Publications by authors named "Lihua Yang"

316 Publications

Identification of a PCSK9-LDLR disruptor peptide with in vivo function.

Cell Chem Biol 2021 Sep 14. Epub 2021 Sep 14.

Novartis Institutes for BioMedical Research, Fabrikstrasse 2, Novartis Campus, 4056 Basel, Switzerland.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employ an affinity-based screen of 10in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to molecules with enhanced function and pharmacokinetic properties (e.g., PCSK9i). In mice, PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner. PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.
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http://dx.doi.org/10.1016/j.chembiol.2021.08.012DOI Listing
September 2021

Systematic analysis of the relationship between ovarian cancer prognosis and alternative splicing.

J Ovarian Res 2021 Sep 15;14(1):120. Epub 2021 Sep 15.

Department of Gynaecology, the 2nd Afliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Background: Ovarian cancer(OC) is the gynecological tumor with the highest mortality rate, effective biomarkers are of great significance in improving its prognosis. In recent years, there have been many studies on alternative splicing (AS) events, and the role of AS events in tumor has become a focus of attention.

Methods: Data were downloaded from the TCGA database and Univariate Cox regression analysis was performed to determine AS events associated with OC prognosis.Eight prognostic models of OC were constructed in R package, and the accuracy of the models were evaluated by the time-dependent receiver operating characteristic (ROC) curves.Eight types of survival curves were drawn to evaluate the differences between the high and low risk groups.Independent prognostic factors of OC were analyzed by single factor independent analysis and multi-factor independent prognostic analysis.Again, Univariate Cox regression analysis was used to analyze the relationship between splicing factors(SF) and AS events, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on OS-related SFs to understand the pathways.

Results: Univariate Cox regression analysis showed that among the 15,278 genes, there were 31,286 overall survival (OS) related AS events, among which 1524 AS events were significantly correlated with OS. The area under the time-dependent receiver operating characteristic curve (AUC) of AT and ME were the largest and the RI was the smallest,which were 0.757 and 0.68 respectively. The constructed models have good value for the prognosis assessment of OC patients. Among the eight survival curves, AP was the most significant difference between the high and low risk groups, with a P value of 1.61e - 1.The results of single factor independent analysis and multi-factor independent prognostic analysis showed that risk score calculated by the model and age could be used as independent risk factors.According to univariate COX regression analysis,109 SFs were correlated with AS events and adjusted in two ways: positive and negative.

Conclusions: SFs and AS events can directly or indirectly affect the prognosis of OC patients. It is very important to find effective prognostic markers to improve the survival rate of OC.
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http://dx.doi.org/10.1186/s13048-021-00866-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442315PMC
September 2021

Bis(2-ethylhexyl)-tetrabromophthalate induces zebrafish obesity by altering the brain-gut axis and intestinal microbial composition.

Environ Pollut 2021 Sep 6;290:118127. Epub 2021 Sep 6.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Multiple environmental stressors, including chemicals termed obesogens, contribute to the susceptibility of organisms to obesity. Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, is an environmental contaminant that may disrupt lipid metabolism. However, the risk of TBPH leading to obesity remains unknown. Herein, adult female zebrafish fed a normal-fat diet (NFD) or high-fat diet (HFD) were exposed to 0, 0.02 and 2.0 μM TBPH for 6 weeks. The results showed that chronic TBPH exposure lead to significant weight gain, adipocyte hypertrophy, and subcutaneous fat accumulation, which could be enhanced by HFD feeding. HFD individuals also showed significant visceral fat accumulation. Transcription of the main adipokines regulating lipid metabolism associated with the brain-gut axis were significantly affected by TBPH, especially leptin (brain) and adiponectin (intestine). Additionally, peroxisome proliferator-activated nuclear receptor gamma (PPAR-γ) was significantly upregulated in intestine. TBPH increased the abundance of Firmicutes and Bacteroidetes in the gut microbiota in both NFD and HFD groups, resulting in obesity. Interestingly, population diversity analysis indicated that TBPH alone had a comparable impact on gut microbiota composition to that of HDF controls. Thus, TBPH increased the susceptibility of female zebrafish to obesity by disrupting brain-gut axis regulation and gut microbial composition, leading to enhanced fat accumulation under HFD conditions.
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http://dx.doi.org/10.1016/j.envpol.2021.118127DOI Listing
September 2021

Experimental and theoretical studies into the hydroxyl radical mediated transformation of propylparaben to methylparaben in the presence of dissolved organic matter surrogate.

Water Res 2021 Sep 2;204:117623. Epub 2021 Sep 2.

South China Sea Resource Exploitation and Protection Collaborative Innovation Center, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address:

Dissolved humic and biogenic substances might be present in the aphotic zone and contribute to the fate of parabens in natural aquatic ecosystem under the fluctuation of water multi-parameters. Through the combination of batch tests with quantum chemical calculation, hydroxyl radical (•OH) mediated degradation of propylparaben (PP) to methylparaben (MP) has been confirmed in the present study. The interaction of dissolved oxygen with environmental relevant concentration of humic acid (HA), algal and bacterial cell lysis leads to a slow production of •OH. Aqueous PP undergoes a mild removal process with the pseudo-first order rate constant (10, s) higher at 7.43 in HA than at 3.30-4.89 in biogenic cell lysis. PP removal is correlated with the aromaticity of DOM surrogate and the produced •OH concentration, which could be enhanced by the increase of light intensity and DO other than HA. The •OH mediated process on PP removal has been confirmed by the linearly inhibited effect of tert-butanol while totally inhibited effects of higher concentration of sodium azide and co-existent chemical (17β-estradiol). Based on the detection of byproduct MP, two possible reaction pathways, •OH attacking at β-carbon (path-β) and terminal γ-carbon (path-γ) of the propyl side chain of PP, are proposed. Through the analysis of thermal and kinetics parameters, the •OH initiated H-abstraction and the resulting C-C bond cleavage leading to the formation of MP and acetaldehyde in path-β is confirmed to be the dominant reaction mechanism. Considering the universal occurrence of parabens and these DOM surrogates, this mild removal process has special implications for the self-purification of organic pollutants in natural aquatic ecosystems, especially in DOM-rich matrices in the aphotic zone.
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http://dx.doi.org/10.1016/j.watres.2021.117623DOI Listing
September 2021

Dielectric barrier discharge plasma: A green method to change structure of potato starch and improve physicochemical properties of potato starch films.

Food Chem 2021 Aug 31;370:130992. Epub 2021 Aug 31.

College of Food Science and Engineering, Gansu Agricultural University, Gansu 730070, China. Electronic address:

The effects of dielectric barrier discharge (DBD) plasma treatment on the physicochemical properties of potato starch and its films were studied. The results showed that the plasma species caused etching lead to small cracks and pores in potato starch particles and that oxidation, de-polymerization, and crosslinking were the main mechanisms underlying the effects of DBD plasma treatment. As the treatment time extended, starch hydrolysis, turbidity, syneresis, and gelatinization temperatures increased first and then decreased, whereas the solubility, swelling power, and water absorption significantly increased (P < 0.05). There was a decrease in the retrogradation tendency of the starch gels. The surfaces of the DBD plasma-modified potato starch-based films were relatively flat. After a 9-min treatment, the films exhibited the lowest water vapor permeability and highest tensile strength. In conclusion, the use of DBD plasma is a simple and green method to enhance the properties of potato starch and its film.
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http://dx.doi.org/10.1016/j.foodchem.2021.130992DOI Listing
August 2021

Measurement and driving factors of grey water footprint efficiency in Yangtze River Basin.

Sci Total Environ 2021 Aug 14;802:149587. Epub 2021 Aug 14.

School of Business, Hohai University, Nanjing 211100, China.

Water shortages and poor water quality have become an urgent problem that is constraining the sustainable development of China. Grey water has been found to bring greater stress on the water supply than freshwater consumption, and the grey water footprint (GWF) has received significant attention as a comprehensive indicator to assess wastewater pollution. In this study, we analysed the grey water footprint in the Yangtze River Basin from 2003 to 2017 and established a Logarithmic mean divisia index (LMDI) model to decompose the grey water footprint efficiency into six key factors. Our findings are as follows: (1) The average grey water footprint (AGWF) in the central regions was 40% higher than eastern region and 172% higher than western region; (2) Economic effects and capital deepening effects are the main factors affecting positive changes in grey water footprint efficiency; (3) Based on an analysis of the driving factors of greywater footprint efficiency in each province, we conducted a territorial classification according to the primary driving factors in each province. Our results reflect the spatial distribution characteristics of the influencing factors on the grey water footprint effect in the Yangtze River Basin and will enable the government to formulate relevant policies for each subregion.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149587DOI Listing
August 2021

Refinements of Approximation Results of Conditional Restricted Boltzmann Machines.

IEEE Trans Neural Netw Learn Syst 2021 Aug 24;PP. Epub 2021 Aug 24.

Conditional restricted Boltzmann machines (CRBMs) are the conditional variant of restricted Boltzmann machines (RBMs), which are used to simulate conditional probability distributions. While promising for practical applications, there is a lack of theoretical studies on the approximation ability of CRBMs. In this article, by contributing analysis tools, especially designed for the conditional models, we improve the results of the representational power of CRBMs based on existing work on RBMs. We first study the properties of CRBMs to approximate conditional Markov random fields. On this basis, a universal approximation result is obtained by deriving upper bounds on the minimal number of hidden units, which improves the previous result. Furthermore, the result about maximal approximation errors of CRBMs is also improved by reducing the number of hidden units that can guarantee approximations within a given error tolerance. Furthermore, the representational efficiency of CRBMs in computing deterministic conditional distributions is investigated. Specifically, we show that there are exponentially many deterministic conditional distributions that cannot be computed by CRBMs whose size does not exponentially grow with the number of input units. Some specific examples of these hard-to-present deterministic conditional distributions are provided. Finally, some numerical experiments are carried out to verify the theoretical results of the properties of CRBMs to approximate conditional Markov random fields and the universal approximation of CRBMs.
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http://dx.doi.org/10.1109/TNNLS.2021.3105129DOI Listing
August 2021

Phylogenomic and Macroevolutionary Evidence for an Explosive Radiation of a Plant Genus in the Miocene.

Syst Biol 2021 Aug 16. Epub 2021 Aug 16.

Key Laboratory of Plant Resources Conservation and Sustainable Utilization, South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou, China.

Mountain systems harbor a substantial fraction of global biodiversity and, thus, provide excellent opportunities to study rapid diversification and to understand the historical processes underlying the assembly of biodiversity hotspots. The rich biodiversity in mountains is widely regarded as having arisen under the influence of geological and climatic processes as well as the complex interactions among them. However, the relative contribution of geology and climate in driving species radiation is seldom explored. Here, we studied the evolutionary radiation of Oreocharis (Gesneriaceae), which has diversified extensively throughout East Asia, especially within the Hengduan Mountains (HDM), using transcriptomic data and a time calibrated phylogeny for 88% (111/126) of all species of the genus. In particular, we applied phylogenetic reconstructions to evaluate the extent of incomplete lineage sorting accompanying the early and rapid radiation in the genus. We then fit macroevolutionary models to explore its spatial and diversification dynamics in Oreocharis and applied explicit birth-death models to investigate the effects of past environmental changes on its diversification. Evidence from 574 orthologous loci suggest that Oreocharis underwent an impressive early burst of speciation starting ca. 12 Ma in the Miocene, followed by a drastic decline in speciation toward the present. Although we found no evidence for a shift in diversification rate across the phylogeny of Oreocharis, we showed a difference in diversification dynamics between the HDM and non-HDM lineages, with higher diversification rates in the HDM. The diversification dynamic of Oreocharis is most likely positively associated with temperature-dependent speciation and dependency on the Asian monsoons. We suggest that the warm and humid climate of the mid-Miocene was probably the primary driver of the rapid diversification in Oreocharis, while mountain building of the HDM might have indirectly affected species diversification of the HDM lineage. This study highlights the importance of past climatic changes, combined with mountain building, in creating strong environmental heterogeneity and driving diversification of mountain plants, and suggests that the biodiversity in the HDM cannot directly be attributed to mountain uplift, contrary to many recent speculations.
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http://dx.doi.org/10.1093/sysbio/syab068DOI Listing
August 2021

Boosting Antitumor Sonodynamic Therapy Efficacy of Black Phosphorus via Covalent Functionalization.

Adv Sci (Weinh) 2021 Aug 13:e2102422. Epub 2021 Aug 13.

Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Materials for Energy Conversion, Department of Materials Science and Engineering, Anhui Laboratory of Advanced Photon Science and Technology, University of Science and Technology of China, Hefei, 230026, China.

Sonodynamic therapy (SDT) triggered by ultrasound represents an emerging tumor therapy approach with minimally invasive treatment featuring nontoxicity and deep tissue-penetration, and its efficacy sensitively depends on the sonosensitizer which determines the generation of reactive oxygen species (ROS). Herein, for the first time covalently functionalized few-layer black phosphorus nanosheets (BPNSs) are applied as novel sonosensitizers in SDT, achieving not only boosted SDT efficacy but also inhibited cytotoxicity relative to the pristine BPNSs. Three different covalently functionalized-BPNSs are synthesized, including the first fullerene-functionalized BPNSs with C covalently bonded onto the surface of BPNSs (abbreviated as C -s-BP), surface-functionalized BPNSs by benzoic acid (abbreviated as BA-s-BP), and edge-functionalized BPNSs by C (abbreviated as C -e-BP), and the role of covalent functionalization pattern of BPNSs on its SDT efficacy is systematically investigated. Except C -e-BP, both surface-functionalized BPNSs (C -s-BP, BA-s-BP) exhibit higher SDT efficacies than the pristine BPNSs, while the highest SDT efficacy is achieved for BA-s-BP due to its strongest capability of generating the hydroxyl (·OH) radicals, which act as the dominant ROS to kill the tumor cells.
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http://dx.doi.org/10.1002/advs.202102422DOI Listing
August 2021

Body Composition and Metabolic Improvement in Patients Followed Up by a Multidisciplinary Team for Obesity in China.

J Diabetes Res 2021 29;2021:8862217. Epub 2021 Jul 29.

Department of Endocrinology, Peking University First Hospital, China.

Background: This study evaluated the effectiveness of the multidisciplinary team (including a specialist, a dietitian, a physical exercise trainer, a surgeon for bariatric surgery, an acupuncturist, and several health educators) for obesity management and the body composition change and improvements in metabolic biomarkers during a 2-year follow-up.

Materials And Methods: A total of 119 patients participated in the multidisciplinary team for obesity. Patients were followed up at 3 months, 6 months, 1 year, 18 months, and 2 years after their first visit. Individuals were divided into the high-protein diet (HPD) and standard-protein diet (SPD) group according to their results on a diet questionnaire that they filled out during follow-up.

Results: After 1.2 years, the mean body weight of the participants dropped from 89.7 kg to 80.9 kg ( < 0.001). The body adiposity index was reduced from 33.9 to 32.0 ( < 0.001), while the fat-free mass index from 17.0 to 15.2 ( = 0.043). Fasting glucose and HbA1c were also lower after treatment ( = 0.002 and 0.038 for FPG and HbA1c, respectively). Fasting insulin and HOMA-IR were reduced ( = 0.002 and <0.001 for fasting insulin and HOMA-IR, respectively). HDL-c increased along with weight loss (1.06 mmol/L vs. 1.19 mmol/L, < 0.001), and transaminase levels significantly dropped ( = 0.001 and 0.021 for ALT and AST, respectively). During treatment, mean protein intake was 29.9% in the HPD group and 19.5% in the SPD group ( < 0.001). Weight loss, reduction of visceral fat area, maintenance of lean body mass, body adiposity index, and fat-free mass index showed no statistical significance between the HPD and SPD groups, as well as glucose metabolic variables.

Conclusions: A multidisciplinary team for obesity management could significantly reduce body weight and improve metabolic indicators, including HDL-c, transaminase, and insulin resistance. A high-protein diet does not produce better weight control or body composition compared with a standard calorie-restricted diet.
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http://dx.doi.org/10.1155/2021/8862217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342138PMC
July 2021

Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma.

ACS Appl Nano Mater 2020 Nov 29;3(11):11129-11134. Epub 2020 Oct 29.

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Diffuse intrinsic pontine glioma (DIPG) is an invasive pediatric brainstem malignancy exclusively in children without effective treatment due to the often-intact blood-brain tumor barrier (BBTB), an impediment to the delivery of therapeutics. Herein, we used focused ultrasound (FUS) to transiently open BBTB and delivered radiolabeled nanoclusters (Cu-CuNCs) to tumors for positron emission tomography (PET) imaging and quantification in a mouse DIPG model. First, we optimized FUS acoustic pressure to open the blood-brain barrier (BBB) for effective delivery of Cu-CuNCs to pons in wildtype mice. Then the optimized FUS pressure was used to deliver radiolabeled agents in DIPG mouse. Magnetic resonance imaging (MRI)-guided FUS-induced BBTB opening was demonstrated using a low molecular weight, short-lived Ga-DOTA-ECL1i radiotracer and PET/CT before and after treatment. We then compared the delivery efficiency of Cu-CuNCs to DIPG tumor with and without FUS treatment and demonstrated the FUS-enhanced delivery and time-dependent diffusion of Cu-CuNCs within the tumor.
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http://dx.doi.org/10.1021/acsanm.0c02297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320805PMC
November 2020

Development and validation of a novel reporter gene assay for determination of recombinant human thrombopoietin.

Int Immunopharmacol 2021 Oct 29;99:107982. Epub 2021 Jul 29.

School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, Liaoning 110016, China. Electronic address:

Recombinant human thrombopoietin (rhTPO) was approved by the National Medical Products Administration in 2010 for the treatment of thrombocytopenia in patients with immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia. Nevertheless, no method for determining rhTPO bioactivity has been recorded in different national/regional pharmacopoeia. Novel methods for lot release and stability testing are needed that are simpler, quicker, and more accurate. Here, we developed a novel reporter gene assay (RGA) for rhTPO bioassay with Ba/F3 cell lines that stably expressed human TPO receptor and luciferase reporter driven by sis-inducible element, gamma response region, and gamma-interferon activated sequence. During careful optimization, the RGA method demonstrated high performance characteristics. According to the International Council for Harmonization Q2 (R1) guidelines and the Chinese Pharmacopoeia 2020 edition, the validation results demonstrated that this method is highly time-saving, sensitive, and robust for research, development, manufacture, and quality control of rhTPO.
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http://dx.doi.org/10.1016/j.intimp.2021.107982DOI Listing
October 2021

Magnetically modified in-situ N-doped Enteromorpha prolifera derived biochar for peroxydisulfate activation: Electron transfer induced singlet oxygen non-radical pathway.

Chemosphere 2021 Jul 2;284:131404. Epub 2021 Jul 2.

College of Resources & Environment, Hunan Agricultural University, Changsha, 410128, China.

Herein, in-situ N-doped Enteromorpha prolifera derived magnetic biochar (MBC) was prepared by loading FeO. It can effectively activate peroxodisulfate (PDS) to degrade tetracycline (TC) and easy recycling. The removal rate of TC reached 87.2%, and its possible degradation pathway was revealed through a liquid chromatography-mass spectrometer. This work first proposes the mechanism of in-situ N-doping and Fe synergistic effect on PDS activation. Unlike the well-reported role of N doping in activating PDS, except for the edge pyridine N plays a significant role in the activation of PDS. After the load of Fe, the synergistic effect of Fe and graphite N induces a non-radical path dominated by singlet oxygen (O) due to the excellent electron transfer function. Through chemical quenching experiment, electron spin detection, and electrochemical analysis, the mechanism of PDS activation by MBC was thoroughly investigate. This research will deepen the understanding of the mechanism of transition metals and carbon materials in synergistically driving PDS activation, and guide biochar-mediated PDS activation in environmental remediation.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131404DOI Listing
July 2021

Changes in chilled beef packaged in starch film containing sea buckthorn pomace extract and quality changes in the film during super-chilled storage.

Meat Sci 2021 Dec 7;182:108620. Epub 2021 Jul 7.

College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, China. Electronic address:

This study aimed to evaluate the effects of super-chilled storage (-1.3 °C) combined with starch film packaging containing different contents of sea buckthorn pomace extract (SSF, 0, 1, 2, and 3%, w/w) on the quality of chilled beef. The release kinetics, microstructure, and mechanical properties of the film were also measured to investigate its suitability for super-chilled storage. The results of the meat quality assessment showed that the L*, a*, and sensory evaluation values of the SSF-3% samples were significantly higher (P < 0.05), and the pH, b*, thiobarbituric acid reactive substance (TBARS), total volatile basic nitrogen (TVB-N), and total viable count (TCA) were significantly lower (P < 0.05) than the SSF-0%. The release of SBP from the SSF film was controlled by diffusion. Furthermore, SSF-3% was found to have a compact microstructure and good mechanical properties at the end of the super-chilled storage. The results demonstrated that SSF is an effective packaging material for beef at super-chilling temperatures.
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http://dx.doi.org/10.1016/j.meatsci.2021.108620DOI Listing
December 2021

Effects of undissociated SiO and TiO nano-particles on molting of Daphnia pulex: Comparing with dissociated ZnO nano particles.

Ecotoxicol Environ Saf 2021 Oct 5;222:112491. Epub 2021 Jul 5.

School of Life Sciences/State Key Laboratory of Biocontrol, Sun Yat-sen University, Guangzhou, PR China. Electronic address:

The toxic effects of different nanoparticles (NPs) have been reported to be quite different. The present study exposed Daphnia pulex to undissociated TiO NPs and SiO NPs, and dissociated ZnO NPs. The acute toxicity of the three oxide NPs and their influence on D. pulex molting, as well as the expressions of genes related to molting, energy metabolism and genetic material expression were compared. The results showed that the toxicities of TiO NPs and SiO NPs to D. pulex were weaker than ZnO NPs. During the exposure period, agglomerates of undissociated TiO NPs and SiO NPs influenced movements of D. pulex, and induced their molting after attaching to the body surface. Meanwhile, gene expressions of molting (eip) and energy metabolism (scot and idh) were up-regulated. Therefore, we inferred that the adhering to the surface of daphnids, promoting their molting and improving their energy metabolism may be parts of the toxicity mechanisms of undissociated NPs to D. pulex. On the contrary, dissociated ZnO NPs inhibited molting and gene expressions of eip, scot and idh, which showed a similar trend as bulk ZnO and ZnSO·7HO under the low-dose exposure condition. This indicates that the toxic effects of dissociated ZnO NPs were primarily caused by released Zn ions. The results provided direct evidence about the effect of nanoparticles on molting and revealed that the toxicity mechanisms of dissociated NPs were different from undissociated NPs.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112491DOI Listing
October 2021

Efficacy and biomarker exploration of camrelizumab combined with apatinib in the treatment of advanced primary liver cancer: a retrospective study.

Anticancer Drugs 2021 Jul 4. Epub 2021 Jul 4.

Department of Medical Oncology Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China.

This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0-47.7] and the overall DCR was 57.8% (95% CI, 42.8-72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9-13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.
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http://dx.doi.org/10.1097/CAD.0000000000001127DOI Listing
July 2021

Predicting intraoperative bleeding in patients undergoing a hepatectomy using multiple machine learning and deep learning techniques.

J Clin Anesth 2021 Jul 1;74:110444. Epub 2021 Jul 1.

Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2021.110444DOI Listing
July 2021

Applicability of the Smart Vision Screening Instrument among Chinese Primary School Students.

Iran J Public Health 2021 Jan;50(1):111-120

School of Health Sciences, Wuhan University, Wuhan, China.

Background: A smart vision screening instrument was applied for screening low eyesight in primary school students in Wuhan, China. We aimed to compare the differences in test results between this instrument and lamp-box visual acuity charts, assess the validity of the screening results, and perform a preliminary comparison of the cost inputs of the two approaches.

Methods: In this cross-sectional study conducted in Wuhan, China in 2017, vision tests were performed on the same day among enrolled primary school students by using the two approaches. The -test and test were performed to compare the differences, and the indicators of validity were calculated and receiver operating characteristic (ROC) curves were drawn. Existing cost-input data were collected and the budget was analyzed.

Results: In total, 1001 schoolchildren were included, and the prevalence of low eyesight was 21.18% (95% CI: 18.71-23.87%). The test results of the two approaches were not statistically different (=1.929, >0.05) and showed moderate consistency (=0.519, 0.001). Sensitivity and specificity of the instrument were 84.90% (95% CI: 79.21-89.30%) and 91.63% (95% CI: 89.42-91.64%), respectively; positive predictive value was 73.17% (95% CI: 67.10-78.51%); and negative predictive value was 95.76% (95% CI: 94.00-97.04%). Area under the ROC curve was 0.883 (95% CI: 0.853-0.913) and significantly differed from 0.5 (<0.001). The budget when using the instrument decreased 48.07% compared to that when using lamp-box visual acuity charts.

Conclusion: The test result of the instrument is reliable, and using it to conduct screening is cost-saving. Therefore, it might be popularized for vision monitoring in schoolchildren.
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http://dx.doi.org/10.18502/ijph.v50i1.5077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213619PMC
January 2021

Occurrence and risk assessment of pharmaceuticals and personal care products (PPCPs) against COVID-19 in lakes and WWTP-river-estuary system in Wuhan, China.

Sci Total Environ 2021 Oct 12;792:148352. Epub 2021 Jun 12.

Department of Environmental Science, Zhejiang University, Hangzhou 310058, PR China; Zhejiang Provincial Key Laboratory of Organic Pollution Process and Control, Hangzhou 310058, PR China.

The consumption of pharmaceuticals and personal care products (PPCPs) for controlling and preventing the COVID-19 would have sharply increased during the pandemic. To evaluate their post-pandemic environmental impacts, five categories of drugs were detected in lakes and WWTP-river-estuary system near hospitals of Jinyintan, Huoshenshan and Leishenshan in the three regions (J, H and L) (Regions J, H and L) in Wuhan, China. The total amount of PPCPs (ranging from 2.61 to 1122 ng/L in water and 0.11 to 164 ng/g dry weight in sediments) were comparable to historical reports in Yangtze River basin, whereas the detection frequency and concentrations of ribavirin and azithromycin were higher than those of historical studies. The distribution of concerned drugs varied with space, season, media and water types: sampling sites located at WWTPs-river-estuary system around two hospitals (Regions L and J) usually had relatively high waterborne contamination levels, most of which declined in autumn; lakes had relatively low waterborne contamination levels in summer but increased in autumn. The potential risks of detected PPCPs were further evaluated using the multiple-level ecological risk assessment (MLERA): sulfamethoxazole and azithromycin were found to pose potential risks to aquatic organisms according to a semi-probabilistic approach and classified as priority pollutants based on an optimized risk assessment. In general, the COVID-19 pandemic did not cause serious pollution in lakes and WWTPs-river-estuary system in Wuhan City. However, the increased occurrence of certain drugs and their potential ecological risks need further attention. A strict source control policy and an advanced monitoring and risk warning system for emergency response and long-term risk control of PPCPs is urgent.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197610PMC
October 2021

Facile one-pot magnetic modification of Enteromorpha prolifera derived biochar: Increased pore accessibility and Fe-loading enhances the removal of butachlor.

Bioresour Technol 2021 Oct 13;337:125407. Epub 2021 Jun 13.

College of Resources & Environment, Hunan Agricultural University, Changsha 410128, China.

In this work, Enteromorpha prolifera derived magnetic biochar (MBC) is prepared for the removal of butachlor (BTR) and characterized. The NaOH added during the magnetic loading process has an activating effect and enhancing the accessibility of the pores. Based on the BET result, the importance of pore accessibility rather than the specific surface area has been proposed. The maximum adsorption capacity of BTR for MBC is 158.5 mg/g. Then, the batch experiment shows that the adsorption of MBC to BTR fitted with the quasi-second-order kinetic model. The effect factors on the BTR removal were studied. Through the result of BET, Raman, XPS and FT-IR, the mechanism of MBC adsorption of butachlor was explored. After 3 cycles, the prepared MBC has a negligible reduction in the removal capacity of BTR, which provides a reference scheme for the large-scale application of Enteromorpha prolifera and the water treatment of BTR.
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http://dx.doi.org/10.1016/j.biortech.2021.125407DOI Listing
October 2021

Early-life exposure to tris (1,3-dichloro-2-propyl) phosphate caused multigenerational neurodevelopmental toxicity in zebrafish via altering maternal thyroid hormones transfer and epigenetic modifications.

Environ Pollut 2021 Sep 28;285:117471. Epub 2021 May 28.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), an alternative to brominated flame retardants, might pose an exposure risk to humans and wild animals during fetal development. Our recent study suggested that short-term TDCIPP exposure during early development caused sex-dependent behavioral alteration in adults. In the present study, multigenerational neurodevelopmental toxicity upon early-life exposure of parental zebrafish was evaluated, and the possible underlying mechanisms were further explored. Specifically, after embryonic exposure (0-10 days post-fertilization, dpf) to TDCIPP (0, 0.01, 0.10, and 1.00 μM), zebrafish larvae were cultured in clean water until the sexually matured to produce progeny (F1). The results confirmed neurodevelopmental toxicity in F1 larvae characterized by changes of developmental endpoints, reduced thigmotaxis, as well as altered transcription of genes including myelin basic protein a (mbpa), growth associated protein (gap43) and synapsin IIa (syn2a). Sex-specific changes in thyroid hormones (THs) indicated the relationship of abnormal THs levels with previously reported neurotoxicity in adult females after early-life exposure to TDCIPP. Similar changing profiles of TH levels (increased T3 and decreased T4) in adult females and F1 eggs, but not in F1 larvae, suggested that the TH disruptions were primarily inherited from the maternal fish. Further results demonstrated hypermethylation of global DNA and key genes related to TH transport including transthyretin (ttr) and solute carrier family 16 member 2 (slc16a2), which might affect the transport of THs to target tissues, thus at least partially contributing to the neurodevelopmental toxicity in F1 larvae. Overall, our results confirmed that early-life TDCIPP exposure of parental fish could affect the early neurodevelopment of F1 offspring. The underlying mechanism could involve altered TH levels inherited from maternal zebrafish and epigenetic modifications in F1 larvae.
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http://dx.doi.org/10.1016/j.envpol.2021.117471DOI Listing
September 2021

Influencing Factors of Depression among Adolescent Asians in North America: A Systematic Review.

Healthcare (Basel) 2021 May 4;9(5). Epub 2021 May 4.

Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang 550002, China.

Background: Asian American adolescents experience rates of depression comparable to or greater than those of other ethnic minorities. The purpose of this systematic review is to summarize psychosocial factors related to depressive symptoms of Asian American adolescents between the ages of 10 to 19.

Methods: Various electronic databases were systematically searched to identify research articles published from 2000 to 2021, and the psychosocial factors influencing depression among Asian adolescents in North America were examined.

Results: A total of 81 studies were included in this systematic review. Consistent findings on relationships between depressive symptoms and influencing factors included (a) acculturative stress, (b) religious or spiritual significance for females, (c) parent-child cohesion, (d) harsh parenting style, (e) responsive parenting style, (f) racial or ethnic discrimination, (g) being bullied, (h) positive mentor presence, and (i) exposure to community violence. Collectively, the majority of included studies suggest that depressive symptoms were more likely found among Asian American adolescents who (a) are older, (b) are female, (c) have immigrant status, (d) exhibit coping behaviours, (e) face academic challenges, (f) face a poor socioeconomic situation, (g) perceive parent-child conflict, (h) perceive maternal disconnectedness, and (i) perceive negative peer relations. A number of conflictive findings also existed.

Discussion/conclusions: This systematic review provides a summary of the various psychosocial factors on individual, familial, and social levels, which influenced the depressive symptoms of Asian American adolescents. Such findings offer a starting point to examine what factors should be necessarily included in related depression-preventive intervention design and evaluation. Culturally sensitive care, strengthened family-school-community collaboration, and targeted research efforts are needed to meet the needs of Asian adolescents experiencing a range of depressive symptoms.
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http://dx.doi.org/10.3390/healthcare9050537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147770PMC
May 2021

Streptavidin-functionalized terahertz metamaterials for attomolar exosomal microRNA assay in pancreatic cancer based on duplex-specific nuclease-triggered rolling circle amplification.

Biosens Bioelectron 2021 Sep 9;188:113314. Epub 2021 May 9.

Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address:

Exosomal microRNA (miRNA) is a promising non-invasive biomarker for liquid biopsies. Herein, we fabricated a terahertz (THz) metamaterial biosensor that comprises an array of gold (Au) discs surrounded by annular grooves for exosomal miRNA assays based on duplex-specific nuclease (DSN)-triggered rolling circle amplification (RCA). In this strategy, the target miRNA is captured by a probe P0 immobilized on magnetic beads (MBs); it then repeatedly releases a primer P1 under the action of DSN, which acts as a highly specific initiator of the subsequent RCA step utilizing biotin-dUTP. After target recycling and nucleic acid amplification, the biotinylated amplification products were captured by the streptavidin (SA)-functionalized THz metamaterials, and further conjugated to SA-modified AuNPs that permit formation of a trimeric complex of SA-biotinylated RCA products-AuNP. The complex population scales with the starting concentration of the target miR-21, resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 84 aM. Significant distinctions are seen in the frequency shifts for exosomal miR-21 quantitation in clinical plasma samples between pancreatic cancer patients and healthy controls. The frequency shifts of the THz metamaterials are consistent versus the reverse transcription-polymerase chain reaction (RT-PCR) results, illustrating the applicability and accuracy of our assay in real clinical samples.
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http://dx.doi.org/10.1016/j.bios.2021.113314DOI Listing
September 2021

Mst1/2 Kinases Inhibitor, XMU-MP-1, Attenuates Angiotensin II-Induced Ascending Aortic Expansion in Hypercholesterolemic Mice.

Circ Rep 2021 Apr 20;3(5):259-266. Epub 2021 Apr 20.

Saha Cardiovascular Research Center, University of Kentucky Lexington, KY USA.

Ascending and abdominal aortic aneurysms (AAs) are asymptomatic, permanent dilations of the aorta with surgical intervention as the currently available therapy. Hippo-Yap signaling cascade plays a critical role in stem cell self-renewal, tissue regeneration and organ size control. By using XMU-MP-1, a pharmacological inhibitor of the key component of Hippo-Yap signaling, MST1/2, we examined the functional contribution of Hippo-Yap in the development of AAs in Angiotensin II (AngII)-infused hypercholesterolemic mice. MST, p-MST, p-YAP, p-MOB and TAZ proteins in AngII-infused ascending and abdominal aortas were assessed by immunohistochemical and western blot analyses. To examine the effect of MST1/2 inhibition on AAs, western diet-fed low density lipoprotein (LDL) receptor -/- mice infused with AngII were administered with either vehicle or XMU-MP-1 for 5 weeks. Hippo-YAP signaling proteins were significantly elevated in AngII infused ascending and abdominal aortas. XMU-MP-1 administration resulted in the attenuation of AngII-induced ascending AAs without influencing abdominal AAs and aortic atherosclerosis. Inhibition of Hippo-YAP signaling also resulted in the suppression of AngII-induced matrix metalloproteinase 2 (MMP2) activity, macrophage accumulation, aortic medial hypertrophy and elastin breaks in the ascending aorta. The present study demonstrates a pivotal role for the Hippo-YAP signaling pathway in AngII-induced ascending AA development.
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http://dx.doi.org/10.1253/circrep.CR-20-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099673PMC
April 2021

Nonalcoholic Fatty Liver Disease Development in Zebrafish upon Exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate, a Novel Brominated Flame Retardant.

Environ Sci Technol 2021 05 2;55(10):6926-6935. Epub 2021 May 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, can potentially cause lipid metabolism disorder; however, its biological effects on lipid homeostasis remain unknown. We investigated its ability to cause nonalcoholic fatty liver disease (NAFLD) in zebrafish. Female zebrafish were fed a high-fat diet (HFD, 24% crude fat) or normal diet (ND, 6% crude fat), and exposed to TBPH (0.02, 2.0 μM) for 2 weeks. Consequently, HFD-fed fish showed a higher measured concentration of TBPH than ND-fed fish. Further, TBPH-treated fish in the HFD group showed higher hepatic triglyceride levels and steatosis. In comparison to ND-fed fish, treating HFD-fed fish with TBPH led to an increase in the concentration of several proinflammatory markers (e.g., TNF-α, IL-6); TBPH exposure also caused oxidative stress. In addition, the mRNA levels of genes encoding peroxisome proliferator-activated receptors were increased, and the transcription of genes involved in lipid synthesis, transport, and oxidation was upregulated in both ND- and HFD-fed fish. Both the ND and HFD groups also showed demethylation of the peroxisome proliferator-activated receptor-γ coactivator 1-α gene promoter, accompanied by the upregulation of and transcription. To summarize, we found that TBPH amplified the disruption of lipid homeostasis in zebrafish, leading to the enhancement of diet-induced NAFLD progression.
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http://dx.doi.org/10.1021/acs.est.1c01476DOI Listing
May 2021

Dissipation behavior, residue distribution, and dietary risk assessment of fluopimomide and dimethomorph in taro using HPLC-MS/MS.

Environ Sci Pollut Res Int 2021 Aug 12;28(32):43956-43969. Epub 2021 Apr 12.

College of Resources and Environment, Hunan Agricultural University, Changsha, 410128, China.

Dimethomorph is a morpholine broad-spectrum fungicide and effectively controls taro blight, cucumber downy mildew, rice blast disease, and others. Fluopimomide is a newly developed broad-spectrum fungicide to primarily control oomycetes and rhizoctonia diseases. Taro, one of the earliest cultivated crops, is a staple food in Africa, Oceania, and Asia. Recently, a commercial suspension concentrate formulation containing 15% fluopimomide and 25% dimethomorph has been registered in China, the second largest taro producer in the world. The objective of this study was to develop a high-performance liquid chromatography tandem mass spectrometry method to detect the residues of fluopimomide and dimethomorph concurrently in taro samples. The results showed that the average recoveries of fluopimomide and dimethomorph ranged from 83 to 108%, and relative standard deviations (RSD) ranged from 1 to 11%. The limit of quantitation (LOQ) was 0.01 mg kg for the two compounds. The dissipation results demonstrated that both fluopimomide and dimethomorph in taro degraded rapidly in taro fields, and the residues of the two fungicides were below the LOQ within 14 days post-application. The final residue levels of fluopimomide and dimethomorph in taro were lower than 0.066 mg kg 28 days post-application. For dietary risk assessments, the dietary structure of different genders and age of people in China exposure risk assessment and whole diet exposure risk assessment shows that the risk quotient (RQ) values were substantially lower than 100%, suggesting that the long-term risks of fluopimomide/dimethomorph mixed formulation in taro at the recommended dosage were negligible. In summary, our combined results from the dissipation behaviors, terminal residues, and dietary risk assessments provide the critical empirical data for the establishment of the maximum residue levels (MRLs) of the two broad-spectrum fungicides in taro, a traditional food for African, Oceanic, and South Asian cultures.
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http://dx.doi.org/10.1007/s11356-021-13713-zDOI Listing
August 2021

Clinical therapeutic evaluation of vacuum sealing drainage and precise ultrasound-guided debridement in the treatment of non-lactational mastitis.

Exp Ther Med 2021 May 12;21(5):480. Epub 2021 Mar 12.

Department of Thoracic and Breast Surgery, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian 361000, P.R. China.

The aim of the present study was to compare the efficacy of vacuum sealing drainage (VSD) and precise ultrasound-guided debridement in the treatment of non-lactational mastitis and to determine the optimal surgical treatment. A set of 60 cases diagnosed with non-lactational mastitis who had received surgical treatment at the Department of Thoracic and Breast Surgery of Xiamen Hospital of Traditional Chinese Medicine (Xiamen, China) between July 2017 and June 2019 were included. According to the surgical method, 30 patients were assigned to the VSD group and 30 patients were assigned to the precise ultrasound-guided debridement group. The clinicopathological data of the two groups were compared. The overall rates of recurrence and new incidence were 6.8 and 8.5%, respectively. The mean total disease course was 5.3 months and all of the patients were cured after treatment. Except for the hospitalization time and postoperative pain scores, the clinicopathological data between the two groups were similar. The hospitalization time in the VSD group was significantly longer than that in the precise ultrasound-guided debridement group. Pain scores on the first and third days after the operation in the precise ultrasound-guided debridement group were significantly higher than those in the VSD group (P=0.008 and 0.001, respectively). In conclusion, the efficacies of VSD and precise ultrasound-guided debridement for the treatment of non-lactational mastitis were generally both satisfactory without significant differences. Of note, the former is suitable for patients with inverted nipples and obvious skin ulcerations, while the latter is mainly suitable for patients with abscesses, small surgical incisions and those who require short hospital stays.
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http://dx.doi.org/10.3892/etm.2021.9911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976372PMC
May 2021

Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice.

Arterioscler Thromb Vasc Biol 2021 05 25;41(5):1694-1709. Epub 2021 Mar 25.

Saha Cardiovascular Research Center (L.M., M.O., A.J., D.T., W.J., J.J.M., L.Y., A.B., D.A.H., V.S.), University of Kentucky, Lexington.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062307PMC
May 2021

pH-Sensitive Nanoparticles Composed Solely of Membrane-Disruptive Macromolecules for Treating Pancreatic Cancer.

ACS Appl Mater Interfaces 2021 Mar 9;13(11):12824-12835. Epub 2021 Mar 9.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, China.

Pancreatic tumor is extremely lethal because its cancerous structures are sheltered by dense stromal barriers that hinder the infiltration of therapeutics. To facilitate the infiltration of therapeutics through the stromal barrier, remodeling the stroma with an adjuvant prior to or together with gemcitabine-the current chemotherapeutic standard for pancreatic cancer-is a widely studied strategy; nevertheless, the intrinsic nonuniformity in distribution (spatial and/or temporal) of the adjuvant and gemcitabine has raised the increased risk of tumor metastasis as a major concern. In this work, we propose long-circulating, pH-sensitive nanoparticles composed solely of cellular membrane-disruptive molecules as a new approach for treating pancreatic cancer. Using a micelle of a polymeric mimetic of host defense peptides as the model for such nanoparticles, we showed that this nanoparticle exhibited acid-activated cytotoxicity indiscriminately to both cancerous and fibroblast cells, and the underlying activity mode was acid-activatable disruption of cellular membrane integrity. As a result, our acid-activatable nanoparticle effectively permeabilized the stromal barrier and eradicated the otherwise sheltered pancreatic cancer cells, as demonstrated with a three-dimensional spheroid in which a shell of fibroblast NIH-3T3 cells was cultured over a core of pancreatic BxPC-3 cells. When administered intravenously into mouse models bearing xenograft pancreatic BxPC-3 tumors, our acid-activatable nanoparticle efficiently inhibited tumor growth without causing noticeable off-target adverse effects or promoting tumor metastasis. Notably, this nanoparticle permeabilized the otherwise dense pancreatic tumor tissue while significantly suppressing the expression of extracellular matrix components and activated cancer-associated fibroblasts. Although the feasibility of our approach was demonstrated with a micelle of a polymeric molecule, we trust that future research efforts in this pathway may eventually offer translational formulations for improving the therapeutic efficacy of pancreatic cancer.
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http://dx.doi.org/10.1021/acsami.0c16576DOI Listing
March 2021
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