6
Xingyu Fan,Botao Chen,Hui Xu,Anqiang Pan,Shuquan Liang,Songwen Tan,Yongju He
Depleting intracellular glutathione (GSH) has emerged as a potent strategy to combat cancer. However, the existing GSH-depleting agents are too toxic or ineffective and standalone GSH depletion fails to yield a satisfactory curative effect. Herein, we present an intelligent nanoparticle that possesses GSH depletion, glucose consumption accompanied with H2O2 production, and NO generation properties for multimodal cancer therapy. The nanoparticle is constructed by synthesis of tetrasulfide bond-doped mesoporous silica nanoparticles followed by conjugating glucose oxidase (GOx) on the surface and loading l-arginine (l-Arg) into the mesopores. In this nanoparticle, the doped tetrasulfide bonds can quickly deplete GSH, which increases the cellular reactive oxygen species concentration to induce ferroptosis and meanwhile triggers particle biodegradation to expose the loaded l-Arg. Moreover, the elevated H2O2 level activates l-Arg to release NO for NO therapy. GOx consumes glucose to initiate starvation therapy and simultaneously produces a large amount of H2O2. Importantly, the produced H2O2 can not only potentiate ferroptosis but also promote NO release to enhance NO therapy. Besides, NO could in turn improve the efficacy of starvation therapy by damaging the mitochondria to block energy supply. In vitro and in vivo studies demonstrate that the nanoparticles show a great synergistic effect of ferroptosis/starvation/NO therapy, which can significantly kill cancer cells and remarkably inhibit tumor growth without obvious side effects. Therefore, we think that the designed nanoparticles may provide a promising paradigm for synergistic cancer therapy and hold a prospect in clinical trials.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
治疗学
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Kaili Wang,Hao Chen,Jiani Zheng,Jiali Chen,Yixuan Chen,Yue Yuan
Dual pathological barriers, including capillarized liver sinusoidal endothelial cells (LSECs) and deposited extracellular matrix (ECM), result in insufficient drug delivery, significantly compromising the anti-fibrosis efficacy. Additionally, excessive reactive oxygen species (ROS) in the hepatic microenvironment are crucial factors contributing to the progression of liver fibrosis. Hence, hyaluronic acid (HA) modified liposomes co-delivering all-trans retinoic acid (RA) and L-arginine (L-arg) were constructed to reverse hepatic fibrosis. By exhibiting exceptional responsiveness to the fibrotic microenvironment, our cleverly constructed liposomes efficiently disrupted the hepatic sinus pathological barrier, leading to enhanced accumulation of liposomes in activated hepatic stellate cells (HSCs) and subsequent induction of HSCs quiescence. Specially, excessive ROS in liver fibrosis promotes the conversion of loaded L-arg to nitric oxide (NO). The ensuing NO serves to reestablish the fenestrae structure of capillarized LSECs, thereby augmenting the likelihood of liposomes reaching the hepatic sinus space. Furthermore, subsequent oxidation of NO by ROS into peroxynitrite activates pro-matrix metalloproteinases into matrix metalloproteinases, which further disrupts the deposited ECM barrier. Consequently, this NO-induced cascade process greatly amplifies the accumulation of liposomes within activated HSCs. More importantly, the released RA could induce quiescence of activated HSCs by significantly downregulating the expression of myosin light chain-2, thereby effectively mitigating excessive collagen synthesis and ultimately leading to the reversal of liver fibrosis. Overall, this integrated systemic strategy has taken a significant step forward in advancing the treatment of liver fibrosis.
研究领域:
药理学
·
肝病学
·
药物递送系统
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Yong Wang,Chaoyu Pu,Zeyu Han,Yawei Du,Liang Chen,Yanran Huang,Yue Luo,Chao Xiang,Jiangtao He,Lu Chen,Wenguo Cui,Ke Jiang,Yuling Li
Efferocytosis in macrophages typically engages an anti-inflammatory positive feedback regulatory mechanism. In osteoarthritis (OA), characterized by imbalanced inflammatory homeostasis, the proinflammatory state of macrophages in the immune microenvironment can be reversed through enhanced efferocytosis. This study develops an in situ proefferocytosis hydrogel microsphere (macrophage polarity converter, H-C@IL) for OA treatment. Immunoliposomes (IL), CD16/32 antibody-modified clodronate liposomes, are initially prepared using the Re-emulsion method. Then, the IL is loaded into CCL19-modified HAMA microspheres through microfluidic technology. In vitro, H-C@IL can specifically recruit M0 and M1 macrophages via CCL19, induce apoptosis in M1 macrophages through secondary targeting with IL, and provide “Find/Eat-me” signals to enhance in situ efferocytosis. Additionally, it promotes macrophage polarization toward the M2 phenotype. In vivo, behavioral, imaging, and histological analyses demonstrate that H-C@IL effectively facilitates macrophage polarization toward M2, inhibits inflammation, and promotes cartilage regeneration. Mechanistically, H-C@IL enhances efferocytosis by activating proteins such as PROS1 and TIMD4 in M0 macrophages. Concurrently, signaling pathways, including PQLC2-Arg-Rac1 and Pbx1/IL-10, are activated to drive the polarization of macrophages from M0 to M2. In summary, H-C@IL promotes M0 macrophage efferocytosis in situ, facilitates macrophage polarization toward M2, restores inflammatory homeostasis, and promotes cartilage regeneration, offering a comprehensive treatment strategy for OA.
研究领域:
生物医学工程
·
免疫学
·
骨科
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Energy
·
2021
·
IF 17.881
Congyu Wang,Peng Wang,Junhuan Chen,Liyang Zhu,Dun Zhang,Yi Wan,Shiyun Ai
Gram-positive bacterial concentration , such as Staphylococcus aureus (S. aureus) , is a crucial criterion for evaluating water quality and influencing human health, developing effective and specific detection of Gram-positive bacteria is important for prevention of their threats. In our proof-of-concept work, a self-powered biosensing system based on the vertical contact-separation triboelectric nanogenerator (TENG) was developed to specifically detect Gram-positive bacteria in solution. In the biosensing system, vancomycin was utilized to identify and capture Gram-positive bacterial cells via specific vancomycin-bacteria wall interactions, guanidine functionalized multi-walled carbon nanotubes (CNT-Arg) was adopted as signal amplification material due to its high electrical conductivity , and TENG was adopted as a stable voltage signal source. Thus, the self-powered biosensing system could specifically detect the Gram-positive bacteria in solution by determining the measured voltage variation of biosensor. It was proven that the self-powered biosensing system was applied to detect S. aureus (employed as a model) with a linear relationship, low limit of detection (2 × 10 3 CFU mL −1 ) and high selectivity. Moreover, a warning program of Labview was written in this work, and the warning program could convert the voltage signal into visual signal for convenient observation. This work provides a design concept for self-powered biosensing system with TENG, and by replacing the molecular probes, the system can facilitate the application of TENG in many relevant fields, such as environmental pollution, iatrogenic diseases and microbiological corrosion .
研究领域:
生物传感
·
纳米技术
·
微生物学
·
环境监测
·
生物医学工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）