JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xiao-chen Li,Shuai Wang,Xin-xin Yang,Tian-jiao Li,Jia-xing Gu,Lin Zhao,Yong-rui Bao,Xian-sheng Meng
Ethnopharmacological relevance At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle . It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. Aim of the study: To investigate P.V in treating CRC and clarify the underlying mechanism. Materials and methods This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology , and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot . Results The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF- α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. Conclusion P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment.
研究领域:
肿瘤学
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药理学
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Siyue Chen,Yuming Liu,Yutian Zhang,Xu Guo,Tinghui Bai,Kai He,Yanfang Zhu,Yi Lei,Mei Du,Xiaohong Wang,Qiang Liu,Hua Yan
Background and Purpose Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Experimental Approach Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1 -knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. Key Results BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. Conclusion and Implications BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis. Graphical
研究领域:
眼科学
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免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Huang Zhusheng,Huang Shiqian,Song Simin,Ding Yankui,Zhou Hao,Zhang Shaoyin,Weng Lixing,Zhang Ying,Hu Yiqiao,Yuan Ahu,Dai Yunlu,Luo Zhimin,Wang Lianhui
The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T 2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.
研究领域:
癌症研究
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纳米技术
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免疫治疗
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放射治疗
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
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IF 4.8
Yiming Ren,Liang Li
Probiotics have numerous biological functions and clinical studies have reported that consuming probiotic foods could promote hair growth and hair follicle health. Bifidobacterium longum BB536 was selected to investigate the possibility of treating hair loss with Cell-Free Supernatant (CFS) of B. longum BB536 and the alleviation mechanism of CFS on dihydrotestosterone (DHT)-damaged human dermal papilla cells (HDPCs). The results showed that HDPCs treated with 10% CFS of B. longum BB536 for 24 h could significantly promote cell proliferation, repair cell damage, accelerate the process of cell cycle and increase the secretion of VEGF. The CFS of B. longum BB536 reduced the apoptosis rate of DHT-damaged HDPCs. In addition, it could reduce the level of pro-inflammatory factors and improve the alkaline phosphatase (ALP) activity. Metabolites of B. longum BB536 may increase the protein expression of Wnt10b, β-catenin and LEF-1 by activating Wnt/β-catenin signaling pathway and inhibit the expression of DHT-induced negative feedback factors DKK1 and GSK-3β, which alleviates the damage of DHT on HDPCs, some protein expression levels such as LEF-1 are close to minoxidil (common drugs for hair loss). So, metabolites of B. longum BB536 can be used as new treatment for hair loss due to its safety. This study provides theoretical basis for probiotics to prevent androgenic alopecia.
研究领域:
微生物学
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细胞生物学
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药理学
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皮肤病学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Jinwei Lin,Chenxi Lian,Leilei Xu,Zhengshang Li,Qiaoxin Guan,Wenying Wei,Honglian Dai,Jianguo Guan
Multifunctional nanoagents are robust to remodel environments for managing chronic diabetic wounds. However, their delivery primarily relies on Brownian motion and randomly enhanced diffusion. Here, taking advantage of wound heterogeneity, such as the uneven distribution of glucose, hyperglycemia targeting nanomotors are proposed. They are capable of efficiently targeting hyperglycemic interfaces in diabetic wounds for significantly accelerating their healing by employing endogenous glucose-activated cascade reactions and responding to local glucose gradients. Compared to previous counterparts, they show a four-fold enhancement in effective coverage within 60 s and a multiplied accumulation at hyperglycemic interfaces, facilitating deep penetration. Correspondingly, the downregulation of glucose levels is apparently enhanced, while pH-lowering and oxygen-supplying are both improved. In comparison to the counterparts delivered by passive diffusion and randomly enhanced diffusion, the hyperglycemia targeting nanomotor-based spray accelerates the wound healing upon diabetic mice by approximately 30% and 23%, resulting from the restricted inflammatory response, effective reactive oxygen species (ROS) scavenging and elevated vascular endothelial growth factor levels (VEGF). This study presents a generally efficient approach to facilitating the targeted delivery of nanoagents for the effective management of diabetic wounds by utilizing wound heterogeneity, which can be extended to other therapeutic systems.
研究领域:
纳米技术
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生物医学工程
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伤口愈合
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糖尿病管理
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 25
·4017-4029
·
IF 5.047
Shuaibing Jiang,Jingxian Wu,Yingjie Hang,Qi Liu,Dan Li,Hong Chen,John L. Brash
Glycosaminoglycans (GAG) play a vital role in the regulation of various cellular functions through their interactions with key proteins involved in cell signaling and can be useful as bioactive agents in the design of biomaterials. However available “natural” GAG that might be used for this purpose suffer a number of drawbacks including structural heterogeneity and the presence of impurities. Alternatively, GAG-mimicking polymers have shown promise for the modification of biomaterials to support the behavior and function of adherent cells. In the study reported herein, a series of glycopolymers of tailored structure were synthesized using a novel “unit-recombination” strategy. These were intended as surface modifiers for the promotion of surface endothelialization. Two key structural units, sulfonate and saccharide, from the building blocks of GAG, were “recombined” to give GAG analogues by copolymerization of sodium 4-vinylbenzenesulfonate (as the sulfonate unit) and 2-methacrylamido glucopyranose (as the saccharide unit). The composition and molecular weight of the copolymers were adjusted to obtain maximum endothelial cell (EC) proliferation. The glycopolymer with sulfonate and saccharide units in a ratio of approximately 1.0 and a molecular weight of 9.8 kDa was found to be optimal. Interestingly, the data emphasized the key role of saccharide units in GAG bioactivity, rather than the commonly believed decisive role of sulfonate units. The optimized glycopolymer was incorporated into fibrous polycaprolactone (PCL) materials by coaxial electrospinning. These materials showed controlled release of the GAG-mimicking polymers over prolonged periods. The proliferation, migration and function of EC on the glycopolymer-modified PCL fiber mats were greatly improved compared to those on unmodified PCL mats. A likely mechanism underlying these improvements is that the glycopolymers significantly enhance the binding of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to their receptors on the cell membrane. These findings demonstrate that these structurally-tailored glycopolymers modulate the functions of EC adherent to materials and may be effective as modifiers for the promotion of endothelialization of blood-contacting implants.
研究领域:
生物材料
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组织工程
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细胞生物学
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聚合物化学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Jianqing Peng,Qin Wang,Jia Zhou,Shuli Zhao,Pan Di,Yan Chen,Ling Tao,Qianming Du,Xiangchun Shen,Yi Chen
Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro , attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo . Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.
研究领域:
药学
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肿瘤学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2018
·Vol. 18
·期 4
·2379-2386
·
IF 1.354
Gong Xiaojin,Zhao Qian,Song Mu,Xue Feng
In our study, we report on the design and characterization of a combined angiogenesis therapy for breast cancer based on well-formed amine-functionalized silica nanoparticles (SLNs). The aminefunctionalized SLNs was employed to simultaneously deliver angiostatin (ANG) plasmid and candesartan
(CD) to the same cancer cell. The well-formed ANG/CD/SLNs exhibited small particle size, reasonable positive charges, excellent loading of drug and gene in vitro. Moreover, aminefunctionalized SLNs were almost no cytotoxicity. ANG/CD/SLNs resulted in enhanced gene transfection compared
to naked plasmid. More importantly, ANG/CD/SLNs as a co-delivery system achieved a stronger inhibitory effect on angiogenesis in vitro, possibly resulting from significant downregulation of vascular endothelial growth factor (VEGF) expression via different pathways. In particular, in
vivo investigation on nude mice bearing MCF-7 xenografts confirmed that ANG/CD/SLNs codelivery system exerted strong anti-tumor efficacy by synergistic antiangiogenic mechanism.
研究领域:
纳米技术
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癌症治疗
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分子生物学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2024
·
IF 2.5
Runzhi Xiang,Jialu Chen,Jiarui Dang,Hong Zhu,Zhihui Ran,Yuehan Dong,Xiangjie Wu,Yuran Yang,Huan Deng,Chengjie Xiong,Zhijun Huang,Peihu Xu,Wenjin Xu,Haixing Xu
Angiogenesis plays a crucial role in peripheral nerve regeneration after injury. We introduce a proangiogenic hydrogel-filled nerve conduit, designed to promote peripheral nerve regeneration. The hydrogel was synthesized by chemically crosslinking carboxylated silk fibroin (cSF) and chitosan (CS), enriched with vascular endothelial growth factor (VEGF) to initiate angiogenesis. Complementarily, a nerve conduit was fabricated using coaxial electrospinning of poly-lactic acid (PLA), silk fibroin (SF), and ibuprofen (IBU) was incorporated to further support nerve regeneration. The hydrogel exhibited optimal properties including rapid gelation, uniform porosity and full biodegradation within four weeks. The nerve conduit, on the other hand, displayed enhanced mechanical strength, elasticity, and controlled biodegradability. In vitro assays demonstrated a sustained release of VEGF and IBU, which significantly enhanced cell adhesion, proliferation, migration and angiogenesis in Human umbilical vein endothelial cells (HUVEC), as well as promoted adhesion and proliferation in rat Schwann cells (RSC96). This proangiogenic hydrogel-filled nerve conduit thus emerged as a potent candidate for advancing peripheral nerve regeneration.
研究领域:
组织工程
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生物材料
·
神经科学
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Dong Lou,Yu Luo,Qian Pang,Wei-Qiang Tan,Lie Ma
Diabetic chronic wound, characterized by prolonged inflammation and impaired angiogenesis, has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide. Although a great variety of wound dressings have been developed, few of encouraged achievements were obtained so far. In this study, the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor (VEGF) and achieve better healing outcomes by regulating inflammation and promoting angiogenesis. The gene-activated bilayer dermal equivalents (Ga-BDEs), which has good biocompatibility, were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent. The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro. To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human, a reformative rat model of full-thickness diabetic chronic wound was adopted. Under the treatment of Ga-BDEs, speeding wound healing was observed, which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases, respectively. These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously. Subsequently, the better regeneration outcomes, including deposition of oriented collagen and fast reepithelialization, were achieved. All these results indicated that, being different from traditional pro-angiogenic concept, the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
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组织工程
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Junjie Li,Gang Wei,Gongwen Liu,Yawei Du,Ruizhi Zhang,Aifei Wang,Baoshan Liu,Wenguo Cui,Peng Jia,Youjia Xu
Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH-responsive shell–core structured micro/nano-hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross-linking technology are developed. This micro/nano-hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to bone tissue, and thus negatively affecting intraosseous angiogenesis and osteoclastogenesis. According to biodistribution data, PDAP@Alg/Cs can successfully enhance drug intestinal absorption and bioavailability through intestine adhesion and bone targeting after oral administration. In vitro and in vivo experiments reveal that PDAP@Alg/Cs promoted type H vessel formation and inhibited bone resorption, effectively mitigating bone loss by activating HIF-1 α /VEGF signaling pathway and promoting heme oxygenase-1 (HO-1) expression. In conclusion, this novel oral micro/nano-hydrogel microsphere system can simultaneously accelerate intraosseous vascularization and decrease bone resorption, offering a brand-new approach to prevent postmenopausal osteoporosis.
研究领域:
药学
·
生物医学工程
·
骨科
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
Lanjie Lei,Xiangguo Wang,Yulin Zhu,Wentao Su,Qizhuang Lv,Dong Li
Growth factors are vital to regulate cellular responses for wound healing process. Engineered microspheres provide a promising tool for developing effective growth factor-loaded matrix for regenerative medicine therapy. Here, we report a novel multifunctional chitosan microsphere that enables facile one-step capture and efficient growth factor delivery for enhanced wound repair. The microfluidic technique was used to fabricate magnetic chitosan (MCS) microspheres. By immobilization with Zn 2+ ions, the biohybrid MCS allowed for the flexible operation to capture histidine-tagged vascular endothelial growth factor (VEGF) produced in Escherichia coli (E. coli) . The VEGF-conjugated MCS were then applied onto the wounds to examine their capabilities in promoting wound healing. Zn 2+ and chitosan in MCS exhibited a synergetic antibacterial effect towards both Gram-positive and Gram-negative bacteria. Using a rat model, we further demonstrated that the microspheres significantly promoted wound healing process, as evidenced by rapid wound closure, induced epithelialization and angiogenesis, and reduced inflammation response. Together, our data indicated the presented MCS as a versatile tool for capturing and locally delivering growth factors, which can be applied to wound repair. Moreover, with the functional flexibility, this biohybrid MCS could be empolyed in a wide range of biomedical applications by conjugating proteins of interest.
研究领域:
再生医学
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生物医学工程
·
伤口愈合
·
药物递送系统
·
组织工程
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）