查找使用阿拉丁产品的科研文献

Dual-Functional Micelles for Codelivery of Sorafenib and Dehydrodiisoeugenol in Treatment of Hepatocellular Carcinoma

Su-Yu Yang,Shu-Tong Li,Tian-Hua Li,De-Jin Ma,Jun-Jie Yu,Yang Liu,Yang Yu,Xue-Tao Li,Juan Zang,Zi-Min Yuan,Liang Kong

Hepatocellular carcinoma (HCC) represents a significant health challenge that requires urgent attention, primarily due to the limited application of chemotherapeutic drugs. This limitation arises from the high infiltration of immune cells within the tumor microenvironment, which diminishes the effectiveness of the therapeutic agents. Consequently, exploring the combination of drug therapy with the M1 polarization mechanism is considered a promising strategy to address this issue. In this study, we designed a hierarchically targeted micelle system responsive to reactive oxygen species (ROS), enabling the synergistic delivery of the hydrophobic drugs sorafenib (Sof) and dehydrodiisoeugenol (Deh) through the integration of a ROS-sensitive bond (thioacetal ketones, TK) and a specific targeting group (glycyrrhetinic acid, GA). The results demonstrated that TK-GA-Sof/Deh-Ms exhibited excellent encapsulation efficiency and stability. The cumulative release rates of Sof and Deh from TK-GA-Sof/Deh-Ms at 48 h were recorded as 49.67 ± 0.02% and 43.90 ± 0.01%, respectively. The online SynergyFinder2.0 software was used to calculate a ZIP synergy score of 6.339 for Sof and Deh, indicating synergy. The combination showed a more significant antitumor effect. The IC50 value of TK-GA-Sof/Deh-Ms was 13.21 ± 1.36 μM. Notably, Deh not only promotes the polarization of M1 macrophages but also effectively inhibits the activation of M2 macrophages. In summary, this study introduces a stepwise-targeting micelle system for liver cancer that possesses dual functions─tumor inhibition and macrophage regulation, thereby paving the way for innovative treatment strategies for hepatocellular carcinoma.

Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression

Xiaoling Zeng,Baohui Chen,Luping Wang,Yingxiao Sun,Zhao Jin,Xuanyong Liu,Liping Ouyang,Yun Liao

Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1β and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.

Follicle-stimulating hormone peptide-conjugated liposomes in the treatment of epithelial ovarian cancer through the induction of M2-to-M1 macrophage repolarization

Shengxia Hu,Dan Sun,Ling Tang,Liang Kong,Yang Liu,Fang Liu,Dongmei Tang,Xuhong Lu,Yuanyuan Wang

Introduction The silent killer epithelial ovarian cancer (EOC) is a lethal malignancy with high mortality rate and often diagnosed at an advanced stage. Traditional chemotherapy for EOC remains unsatisfactory as the tumor microenvironment (TME) is complicated and contains multiple factors such as tumor associated macrophages (TAMs). Therefore, a drug delivery system which codelivery chemotherapy drug and immune modulator for EOC treatment is urgently needed. Methods Follicle-stimulating hormone peptide-conjugated paclitaxel and ginsenoside Rh2 codelivery liposomes (FSH@PTX-Rh2-Lips) were prepared in this study. FSH was decorated on the liposomal surface to enhance cellar uptake, PTX was used to kill cancer cells, and Rh2 was added to induce macrophages repolarization as well as a member material. The targeting, anti-tumor effect and impact on macrophage repolarization of FSH@PTX-Rh2-Lips were evaluated in vitro and in vivo. Results With the ideal physicochemical properties, FSH@PTX-Rh2-Lips displayed increased cellular uptake, strong cytotoxicity to ID8 cells, inhibitory effect of tumor cell metastasis, and ability to induce macrophage repolarization from M2 to M1 in vitro. The tumor-bearing mice model suggested FSH@PTX-Rh2-Lips showed significant effect on antitumor and tumor recurrence, and the mechanism of FSH@PTX-Rh2-Lips in treatment of EOC was related to inhibiting tumor growth and inducing macrophage repolarization. Conclusion FSH@PTX-Rh2-Lips with function of affecting TAMs repolarization and altering the TME were successfully prepared and might offer an effective therapeutic strategy against EOC.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism

Li Gao,Ai-ping Zhang,Lei Fu,Qian-wen Li,Xue-mei Qin,Jing Zhao

Background The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. Purpose The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. Methods The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. Results Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 μM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. Conclusion In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Glucomannan from Aloe vera Gel Strengthens Intestinal Barrier by Suppressing Macrophage M1 Polarization via the Lactic Acid–Piezo1–Ca2+ Axis

Jiawen Yu,Kunying Chen,Yujing Zhang,Xujie Wang,Yangchun Shen,Yu Deng,Xingtao Zhou

Abstract Modulating intestinal macrophage polarization is critical for maintaining intestinal barrier integrity. Our previous study demonstrated that glucomannan from Aloe vera gel (AGP) improved the intestinal barrier, yet its direct impact on intestinal macrophages remained undefined. Here, we demonstrated that AGP reduced M1 macrophage infiltration in colonic tissue. Integrated serum untargeted metabolomics identified lactic acid as a key AGP-induced metabolite, with 16S rRNA sequencing pointing to the gut microbiota as its potential source. Mechanistically, lactic acid suppressed M1 polarization by inhibiting the mechanosensitive cation channel Piezo1, thereby attenuating calcium influx, concurrently dampening STAT3 activation and ROS production─core drivers of M1 commitment. Critically, these effects were abrogated by a Piezo1 agonist, confirming the centrality of the lactic acid–Piezo1–Ca2+ axis. Collectively, our study defines a novel immunometabolic pathway wherein AGP fortifies the intestinal barrier through microbiota-derived lactic acid, which restrains macrophage M1 polarization via the lactic acid–Piezo1–calcium axis.

β-hydroxybutyrate regulates microglia M1/M2 polarization and phagocytosis through the JAK1/STAT1 pathway to reduce neuroinflammation and exert anti-epileptic effects

Yang Hui,Wang Huifen

Callicarpa nudiflora-derived extracellular vesicle-like particles loaded with budesonide enhance the treatment of ulcerative colitis by regulating M1/M2 macrophage polarization

Yuxin Xi,Jiayi Zou,Liang Chen,Xinyao Ma,Yishan Yan,Desheng Liang,Fan Liao,Haijun Zhong,Feng Guo

Conventional drug therapy effectively controls early-stage ulcerative colitis (UC) symptoms, but long-term use and high doses may compromise safety and patient tolerance. Here, Callicarpa nudiflora -derived extracellular vesicle-like particle (CN-EVLP) was extracted from the fresh leaves of Callicarpa nudiflora . An oral delivery system of budesonide using CN-EVLP (CN-EVLP-Bud) was designed, and the loading conditions were explored and optimized to improve the encapsulation efficiency and drug loading. We found that encapsulating budesonide in CN-EVLP enhanced its biocompatibility and promoted cellular uptake in both Caco-2 and Raw264.7 cells. In lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium (DSS)-induced murine colitis models, CN-EVLP-Bud showed significantly stronger anti-inflammatory and antioxidant effects than free budesonide, including suppressing pro-inflammatory cytokines (IL-6, TNF-α) and reducing oxidative stress. Moreover, CN-EVLP could modulate macrophage M1/M2 polarization, further enhancing its anti-inflammatory efficacy. Thus, CN-EVLP shows promising potential as a novel nanomedicine delivery vehicle for UC therapy.

Simultaneously responsive microfluidic chip aptasensor for determination of kanamycin, aflatoxin M1, and 17β-estradiol based on magnetic tripartite DNA assembly nanostructure probes

He Liyong,Shen Zhipeng,Wang Jiaqi,Zeng Jin,Wang Wenhai,Wu Huihui,Wang Qiqin,Gan Ning

The authors describe a microfluidic chip-based aptasensor platform combined with magnetic tripartite DNA structure-functionalized nanocomposites to achieve simultaneous determination of kanamycin (KANA), aflatoxin M1 (AFM1), and 17β-estradiol (E2) in milk. The two-duplex tripartite DNA nanostructure was first assembled on the surface of magnetic beads. When the aptamer on the probes recognized the specific target, the aptamer-target would be released into the supernatant. The pre-primer@circular DNA template structure initiates rolling circle amplification (RCA) by phi29 polymerase. After magnetic separation, the magnetic nanocomposites were added into a solution containing three different lengths of complementary strands to the RCA products. The number of complementary strands significantly decrease, and this can be quantitated by the microfluidic chip. Further, the employment of magnetic nanocomposites and microfluidic chip not only resolve the complex matrix interference, but also dramatically enhances the determination selectivity and sensitivity. This aptasensor allows for determination of KANA, AFM1, and E2 with limits of detection as low as 0.32 pg mL −1 , 0.95 pg mL −1 , and 6.8 pg mL −1 , respectively. This novel method exhibits the advantages of excellent stability and fast response time (< 3 min on microfluidic chip platform) for simultaneous determination of KANA, AFM1, and E2 in milk samples and ensures food safety. Graphical abstract

Nanoparticle-Loaded Polarized-Macrophages for Enhanced Tumor Targeting and Cell-Chemotherapy

Hou Teng,Wang Tianqi,Mu Weiwei,Yang Rui,Liang Shuang,Zhang Zipeng,Fu Shunli,Gao Tong,Liu Yongjun,Zhang Na

A polarized-macrophages-based drug delivery system (M1/SLNP) was presented for the cell-chemotherapy of cancer. Polarized-macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver chemotherapeutic drugs to tumor tissues for chemotherapy simultaneously. M1/SLNP was a multifunctional delivery system with simple structure, excellent safety, and without complex synthesis process.

Mannose-Glycated Metal-Phenolic Microcapsules Orchestrate Phenotype Switch of Macrophages for Boosting Tumor Immunotherapy

Xin Tan,Renwang Sheng,Weikun Li,Yinghua Tao,Zonghao Liu,Ning Yang,Syeda Safia Hashmi,Feiling Feng,Fangzhou Liu,Liqin Ge

Microcapsules are advancing in immunotherapy, with both their core and shell being capable of loading immunoregulatory substances. Notably, microcapsules with intrinsic bioactivities can more directly modulate the immune microenvironment, while current research in this area remains scarce. Herein, immunomodulatory metal-phenolic microcapsules (mMPMs) is developed through the one-step assembly of dopamine-modified hyaluronic acid (HADA) and Fe III onto mannose-glycated bovine serum albumin microbubbles (Man-BSA MBs). Specifically, Man-BSA formed during the early stages of the Maillard reaction is sonicated to produce microbubbles as templates for capsule preparation. Subsequently, HADA is rapidly coated on the templates and coordinates with Fe III to form microcapsules after air escapes from MBs. Mass spectrometry analysis identifies abundant lysine glycation sites on Man-BSA, with the highest glycation site percentage reaching 94.88%. Man-BSA within mMPMs effectively promotes macrophage internalization, induces the accumulation of pro-inflammatory mediators, and thereby results in the M1 polarization of macrophages, as further corroborated by proteomic analysis. Consequently, the compelling anti-tumor effects of mMPMs are demonstrated both in vitro and in vivo. Overall, this work presents an immunomodulatory microcapsule that activates pro-inflammatory phenotype macrophages, which is a promising microcarrier to improve immunotherapeutic effects.

Nano-mechanical Immunoengineering: Nanoparticle Elasticity Reprograms Tumor-Associated Macrophages via Piezo1

Zichen Yang,Yuge Zhao,Xiaoyou Zhang,Li Huang,Kun Wang,Jiuyuan Sun,Nana Chen,Weimin Yin,Shiyu Chen,Hui Zhi,Liangyi Xue,Lulu An,Rongjie Li,Haiqing Dong,Jinfu Xu,Yan Li,Yongyong Li

The mechanical properties of nanoparticles play a crucial role in regulating nanobiointeractions, influencing processes such as blood circulation, tumor accumulation/penetration, and internalization into cancer cells. Consequently, they have a significant impact on drug delivery and therapeutic efficacy. However, it remains unclear whether and how macrophages alter their biological function in response to nanoparticle elasticity. Here, we report on the nano-mechanical biological effects resulting from the interactions between elastic silica nanoparticles (SNs) and macrophages. The SNs with variational elasticity Young’s moduli ranging from 81 to 837 MPa were synthesized, and it was demonstrated that M2 [tumor-associated macrophages (TAMs)] could be repolarized to M1 by the soft SNs. Additionally, our findings revealed that cell endocytosis, membrane tension, the curvature protein Baiap2, and the cytoskeleton were all influenced by the elasticity of SNs. Moreover, the mechanically sensitive protein Piezo1 on the cell membrane was activated, leading to calcium ion influx, activation of the NF-κB pathway, and the initiation of an inflammatory response. In vivo experiments demonstrated that the softest 81 MPa SNs enhanced tumor penetration and accumulation and repolarized TAMs in intratumoral hypoxic regions, ultimately resulting in a significant inhibition of tumor growth. Taken together, this study has established a cellular feedback mechanism in response to nanoparticle elasticity, which induces plasma membrane deformation and subsequent activation of mechanosensitive signals. This provides a distinctive “nano-mechanical immunoengineering” strategy for reprogramming TAMs to enhance cancer immunotherapy.

Molybdenum and cadmium co-exposure promotes M1 macrophage polarization through oxidative stress-mediated inflammatory response and induces pulmonary fibrosis in Shaoxing ducks (Anas platyrhyncha)

Gang Huang,Junrong Luo,Huiling Guo,Xueru Wang,Zhisheng Hu,Wenjing Pu,Xuesheng Chu,Caiying Zhang

High molybdenum (Mo) and cadmium (Cd) are harmful to the body, but pulmonary toxicity induced by Mo and Cd co-exposure is unknown. To assess the combined impacts of Mo and Cd on fibrosis through M1 polarization in the lung of ducks, 80 healthy 8-day-old Shaoxing ducks ( Anas platyrhyncha ) were randomly assigned to 4 groups and fed with containing unequal doses of Mo or/and Cd diet. Lung tissues were collected on the 16th week. Results indicated that Mo or/and Cd significantly increased their contents in the lungs, and led to trace elements disorder and histological abnormality, and oxidative stress accompanied by promoting contents of H 2 O 2 and MDA and decreasing activities of T-SOD, GSH-Px, and CAT, then activated the TLR4/NF-κB/NLRP3 pathway accompanied by upregulating Caspase-1, ASC, IL-18, IL-1β, TLR4, NF-κB, and NLRP3 expression levels, and disrupted M1/M2 balance to divert toward M1, which evoked the TGF-β/Smad2/3-mediated fibrosis by elevating TGF-β1, Smad2, Smad3, COL1A1, α-SMA, and MMP2 expression levels, and decreasing Smad7 and TIMP2 expression levels. The changes of the combined group were most obvious. To sum up, the research demonstrated that Mo or/and Cd may cause macrophages to polarize toward M1 by oxidative stress-mediated the TLR4/NF-κB/NLRP3 pathway, then result in fibrosis through the TGF-β1/Smad2/3 pathway in duck lungs. Mo and Cd may worsen lung damage.