[IF=28.824]Nature Cell Biology Pubmed ID : 34616019文献引用抗体：bs-1754R-AF555| Anti-ECP/AF555 pAb | IFInstitution : 中国广州中山大学孙中山纪念医院医学研究中心广东省恶性肿瘤表观遗传学与基因调控重点实验室摘要：Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25–ILK–PKCα–CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.
[IF=25.841]Journal of Extracellular Vesicles Pubmed ID : 34623756
Institution : 中国科学院上海药物研究所药物研究与药剂学中心国家重点实验室摘要：Multivesicular bodies (MVBs) fuse with not only the plasma membranes to release extracellular vesicles (EVs) but also lysosomes for degradation. Rab7 participates in the lysosomal targeting of MVBs. However, the proteins on MVB that directly bind Rab7, causing MVB recruitment of Rab7 remain unidentified. Here, we show that Coro1a undergoes neddylation modification at K233 by TRIM4. Neddylated Coro1a is associated with the MVB membrane and facilitates MVB recruitment and activation of Rab7 by directly binding Rab7. Subsequently, MVBs are targeted to lysosomes for degradation in a Rab7-dependent manner, leading to reduced EV secretion. Furthermore, a decrease in neddylated Coro1a enhances the production of tumour EVs, thereby promoting tumour progression, indicating that neddylated Coro1a is an ideal target for the regulation of EV biogenesis. Altogether, our data identify a novel substrate of neddylation and reveal an unknown mechanism for MVB recruitment of Rab7, thus providing new insight into the regulation of EV biogenesis.
[IF=25.841]Journal of Extracellular Vesicles Pubmed ID : 34719860文献引用抗体：bs-0813R | Anti-casein pAb | FCInstitution : 福建省厦门市集美大学食品与生物工程学院生物工程系摘要：Extracellular vesicles (EVs) have demonstrated unique advantages in serving as nanocarriers for drug delivery, yet the cargo encapsulation efficiency is far from expectation, especially for hydrophilic chemotherapeutic drugs. Besides, the intrinsic heterogeneity of EVs renders it difficult to evaluate drug encapsulation behaviour. Inspired by the active drug loading strategy of liposomal nanomedicines, here we report the development of a method, named “Sonication and Extrusion-assisted Active Loading” (SEAL), for effective and stable drug encapsulation of EVs. Using doxorubicin-loaded milk-derived EVs (Dox-mEVs) as the model system, sonication was applied to temporarily permeabilize the membrane, facilitating the influx of ammonium sulfate solution into the lumen to establish the transmembrane ion gradient essential for active loading. Along with extrusion to downsize large mEVs, homogenize particle size and reshape the nonspherical or multilamellar vesicles, SEAL showed around 10-fold enhancement of drug encapsulation efficiency compared with passive loading. Single-particle analysis by nano-flow cytometry was further employed to reveal the heterogeneous encapsulation behaviour of Dox-mEVs which would otherwise be overlooked by bulk-based approaches. Correlation analysis between doxorubicin auto-fluorescence and the fluorescence of a lipophilic dye DiD suggested that only the lipid-enclosed particles were actively loadable. Meanwhile, immunofluorescence analysis revealed that more than 85% of the casein positive particles was doxorubicin free. These findings further inspired the development of the lipid-probe- and immuno-mediated magnetic isolation techniques to selectively remove the contaminants of non-lipid enclosed particles and casein assemblies, respectively. Finally, the intracellular assessments confirmed the superior performance of SEAL-prepared mEV formulations, and demonstrated the impact of encapsulation heterogeneity on therapeutic outcome. The as-developed cargo-loading approach and nano-flow cytom.
摘要：The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.
[IF=16.806]Advanced Science Pubmed ID : 34719890文献引用抗体：bsm-33283M | Mouse Anti-Bax mAb | IHCInstitution : 广东省口腔疾病诊疗工程研究中心北京大学深圳医院广东省高水平临床重点专科口腔颌面外科摘要：Chemodynamic therapy (CDT) is an emerging treatment that usually employs chemical agents to decompose hydrogen peroxide (H₂O₂) into hydroxyl radical (•OH) via Fenton or Fenton-like reactions, inducing cell apoptosis or necrosis by damaging biomacromolecules such as, lipids, proteins, and DNA. Generally, CDT shows high tumor-specificity and minimal-invasiveness in patients, thus it has attracted extensive research interests. However, the catalytic reaction efficiency of CDT is largely limited by the relatively high pH at the tumor sites. Herein, a 808 nm laser-potentiated peroxidase catalytic/mild-photothermal therapy of molybdenum diphosphide nanorods (MoP₂ NRs) is developed to improve CDT performance, and simultaneously achieve effective tumor eradication and anti-infection. In this system, MoP₂ NRs exhibit a favorable cytocompatibility due to their inherent excellent elemental biocompatibility. Upon irradiation with an 808 nm laser, MoP₂ NRs act as photosensitizers to efficiently capture the photo-excited band electrons and valance band holes, exhibiting enhanced peroxidase-like catalytic activity to sustainedly decompose tumor endogenous H₂O₂ to •OH, which subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria. As demonstrated both in vitro and in vivo, this system exhibits a superior therapeutic efficiency with inappreciable toxicity. Hence, the work may provide a promising therapeutic technique for further clinical applications.
[IF=15.828]Cell Death And Differentiation Pubmed ID : 34635817文献引用抗体：bsm-33235M | Mouse Anti-alpha Tubulin (Acetyl Lys40) mAb | IFInstitution : 南京医科大学生殖医学国家重点实验室摘要：Many integral membrane proteins might act as indispensable coordinators in specific functional microdomains to maintain the normal operation of known receptors, such as Notch. Gm364 is a multi-pass transmembrane protein that has been screened as a potential female fertility factor. However, there have been no reports to date about its function in female fertility. Here, we found that global knockout of Gm364 decreased the numbers of primordial follicles and growing follicles, impaired oocyte quality as indicated by increased ROS and γ-H2AX, decreased mitochondrial membrane potential, decreased oocyte maturation, and increased aneuploidy. Mechanistically, Gm364 directly binds and anchors MIB2, a ubiquitin ligase, on the membrane. Subsequently, membrane MIB2 ubiquitinates and activates DLL3. Next, the activated DLL3 binds and activates Notch2, which is subsequently cleaved within the cytoplasm to produce NICD2, the intracellular active domain of Notch2. Finally, NICD2 can directly activate AKT within the cytoplasm to regulate oocyte meiosis and quality.
[IF=14.65] Microbiome Pubmed ID : 34602091文献引用抗体：bs-0737R | Anti-HIF-1α pAb | FCInstitution : 扬州大学动物科学与技术学院动物生理与分子营养实验室摘要：Background: Intestinal Peyer’s patches (PPs) form unique niches for bacteria-immune cell interactions that direct host immunity and shape the microbiome. Here we investigate how peroral administration of probiotic bacterium Limosilactobacillus reuteri R2LC affects B lymphocytes and IgA induction in the PPs, as well as the downstream consequences on intestinal microbiota and susceptibility to inflammation. Results: The B cells of PPs were separated by size to circumvent activation-dependent cell identification biases due to dynamic expression of markers, which resulted in two phenotypically, transcriptionally, and spatially distinct subsets: small IgD+/GL7−/S1PR1+/Bcl6, CCR6-expressing pre-germinal center (GC)-like B cells with innate-like functions located subepithelially, and large GL7+/S1PR1−/Ki67+/Bcl6, CD69-expressing B cells with strong metabolic activity found in the GC. Peroral L. reuteri administration expanded both B cell subsets and enhanced the innate-like properties of pre-GC-like B cells while retaining them in the sub-epithelial compartment by increased sphingosine1-phosphate/S1PR1 signaling. Furthermore, L. reuteri promoted GC-like B cell differentiation, which involved expansion of the GC area and autocrine TGFβ-1 activation. Consequently, PD-1-T follicular helper cell-dependent IgA induction and production was increased by L. reuteri, which shifted the intestinal microbiome and protected against dextran-sulfate-sodium induced colitis and dysbiosis. Conclusions: The Peyer’s patches sense, enhance and transmit probiotic signals by increasing the numbers and effector functions of distinct B cell subsets, resulting in increased IgA production, altered intestinal microbiota, and protection against inflammation.
摘要：Low-dose photodynamic therapy (PDT) holds great promise for reducing undesired patient photosensitivity in cancer treatment. Yet, its therapeutic effect is significantly affected by intracellular cytoprotective processes, such as autophagy. Here, an efficient autophagy suppressor is developed, which is a multifunctional DNA nanoflower (DNF) consisted of tumor-targeting aptamers and DNAzymes for silencing autophagy-related genes, with surface modification of low-dose photosensitizer (Ce6). It is found that the multifunctional DNF can specifically target tumor cells and generate reactive oxygen species (ROS) under light irradiation to trigger self-disassembly of DNF, enhancing the bioavailability of encoded DNAzymes, leading to amplified autophagy suppression. As a facile spatiotemporally programmable photogene therapy platform, the designed DNF is able to suppress tumor growth in vivo with a very low injection dose of Ce6 (18 µg kg−1, around 100 times lower than the generally applied dose), representing a promising strategy for cancer therapy with safely low-dose PDT.
Institution : 中国核工业集团公司成都医学院第二附属医院416医院摘要：As an innovative treatment strategy for cancer treatment, Fenton reaction-mediated Chemodynamic therapy (CDT) dependent on the conversion of endogenous hydrogen peroxide (H₂O₂) into cytotoxic hydroxyl radical (•OH) to destroy tumor cells has attracted increasing interest. However, the insufficient supply of H₂O₂ has greatly hindered the anticancer efficacy of CDT in the tumor microenvironment, and this inherent disadvantage has rarely attracted attention. In order to develop a strategy with high-efficiency H₂O₂ self-supply ability to enhance the CDT efficacy, we constructed a Fe-based metal–organic framework (MOF) as a carrier for the drug Juglone (JUG), which can not only increase the intracellular H₂O₂ concentration, but also serve as an inhibitor of the peptidyl-prolyl cis–trans isomerase NIMA-interacting 1 (Pin1), which is a key regulator for multiple physiological processes in cancer cells. Once internalized by tumor cells, the acidic environment of the tumor promotes the release of JUG for drug therapy, and the released Fe ions trigger the Fenton reaction to produce •OH from sufficient H₂O₂, thereby achieving significant antitumor effects. Furthermore, the coating of cancer cell membranes onto the JUG-loaded MOF could enable it with homologous tumor targeting ability. Both in vitro and in vivo results show that the use of drugs can activate the cascade to provide sufficient H₂O₂ with outstanding anti-tumor efficacy, which paves a new avenue for the realization of drug/CDT synergistic therapy.
bs-0061R | Anti-β-actin pAb | WBInstitution : 温州医科大学口腔医学院摘要：Endowed with superior tailorability and functionality, metal–organic frameworks (MOFs) have been exploited for their diverse applications in biomedicine. However, the instability of MOFs under an aqueous environment causes an accelerated degradation preventing their clinical applications and commercialization. To address this issue, studies have reported the incorporation of hydrophobic functional groups into MOF to enhance its stability. In this study, we aimed to fabricate a multifunctional coating on titanium implants by exploiting the synergy between Zn-based MOFs and raloxifene (Ral). We theorized that the integration of MOF and Ral will not only locally deliver the drug, but also take advantage of the hydrophobic functional group of Ral to enhance the stability of MOF in an aqueous environment. The release studies showed a sustained release of both Zn2+and Ral for more than 14 d. In-depth in vitro investigations also verified that MOF/Ral coatings significantly enhanced the cell viability and osteogenic differentiation of osteoblasts, as well as decreasing the tartrate-resistant acid phosphatase activity and osteoclastic biomarker expressions. In addition, both micro-computed tomography and immunohistochemical analysis further confirmed the efficacy of MOF/Ral coatings in the formation of new bone within the femurs of osteoporotic rats. The feasibility of MOF/Ral coated titanium implants in inhibiting osteolysis and promoting osteogenesis has undoubtedly proved their clinical prospects in the treatment of osteoporotic bone injury.