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Food & Function · 2022 ·Vol. 13 ·期 23 ·12330-12341 · IF 6.317

Protective effect of β-carotene on OVA-induced food allergy in mice by strengthening intestinal epithelial barrier function and regulating intestinal microflora

Huiying Kuang,Yu Ma,Yixiang Liu

β-Carotene is a dietary source of vitamin A, and its physiological functions, such as anti-inflammatory activity, immune regulation, and improvement of intestinal flora, are attracting increasing attention. Recent studies have shown that the development of food allergy is closely related to intestinal dysfunction. Therefore, the present study investigated the potential anti-food allergy activity of β-carotene and its regulatory intestinal homeostasis pathway. The results obtained using an ovalbumin (OVA)-induced food allergy mouse model indicated that the clinical allergic symptoms were alleviated, and the levels of anaphylactic mediators (such as immunoglobulin (Ig) E, IgG, and histamine) were reduced after β-carotene supplementation at 5.00 mg per kg per day. In addition, the expression of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1) increased by 38.58%, 24.39%, and 26.23%, respectively. Additionally, the secretion of secretory IgA (sIgA) and the regeneration of islet-derived protein (Reg) IIIγ were promoted in the intestinal mucous after β-carotene administration. Furthermore, the alpha and beta diversity analysis showed that the composition and diversity of the intestinal flora in the β-carotene group tended to be normalized compared to the model group. Higher levels of beneficial bacteria, such as Clostridiaceae, were evident in the intestinal microflora of the sensitized mice after β-carotene administration, while pathogenic bacteria, such as Streptococcaceae, were reduced. Consequently, β-carotene may protect against food allergy by strengthening intestinal epithelial barrier function and regulating intestinal microflora.

研究领域: 免疫学 · 营养学 · 胃肠病学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2026 · IF 5.6

DEC-205-mediated liposomal delivery of OVA and Eucommia polysaccharides: dendritic cell targeting, adjuvant activity, and TLR-NF-κB-mediated immune enhancement

Shuhui Yang,Yan Yang,Qian Yang,Ziwei Liu,Hangyu Li,Yanwen Yang,Yao Wang,Shanshan Li,Juan Liu,Haibo Feng

DEC-205 monoclonal antibodies were assembled on the surface of liposomes carrying OVA antigen and Eucommia ulmoides polysaccharides to generate a delivery system with targeted dendritic cells. The liposomal encapsulation process of Eucommia ulmoides polysaccharide was optimized, and DEC-205-EUPS-OVA-LP was synthesized under optimal conditions to improve the utility of Eucommia ulmoides polysaccharide. Meanwhile, the physicochemical properties and adjuvant activity of the delivery system were evaluated in vitro .The optimized liposomes exhibited uniform particle size (<220 nm), suitable zeta potential (−11 to −15 mV), good dispersity (PDI < 0.3), and favorable encapsulation efficiency. 39.1 μg/mL DEC-205-EUPS-OVA-LP can promote the proliferation of dendritic cells and promote their antigen uptake. Furthermore, DEC-205-EUPS-OVA-LP significantly enhanced the secretion of IL-2, IL-6, IFN-γ, and TNF-α and elevated the expression of the co-stimulatory molecules CD80, CD86, and MHC-II on dendritic cells. High-throughput sequencing and Western blot results showed that DEC-205-EUPS-OVA-LP upregulated immune-related genes in dendritic cells and enhanced immunity via the TLR-NF-κB pathway. In summary, DEC-205-EUPS-OVA-LP targets dendritic cells to facilitate antigen uptake, processing, and presentation, promotes dendritic cell maturation, and enhances the immune response.

✓ 已验证 DOI PubMed 高影响因子
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Food Bioscience · 2026 · IF 6.2

Fucoidan from Saccharina japonica alleviates OVA-induced allergy in mice: A role for the AMPK/SIRT1/FOXO1 pathway in enhancing intestinal barrier function

Qing Liu,Zengying Sui,Shiyi Li,Miaomiao Wan,Meilan Xue,Xia Qiu,Hui Liang,Lirui Sun

Fucoidan is a sulfated polysaccharide derived from brown algae ( Saccharina japonica ), and exhibits immunomodulatory properties. Emerging evidence suggests a strong correlation between the development of food allergy and intestinal dysfunction. The present study aimed to investigate the potential anti-food allergy activity of fucoidan and to elucidate its mechanism at the intestinal barrier function. The ovalbumin (OVA)-induced allergy mouse model was established, exhibiting increased OVA-specific IgE, histamine, Th2 inflammatory response, and intestinal damage. Oral administration of fucoidan markedly alleviated allergic symptoms by inhibiting mast cell activation and modulating intestinal immune responses. Furthermore, fucoidan significantly ameliorated intestinal immunological dysregulation, maintained barrier integrity, modulated gut microbiota composition, and enhanced short-chain fatty acid (SCFA) production. Mechanistically, the protective effects of fucoidan were closely associated with activation of the AMPK/SIRT1/FOXO1 pathway, which correlated with improved intestinal barrier function. Collectively, these results demonstrate that fucoidan may protect against food allergy by enhancing intestinal barrier function, highlighting the potential of natural biological substances in addressing food allergy.

✓ 已验证 DOI 高影响因子
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Food & Function · 2023 ·Vol. 14 ·期 16 ·7375-7386 · IF 6.1

Sea cucumber chondroitin sulfate polysaccharides attenuate OVA-induced food allergy in BALB/c mice associated with gut microbiota metabolism and Treg cell differentiation

Cheng Li,Yang Tian,Jiahuan Pei,Yuyang Zhang,Daokuan Hao,Tianjiao Han,Xiaoqin Wang,Shuang Song,Linjuan Huang,Zhongfu Wang

Previous research studies have shown that sulfated polysaccharides can inhibit food allergy, but the detailed mechanism remains largely unknown. In this study, RBL-2H3 cells were used to compare the anti-allergic activities of four sulfated polysaccharides, and an ovalbumin (OVA)-sensitized allergic mouse experiment was used to explore their desensitization effect, with regard to the alteration in gut microbiota and immune cell differentiation. Compared with the shark, bovine and porcine chondroitin sulfate, sea cucumber chondroitin sulfate (SCCS) significantly inhibited the degranulation of RBL-2H3 cells. SCCS reduced allergic symptoms and protected the jejunum from injury in mice. Furthermore, SCCS increased the relative abundance of Lachnospiraceae NK4A136, decreased the relative proportion of Prevotellaceae NK3B31, and up-regulated the secretion of short chain fatty acids such as butyric acid in the feces, resulting in an increase in the mucin 2 (MUC2) secretion by goblet cells HT-29. Meanwhile, SCCS induced the differentiation of regulatory T cells in the mesenteric lymph nodes of mice. This study provides a deeper understanding of the functioning mechanism of SCCS in alleviating food allergy and may guide the development and production of anti-allergy active ingredients.

研究领域: 免疫学 · 营养学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2022 · IF 6.656

A novel iridoid glycoside leonuride (ajugol) attenuates airway inflammation and remodeling through inhibiting type-2 high cytokine/chemokine activity in OVA-induced asthmatic mice

La Yi,Yaolong Zhou,Jingrong Song,Weifeng Tang,Hang Yu,Xi Huang,Hanlin Shi,Mengmeng Chen,Jing Sun,Ying Wei,Jingcheng Dong

Background Asthma is a chronic airway disorder with a hallmark feature of airflow obstruction that associated with the remodeling and inflammation in the airway wall. Effective therapy for controlling both remodeling and inflammation is still urgently needed. Leonuride is the main pharmacological component identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in treatment of lung diseases. However, no pharmacological effects of leonuride in asthma were reported. Purpose Here we aimed to investigated whether leonuride provided a therapeutic efficacy in reversing asthma airway remodeling and inflammation and uncover the underlying mechanisms. Study design and methods Mouse models of chronic asthma were developed with ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology and asthma-related cytokines were examined. Lung tissues were analyzed using RNA sequencing to reveal the transcriptional profiling changes. Results After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. Leonuride suppressed airway inflammation evidenced by the significant reductions in accumulation of inflammatory cells around bronchi and vessels, leukocyte population counts and the abundance of type 2 inflammatory mediators (OVA specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On the other hand, leonuride slowed down the process of active remodeling as demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung histopathology and lower transforming growth factor (TGF)-β1 levels in serum and BALF in comparison to mice treated with OVA only. Furthermore, we uncovered transcriptional profiling alternations in lung tissue of mice after OVA exposure and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine activity stood out in leonuride target transcripts. Those upregulated (Bmp10, Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all reversely regulated by leonuride treatment. Conclusions Our results revealed the therapeutic efficacy of leonuride in experimental chronic asthma for the first time, and implied that its anti-inflammatory and antifibrotic properties might be mediated by regulation of type-2 high cytokine/chemokines responses.

CAS / MDL: 136310-93-5
研究领域: 药理学 · 免疫学 · 呼吸医学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FASEB JOURNAL · 2024 ·Vol. 38 ·期 13 ·e23756 · IF 4.4

FOXK2 facilitates the airway remodeling during chronic asthma by promoting glycolysis in a SIRT2-dependent manner

Lishen Shan,Li Chen,Wenxin Shen,Qianlan Zhou,Si Liu,Lina Han,Qinzhen Zhang,Bing Dai,Yuhong Zhao

Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as “airway remodeling”, are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-β1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-β1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-β1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-β1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-β1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.

CAS / MDL: 9006-59-1
研究领域: 呼吸病学 · 免疫学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Asthma and Allergy · 2022 · IF 3.027

MAF bZIP Transcription Factor B (MAFB) Protected Against Ovalbumin-Induced Allergic Rhinitis via the Alleviation of Inflammation by Restoring the T Helper (Th) 1/Th2/Th17 Imbalance and Epithelial Barrier Dysfunction

Yang Sun,Tiancong Liu,Weiliang Bai

Purpose This work aimed to investigate the effects of MAF bZIP transcription factor B (MAFB) on the progression of allergic rhinitis (AR). Patients and Methods Nasal mucosa was isolated from AR patients and healthy individuals from Shengjing Hospital of China Medical University. The experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University (2019PS341K) in accordance with the Declaration of Helsinki. Informed consents were signed by participants or a parent/legal guardian of the participants under 18 years old of age. Then, an AR mouse model with MAFB overexpression was established with 25 μg ovalbumin (OVA) sensitization on day 0, 7, 14, followed by an injection with 1×10 7 TU/mL lentivirus MAFB on day 19 and a nasal challenge with 500 μg OVA from day 21 to 27. Results The results revealed that MAFB was down-regulated in the nasal mucosa of AR patients. The up-regulation of MAFB protected the AR mice against the OVA-induced allergic symptoms (sneezing and nasal rubbing) by alleviating the OVA-induced epithelial thicknesses, goblet cell hyperplasia, and inflammation including the eosinophil and mast cell infiltration. Moreover, MAFB facilitated the T helper (Th) 1 response and inhibited the Th2 and Th17 responses by the down-regulation of T-box transcription factor 21 and the up-regulation of GATA binding protein-3 as well as retinoid-related orphan receptor-γt in the splenocytes of AR mice. MAFB was found to repress the differentiation of naive CD4 + T cells into Th2 cells. Subsequently, MAFB overexpression reversed the OVA-induced enhancement of epithelial permeability, downregulation of tight junctions, and upregulation of cadherin-26, indicating the protective role of MAFB on epithelial barrier integrity. Conclusion MAFB protected against OVA-induced AR via the alleviation of inflammation by restoring the Th1/Th2/Th17 imbalance and epithelial barrier dysfunction.

研究领域: 免疫学 · 分子生物学 · 转化医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2022 · IF 11.467

Self-degradable poly(β-amino ester)s promote endosomal escape of antigen and agonist

Hong Liu,Zhitao Hu,Haolin Chen,Yanzi Yan,Zhicheng Le,Cong Wei,Wenqiang Cao,Tianfeng Chen,Yongming Chen,Lixin Liu

Vaccination with subunit nanovaccines is a promising strategy to combat virus infection and tumor development. However, immunogenicity of present nanovaccines is still unsatisfied for clinical translation. Here, we developed a nanovaccine loading a STING agonist, 2′3′-cGAMP and, a model subunit antigen, OVA , by using a well-defined self-degradable poly(β-amino ester)s to treat B16F10-OVA melanoma tumors. The polymer underwent slow hydrolysis at pH 5.5 but self-degraded induced by the amino groups along the polyester chain at pH > 6.5. It is shown that the self-degradation products facilitated the release of 2′3′-cGAMP and OVA from early endolysome to the cytosol, where the two components strongly activated CD8 + T lymphocytes (CTLs) and significantly enhanced Ifn1, TNF , Cxcl9, and Cxcl10 expression. In turn, the tumor microenvironment was remolded from cold to hot. Moreover, the nanovaccine could be quickly drained to sentinel lymph nodes after intratumoral injection. The nanovaccine with strong immunogenicity also could reduce the side effects of systemic inflammatory reaction caused by molecular 2′3′-cGAMP. The tumor progression of animals was inhibited, and their survival rates increased significantly. Thus, the multifunctional biodegradable material provided a new delivery system for a cancer vaccine to translate to clinics.

研究领域: 癌症研究 · 免疫学 · 生物医学工程 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMACROMOLECULES · 2023 · IF 6.2

Multifunctional Covalent Organic Framework-Based Microneedle Patch for Melanoma Treatment

Pan Li,Chun Hui Liu,Yan Yan Zhao,Da Dong Cao,Bo Zhi Chen,Xin Dong Guo,Weifen Zhang

Melanoma is resistant to conventional chemotherapy and radiotherapy. Therefore, it is essential to develop a targeted, low-toxic, and minimally invasive treatment. Here, DTIC/ICG-Fe3O4@TpBD BSP/HA microneedles (MNs) were designed and fabricated, which can enhance targeting to melanoma and perform photothermal therapy (PTT) and chemotherapy simultaneously to synergistically exert anticancer effects. The system consisted of magnetic nanoparticles (DTIC/ICG-Fe3O4@TpBD), dissoluble matrix (Bletilla polysaccharide (BSP)/hyaluronic acid (HA)), and a polyvinyl alcohol backing layer. Due to the good magnetic responsiveness of Fe3O4@TpBD, dacarbazine (DTIC) and indocyanine green (ICG) can be better targeted to the tumor tissue and improve the therapeutic effect. BSP and HA have good biocompatibility and transdermal ability, so that the MNs can completely penetrate the tumor tissue, be dissolved by the interstitial fluid, and release DTIC and ICG. Under near-infrared (NIR) light irradiation, ICG converts light energy into thermal energy and induces ablation of B16-OVA melanoma cells. In vivo results showed that DTIC/ICG-Fe3O4@TpBD BSP/HA MNs combined with chemotherapy and PTT could effectively inhibit the growth of melanoma without tumor recurrence or significant weight loss in mice. Therefore, DTIC/ICG-Fe3O4@TpBD BSP/HA MNs are expected to provide new ideas and therapeutic approaches for the clinical treatment of melanoma.

CAS / MDL: 4342-03-4
研究领域: 癌症治疗 · 生物医学工程 · 纳米技术 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2024 ·Vol. 12 ·期 24 ·5848-5860 · IF 6.1

Peptide nanovaccine conjugated via a retro-Diels–Alder reaction linker for overcoming the obstacle in lymph node penetration and eliciting robust cellular immunity

Kuncheng Lv,Sheng Ma,Liping Liu,Hongyu Chen,Zichao Huang,Zhenyi Zhu,Yibo Qi,Wantong Song

Nanoparticles have been regarded as a promising vaccine adjuvant due to their innate immune potentiation and enhanced antigen transport. However, the inefficient infiltration into the lymph node (LN) paracortex of nanoparticles caused by subcapsular sinus (SCS) obstruction is the main challenge in further improvement of nanovaccine immune efficacy. Herein, we propose to overcome paracortex penetration by using nanovaccine to spontaneously and continuously release antigens after retention in the SCS. In detail, we utilized a spontaneous retro-Diels–Alder (r-D–A) reaction linker to connect poly{(2-methyl-2-oxazoline)80-co-[(2-butyl-2-oxazoline)15-r-(2-thioethyl-2-oxazoline)8]} (PMBOxSH) and peptides for the peptide nanovaccine construction. The r-D–A reaction linker can spontaneously break over time, allowing the nanovaccine to release free antigens and adjuvants upon reaching the LN, thereby facilitating the entry of released antigens and adjuvants into the interior of the LNs. We showed that the efficacy of the peptide nanovaccine constructed using this dynamic linker could be significantly improved, thus greatly enhancing the tumor inhibition efficacy in the B16-OVA model. This dynamic-covalent-chemistry-based vaccine strategy may inspire designing more efficient therapeutic vaccines, especially those that require eliciting high-amount T cell responses.

研究领域: 纳米技术 · 免疫学 · 药学 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2020 · IF 5.977

Fluorous-paired derivatization approach towards highly sensitive and accurate determination of long chain unsaturated fatty acids by liquid chromatography-tandem mass spectrometry

Jia-Yi Zheng,Ying-Ying Jin,Zi-Qi Shi,Jian-Liang Zhou,Li-Fang Liu,Gui-Zhong Xin

Long chain unsaturated fatty acids (LCUFAs) are emerging as critical contributors to inflammation and its resolution. Sensitive and accurate measurement of LCUFAs in biological samples is thus of great value in disease diagnosis and prognosis. In this work, a fluorous-derivatization approach for UPLC-MS/MS quantification of LCUFAs was developed by employing a pair of fluorous reagents, namely 3-(perfluorooctyl)-propylamine (PFPA) and 2-(perfluorooctyl)-ethylamine (PFEA). With this method, the LCUFAs in biological samples were perfluoroalkylated with PFPA and specifically retained on a fluorous-phase LC column, which largely reduced matrix interferences-induced quantitation deviation. Moreover, PFEA-labeled LCUFAs standards were introduced as one-to-one internal standards to farthest ensure unbiased results. Application of the proposed method enabled a reliable determination of eight typical LCUFAs with high sensitivity (LLOQ ranged from 30 amol to 6.25 fmol) and low matrix interferences (almost less than 10%). Such a high sensitivity could facilitate the determination of small-volume and low-concentration bio-samples. Further metabolic characterization of these targeted LCUFAs was monitored in OVA-induce asthma mice, requiring only 5 μL serum sample. Our results showed that asthmatic attack led to significant disturbances not only in the concentrations but also in the ratio among these LCUFAs. In view of the favorable advantages in sensitivity and accuracy, the present fluorous-paired derivatization approach will be expected to serve as a new avenue for dissecting the physiological and clinical implications of LCUFAs, thereby shedding light on the management of diseases related to their disturbances.

研究领域: 分析化学 · 生物化学 · 临床化学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2020 ·Vol. 16 ·期 46 ·2004345 · IF 11.459

Artificial Metalloprotein Nanoanalogues: In Situ Catalytic Production of Oxygen to Enhance Photoimmunotherapeutic Inhibition of Primary and Abscopal Tumor Growth

Rongtao Huang,Zhaoyang Ding,Bang-Ping Jiang,Zilan Luo,Ting Chen,Zhengxi Guo,Shi-Chen Ji,Hong Liang,Xing-Can Shen

Photoimmunotherapy (PIT) has shown enormous potential in not only eliminating primary tumors, but also inhibiting abscopal tumor growth. However, the efficacy of PIT is greatly limited by tumor hypoxia, which causes the attenuation of phototherapeutic efficacy and is a feature of the immunosuppressive tumor microenvironment (TME). In this study, one type of brand-new artificial metalloprotein nanoanalogues is developed via reasonable integration of a “phototherapy-enzymatic” RuO 2 and a model antigen, ovalbumin (OVA) for enhanced PIT of cancers, namely, RuO 2 -hybridized OVA nanoanalogues (RuO 2 @OVA NAs). The RuO 2 @OVA NAs exhibit remarkable photothermal/photodynamic capabilities under the near-infrared light irradiation. More importantly, the photoacoustic imaging and immunofluorescence staining confirm that RuO 2 @OVA NAs can remarkably alleviate hypoxia via in situ catalysis of hydrogen peroxide overexpressed in the TME to produce oxygen (O 2 ). This ushers a prospect of concurrently enhancing photodynamic therapy and reversing the immunosuppressive TME. Also, OVA, as a supplement to the immune stimulation induced by phototherapy, can activate immune responses. Finally, further combination with the cytotoxic T-lymphocyte-associated protein 4 checkpoint blockade is reported to effectively eliminate the primary tumor and inhibit distant tumor growth via the abscopal effect of antitumor immune responses, prolonging the survival.

CAS / MDL: 10602-37-6 5471-63-6
研究领域: 肿瘤学 · 生物医学工程 · 免疫治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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