Jove-Journal of Visualized Experiments
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2024
·
IF 1.2
Miao Cui,Lijuan Jiang,Wei Yang,Wenfeng Zhang
The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development.Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67.The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.
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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动物模型
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分子生物学
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组织病理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Yumei Sun,Jihong Wang,Peiyao Hu,Yi Tang,Yanwen Wang,Jianzhou Ye,Xuesong Yang,Junlin Yin
Tripterygium hypoglaucum (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3- O -acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I κ B α , NF- κ B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR γ t / Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.
研究领域:
药理学
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免疫学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Shuting Zhang,Hong Zhou,Xuan Chen,Shasha Zhu,Dan Chen,Dan Luo,Siyuan Chen,Wei Liu
Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, β-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.
研究领域:
药学
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纳米技术
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皮肤科
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
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IF 3.743
Xue Li,Hao Liu,Wenqian Yu,Xiaomei Liu,Caixia Liu
Objective Congenital diaphragmatic hernia (CDH) is a common and often lethal birth defect characterized by congenital lung malformation, which severely affects neonate prognosis and mortality. This study aimed to investigate differences in protein expression in order to elucidate the mechanism of CDH-associated pulmonary hypoplasia during the early stage of lung development using tandem mass tag (TMT) quantitative proteomics. Methods Nitrofen was administered orally to establish a rat CDH model, and pathological changes were evaluated through hematoxylin-eosin (H&E), PCNA, and Ki67 staining at the pseudoglandular stage. Fetal lungs were then collected, pooled before TMT labeling, and subjected to mass spectrometry. Immunohistochemistry (IHC), Western blotting, and Q-PCR were used to further validate the candidate proteins. Results A total of 79 differentially expressed proteins (DEPs) were identified when CDH and control lungs were compared, and further bioinformatics analysis showed that these proteins play important roles in tight-junctions, phospholipase D signaling, and the HIF-1 signaling pathway. Three differentially expressed proteins, Cldn3, Magi1, and Myh9 are involved in the tight-junction pathway (P < 0.05), and their differential expressions were confirmed by IHC, Western blotting, and Q-PCR. Conclusion These findings indicate that alterations of tight-junction protein expression may play an important role in the pathogenesis of abnormal lung development in CDH. Further studies are warranted to verify the mechanism by which these tight-junction proteins influence the pathogenesis of CDH-associated pulmonary hypoplasia.
研究领域:
发育生物学
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蛋白质组学
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儿科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LUNG
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2022
·Vol. 200
·期 5
·619-631
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IF 3.777
Zhai Cui,Zhang Nana,Wang Jian,Cao Meng,Luan Jing,Liu Huan,zhang Qianqian,Zhu Yanting,Xue Yuxin,Li Shaojun
Purpose It has been shown that activation of autophagy promotes the development of pulmonary arterial hypertension (PAH). Meanwhile, forkhead box M1 (FOXM1) has been found to induce autophagy in several types of cancer. However, it is still unclear whether FOXM1 mediates autophagy activation in PAH, and detailed mechanisms responsible for these processes are indefinite. Method PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) to rats. The right ventricle systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), percentage of medial wall thickness (%MT), α-smooth muscle actin (α-SMA) staining, and Ki67 staining were performed to evaluate the development of PAH. The protein levels of FOXM1, phospho-focal adhesion kinase (p-FAK), FAK, and LC3B were determined by immunoblotting or immunohistochemistry. Results FOXM1 protein level and FAK activity were significantly increased in MCT-induced PAH rats, this was accompanied with the activation of autophagy. Pharmacological inhibition of FOXM1 or FAK suppressed MCT-induced autophagy activation, decreased RVSP, RVHI and %MT in MCT-induced PAH rats, and inhibited the proliferation of pulmonary arterial smooth muscle cells and pulmonary vessel muscularization in MCT-induced PAH rats. Conclusion FOXM1 promotes the development of PAH by inducing FAK phosphorylation and subsequent activation of autophagy in MCT-treated rats.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2020
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IF 5.88
Yongtai Zhang,Zehui He,Yanyan Li,Qing Xia,Zhe Li,Xuefeng Hou,Nianping Feng
Tumor cell membrane-derived nanostructures targeting homologous tumors are promising biomimetic drugs. Herein, curcumin (Cur) and chlorin e6 (Ce6) were co-loaded into PLGA nanoparticles (NPs), and then the NPs were coated with MCF-7 cell membranes (MCNPs). Cell membrane coating sharply increased the uptake of MCNPs by homologous cells, as compared to that with naked NPs. The NPs co-loaded with Cur and Ce6 (Cur/Ce6-NPs) showed a stronger proliferation-inhibitory effect on MCF-7 cells than the NP groups loaded with Cur and Ce6 alone. Cytotoxicity and apoptosis rates of MCF-7 cells in the Cur/Ce6-MCNPs group were significantly higher than those in the uncoated Cur/Ce6-NPs group. Both Cur/Ce6-NPs and Cur/Ce6-MCNPs significantly inhibited the migration of MCF-7cells, although Cur/Ce6-MCNPs showed a stronger effect. Compared to that of Cur/Ce6-NPs, the elimination of Cur/Ce6-MCNPs was both decreased and retarded, prolonging their in vivo systemic circulation and resulting in improved bioavailability. After intravenous administration for 24 h, the fluorescence intensity of drugs in the liver and spleen of the Cur/Ce6-MCNPs group was significantly weaker than that in the Cur/Ce6-NPs group, but that in tumor tissue was enhanced. Further, Cur/Ce6-MCNPs treatment achieved significantly better tumor-suppressive effects in vivo than Cur/Ce6-NPs, resulting in smaller tumor weights, increased apoptosis rates, and the down regulation of Ki67 protein in the tumor tissue. Thus, the tumor cell membrane-camouflaged nanocomposites have potential for homologous tumor-targeted therapy. Furthermore, photodynamic therapy combined with chemotherapy has promising future prospects.
研究领域:
癌症研究
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药学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Yuanping Hao,Wenwen Zhao,Hao Zhang,Weiping Zheng,Qihui Zhou
Triggering the repair process of diabetic wounds is a huge clinical challenge due to microbial infection, the reduced migration and proliferation of fibroblasts, decreased angiogenesis and collagen formation caused by the long-term negative stimulation of high blood glucose levels . Herein, bio-multifunctional benzaldehyde-terminated 4-arm PEG (4-arm-PEG-CHO)/carboxymethyl chitosan (CMCS)/basic fibroblast growth factor (bFGF) hydrogels (BP/CS-bFGF) are prepared via the dynamic Schiff base reaction for diabetic wound treatment. BP/CS-bFGF hydrogel dressing shows strong wet-tissue adhesion, self-mending, and antibacterial property . Biological assessments display that the BP/CS-bFGF hydrogel has excellent biocompatibility and fast hemostasis capacity. Importantly, BP/CS-bFGF hydrogel dressing significantly accelerates full-thickness diabetic wound repair by increasing the production of Ki67, promotes the generation of epithelialization and collagen, induces the formation of hair follicles, and enhances neovascularization by upregulating the production of CD31 and CD34 . Thus, our work demonstrates that BP/CS-bFGF hydrogel dressing displays great potential for diabetic chronic wound management.
研究领域:
材料科学
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生物医学工程
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药剂学
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伤口愈合
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2017
·
IF 6.319
Yang Fan,Qingjie Wang,Guimei Lin,Yanbin Shi,Zili Gu,Tingting Ding
In this study, novel prodrug-modified cationic liposome nanocomplexes (Combo NCs) were reported for gemcitabine (GEM) and docetaxel (DTX) co-delivery. This nanoplatform exhibited multiple favorable characteristics, such as a ‘green’ fabrication with a one-step chemical reaction, appropriate size (∼200 nm) and distribution (PDI < 0.2), low zeta potential (−31.1 mv), high drug-loading efficiency (9.3% GEM plus 3.1% DTX, wt%) and pH and enzymatic dual-stimulus-responsive release properties. Immunofluorescence and cellular uptake studies showed that Combo NCs efficiently targeted overexpressed CD44 in MDA-MB-231 carcinoma. In vitro studies revealed that Combo NCs played a critical role in the synergistic induction of cytotoxicity, apoptosis and inhibition of wound healing. Combo NCs were confirmed to exhibit great potency for increasing S phase arrest and remodeling the CDA and dCK balance by decreasing the mRNA expression of CDA down to 0.09-fold and increasing the mRNA expression of dCK by 1.36-fold, remarkably increasing the dCK/CDA ratio to 15.3-fold compared with the blank control. The biodistribution results obtained in vivo revealed an effective accumulation in tumor foci. All of these advantages of Combo NCs contributed to their remarkable anti-tumor efficacy without systemic toxicity as well as their apoptosis-enhancing and anti-proliferative capacities, as determined by TUNEL and Ki67 immunohistochemistry in vivo . Consequently, such a rationally contemplated co-delivery system demonstrated the promising potential of clinical applications for triple-negative breast cancer therapy. State of Significance The Combo NCs were innovatively applied for co-delivery of hydrophilic GEM and hydrophobic DTX. The ester bond linking and shielding effect of HA-GEM made the carriers achieve synchronous release properties, which was determined in in vitro release study. Due to the HA modification, the vectors own great potency for positive targeting to CD44 overexpressed triple-negative breast cancer cells MDA-MB-231. Cytotoxicity and apoptosis studies confirmed the targeting effect and synergism between two drugs. Interestingly, we found in cell cycle study, drug combinations (free combination or Combo NCs) didn’t show a rise in G2M phase, which was significantly higher when treated DTX alone. We further discovered the role of DTX in combinations may involve in modulating GEM associated enzymes thus enhancing the efficacy of GEM. Consequently, this nanoplatform provided a novel solution for achieving targeted co-delivery and potentiating effect in cancer therapy.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 41
·2105614
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IF 18.808
Xiangyi Yin,Yuanping Hao,Yun Lu,Dongjie Zhang,Yaodong Zhao,Li Mei,Kunyan Sui,Qihui Zhou,Jilin Hu
Developing bio-multifunctional patches with natural extracellular matrix-like structures, excellent high adhesion in the wet state, self-healing ability, antibacterial activity, and favorable cell responses for accelerating tissue healing is highly desirable in clinical applications. Herein, bio-multifunctional composite hydrogels are developed by coupling carboxymethyl chitosan and 4-arm poly (ethylene glycol) aldehyde for full-thickness abdominal wall defect repair. The prepared hydrogels exhibit excellent self-healing and mechanical properties, high adhesion in the wet state, and significant antibacterial ability. In vitro cellular experiments show that the hydrogels combined with recombinant bovine basic fibroblast growth factor remarkably promote cell proliferation and then accelerate full-thickness abdominal wall defect repair in a rat model. The histomorphological evaluation shows that compared to the commercial polypropylene mesh used clinically, the designed hydrogel patches facilitate an increase in the thickness and integrity of the abdominal wall tissue by upregulating the production of Ki67, enhancing the formation of collagen, inducing neovascularization, and inhibiting inflammation by reducing the expression of IL-6, TNF-α, and IL-1β. The results demonstrate that this novel bio-multifunctional hydrogel patch holds great potential for the treatment of full-thickness abdominal wall defects.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
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伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）