ACS Nano
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2023
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IF 17.1
Yusheng Gong,Shuai Tong,Xixuan Li,Xiuli Chen,Yushuang Liu,Nan Li,Jiarong Xu,Rengui Xu,Yusong Guo,Fei Xiao,Xiaoyuan Chen,Wei Chen
The mucosa-interfacing systems based on bioinspired engineering design for sampling/drug delivery have manifested crucial potential for the monitoring of infectious diseases and the treatment of mucosa-related diseases. However, their efficiency and validity are severely restricted by limited contact area for molecular transfer and dissatisfactory capture/detachment capability. Herein, inspired by the multilayer villus structure of the small intestine that enables high nutrient absorption, a trigonometric function-based periodic pattern was fabricated and integrated on the base layer of the microneedle patch, exhibiting a desirable synergistic effect with needle tips for deep sample enrichment and promising molecular transfer, significantly improving the device-mucosa bidirectional interaction. Moreover, mathematical modeling and finite element analysis were adopted to visualize and quantify the microcosmic molecular transmission process, guiding parameter optimization in actual situation. Encouragingly, these intestinal villi-inspired mathematically base-layer engineered microneedles (IMBEMs) have demonstrated distinguished applicability among mucosa tissue with varying surface curvatures, tissue toughness, and local environments, and simultaneously, have gained favorable support from healthy volunteers receiving preliminary test of IMBEMs patches. Overall, validated by numerous in vitro and in vivo tests, the IMBEMs were confirmed to act as a promising candidate to facilitate mucosa-based sampling and topical drug delivery, indicating highly clinical translation potential.
研究领域:
生物医学工程
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药剂学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
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IF 4.5
You Xiao,Yuanyuan He,Chongsi Xu,Mei Li,Fan Hu,Wei Wang,Zhenquan Wang,Yi Cao
MoS 2 nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS 2 NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS 2 NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS 2 NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS 2 materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
研究领域:
纳米技术
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分子生物学
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毒理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yaozhong Lv,Yajun Yang,Ying Chen,Dongfan Wang,Yipeng Lei,Mingyue Pan,Zhenzhong Wang,Wei Xiao,Yujie Dai
In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides , a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography . PCP-2 is a heteropolysaccharide composed of glucose, galactose , mannose , and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3- β -D-Glc and 1,6- β -D-Glc as the backbone glucans and 1,6- α -D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF- α . In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3 + CD4 + T cells , increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.
研究领域:
免疫学
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药理学
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生物化学
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真菌学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2021
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IF 8.071
Jiajing Xin,Saihong Yan,Xiangsheng Hong,Huan Zhang,Jinmiao Zha
Clozapine (CLZ) is a neuroactive pharmaceutical that is frequently detected in aquatic environments. Although the cardiotoxicity, developmental toxicity, and neurotoxicity of CLZ in aquatic non-target organisms have been reported, its lipotoxicity and underlying mechanism are unknown. Therefore, in this study, 2-month-old Chinese rare minnows were exposed to 0, 0.1, 1, and 10 μg/L CLZ for 90 days. Overt dyslipidemia was observed after CLZ exposure, whereas the body weights of females significantly increased after CLZ exposure (p < 0.05). In addition, obvious hepatocyte vacuolization and hepatic lipid droplet accumulation were observed at all treatment groups (p < 0.05). The activities of sterol regulatory element binding proteins 1 (SREBP1) and fatty acid synthase (FAS) were significantly upregulated at the 1 and 10 μg/L CLZ treatment groups (p < 0.05). Moreover, evident cell boundary disintegration of the intestinal villi and increasing mucus secretion were observed at all treatment groups (p < 0.05). Furthermore, the diversity of the gut microbiota increased, whereas the relative abundances of Proteobacteria , Firmicutes and Bacteroidetes significantly increased after CLZ exposure (p < 0.05). Furthermore, significantly increased bacterial secondary bile acid biosynthesis activity in Chinese rare minnows was observed after 1 μg/L CLZ exposure (p < 0.05). Therefore, our findings confirmed that CLZ induced lipotoxicity by stimulating SREBP1 and affecting the bacterial secondary bile acid biosynthesis activity in Chinese rare minnows.
研究领域:
环境科学
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毒理学
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水生生物学
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微生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Muhammad Junaid,Shulin Liu,Qiang Yue,Jun Wang
Nanoplastics (NPs) interact with cooccurring chemicals and natural organic matter (NOM) in the environment, forming complexes that can change their bioavailability and interfacial toxicity in aquatic organisms . This study aims to elucidate the single and combined impacts of 21-day chronic exposure to low levels of polystyrene NPs (size 80 nm) at 1 mg/L and 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES or F53B) at 200 μg/L in the presence and absence of NOM (humic acid-HA and bovine serum albumin-BSA at 10 mg/L) in adult zebrafish ( Danio rerio ). Our findings through multiple bioassays, revealed that the mixture group (M), comprising of NPs, F53B, HA, and BSA, caused a higher level of toxicity compared to the single NPs (AN), single F53B (AF), and combined NPs+F53B (ANF) groups. The mixture exposure caused the highest level of vacuolization and nuclear condensation in hepatocytes, and most of the intestinal villi were fused and highly reduced in villi length and crypt depth. Further, the T-AOC levels were significantly lower ( p < 0.05), while the MDA levels in the liver and intestine were significantly higher ( p < 0.05) in the M group with downregulation of nfkbiaa , while upregulation of prkcda , csf1ra , and il1b apoptosis genes in the liver. Pairwise comparison of gut microbiota showed significantly higher ( p < 0.05) abundances of various genera in the M group, including Gordonia , Methylobacterium , Tundrisphaera , GKS98 , Pedomicrobium , Clostridium , Candidatus and Anaerobacillus , as well as higher abundance of genera including pathogenic strains, while control group showed higher abundance of probiotic genus ZOR0006 than exposed group ( p < 0.01). The transcriptomic analysis revealed highest number of DEGs in the M group (2815), followed by the AN group (506) and ANF group (206) with the activation of relaxin signaling pathway-RSP ( slc9a1 , slc9a2 ) and AMP-activated protein kinase (AMPK) pathway ( plin1 ), and suppression of the toll-like receptor (TLR) pathway ( tlr4a , tlr2 , tlr1 ), cytokine-cytokine receptor interaction (CCRI) pathway ( tnfb , il21r1 , il21 , ifng1 ), and peroxisome proliferator-activated receptors (PPAR) pathway ( pfkfb3 ). Overall, toxicity in the M group was higher, indicating that the HA and BSA elevated the interfacial impacts of NPs and F53B in adult zebrafish after chronic environmentally relevant exposure, implying the revisitation of the critical interaction of NOM with co-occurring chemicals and associated impacts
研究领域:
环境科学
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毒理学
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水生生物学
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分子生物学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Zulikeyan Manafu,Ronglijiao Du,Tuerhong Kudereti,Gulimire Abulikemu,Shakeel Ahmed Lakho,Lijun Xue,Ayibike Bierdelieke,Faiz Muhammad Khand,Ambreen Leghari,Yuan Xie,Saifuding Abula,Bateer Bake,Qingyong Guo,Adelijiang Wusiman
This study investigated the structure of acid Alhagi camelorum Fischa polysaccharide (aAP) and its impact on intestinal activity in mice. The results showed that aAP comprised of the fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galacturonic acid, glucuronic acid with the molar ratio of 0.81:14.97:10.84:11.14:3.26:0.80:0.80:54.92:2.47 with the molecular weight (Mw) of 22.734 kDa. Additionally, the composition of aAP was assessed via FT-IR, methylation, and NMR analyses, indicating that the backbone of the aAP was consisted of →4)-α-D-Gal p A-6-OMe-(1 → 4)-α-Gal p A-(1 → and →4)-α-D-Gal p A-6-OMe-(1 → 2)-α-L-Rha p -(1→, as well as →4)-β-D-Gal p - and →5)-α-L-Ara f - for the branched chain. Furthermore, ICR mice underwent intragastric administration of different concentrations of aAP for 7 consecutive days. The results showed that aAP enhanced the murine spleen and thymus indices, promoted the secretion of serum lgG antibody, intestinal lgA antibody and intestinal cytokines, improved the morphology of intestinal villi and crypts, enhanced quantity of intestinal IELs and IgA+ cells, and activated T lymphocytes and DC cells in MLNs. In summary, these findings suggest that the utilization of aAP could enhance the immune response of the murine intestinal mucosa.
研究领域:
药理学
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免疫学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Fang Wu,Yaqiong Liu,Ming Zhang,Xinlei Yuan,Tengteng Ji,Yutong Jin,Yixuan Li,Ran Wang,Yanling Hao,Bing Fang
Recent studies have shown that 1-oleo-2-palmito-3-linoleyl glycerol (OPL) is the most abundant triacylglycerol in human breast milk in China. Epidemiologic studies have shown that sn -2 palmitate improves the absorption of fatty acids and calcium in infants. However, there have been few studies of the specific mechanism by which OPL affects intestinal function. In the present study, we have characterized the effects of various levels of OPL supplementation on the development of the intestinal epithelium and the intestinal microbiota of neonatal mice. OPL supplementation increased the body masses and intestinal lengths of weaned mice and promoted defecation. These positive effects were related to the effect of OPL to promote the development of intestinal villi and crypts. OPL increased the expression of the intestinal stem cell markers Olfm4 and Sox9 in the jejunum and ileum, which promoted their differentiation into goblet cells and Paneth cells. It also promoted the integrity of the epithelial barrier by increasing the secretion of mucin 2 and lysozyme 1 and the expression of the tight junction proteins occludin, ZO1, claudin 2, and claudin 3. More importantly, we found that low dose-OPL promotes the transformation of the intestinal microbiota of neonatal mice to the mature state in 3-month-old mice, increases the proportion of Firmicutes, and reduces the proportion of Bacteroidota. The proportions of anaerobic genera of bacteria, such as Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ligilactobacillus, and Bifidobacterium were higher, as were the key producers of short-chain fatty acids, such as Bacteroides and Blautia . OPL also increased the butyric acid content of the feces, which significantly correlated with the abundance of Lactobacillus . High-dose OPL tended to be more effective at promoting defecation and the development of the villi and crypts, but these effects did not significantly differ from those achieved using the lower dose. A low dose of OPL was more effective at increasing the butyric acid content and causing the maturation of microbes. In summary, the OPL supplementation of newborn mice promotes the establishment of the intestinal epithelial layer structure and barrier function, and also promotes the transformation of the intestinal microbiota to a mature state. This study lays a theoretical foundation for the inclusion of OPL in infant formula and provides a scientific basis for the development of intestinal health products.
研究领域:
营养学
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胃肠病学
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微生物学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）