JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2022
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IF 3.571
Gugu Hao,Rong Hu,Xiaoqin Wang,Pan Gao,Lin Wang,Manhua Jiang,Libo Xin,Guoying Tan,Yanping Zhao,Fuzhou Sun,Dexin Chu,Jinqian Lv,Jinsong You,Fangfang Huang,Xuezhi Song
In recent years, nitrosamines have been discovered in some types of drug products that becomes a current regulatory hotspot, and have attracted a lot attention from both regulatory authorities and industry. This manuscript provided an industry perspective on the nitrosamines research. A liquid chromatography coupled with tandem mass spectrometry（LC-MS/MS）method was developed and applied for the quantification of N-nitrosodimethylamine (NDMA) in metformin hydrochloride sustained-release tablets (MET). The key factors resulting in the NDMA formation in MET were identified through forced degradation and drug-excipient studies, which included high temperature, dimethylamine , strong alkali and oxidation conditions, peroxide and alkaline components contained in the formulation as well as the nitrite and nitrate impurities that might be presented in certain excipients. Further, API particle size and water content of the drug product would also affect the growth rate of NDMA. Therefore, the following mitigation strategies to reduce the risk of nitrosamines in the finished drug product are proposed in this manuscript: 1) avoid the use of excipients containing nitrite, nitrate and peroxide impurities; 2) avoid high temperature and strong alkaline environment in the production and storage condition; 3) maintain an appropriate water content level in the formulation. Based on the above principles, it was recommended to add antioxidant or incorporate excipient such as Na 2 CO 3 to modify the formulation pH to weak basic environment in the formulation of MET, which can could effectively prevent formation of NDMA in the stability process.
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JOURNAL OF HAZARDOUS MATERIALS
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2022
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IF 14.224
Tingting Zhang,Dan Li,Xuan Zhu,Minglu Zhang,Jianhua Guo,Jianmin Chen
Nano-Al 2 O 3 has been widely used in various consumer products and water treatment processes because of its unique physicochemical properties . The probability of human exposure to nano-Al 2 O 3 increases significantly, of which oral ingestion is an important route. However, effects and underlying mechanisms of nano-Al 2 O 3 on gut microbiota and resistome are still not well delineated. Here, we systematically investigated the effects of nano-Al 2 O 3 on the human gut microbiome by an in vitro simulator of human colon microbial ecosystem. Results indicated that nano-Al 2 O 3 interfered with the gut microbiota, and significantly suppressed the short-chain fatty acids metabolism, which might pose adverse effects on the host. More seriously, high level of nano-Al 2 O 3 (50 mg/L) was more destructive to the gut flora, though the damage might be temporary. In addition, sub-inhibitory low-dose of nano-Al 2 O 3 (0.1 mg/L) significantly enhanced the abundance of antibiotic resistance genes (ARGs) after 7-day exposure. This is attributed to that low concentration of nano-Al 2 O 3 can promote horizontal transfer of ARGs by increasing cell membrane permeability and relative abundance of transposase (e.g. tnpA , IS613 , and Tp614 ). Our findings confirmed the adverse effects of nano-Al 2 O 3 on the human gut resistome and emphasized the necessity to assess potential risks of nanomaterials on the human gut health.
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Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Peng Wei,Zhang Shiwen,Zhou Wei,Zhao Xinchen,Wang Kexue,Yue Chengxu,Wei Xinyu,Pang Siyan,Dong Wei,Chen Sulian,Chen Changjie,Yang Qingling,Wang Wenrui
A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-β1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.
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CHEMOSPHERE
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2022
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IF 8.943
Xiaohan Yang,Yongguang Bu,Yang Zhao,Hongchao Li,Guandao Gao
The energy-induced peroxydisulfate (PDS) activation is a green and effective approach for pollutant degradation , while the huge energy consumption would significantly increase the cost of wastewater treatment . In this study, by taking carbon nanotubes (CNTs) membrane as the light to heat (LTH) conversion materials, we developed a photothermal PDS activation process for degradation of organic contaminants in a flow-by reactor, with hydroxyl radicals ( • OH) and sulfate radicals (SO 4 •− ) as the main reactive species. This system has excellent in-situ LTH conversion performance and heat transfer ability. As a result, various pollutants are degraded with an efficiency higher than 90%. More importantly, the LTH device exhibits satisfying stability and could be used for pollutant (i.e., methyl orange (MO)) removal under solar irradiation. In addition, some important factors (i.e., irradiation distance, residence time, solution pH, and PDS dosage) that might significantly influence the removal efficiency of pollutants are optimized. This work provides a novel perspective for the activation of PDS via CNTs as photothermal materials for pollutant degradation with a flow-by reactor.
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FOOD AND CHEMICAL TOXICOLOGY
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2022
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IF 5.572
Hui Chen,Lixing Cao,Kai Han,Han Zhang,Jinling Cui,Xuan Ma,Shuang Zhao,Chong Zhao,Shutao Yin,Lihong Fan,Hongbo Hu
Patulin (PAT) is a common food-borne mycotoxin with diverse toxic effects including nephrotoxicity . The induction of oxidative stress is suggested to be a key mechanism contributed to toxicities of PAT. Reduced glutathione (GSH), a sulfhydryl-containing tripeptide , is a key reason for PAT-mediated oxidative stress. Cystine/glutamate antiporter (system x c − )-mediated cystine uptake plays a critical role in maintaining redox balance via promoting GSH biosynthesis. In this study, we addressed if GSH reduction by PAT was associated with inhibition of system x c − -mediated GSH biosynthesis. Results showed that PAT significantly decreased activity of SLC7A11, a core subunit of system x c − , through activating AMPK-mediated formation of beclin1-SLC7A11 complex. Furthermore, PAT promoted ferroptosis induced by a known ferroptosis inducer RSL3 in normal renal cells, and exacerbated folic acid-induced nephrotoxicity in a mouse model of acute kidney injury . The findings of the present study provide new insights into PAT-induced kidney toxicity, and implicate that patients with ferroptosis-associated diseases maybe more susceptible to PAT.
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MOLECULES
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2022
·Vol. 27
·期 13
·4129
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IF 4.927
Taiyu Wang,Hailong Yang,Jie Yang,Ningjie Guo,Guodong Wu,Xueyu Xu,Ming An
A novel method of ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of four potential genotoxic impurities (PGIs) in the active pharmaceutical ingredients of TSD-1, a novel P2Y12receptor antagonist. Four PGIs were named, 4-nitrobenzenesulfonic acid, methyl 4-nitrobenzenesulfonate, ethyl 4-nitrobenzenesulfonate, and isopropyl 4-nitrobenzenesulfonate. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying four PGIs at 15.0 ppm in samples of 0.5 mg/mL concentration. This validated approach presented very low limits (0.1512–0.3897 ng/mL), excellent linearity (coefficients > 0.9900), and a satisfactory recovery range (94.9–115.5%). The method was sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity, and robustness and, thus, has high practicality in the pharmaceutical quality control of TSD-1.Keywords:UPLC-MS/MS;genotoxic impurities;TSD-1;active pharmaceutical ingredients;quantitation;method validation
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GREEN CHEMISTRY
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2022
·Vol. 24
·期 14
·5490-5501
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IF 11.034
Pengzhi Li,Bin Lan,Xutao Zhang,Siyuan Lei,Qi Yang,Pengjian Gong,Chul B. Park,Guangxian Li
As the most produced thermoplastic after polyolefins, an urgent issue for polyesters is to improve their environmentally friendliness in processing, application, and recycling. However, the performance of polyesters significantly deteriorates in the above stages. This work breaks through the difficulties when applying traditional polyesters by the green in situ construction of a novel covalent adaptable network, which has an ultrafast exchange reaction rate attributed to the synergistic catalytic effect of neighboring group participation (NGP) and the tertiary amine structure. This polyester-based vitrimer shows advanced performance in repairability (fast self-healing), foamability (matching fast CO2 diffusion) and recyclability (efficient reprocessing), due to the ultrafast exchange reaction rate in the system. The obtained vitrimer then possesses excellent self-healing behavior, as the damage was recovered within 32 min at 245 °C, possesses great foamability, as the foam prepared via green scCO2 foaming technology has a density as low as 0.039 g cm−3 and has a thermal conductivity as low as 28 mW/(m K)−1, and, meanwhile, possesses an advanced reprocessing ability without performance loss. Furthermore, the proposed strategy shortens the preparation time of the vitrimer to 3.5 min, providing a practical green method for the continuous process and industrial production of the polyester vitrimer via the synergistic catalytic effect of NGP and the tertiary amine structure, which is also constructive to the improved performance, environmentally friendly upcycling, and green application of the polyester vitrimer.
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Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Yang Yiling,Wang Wenbin,Liu Kefeng,Zhao Jie
Senescence is a major inductive factor of aging-related diseases in connection with an accumulation of reactive oxygen species (ROS). Therefore, it is important to maintain ROS at an appropriate level to keep homeostasis in organisms. Superoxide dismutase (SOD) is a vital enzyme in defending against oxidative damage in vivo. Because of the defects in the direct application of SOD and SOD mimics, mounting delivery systems have been developed for the efficient applications of SOD to realize antioxidant treatment. Among these systems, mesoporous silica nanoparticles (MSNs) have been widely studied because of various advantages such as desirable stability, low toxicity, and adjustable particle sizes. Herein, SOD was immobilized on MSNs using a physical absorption strategy to construct the nanosystem SOD@MSN. The nematode Caenorhabditis elegans (C. elegans) was selected as the model organism for the subsequent antioxidant and anti-aging studies. The research results suggested the nanosystem could not only be effectively internalized by C. elegans but could also protect the nematode against external stress, thus extending the lifespan and healthspan of C. elegans. Therefore, SOD@MSN could be applied as a promising medicine in anti-aging therapeutics.
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AQUACULTURE
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2022
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IF 5.135
Yang Hu,Huan Wang,Lei Liu,Jia-yun Yao,Jiong Chen
Micropterus salmoides rhabdovirus (MSRV) is a fish viral pathogen that causes severe disease and huge economic losses in the largemouth bass (M. salmoides ) farming industry in aquaculture. Currently, there is no treatment strategy for MSRV. Thus, anti-MSRV drugs are urgently needed. In this study, it was found that the ethanol extract of Arctium lappa L. had good anti-MSRV activity, and the inhibition rate of G and N protein expression of MSRV was >95%. Further studies showed that arctigenin, a natural component of A. lappa L., could inhibit MSRV infection in a dose-dependent mode on grass carp ovary (GCO) cells. In addition, arctigenin could effectively inhibit the cytopathic changes caused by virus and significantly reduce the titer of virus. The pretreatment and post-treatment experiments showed that arctigenin had preventive and therapeutic effects on MSRV infection. TOA and TOR studies indicated that arctigenin may play an antiviral role in the early stage of virus replication. Interestingly, we found that arctigenin treatment significantly inhibited mitochondrial damage in GCO cells by preserving mitochondrial function and maintaining mitochondrial membrane potential levels (ΔΨm). More importantly, arctigenin was also effective against MSRV infection in largemouth bass. The survival rate of infected fish was increased by 16% and 20% respectively by adding 0.5% and 1% arctigenin in the diet. Additionally, the virus titer of the largemouth bass in the arctigenin treatment group was significantly decreased. In summary, arctigenin is confirmed to be a natural product with the excellent anti-MSRV activity, and its application in the treatment of MSRV is promising in aquaculture.
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CHEMICAL ENGINEERING SCIENCE
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2022
·
IF 4.889
Yuan Shu,Xuefeng Ma,Xiaolan Duan,Dandan Liu,Li Wang,Qiang Niu,Pengfei Zhang
Designing highly dispersed metal nanoparticles (NPs) working at high temperature reductive atmosphere remains a challenge, especially for non-noble metal NPs (e.g., Ni NPs). Here, a solid-state co-precipitate method was developed to prepare sintering-resistance Ni-ZnO catalyst. The catalyst featured as high Ni dispersion by this solid-state co-precipitate method in solid solution, and ∼ 6 nm Ni NPs were obtained even in a long-term reduction pre-treatment (500 °C, H 2 ). Interestingly, a well-established strong metal and support interaction (SMSI) effect of Ni-ZnO was observed during the reduction process. A thin ZnO overlay was clearly deposited on the Ni metal NPs, effectively tuning the geometry and electronic structure of the exposed Ni metallic sites. Combined with the evidence of CO-TPD, H 2 O-TPD, H 2 O-titration, and CO-H 2 O TPSR, the existence of Ni-ZnO SMSI strongly provides the unusual pathway of redox mechanism during water gas shift (WGS) reaction, avoiding the tendency of CO methanation reaction in traditional Ni-based catalytic systems.
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FASEB JOURNAL
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2022
·Vol. 36
·期 9
·e22505
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IF 5.834
Xia Wu,Xueliang Zhou,Songqing Lai,Jichun Liu,Jianwei Qi
The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM). Nuclear factor erythroid2-related factor2 (Nrf2), a transcriptional activator, enhances its ability to resist oxidative stress by activating multiple downstream anti-oxidants, anti-inflammatory proteins, and detoxifying enzymes. However, the mechanism of Nrf2 signaling in HG-induced DCM is unclear. In this study, we used HG pretreated H9c2 cells as the experimental basis in vitro, and established a high fat-diet, streptozotocin (STZ) induced Type 2 diabetic rat model in vivo. Meanwhile, we used shRNA-Nrf2 and curcumin (CUR) (as an activator) to affect H9c2 cells, to verify the role of the Nrf2 signaling pathway in DCM. The results showed that the excessive production of ROS caused by HG, which could inhibit the activation of Nrf2-related signaling, resulting in a decrease in cell energy metabolism and an increase in cell apoptosis. Surprisingly, we found that the activation of the Nrf2 signaling pathway significantly increased cardiomyocyte viability, reduced ROS formation, increased antioxidant enzyme activity, and inhibited cardiomyocyte apoptosis. In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation.
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ENVIRONMENTAL TECHNOLOGY
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2022
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IF 3.475
Jiyang Liu,Haojie Yu,Li Wang
The treatment of wastewater containing organic pollutants has become a serious issue, and one of the advanced oxidation process, Fenton oxidation is recognized as an ideal way owing to its universality and environmental friendliness, thus efficient and economic catalysts are in great demand. Herein by incorporating Fe2+ containing compound as ligand, a tremella-like iron containing metal–organic framework (TFMOF) was synthesized with zirconium acetate and 1,1′-ferrocene-dicarboxylic acid though a facile solvothermal method. The TFMOF combined the merits of both ferrocene moiety with well dispersed Fe2+ sites in the molecular level and MOF films with large surface areas and exposed sites. And the morphology and crystal structure of TFMOF were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Moreover, employed as an effective catalyst in Fenton oxidation, over 99%, 95% and 97% of rhodamine B, methyl orange and reactive black V were rapidly degraded without the assistance of additional irradiation, and degradation conditions like pH, H2O2 and initial pollutant concentrations as well as the reaction kinetic was investigated, indicating the hydroxyl radical generated in the presence of TFMOF and H2O2 was able to degrade the pollutants into non-toxic molecular. Besides, the catalytic activity of TFMOF maintained well after three cycles. The good activity and universality of TFMOF make it a promising catalyst for the treatment of wastewater.
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