查找使用阿拉丁产品的科研文献

Nanoparticle-mediated SIRT1 inhibition suppresses M2 macrophage polarization and hepatocarcinogenesis in chronic hepatitis B

Zhang He,Yuan Feng,Zhao Nan,Tang Wenqiang,Zhao Pengwei,Liu Chunfa,Chen Shan,Hou Xiaolin,Xia Changyou,Chu Jun

Hepatocellular carcinoma (HCC) is a major complication of chronic hepatitis B (CHB), with macrophage M2 polarization playing a critical role in shaping the tumor-promoting hepatic immune microenvironment. Sirtuin 1 (SIRT1) has been implicated in immune modulation and liver carcinogenesis. This study investigates the potential of Mimetic Nanoparticles (MNPs) for delivering SIRT1 inhibitors to regulate macrophage polarization and remodel the hepatic immune microenvironment, aiming to prevent HCC development post-CHB. A transgenic mouse model of CHB was established, and RNA sequencing (RNA-seq) and proteomics analyses revealed significant dysregulation of genes associated with M2 macrophage polarization, particularly SIRT1. Functional enrichment analysis highlighted key pathways, including PI3K-Akt and NF-κB, that contribute to CHB-driven immune alterations. Synthesized and characterized MNPs successfully delivered SIRT1 inhibitors, effectively inhibiting M2 macrophage polarization in vitro. In vivo administration of MNPs-SIRT1-FN significantly reduced M2 macrophage infiltration and suppressed tumor growth. These findings suggest that nanoparticle-mediated SIRT1 inhibition is a promising strategy for immunomodulation and HCC prevention in CHB patients. This study provides novel insights into nanoparticle-based immunotherapy for CHB-related HCC and highlights a potential therapeutic avenue for liver cancer prevention.

Chitosan-based hydrogel dressings for diabetic wound healing via promoting M2 macrophage-polarization

Xuelian Wei,Caikun Liu,Zhiqian Li,Zhengxiang Gu,Junxiao Yang,Kui Luo

A long-term inflammatory phase of diabetic wounds is the primary cause to prevent their effective healing. Bacterial infection, excess reactive oxygen species (ROS), especially failure of M2-phenotype macrophage polarization can hinder the transition of diabetic wounds from an inflammation phase to a proliferation one. Herein, a chitosan-based hydrogel dressing with the ability of regulating M2 macrophage polarization was reported. The PAAc/CFCS-Vanillin hydrogel dressing was synthesized by one step thermal polymerization of catechol-functionalized chitosan (CFCS), acrylic acid , catechol functional methacryloyl chitosan‑silver nanoparticles (CFMC-Ag NPs) and bioactive vanillin. The PAAc/CFCS-Vanillin hydrogel possessed sufficient mechanical strength and excellent adhesion properties, which helped rapidly block bleeding of wounds. Thanks to CFCS , CFMC-Ag NPs and vanillin in the hydrogel, it displayed excellent antibacterial infection in the wounds. Vanillin helped scavenge excess ROS and regulate the levels of inflammatory factors to facilitate the polarization of macrophages into the M2 phenotype. A full-thickness skin defect diabetic wound model showed that the wounds treated by the PAAc/CFCS-Vanillin hydrogel exhibited the smallest wound area, and superior granulation tissue regeneration , remarkable collagen deposition, and angiogenesis were observed in the wound tissue. Therefore, the PAAc/CFCS-Vanillin hydrogel could hold promising potential as a dressing for the treatment of diabetic chronic wounds.

A polysaccharide from Periplaneta americana promotes macrophage M2 polarization, exhibiting anti-inflammatory and wound-healing activities

Xin Xiao,Ailian Zhu,Gang He,Seiichi Tokula,YiTing Yang,Yang Qing,Yali Liu,HanWen Hu,Qin Song

A miscellaneous polysaccharide, PAP55–3-1, with a molecular weight of 23.03 kDa, was isolated from Periplaneta americana through extraction with dilute alkali solution, ethanol precipitation, and column chromatography purification. Structural analysis shows that PAP55–3-1 is mainly composed of five monosaccharides: galactosamine hydrochloride, glucosamine hydrochloride, galactose, glucose and mannose. Its main glycosidic bonds are: Manp-(1→, Galp-(1→, →3)-Galp-(1→, →3,6)-Manp-(1→, →2,6)-Manp-(1→, →6)-Manp-(1→, →4)-Galp-(1→, →6-Glcp-(1→, →6)-Galp-(1→, →2)-Manp-(1 →, →3,4)-Glcp-(1→, →3,6)-Galp-(1→. In vitro experiments demonstrated that PAP55–3-1 can effectively inhibit reactive oxygen species (ROS) and O 2 − production following H 2 O 2− induction. After H 2 O 2− induction, HIF-1α (hypoxia-inducible factor) was translocated in mitochondria PAP55–3-1 increased localization of HIF-1α was located on mitochondria to maintain the stability of mitochondrial function stability, thereby effectively inhibiting H 2 O 2 -induced mitochondrial oxidative damage. Additionally, PAP55–3-1 inhibited the M1 polarization of macrophages stimulated by H 2 O 2 and promoted the phenotype polarization of macrophages from M1 to M2, displaying anti-inflammatory and pro-repair properties. In vivo experimental results indicated that PAP55–3-1 promoted wound healing in mice. Immunohistochemical experiments revealed a reduction in CD68 expression and increase in CD206 expression in both positive and the high-dose polysaccharide group control group. This further demonstrated that PAP55–3-1 promotes the phenotype polarization of macrophages from M1 to M2, exerting anti-inflammatory and wound-healing activities.

Huaier polysaccharides inhibits hepatocellular carcinoma via gut microbiota mediated M2 macrophage polarization

Xiaoxuan Li,Hongyun Zhang,Yufei Deng,Fang qian,Xiaohui Zhang,Shuiping Ding,Xiaoying Hou,Hongzhi Du

Liver cancer was the third cause of global cancer death, while China has the largest number of patients. And traditional Chinese medicine is an important strategy for liver cancer. There into, Huaier polysaccharides (HP), the major component of Trametes robiniophila Murr., as a preparation of Huaier granule, is recommended by clinical guidelines for Hepatocellular carcinoma (HCC). However, the anti-HCC mechanism remains unclear. Herein, we investigated whether HP could suppress HCC and revealed the underlying mechanism. Firstly, HP showed a weaker proliferation inhibitory effect on the mouse source and human HCC cells in vitro , but exhibited stronger anti-HCC effects in animals. And nude mice models confirmed that macrophages play an important role in the anti-HCC effect of HP. Then, we observed that HP reduced the polarization of M2 macrophages in tumor microenvironment and increased the secretion of pro-inflammatory factors by macrophages. Moreover, 16 s rRNA gene sequencing and non-targeted metabolomics analysis revealed that HP altered the gut microbiota and related metabolites. Eventually, antibiotic intervention eliminated the efficacy and reduced the expression of pro-inflammatory factors, confirming that the gut microbiota is a key molecule for HP efficacy. In addition, MTT and EdU assay indicated that Chenodeoxycholic acid (CDCA) were potential microbial metabolites influencing efficacy of HP. In conclusion, our data revealed that Huaier polysaccharides inhibited HCC via gut microbiota mediated M2 macrophage polarization, providing sufficient scientific support for Huaier polysaccharides clinical application and indicating the indispensable role of polysaccharides in life health.

M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury

Guan Pengfei,Fan Lei,Zhu Zhaobo,Yang Qinfeng,Kang Xinchang,Li Junji,Zhang Zuyu,Liu Shencai,Liu Can,Wang Xuelian,Xu Jing,Wang Kun,Sun Yongjian

Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along the spinal cord’s conduction pathway. Nonetheless, the application of hydrogels composed of diverse electroconductive materials has demonstrated limited capacity to mitigate the post-SCI inflammatory response. Recent research has indicated that the transplantation of M2 microglia effectively fosters SCI recovery by attenuating the excessive inflammatory response. Exosomes (Exos), small vesicles discharged by cells carrying similar biological functions to their originating cells, present a compelling alternative to cellular transplantation. This investigation endeavors to exploit M2 microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded to electroconductive hydrogels through hydrogen bonding for synergistic promotion of SCI repair to synergistically enhance SCI repair. In vitro experiments substantiated the significant capacity of M2-Exos-laden electroconductive hydrogels to stimulate the growth of neural stem cells and axons in the dorsal root ganglion and modulate microglial M2 polarization. Furthermore, M2-Exos demonstrated a remarkable ability to mitigate the initial inflammatory reaction within the injury site. When combined with the electroconductive hydrogel, M2-Exos worked synergistically to expedite neuronal and axonal regeneration, substantially enhancing the functional recovery of rats afflicted with SCI. These findings underscore the potential of M2-Exos as a valuable reparative factor, amplifying the efficacy of electroconductive hydrogels in their capacity to foster SCI rehabilitation.

Butyrate protects against MRSA pneumonia via regulating gut-lung microbiota and alveolar macrophage M2 polarization

Yan Zhao,Haoming Sun,Yiwei Chen,Qiang Niu,Yiting Dong,Mei Li,Ye Yuan,Xiaojun Yang,Qingzhu Sun

High CYP2E1 activity aggravates hepatofibrosis by limiting macrophage polarization towards the M2 phenotype

Yuan-yuan Guo,Chen Xu,Yan Fang,Cai-e Wang,Na Gao,Qiang Wen,Hai-ling Qiao

Cytochrome P450 2E1 (CYP2E1) is an important drug-metabolizing enzyme that has been recognized as one of the risk factors for hepatofibrosis. Macrophages play key roles in regulating hepatofibrosis progression and resolution. However, whether CYP2E1 is involved in the regulation of macrophage polarization during hepatofibrosis is still unclear. Herein, we measured CYP2E1 activity and the expression of CD163 (an M2 marker) and CD68 (a pan-macrophage marker) in hepatofibrotic tissue from HCC patients (n = 26) with comparison to normal liver tissue (n = 26). The relationship of CYP2E1 activity in vivo and the CD163/CD68 ratio (an indicator of M2 polarization), as well as the extent of hepatofibrosis, were evaluated in diethylnitrosamine (DEN)-treated Sprague-Dawley rats. Strikingly, CYP2E1 activity and expression of CD68 increased and the CD163/CD68 ratio decreased, especially in hepatofibrotic tissue with higher CYP2E1 activity. Expression of α-SMA, Ki67, and PCNA were positively correlated with CYP2E1 activity and inversely correlated with the CD163/CD68 ratio. Furthermore, CYP2E1 activity showed an inverse correlation with the CD163/CD68 ratio. Overall, high CYP2E1 activity aggravates hepatofibrosis by restraining M2 macrophage polarization, providing a novel insight for understanding the profibrotic activity of CYP2E1 and a promising avenue for hepatofibrosis therapy.

BMSC-derived exosomes promote osteoporosis alleviation via M2 macrophage polarization

Zhang Yanbin,Bai Jing,Xiao Bin,Li Chunyan

Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis.

HA-coated collagen nanofibers for urethral regeneration via in situ polarization of M2 macrophages

Niu Yuqing,Stadler Florian J.,Yang Xu,Deng Fuming,Liu Guochang,Xia Huimin

In situ tissue engineering utilizes the regenerative potential of the human body to control cell function for tissue regeneration and has shown considerable prospect in urology. However, many problems are still to be understood, especially the interactions between scaffolds and host macrophages at the wound site and how these interactions direct tissue integration and regeneration. This study was designed to evaluate the efficacy of hyaluronic acid (HA) functionalized collagen nanofibers in modulating the pro-healing phenotype expression of macrophages for urethral regeneration. Tubular HA-collagen nanofibers with HA-coating were prepared by coaxial electrospinning. The formation of a thin HA-coating atop each collagen nanofiber endowed its nanofibrous mats with higher anisotropic wettability and mechanical softness. The macrophages growing on the surface of HA-collagen nanofibers showed an elongated shape, while collagen nanofibers’ surface exhibited a pancake shape. Immunofluorescence and ELISA analysis showed that elongation could promote the expression of M2 phenotype marker and reduce the secretion of inflammatory cytokines. In vivo experiments showed that tubular HA-collagen nanofibers significantly facilitate male puppy urethral regeneration after injury. In the regenerated urethra bridged by tubular HA-collagen nanofibers, anti-inflammatory M2 macrophages are recruited to the surface of the scaffold, which can promote angiogenesis and endogenous urothelial progenitor cell proliferation.

Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection

Li An,Qianwen Zhai,Keyu Tao,Yingcai Xiong,Weiying Ou,Ziwei Yu,Xingyu Yang,Jianjian Ji,Mengjiang Lu

Background Quercetin has received extensive attention for its therapeutic potential treating respiratory syncytial virus (RSV) infection diseases. Recent studies have highlighted quercetin's ability of suppressing alveolar macrophages (AMs)-derived lung inflammation. However, the anti-inflammatory mechanism of quercetin against RSV infection still remains elusive. Purpose This study aims to elucidate the mechanism about quercetin anti-inflammatory effect on RSV infection. Methods BALB/c mice were intranasally infected with RSV and received quercetin (30, 60, 120 mg/kg/d) orally for 3 days. Additionally, an in vitro infection model utilizing mouse alveolar macrophages (MH-S cells) was employed to validate the proposed mechanism. Results Quercetin exhibited a downregulatory effect on glycolysis and tricarboxylic acid (TCA) cycle metabolism in RSV-infected AMs. However, it increased itaconic acid production, a metabolite derived from citrate through activating immune responsive gene 1 (IRG1), and further inhibiting succinate dehydrogenase (SDH) activity. While the suppression of SDH activity orchestrated a cascading downregulation of Hif-1α/NLRP3 signaling, ultimately causing AMs polarization from M1 to M2 phenotypes. Conclusion Our study demonstrated quercetin stimulated IRG1-mediated itaconic acid anabolism and further inhibited SDH/Hif-1α/NLRP3 signaling pathway, which led to M1 to M2 polarization of AMs so as to ameliorate RSV-induced lung inflammation.

Development of an Antiswelling Hydrogel System Incorporating M2-Exosomes and Photothermal Effect for Diabetic Wound Healing

Weichang Li,Shujie Wu,Lin Ren,Bingyu Feng,Zhipei Chen,Zongtai Li,Bin Cheng,Juan Xia

Diabetic wounds represent a persistent global health challenge with a substantial impact on patients’ health and overall well-being. Herein, a hydrogel system that integrates functionalized gold nanorods (AuNRs) and M2 macrophage-derived exosomes (M2-Exos) was developed to achieve an efficient and synergistic therapy for diabetic wounds. We introduced an ion-cross-linked dissipative network into a prefabricated covalent cross-linked network (long-chain polymer network), which was prepared using AuNRs as a specific cross-linker. The ion network was then cross-linked with the long-chain polymer in situ to form a specific network structure, imparting antiswelling and photothermal effects to the hydrogel. This integrated hydrogel system effectively scavenged reactive oxygen species levels, inhibited inflammation, promoted angiogenesis, and stimulated photothermal antibacterial activity through near-infrared (NIR) irradiation. To demonstrate the potential of the hydrogel, we established experimental animal models of oral mucosa ulceration and full-thickness skin defects. In vivo results confirmed that M2-Exos released from the hydrogels played a crucial role in wound closure. Furthermore, the synergistic effect of AuNRs and NIR photothermal effects eradicated bacterial infections in the wound area. Overall, our integrated hydrogel system is a promising tool for accelerating chronic diabetic wound healing and tissue regeneration. This study highlights the potential benefits of combining bioactive M2-Exos and the photothermal effect of AuNRs into an antiswelling hydrogel platform to achieve satisfactory wound healing in patients with diabetes.

Chiral hydrogels facilitate rapid diabetic wound healing by promoting macrophage M2 polarization and cellular proliferation

Yi-Ping Hu,Kui Xiao,Ma-Chao Si,Cai-Xia Wang,Yong Miao,Zhi-Qi Hu

Macrophage M2 polarization is one of the most important processes for promoting diabetic wound healing, but how chirality regulates this process is still unknown. Thus, chiral hydrogels based on amino acid derivatives (L-Fmoc-NV and D-Fmoc-NV) were applied to investigate the influence of chirality on macrophage M2 polarization. Compared to the right-handed nanofibers of D-Fmoc-NV, the left-handed helical nanofibers of L-Fmoc-NV can significantly affect the polarization of macrophages towards the M2 phenotype. Furthermore, the left-handed helical nanofibers of L-Fmoc-NV can more significantly promote cell adhesion, proliferation, and antibacterial responses than the nanofibers of D-Fmoc-NV. Based on these advantages of the left-handed helical nanofibers of L-Fmoc-NV, a more expedited healing trajectory (∼14 days) was observed in the L-Fmoc-NV systems. This work offers a new approach for chronic diabetic wound healing via the chirality-induced polarization of macrophages towards the M2 phenotype.