Advanced Biology
·
2024
·
IF 3.2
Weidong Zhong,Jinshui Chen,Qifeng Xie,Wenyue Cheng,Meibiao Zhao,Yang Sun,Jing Dai,Jian Zhang
Biological scaffolds are widely utilized in hernia treatment due to their exceptional pro-regenerative properties, which mitigate scar formation. However, serious complications occurred, caused by inflammatory response, premature degradation, and mechanical failure. Consequently, improvements of the biological scaffold are necessary to mitigate these risks. In this study, a novel biological scaffold integrating basement membrane-containing urinary bladder matrix (UBM) and small intestinal submucosa (SIS) is developed, and its safety and effectiveness are assessed in comparison to a commercial SIS (c-SIS) scaffold. The introduction of UBM as top surface layers significantly promotes cell adhesion, facilitating rapid formation of isolated regeneration zone. Proteomic analysis has demonstrated a more efficient decellularization of the UBM/SIS scaffold, which subsequently mitigates inflammation in murine models, and promotes the polarization of macrophages toward the pro-healing M2 phenotype in a rat model of abdominal wall muscle defect. Furthermore, a two-year repair trial is conducted on a full-thickness abdominal wall muscle defect in canine model and confirmed that the UBM/SIS scaffold exhibits reduced seroma occurrences and enhanced tissue repair performances. Overall, the efficacy of this novel biological scaffold suggests its potential to minimize hernia recurrence in clinical practice and mitigate patient suffering from severe inflammatory responses.
研究领域:
生物医学工程
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再生医学
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材料科学
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DOI
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Miaomiao Sun,Honghong Zhan,Xiaoliang Long,Ali M. Alsayed,Zhe Wang,Fancheng Meng,Guowei Wang,Jingxin Mao,Zhihua Liao,Min Chen
Background Irinotecan (CPT-11) is used as chemotherapeutic drug for treatment of colorectal cancer. However, without satisfactory treatments, its gastrointestinal toxicities such as diarrhea and intestinal inflammation severely restrained its clinical application. Roots of Aucklandia lappa Decne. are used as traditional Chinese medicine to relieve gastrointestinal dysfunction and dehydrocostus lactone (DHL) is one of its main active components. Nevertheless, the efficacy and mechanism of DHL against intestinal mucositis remains unclear. Purpose The present study aimed to investigate the protective effects of DHL on CPT-11-induced intestinal mucositis and its underlying mechanisms. Methods The protective effect of DHL was investigated in CPT-11-induced mice and lipopolysaccharide (LPS)+CPT-11 induced THP-1 macrophages. Body weight, diarrhea score, survival rate, colon length, and histopathological changes in mice colon and jejunum were analyzed to evaluate the protective effect of DHL in vivo . And DHL on reducing inflammatory response and regulating TLR4/NF‐κB/NLRP3 pathway in vivo and in vitro were explored. Moreover, DHL on the interaction between TLR4 and MD2 was investigated. And silencing TLR4 targeted by siRNA was performed to validate the mechanisms of DHL on regulating the inflammation. Results DHL prevented CPT-11-induced intestinal damage, represented by reducing weight loss, diarrhea score, mortality rate and the shortening of the colon. Histological analysis confirmed that DHL prevented intestinal epithelial injury and improved the intestinal barrier function in CPT-11 induced mice. Besides, DHL significantly downregulated the level of inflammatory cytokines by inhibiting TLR4/NF-κB/NLRP3 signaling pathway in CPT-11-induced mice and LPS+CPT-11-induced THP-1 macrophages. In addition, DHL blocked TLR4/MD2 complex formation. Molecular docking combined with SIP and DARTS assay showed that DHL could bind to TLR4/MD2 and occludes the hydrophobic pocket of MD2. Furthermore, Silencing TLR4 abrogated the effect of DHL on LPS+CPT-11 induced inflammatory response in THP-1 macrophages. Additionally, DHL ameliorate the CPT-11-induced intestinal mucositis without affecting the anti-tumor efficacy of CPT-11 in the tumor xenograft mice. Conclusion This study found that DHL exhibited the anti-inflammatory effects in CPT-11-induced intestinal mucositis by inhibiting the formation of TLR4/MD2 complex and then regulation of NF-κB/NLRP3 signaling pathway. DHL is potentially served as a novel strategy of combined medication with CPT-11.
研究领域:
药理学
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免疫学
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肿瘤学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Changhong Wu,Jie Yang,Chenxiao Ye,Hui Wu,Wenxi Shu,Rongrong Li,Sihan Wang,Yi Lu,Haitao Chen,Zewei Zhang,Qinghua Yao
Background 5-Fluorouracil (5-Fu), a prominent chemotherapeutic agent for colorectal cancer (CRC) treatment, is often associated with gastrointestinal toxicities, particularly diarrhea. Our previous study demonstrated that berberine (BBR) ameliorates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota in rats. Nevertheless, the precise molecular mechanism underlying BBR's protective effect on intestinal mucosa remains elusive, and its impact on the anti-tumor efficacy of 5-Fu warrants further investigation. Methods The effect of BBR on 5-Fu-induced intestinal mucosal injury was investigated using a tumor-bearing murine model, employing H&E staining, 16 S rDNA sequencing, transcriptome sequencing, Western blot analysis, cell experiments and constructing a pseudo-germ-free tumor xenograft model. Result Our findings demonstrate that BBR alleviates intestinal mucosal damage, reduces the levels of inflammatory factors (IL-6, TNF-α, and IL-1β), and inhibits epithelial cell apoptosis in 5-Fu-treated mice without compromising 5-Fu's anti-tumor efficacy. Moreover, 16 S rDNA sequencing indicated that BBR significantly increases the abundance of Akkermansia and decreases the abundance of pathogenic bacteria Escherichia/Shigella at the genus level. Mechanistically, transcriptome sequencing and Western blot analysis confirmed that BBR upregulates PI3K/AKT/mTOR expression in the intestinal mucosa. However, this effect was not observed in tumor tissues. Notably, BBR did not demonstrate a direct protective effect on 5-Fu-treated CCD841 and SW480 cells. Additionally, BBR had no effect on the PI3K/AKT/mTOR pathway in the intestinal tissue of the 5-Fu-treated mouse model with a depleted gut microbiota. Conclusion This study indicates that BBR alleviates 5-Fu-induced intestinal mucosal injury by modulating the gut microbiota and regulating the PI3K/AKT/mTOR signaling pathway without compromising the anti-tumor efficacy of 5-Fu.
研究领域:
肿瘤学
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微生物学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
mSphere
·
2024
·Vol. 9
·期 1
·
IF 3.7
Longxian Lv,Siqi Ren,Huiyong Jiang,Ren Yan,Wenyi Chen,Ruiyi Yan,Jinming Dong,Li Shao,Ying Yu
Acetaminophen is a widely used antipyretic and analgesic drug, and its overdose is the leading cause of drug-induced acute liver failure. This study aimed to investigate the effect and mechanism of Lacticaseibacillus casei Shirota (LcS), an extensively used and highly studied probiotic, on acetaminophen-induced acute liver injury. C57BL/6 mice were gavaged with LcS suspension or saline once daily for 7 days before acute liver injury was induced via intraperitoneal injection of 300 mg/kg acetaminophen. The results showed that LcS significantly decreased acetaminophen-induced liver and ileum injury, as demonstrated by reductions in the increases in aspartate aminotransferase, total bile acids, total bilirubin, indirect bilirubin, and hepatic cell necrosis. Moreover, LcS alleviated acetaminophen-induced intestinal mucosal permeability, decreased serum IL-1α and lipopolysaccharide levels, and elevated serum eosinophil chemokine (eotaxin) and hepatic glutathione levels. Furthermore, analysis of the gut microbiota and metabolome showed that LcS reduced the acetaminophen-enriched levels of Cyanobacteria, Oxyphotobacteria, long-chain fatty acids, cholesterol, and sugars in the gut. Additionally, the transcriptomic and proteomic results showed that LcS mitigated the decrease in metabolic and immune pathways as well as glutathione formation during acetaminophen-induced acute liver injury. This is the first study showing that pretreatment with LcS alleviates acetaminophen-enriched acute liver injury, and it provides a reference for the application of LcS.
研究领域:
药理学
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肝病学
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微生物学
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免疫学
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代谢组学
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转录组学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2024
·Vol. 25
·期 23
·12998
·
IF 4.9
Chen Wang,Mei Qiu,Shuo Wang,Jinjin Luo,Ling Huang,Qi Deng,Zhijia Fang,Lijun Sun,Ravi Gooneratne
Intestinal mucosal barrier damage is regarded as the critical factor through which chronic unpredictable mild stress (CUMS) leads to a variety of physical and mental health problems. However, the exact mechanism by which CUMS induces intestinal mucosal barrier damage is unclear. In this study, 14, 28, and 42 d CUMS model mice were established. The indicators related to ileal mucosal barrier damage (IMBD), the composition of the ileal microbiota and its amino acid (AA) and short-chain fatty acid (SCFA) metabolic functions, and free amino acid (FAA) and SCFA levels in the ileal lumen were measured before and after each stress period. The correlations between them are analyzed to investigate how CUMS induces intestinal mucosal barrier damage in male C57BL/6 mice. With the progression of CUMS, butyric acid (BA) levels decreased (14 and 28 d) and then increased (42 d), and IMBD progressively increased. In the late CUMS stage (42 d), the degree of IMBD is most severe and positively correlated with significantly increased BA levels (p< 0.05) in the ileal lumen and negatively correlated with significantly decreased FAAs, such as aspartic, glutamic, alanine, and glycine levels (p< 0.05). In the ileal lumen, the abundance of BA-producing bacteria (Muribaculaceae,Ruminococcus, andButyricicoccus) and the gene abundance of specific AA degradation and BA production pathways and their related enzymes are significantly increased (p< 0.05). In addition, there is a significant decrease (p< 0.05) in the abundance of core bacteria (Prevotella,Lactobacillus,Turicibacter,Blautia, andBarnesiella) that rely on these specific AAs for growth and/or are sensitive to BA. These changes, in turn, promote further colonization of BA-producing bacteria, exacerbating the over-accumulation of BA in the ileal lumen. These results were validated by ileal microbiota in vitro culture experiments. In summary, in the late CUMS stages, IMBD is related to an excessive accumulation of BA caused by dysbiosis of the ileal microbiota and its overactive AA degradation.
研究领域:
神经科学
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微生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Linran Song,Jingjia Ye,Xinrang Zhai,Huiqiang Yuan,Xiaofei Gao,Amoz Thomas Zhao-En Chin,Wei Wei,Wenyan Zhou
The current method of bladder augmentation using the autologous intestine is limited due to complications. Bladder tissue engineering with biomaterials offers alternative solutions to using autologous tissues, helping to avoid related problems. Here, we developed a membrane based on bioactive decellularized small intestinal submucosa (dSIS). To address the limitation of dSIS being nonwaterproof in urinary conditions, we combined dSIS with a biocompatible polymer, polycaprolactone (PCL). The dSIS has been proven to have an acceptably low DNA content as a suitable transplantable material while maintaining bioactive growth factors for regenerative medicine. The content of PCL was optimized to ensure waterproof properties. We demonstrated that the composite membrane could block the permeation of water and is suturable with a 4-0 suture. In vitro biocompatibility tests using simian virus 40 (SV40)-transformed human uroepithelial cells (SV-HUC), human fibroblasts (HF), and mouse skeletal muscle cell line (C1C12) indicated that the dSIS-PCL composite membrane had no negative effects on the cells, including cell viability, proliferation, migration, and even mRNA transcription. Subcutaneous implantation in vivo also showed a low inflammatory response, suggesting the biocompatibility of this composite material. Overall, the dSIS-PCL composite membrane has immense potential as a candidate material for bladder tissue engineering.
研究领域:
生物医学工程
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组织工程
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泌尿外科学
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再生医学
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生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2024
·
IF 3.3
Lin Chen,Qihong Jiang,Shiwei Yao,Chenkai Jiang,Hongling Lu,Wenjun Hu,Shaofang Yu,Mingqian Li,Yongcai Feng,Chin Ping Tan,Xingwei Xiang,Guoxin Shen
BACKGROUND Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome. RESULTS The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria ( Alistipes , Lachnospiraceae_NK4A136_group , Rikenella and Odoribacter ) and decreased pathogenic bacteria ( norank-f-Oscillospiraceae , Ruminococcus and Desulfovibrio ) to maintain intestinal homeostasis. CONCLUSION The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.
研究领域:
药理学
·
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Boqi Li,Yufeng Gao,Xiaohu Luo,Chuanzhi Hu,Mingyu Deng,Jinghua Chen,Gao Min
Natural extracellular matrices (ECM) provide a more accurate simulation of the cellular growth environment, making them excellent substrate materials for in vitro cell culture. The porcine small intestinal submucosa (SIS) is one of the most widely used natural ECM that display superior bioactivity. However, decellularization operations often result in fiber breakage and failure to recover mechanical strength in the SIS. In the current study, 2,3-dialdehyde cellulose (DAC) was synthesized and cross-linked with SIS gel to form hydrogels. The introduction of DAC into the SIS matrix resulted in a tunable increase in stiffness, which was instrumental in promoting stem cell adhesion and spreading, crucial factors for osteogenic differentiation. The cytotoxicity assessment confirmed the biocompatibility of the SIS-DAC hydrogels indicating their suitability for prolonged cell culture. Moreover, the degradation rate of the hydrogel could be effectively controlled by adjusting the DAC content, addressing the rapid degradation issue associated with SIS gels. This work confirmed the feasibility of using cellulose derivatives to modulate the mechanical properties of matrix gels and influence cell differentiation which offers a valuable experimental foundation for the development of advanced matrix gels tailored for cell culture and regenerative medicine applications.
研究领域:
生物材料
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组织工程
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干细胞研究
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jie Tan,Zecai Chen,Zhen Xu,Yafang Huang,Lei Qin,Yufeng Long,Jiayi Wu,Hantao Yang,Xuandu Chen,Weihong Yi,Ruiqiang Hang,Min Guan,Huaiyu Wang,Ang Gao,Dazhi Yang
The 3D printed scaffolds constructed from polymers have shown significant potential in the field of bone defect regeneration. However, the efficacy of these scaffolds can be markedly reduced in certain pathological conditions like diabetes, where the altered microenvironment complicates the integration of these polymers with the host tissue. In this study, the bioactivity of 3D-printed PLGA scaffold is augmented through integration of hydroxyapatite, icariin, and small intestine submucosa (SIS), a form of decellularized extracellular matrix (dECM). In vitro and in vivo studies demonstrate that this functionalized scaffold not only provides desirable immunoregulatory effect, but also facilitates angiogenesis and osteogenesis during the subsequent process. This functionalization approach holds significant promise in advancing the treatment of bone defects within the diabetic population, paving a step forward in the application of polymer-based 3D printing technologies in regenerative medicine.
研究领域:
再生医学
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生物医学工程
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组织工程
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糖尿病研究
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Huan Song,Guo-Qiang Liang,Man-Shu Yu,Yun Shan,Jun Shi,Chun-Bo Jiang,Dao-Lei Ni,Mei-Xiao Sheng
Ethnopharmacological relevance Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. Aim of the study This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. Materials and methods Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. Result Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1β etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. Conclusion SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.
研究领域:
药理学
·
免疫学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Xue Bai,Jianjun Deng,Zhiguang Duan,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Background Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11. Purpose In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy. Study design A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11. Methods In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA). Results The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila , which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect. Conclusion In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.
研究领域:
肿瘤学
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药理学
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微生物学
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分子生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
·
IF 6.1
Huanhuan Xue,Peijie Li,Jing Guo,Tinggui Chen,Shifei Li,Liwei Zhang
Ulcerative colitis (UC) is an idiopathic, relapsing, and etiologically complicated chronic inflammatory bowel disease. Despite substantial progress in the management of UC, the outcomes of mucosal barrier repair are unsatisfactory. In this study, phillygenin (PHI) treatment alleviated the symptoms of chronic colitis in mice, including body weight loss, severe disease activity index scores, colon shortening, splenomegaly, oxidative stress, and inflammatory response. In particular, PHI treatment ameliorated the tight junction proteins (TJs) reduction, fibrosis, apoptosis, and intestinal stem cell activity, indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis. In the NCM460 cells damage model, dextran sulfate sodium triggered the sequential induction of TJs reduction, fibrosis, and apoptosis. Takeda G protein-coupled receptor-5 (TGR5) dysfunction mediated NCM460 cell injury. Moreover, PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function, depending on TGR5 activation. PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids. Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5, indicating that PHI is an agonist of TGR5. The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca 2+ release was involved in NCM460 cell injury as well, which was associated with TGR5 dysfunction. When NCM460 cells were pretreated with PHI, the PERK-eIF2α pathway and elevated Ca 2+ levels were blocked. In conclusion, our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca 2+ pathway through TGR5 activation to against DSS-induced TJs reduction, fibrosis, and apoptosis.
研究领域:
胃肠病学
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药理学
·
细胞生物学
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炎症性肠病
✓ 已验证
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）