AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 7
·1-19
·
IF 3.4
Long Yanqiu,Lei Fang,Hu Jie,Zheng Zhiyun,Gui Shuangying,He Ning
The compound Salvia Recipe has been shown to have a relatively significant curative effect in management of cardiovascular and cerebrovascular diseases. This work aimed to prepare a thermosensitive in situ gel (ISG) delivery system that utilizes Poloxamer 407, Poloxamer 188, and hydroxypropyl methylcellulose for ocular administration of the compound Salvia recipe to treat cardiovascular and cerebrovascular diseases. The central composite design-response surface method was utilized to improve the prescription of the gel. The formulated gel was characterized and assessed in terms of stability, retention time, in vitro release, rheology, ocular irritation, pharmacokinetics studies, and tissue distribution. The gel was a liquid solution at room temperature and became semisolid at physiological temperature, prolonging its stay time in the eye. Pharmacokinetics and tissue distribution experiments indicated that thermosensitive ISG had enhanced targeting of heart and brain tissues. Additionally, it could lower drug toxicity and side effects in the lungs and kidneys. The compound Salvia ophthalmic thermosensitive ISG is a promising drug delivery system for the management of cardiovascular and cerebrovascular illnesses. Graphical Abstract
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MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 5
·1-9
·
IF 5.3
Yan Qinghua,Wu Ruixue,Wang Jiaxin,Mao Jian,Nan Wenbin
Abstract To accurately detect tumor marker carbohydrate antigen 72-4 (CA72-4) of serum samples is of great significance for the early diagnosis of malignant tumors. In the present study, MnO 2 /hollow nanobox metal-organic framework (HNM)-AuPtPd nanocomposites were prepared via multi-step synthesis and superposition method and a series of characterizations were carried out. A highly sensitive immunosensor Ab/MnO 2 /HNM-AuPtPd/GCE based on the composite nanomaterial was further prepared and used to detect the tumor marker CA72-4. The constructed immunosensor achieved signal amplification by increasing the electrocatalytic activity to H 2 O 2 by means of the synergistic effect of MnO 2 ultra-thin nanosheets (MnO 2 UNs) and HNM-AuPtPd. At the same time, the electrochemical properties of the immunosensor were analyzed using cyclic voltammetry, electrochemical impedance, amperometry (with the test voltage of −0.4 V), and differential pulse voltammetry. The experimental results showed that the MnO 2 /HNM-AuPtPd nanocomposites were successfully prepared, and the immunosensor Ab/MnO 2 /HNM-AuPtPd/GCE demonstrated an excellent electrochemical performance. The electrochemical immunosensor had the highest detection sensitivity under the optimal experimental conditions, such as incubation pH of 7.0, incubation time of 60 min, with the addition of 15 μL of H 2 O 2 , and in the concentration range 0.001–500 U/mL. It had a low detection limit of 1.78×10 −5 U/mL (S/N = 3). Moreover, the serum sample recovery were in the range from 99.38 to 100.52%. This study provides a new method and experimental basis for the detection of tumor markers in clinical practice. Graphical Abstract
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AQUACULTURE INTERNATIONAL
·
2024
·
IF 2.2
Cui Jun,Zeng Dan,Guan Peipei,Jiang Ning
Exposure to pathogens induces hyperactivate inflammatory immune responses, oxidative stress and even death in fish. Therefore, suppressing excessive inflammatory responses is a means of treating fish diseases. Scutellariae Radix (SR), an herbal medicine, has anti-inflammatory and antioxidant properties. However, the active ingredients of SR that produce a marked effect and their mechanisms are poorly understood. In this study, 32 active ingredients of SR and their 124 target genes associated with anti-inflammatory effect were screened. These target genes in zebrafish were mainly enriched in biological processes associated with response to stress and stimulus. The KEGG enrichment analysis and pathway–pathway network analysis showed that the MAPK signalling pathway and nine other pathways were the key pathways associated with anti-inflammatory effect. A protein–protein interactions (PPI) network of target genes was constructed, and AKT2 and nine other genes were identified as the hub genes by cytoHubba. Combining the above results, we constructed an active ingredient–hub protein–key pathway network, showing that wogonin-AKT2 was the key regulated module. Molecular docking and SPR-based assays were used to investigate the possible interaction of wogonin with the AKT2 protein. The infected zebrafish and grass carp treated with wogonin displayed a higher survival rate and anti-inflammatory and antioxidant effects than the infected fish without wogonin treatment. Dietary wogonin also enhanced grass carp anti-inflammatory and antioxidant effects. These findings further reveal the molecular biological mechanism by which wogonin from SR exerts anti-inflammatory effects and provide a theoretical basis for the prevention of fish diseases.
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JOURNAL OF FLUORESCENCE
·
2024
·
IF 2.6
Chen Xian,Zhang Menghan,Zheng Lang,Deng Xiaoqin,Chen Qiang,Han Wendi,Huang Zhengjun,Weng Shaohuang
The establishment of a convenient and efficient testing method is crucial and needed for the monitoring of diosmin. In this study, nitrogen doped carbon dots (N-CDs) with the particle size distribution of 2.5–5.7 nm and the average diameter of 4.1 nm were successfully synthesized using a simple strategy. N-CDs exhibited excellent and stable fluorescence performance with the quantum yield of 22.33%. Correspondingly, a fluorescence analytical method was developed for diosmin determination using N-CDs as probe. UV-vis absorbance spectroscopy and the evaluation of internal filtering parameters verified that the mechanism causing the quenching of N-CDs was an internal filtering effect (IFE). The concentration of diosmin can be directly evaluated based on the quenched fluorescence intensities. After optimizing experimental conditions, it was found that the fluorescence quenching efficiency ((F 0 -F)/F 0 ) of N-CDs exhibited a good linear relationship with the concentration of diosmin (C Diosmin ) in the range of 3.0–50 µg/mL. The limit of detection (LOD) was 0.86 µg/mL based on 3σ/slope ( n = 13). This method was successfully applied to accurately determine the content of diosmin in diosmin tablets and human plasma samples with good reproducibility. It stands out for its simplicity, speed, and acceptable determination performance.
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Lipids in Health and Disease
·
2024
·
IF 3.9
Xue Ran,Ying-jie Wang,Shi-gang Li,Chi-bing Dai
Background/aims Research has indicated that treatment with rosuvastatin can improve liver pathology in metabolic-associated fatty liver disease (MAFLD) patients and that treatment with Bifidobacterium can improve MAFLD. Therefore, the effects of Bifidobacterium , rosuvastatin , and their combination on related indices in a rat model of diet-induced MAFLD need to be investigated. Methods Forty rats were divided into five groups: the normal diet group (N), high-fat diet (HFD) model group (M), HFD + probiotic group (P), HFD + statin group (S), and HFD + probiotic + statin group (P-S). To establish the MAFLD model, the rats in Groups M, P, S, and P-S were fed a HFD for 8 weeks. The treatments included saline in Group N and either Bifidobacterium , rosuvastatin , or their combination in Groups P, S, and P-S by intragastrical gavage. After 4 weeks of intervention, the rats were euthanized, and samples were harvested to analyze gastrointestinal motility and liver function, pathological changes, inflammatory cytokine production, and the expression of proteins in key signaling pathways. Results HFD feeding significantly increased the body weight, liver index, and insulin resistance (IR) index of the rats, indicating that the MAFLD model was successfully induced. Bifidobacterium reduced the liver of MAFLD rats, while Bifidobacterium with Rosuvastatin decreased the liver index, IR index, and levels of aspartate aminotransferase and alanine aminotransferase in MAFLD rats. The MAFLD model showed altered expression of proteins in signaling pathways that regulate inflammation, increased production of inflammatory cytokines, an elevated MAFLD activity score (MAS), and pathological changes in the liver. The MAFLD model also showed reduced relative counts of intestinal neurons and enteric glial cells (EGCs), altered secretion of gastrointestinal hormones, and slowed gastrointestinal emptying. Bifidobacterium , rosuvastatin , or their combination inhibited these various changes. HFD feeding changed the rats’ gut microbiota, and the tested treatments inhibited these changes. These results suggest that the gastrointestinal motility disorder and abnormal liver function in MAFLD rats may be related to a reduction in Escherichia-Shigella bacteria and an increase in Asticcacaulis bacteria in the gut microbiota and that the improvement in liver function induced by Bifidobacterium plus rosuvastatin may be related to increases in Sphingomonas and Odoribacter bacteria and a decrease in Turicibacter bacteria in the gut microbiota. Conclusions The combined use of Bifidobacterium and rosuvastatin could better regulate the gut microbiota of MAFLD model rats, promote gastrointestinal emptying, and improve liver pathology and function than single treatment with Bifidobacterium or rosuvastatin . This provides a better strategy for the treatment of MAFLD.
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Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-9
·
IF 6.1
Zheng Rongji,Guan Tian,Hong Chaoqun,Yao Yao,Fang Yutong,Huang Wei,Chen Chunfa,Zeng Huancheng,Huang Jiman,Lin Hui,Chen Bingfeng,Zhang Rendong,Chen Dongmei,Ding Zhechun,Zeng Haoyu,Wu Jundong
ObjectivesSTAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs).Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs.Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway.Conclusion sIn this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.
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JOURNAL OF SOILS AND SEDIMENTS
·
2024
·Vol. 24
·期 6
·2309-2317
·
IF 2.8
Mi Na,Yang Min,Wang Xiaohan,Sun Qian,He Jianzhou,Deng Shaopo,Fan Tingting
Purpose The application of silicon could effectively alleviate Cd contamination in the soil. However, the interaction between silicon and Cd in soils is not well understood. Our research aims to investigate the mechanism of the impact of silicate on the sorption of Cd on metal oxides in soils. Materials and methods Sodium silicate and Cd(II) co-sorption on γ-Al 2 O 3 and goethite at pH 5.5 and 7.5 was studied using a combination of batch sorption experiments, X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Results and discussion Silicate enhanced the sorption of Cd(II) onto γ-Al 2 O 3 at pH 5.5 and 7.5. However, the sorption of Cd(II) on goethite at pH 5.5 and 7.5 was only promoted when the silicate concentration reached 1 mmol L −1 . Cadmium(II) enhanced silicate sorption on γ-Al 2 O 3 at pH 5.5 and on goethite at pH 7.5, while it decreased silicate sorption on γ-Al 2 O 3 at pH 7.5 and had no significant effect on goethite at pH 5.5. At pH 5.5, Cd(II) reacted with silicate to generate Cd 2 SiO 4 , and Cd-Si-Al ternary complexes were formed on γ-Al 2 O 3 . At pH 7.5, silicate promoted the formation of Cd(OH) 2 on γ-Al 2 O 3 , which ultimately transformed into CdCO 3 . When silicate concentration reached 1 mmol L −1 , more silicate complexes were formed through the Fe-O-Si bound on goethite at both pH 5.5 and 7.5 to promote the adsorption of Cd(II) owing to its electronegative functional group on the surface of the complex. Conclusions The type of clay minerals, pH, and the presence of silicate all significantly affected Cd sorption. Furthermore, the sorption mechanism of Cd on γ-Al 2 O 3 and goethite in the presence of silicate has been elucidated. The above findings improve our understanding of the mechanism for immobilizing Cd in soils using silicon-containing materials.
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POLYMER BULLETIN
·
2024
·
IF 3.1
Yu Tingting,Wang Xu,Hu Yuehang,Zhao Yang,Zhu Cenming,Cheng Liang,Kong Linghan,Zheng Han,Yue Baoshan,Zhan Jianbo,Yu Zhenhua,Wang Hao,Zhang Ying
In this work, a bio-based resin of acrylated epoxidized soybean oil (AESO) mixed with three types of active diluents (Isoborneol methacrylates [IBOMA], tripropylene glycol diacrylate [TPGDA], and Ethoxylated trimethylolpropane triacrylate [ETPTA]) is used to form a protective UV-curable coating film on calcium alginate water-carrying microspheres (CA-WCMs). Calcium alginate microspheres (CAMs) have previously been used to encapsulate only ester soluble or oil-in-water core materials, thus limiting their application. After UV-curing with an increased active diluent dose, the pencil hardness, pendulum hardness, and mechanical strength of the CAMs increased. A photopolymerization kinetics study reveals that the maximum double bond (C=C) conversion rates of AESO-IBOMA, AESO-TPGDA, and AESO-ETPTA are 95, 92, and 86%, respectively, and the maximum conversion rate of C=C bond is 87% in their mixed system. Additionally, the water retention rate of the water-carrying microspheres (WCMs) increased with an increasing number of coating layers, plateauing after the number of layers exceeded four. The water retention is favorable, with more than 75% of the water stored for a duration of 50 days. Overall, the cost-effective and environmentally friendly method has shown encouraging results in the acquisition of water-absorbing CAMs, with the potential to overcome existing implementation constraints.
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WATER AIR AND SOIL POLLUTION
·
2025
·Vol. 236
·期 4
·1-13
·
IF 3
Liu Lian,Wang Xin,Gao Zixin,Zhan Yue,Yao Mengqin,Bao Jia
Carbon capture, utilization, and storage (CCUS) has emerged as a critical strategy in combating climate change and global warming. Carbonic anhydrase (CA) exhibits exceptional potential as a biocatalyst for CCUS processes due to its remarkable ability to accelerate CO 2 hydration. In this study, CA was immobilized on ZnO nanocarriers of varying morphologies. The optimal immobilization conditions and enzymatic properties of the immobilized CA were investigated, followed by catalytic CO 2 uptake and mineralization experiments. The immobilization process resulted in several improvements: enhanced overall thermal stability, an elevated optimal reaction pH of 8.50 (compared to 8.00 for free CA), retention of 84.98% original activity after 30 days of storage at 4 °C, and preservation of 85.36% initial activity after five recycling cycles. While the affinity between immobilized CA and its substrate increased, a decrease in activity was observed. The Michaelis constant (Km) for immobilized and free CA were determined to be 17.22 mM and 34.92 mM, respectively, with corresponding catalytic efficiency (Kcat/Km) of 20.49 M −1 -S −1 and 148.91 M −1 -S −1 . The catalytic performance of immobilized CA was investigated by carrying out the CO 2 adsorption assay. Notably, the catalytic efficiency of immobilized CA in CO 2 absorption and mineralization under various conditions was significantly enhanced. Graphical
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-23
·
IF 12.6
Xia Guoyu,Fan Zhongxiong,Wang Qingluo,Li Jianmin,Zhang Yuxiang,Aipire Adila,Su Qiurong,Li Ying,Hou Zhenqing,Li Jinyao
Photodynamic-induced immunotherapy (PDI) is often hampered by low reactive oxygen species (ROS) yield, intra-tumor hypoxia, high glutathione (GSH) concentration, and immunosuppressive microenvironment. In view of this, a ruthenium (Ru)-based nanobattery (termed as IRD) with cascade-charged oxygen (O 2 ), ROS, and photodynamic-induced immunotherapy by coordination-driven self-assembly of transition-metal Ru, photosensitizer indocyanine green (ICG), and organic ligand dithiobispropionic acid (DTPA). Then, IRD is camouflaged with macrophage membranes to obtain a nanobattery (termed as IRD@M) with targeting and immune evasion capabilities. Upon intravenous administration, IRD@M with a core-shell structure, nano diameter, and good stability can specifically hoard in tumor location and internalize into tumor cells. Upon disassembly triggered by GSH, the released Ru³⁺ not only catalyzes the conversion of endogenous hydrogen peroxide (H₂O₂) into O₂ to alleviate tumor hypoxia and reduce the expression of hypoxia-inducible factor-1 α (HIF-1 α ), but also generates hydroxyl radicals (·OH) to elevate intracellular ROS levels. This process significantly enhances the photodynamic therapy (PDT) efficacy of the released ICG. Meanwhile, the released DTPA can significantly downregulate overexpressed GSH to reduce the elimination of ROS deriving from PDT by the exchange reaction of thiol-disulfide bond. It is also found that alleviating the hypoxic tumor microenvironment synergistically enhances the PDT efficacy, which in turn cascades to recharge the subsequent immune response, significantly improving the immunosuppressive tumor microenvironment and activating systemic tumor-specific immunity. Notably, in vitro and in vivo experimental results jointly confirm that such cascade-recharged macrophage-biomimetic Ru-based nanobattery IRD@M can achieve an obvious tumor elimination while results in a minimized side effect. Taken together, this work highlights a promising strategy for simple, flexible, and effective Ru-based immunogenic cell death (ICD) agents within PDI. Graphical
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AQUACULTURE INTERNATIONAL
·
2025
·Vol. 33
·期 3
·1-18
·
IF 2.4
Kong Lingnan,Abulizi Abudula,Cong Jingjing,Meng Weihan,Chang Yaqing,Sun Zhihui
The cytochrome P4503A ( CYP3A ) subfamily has been well characterized in vertebrates, where it plays a pivotal role in xenobiotic detoxification and the regulation of steroid hormone levels. However, their molecular features and functions in invertebrates remain poorly understood. The sea cucumber ( Apostichopus japonicus ) is not only a commercially significant mariculture species but also an excellent model for studying organ development and evolutionary biology. In this study, we identified seven CYP3A genes in A. japonicus using gonadal transcriptomic data. These genes exhibited ubiquitous expression across adult tissues, with significantly higher levels in ovarian tissues compared to testes tissues. Protein sequence analysis revealed that the catalytic residues Ala 306 -Thr 310 -Cys 437 , which are critical for aromatase activity, are highly conserved. This suggests that CYP3A proteins may mediate aromatization-like reactions similar to CYP19A in vertebrates. Additionally, dietary administration of the aromatase inhibitor letrozole led to histological changes in the testes and a reduction in the diameter of large oocytes in the ovaries. These findings provide valuable insights into the molecular mechanisms underlying gonadal development in sea cucumbers and lay the groundwork for future research on the artificial induction of sex reversal in echinoderms.
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Drug Delivery and Translational Research
·
2024
·
IF 5.7
Li Yang,Yu Qin,Lu Yi,Ma Yanyun,Qi Jianping,Chen Zhongjian,Zhu Quangang,Wu Wei
Psoriasis is a prevalent chronic disease affecting 2–3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis. Graphical Abstract
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