Food Bioscience
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2024
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IF 4.8
Mingxin Li,Shugang Li,Chunqing Ai,Wenxiu Zhu,Donglin Sui,Yixuan Li,Binbin Hou,Xiaomeng Ren
The increasing incidence of atopic dermatitis (AD) presents a public health issue, and thus there is an urgent need for safe and effective preventive strategies. In this study, a strategy to reduce the risk of AD in offspring by administering probiotics to the mother was explored. Female mice were given Lactobacillus rhamnosus RL-H3-005 (RL) and Pediococcus acidilactici RP-H3-006 (RP) during pregnancy and lactation period, and their inhibition effects on AD symptoms in offspring mice were evaluated. The results showed that supplementation with RL and RP during pregnancy and lactation period altered not only the gut microbiota community but also microbial community in milk in pregnant mice. Further study showed that pups from RL- and RP-treated pregnant mice had mild symptoms of AD, characterized by reduced epidermal thickness in the ear tissues and numbers of mast cells, which was associated with the reduction in secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and eosinophil cationic protein (Ecp). The underlying mechanism of RL and RP on the inhibition of AD symptom in offspring was closely associated with the alterations of the gut microbiota community in offspring, including an increase in Ligilactobacillus and Bacteroides . This study implies that RL and RP hold the potential to reduce the risk of AD in offspring via gut-mammary axis during the pregnancy and lactation period.
研究领域:
微生物学
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免疫学
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分子生物学
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药理学
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DOI
高影响因子
Science China-Life Sciences
·
2023
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IF 9.1
Tang Kegong,Wang Xiaona,Zhao Yu,Li Xiaobei,Jiang Zhenyu,Mei Song,Chen Mingrui,Ma Yiming,Du Xinyi,Qiao Xiangyu,Sun Na,Liu Jiaqi,Jiang Chengyu
Hypertension has become a growing public health concern worldwide. In fact, hypertension is commonly associated with increased morbidity and mortality. Currently, oligonucleotide drugs have proven to be promising therapeutic agents for various diseases. In the present study, we aimed to demonstrate that a herbal small RNA (sRNA), XKC-sRNA-h3 (B55710460, F221. I000082.B11), exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme (ACE) in mice. When compared with captopril, oral administration of the sphingosine (d18:1)-XKC-sRNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice. Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.
研究领域:
药理学
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分子生物学
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心血管研究
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DOI
PubMed
高影响因子
STEM CELLS AND DEVELOPMENT
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2023
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IF 4
Mr. Genghua Xu,Ms. Nuoya Liu,Ms. Yaqing Qiu,Ms. Jiayu Qi,Prof. Danyan Zhu
The histamine H3 receptor, prominently expressed in neurons with a minor presence in glial cells, acts as both an autoreceptor and an alloreceptor, controlling the release of histamine and other neurotransmitters. The receptor impacts various essential physiological processes. Our team's initial investigations had demonstrated that the histamine H3 receptor antagonists could facilitate the nerve regeneration via promoting the histamine H1 receptors on primary neural stem cells in the traumatic brain injury mouse, which suggested the potential of histamine H3 receptor as a promising target for treating neurological disorders and promoting nerve regeneration. Pitolisant (PITO) is the only histamine H3 receptor antagonist approved by the FDA for treating narcolepsy. However, there are no reports on Pitolisant in neural development or regeneration, and it is urgent to be further studied in strong biological activity models in vitro. The embryonic stem (ES) cells were differentiated into neural cells in vitro, which replicated the neurodevelopmental processes that occur in vivo. It also provided an alternative model for studying neurodevelopmental processes and testing drugs for neurological conditions. Therefore, we aimed to elucidate the regulatory role of Pitolisant in the early differentiation of ES cells into neural cells. Our results demonstrated that Pitolisant could promote the differentiation of ES cells towards neural stem cells (NSCs) and stimulated the formation of growth cones. Furthermore, Pitolisant was capable of inducing the polarization of NSCs through the cAMP-LKB1-SAD/MARK2 pathway, but had no significant effect on later neuronal maturation. Pitolisant altered mitochondrial morphology and up-regulated the levels of mitochondrial-related proteins TOM20, Drp1, and p-Drp1, and reversed the inhibitory effect of Mdivi-1 on mitochondrial fission during the early neural differentiation of ES cells. Additionally, Pitolisant induced the increase in cytosolic Ca2+. Our study provided an experimental foundation for the potential application of histamine H3 receptor-targeted modulators in the field of neuroregeneration.
研究领域:
神经科学
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干细胞生物学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
iScience
·
2024
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IF 4.6
WenYe Liu,Xi Liu,LingYa Li,ZhiPeng Tai,GuoLiang Li,Jing-Xia Liu
Summary Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1 / 2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1 / 2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1 / 2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.
研究领域:
血液学
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分子生物学
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细胞生物学
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表观遗传学
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DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2016
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IF 2.551
Xiaohui Zhuang,Jiaqing Shen,Zhengyu Jia,Airong Wu,Ting Xu,Yuqi Shi,Chunfang Xu
B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l -arginine-induced acute experimental pancreatitis . Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway , and ameliorated the pancreas disruption in l -arginine-induced pancreatitis. In addition, although l -arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells , administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l -arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response.
研究领域:
免疫学
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胃肠病学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
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2024
·Vol. 43
·期 1
·1-16
·
IF 11.4
Li Xing,Sun Shiyu,Zhang Wansong,Liang Ziwei,Fang Yitong,Sun Tianhu,Wan Yong,Ma Xingcong,Zhang Shuqun,Xu Yang,Tian Ruilin
Background Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM. Methods We conducted large-scale CRISPR interference (CRISPRi) screens in GBM cell line U87 MG cells co-cultured with B7-H3 targeting CAR T cells to identify genetic modifiers that can enhance CAR T cell-mediated tumor killing. Flow cytometry-based tumor killing assay and CAR T cell activation assay were performed to validate screening hits. Bioinformatic analyses on bulk and single-cell RNA sequencing data and the TCGA database were employed to elucidate the mechanism underlying enhanced CAR T efficacy upon knocking down the selected screening hits in U87 MG cells. Results We established B7-H3 as a targetable antigen for CAR T therapy in GBM. Through large-scale CRISPRi screening, we discovered genetic modifiers in GBM cells, including ARPC4 , PI4KA , ATP6V1A , UBA1 , and NDUFV1 , that regulated the efficacy of CAR T cell-mediated tumor killing. Furthermore, we discovered that TNFSF15 was upregulated in both ARPC4 and NDUFV1 knockdown GBM cells and revealed an immunostimulatory role of TNFSF15 in modulating tumor-CAR T interaction to enhance CAR T cell efficacy. Conclusions Our study highlights the power of CRISPR-based genetic screening in investigating tumor-CAR T interaction and identifies potential druggable targets in tumor cells that confer resistance to CAR T cell killing. Furthermore, we devised targeted strategies that synergize with CAR T therapy against GBM. These findings shed light on the development of novel combinatorial strategies for effective immunotherapy of GBM and other solid tumors.
CAS / MDL:
研究领域:
肿瘤学
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免疫学
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基因组学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2025
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IF 7.3
Maosheng Gong,Yadong Wei,Hongzhou Zhang,Jingyuan Liu,Xin Zhang,Xuanming Chang,Peiyu Hou,Xijin Xu,Lianqi Zhang
High-capacity Ni-rich cathodes hold considerable promise in advancing both high-energy Li-ion batteries (LIBs) and all-solid-state Li batteries (ASSLBs). Yet, lattice volume changes induced by the H2–H3 phase transition lead to structural degradation. It has been demonstrated that doping approaches can enhance structural stability. Nevertheless, the selection of an appropriate dopant is of considerable importance for the design of high-performance Ni-rich materials with high-entropy doping. Furthermore, the feasibility of high-entropy doped Ni-rich cathodes in ASSLBs has not been reported to date. In this study, leveraging the chemically competitive doping mechanism of Mg, Al, Ti, Nb, and Mo elements, we propose a high-entropy doped LiNi0.8Co0.1Mn0.05Mg0.01Al0.01Ti0.01Nb0.01Mo0.01O2 (HE-NCM) to stabilize Ni-rich cathodes. In-situ X-ray diffraction confirms that the synergistic effect of multiple dopants in high-entropy doping significantly alleviates the H2–H3 phase transition and reduces lattice volume changes, which contribute to the absence of microcracks and improved bulk/interface stability. In ASSLBs, the HE-NCM@LiNbO3 maintains an outstanding capacity retention of 84.5% even after 1700 cycles, demonstrating the feasibility of high-entropy doped Ni-rich cathodes when matched with a sulfide solid-state electrolyte. The application of high-entropy doping methodology for the development of advanced rechargeable batteries has been shown to provide a novel perspective on the improvement of the structural robustness and interfacial compatibility of Ni-rich cathode materials.
研究领域:
材料科学
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电化学
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储能技术
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锂离子电池
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固态电池
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产品关联
DOI
高影响因子
CHINESE CHEMICAL LETTERS
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2016
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IF 1.947
Hong-Lei Xie,Chun-Chi Liu,Yi-Qun Li,Chang-Lin Bai,Chen-Zhou Hao,Jing Guo,Chang-Qun Luo,Dong-Mei Zhao,Mao-Sheng Cheng
A novel series of β -propanamide derivatives as inhibitors of cholesteryl ester transfer protein (CETP) were synthesized. Previously, H3 (IC 50 2 μmol/L) was observed to inhibit CETP moderately (Xie et al ., 2016). Structural modifications based on H3 led to discovery of the successful CETP inhibitor, known as 1-methyl-4-arylpyrazole. Using a similar approach, compound Q08 was identified as a highly potent CETP inhibitor with an IC 50 of 490 nmol/L in vitro .
研究领域:
药物化学
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生物化学
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DOI
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2011
·Vol. 165
·期 3
·963-977
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IF 1.879
Gong Jin-Song,Lu Zhen-Ming,Shi Jing-Song,Dou Wen-Fang,Xu Hong-Yu,Zhou Zhe-Min,Xu Zheng-Hong
Microbial transformation of glycinonitrile into glycine by nitrile hydrolase is of considerable interest to green chemistry. A novel fungus with high nitrile hydrolase was newly isolated from soil samples and identified as Fusarium oxysporum H3 through 18S ribosomal DNA, 28S ribosomal DNA, and the internal transcribed spacer sequence analysis, together with morphology characteristics. After primary optimization of culture conditions including pH, temperature, carbon/nitrogen sources, inducers, and metal ions, the enzyme activity was greatly increased from 326 to 4,313 U/L. The preferred carbon/nitrogen sources, inducer, and metal ions were glucose and yeast extract, caprolactam, and Cu 2+ , Mn 2+ , and Fe 2+ , respectively. The maximum enzyme formation was obtained when F. oxysporum H3 was cultivated at 30 °C for 54 h with the initial pH of 7.2. There is scanty report about the optimization of nitrile hydrolase production from nitrile-converting fungus.
研究领域:
微生物学
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生物化学
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环境科学
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DOI
PubMed
高影响因子
Immunity & Ageing
·
2023
·Vol. 20
·期 1
·1-17
·
IF 7.9
Han Hao,Zhao Yawei,Du Junda,Wang Sushan,Yang Xuehan,Li Weijie,Song Jiayi,Zhang Siwei,Zhang Ziyi,Tan Yongfei,Hatch Grant M.,Zhang Ming,Chen Li
Background Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory.Results Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype.Conclusion The elevated lactate acted as an “accelerator” of the endogenous “lactate timer” in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2026
·
IF 9.7
Liu Xinyi,Du Wenqian,Wang Jingfei,Yin Tingyi,He Ke,Zhang Zhengyi,Liu Meng,Gan Xinyi,Cheng Baochen,Luo Ruiting,Zheng Yan
Background Metabolic reprogramming is a hallmark of cutaneous squamous cell carcinoma (cSCC), yet the underlying mechanisms remain incompletely understood. SLC25A1, a mitochondrial citrate transporter, has been implicated in tumor progression, but its role in cSCC is unclear. Objective This study aimed to investigate the role of SLC25A1 in cSCC progression and elucidate the underlying molecular mechanisms. Methods SLC25A1 expression was examined in cSCC tissues and cell lines using immunohistochemistry, RT-qPCR, and Western blotting. Functional assays, including proliferation, apoptosis, migration, and invasion analyses, were performed following SLC25A1 knockdown or overexpression. RNA sequencing and metabolic assays were conducted to explore underlying mechanisms. Chromatin immunoprecipitation (ChIP)-qPCR was used to assess pan-histone H3 acetylation. In vivo effects were evaluated using DMBA/TPA-induced cSCC mouse models, with pharmacological inhibition by CTPI-2. Results SLC25A1 was significantly upregulated in cSCC and promoted tumor cell proliferation, migration, and invasion while inhibiting apoptosis. Mechanistically, SLC25A1 enhanced glycolysis by increasing pan-histone H3 acetylation at the ALDOC promoter, thereby upregulating ALDOC expression. Knockdown of SLC25A1 reduced glycolytic activity and tumor growth, whereas ALDOC overexpression partially rescued these effects. Pharmacological inhibition of SLC25A1 with CTPI-2 suppressed tumor progression and altered metabolic profiles in vivo. Conclusions SLC25A1 promotes cSCC progression by regulating glycolysis through pan-acetylated H3-mediated transcriptional activation of ALDOC. Targeting SLC25A1 may represent a promising therapeutic strategy for cSCC. Graphical
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DOI
高影响因子
CELL AND TISSUE RESEARCH
·
2021
·Vol. 386
·期 3
·661-677
·
IF 5.249
Tong Yan,Cheng Lu-Qiang,Li Xuan,Yu Xu-Peng,Shu Rui-Hao,Zhang Ji-Hong,Meng Qian,Qin Qi-Lian,Tang Kai,Xu Jian-Xiang,Zhang Huan
Determining the source of primary cells is conductive to enriching sufficient cells with immortal potential thereby improving the success rate of establishing cell lines. However, most of the existing insect cell lines are established by mixing and fragmentation of explants. At present, the origin of cell lines can only be determined according to the cultured tissues, so it is impossible to determine which cell types they come from. In this study, a new cell line designated IOZCAS-Myse-1 was generated from pupal ovaries of the migratory pest Mythimna separata by explant tissues to derive adherent cultures. This paper mainly shows the further descriptive information on the origin of primary cells in the process of ovarian tissue isolation and culture. Phospho-histone H3 antibody-labeled cells with mitotic activity showed that the rapidly developing somatic cells in vivo gradually stopped proliferation when cultured ex vivo. The primary cells dissociated outside the tissue originated from the lumen cells, rather than the germ cells or the follicular epithelium cells. The results suggest that the newly established cell line IOZCAS-Myse-1 had two possible sources. One is the mutation of lumen cells in the vitellarium, and the other is the stem cells with differentiation potential in the germarium of the ovarioles. Moreover, the newly established cell line is sensitive to the infection of Autographa californica multiple nucleopolyhedrovirus, responds to 20-hydroxyecdysone and has weak encapsulation ability. Therefore, the new cell line can be a useful platform for replication of viral insecticides, screening of hormone-based insecticides and immunology research.
研究领域:
昆虫学
·
细胞生物学
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DOI
PubMed
高影响因子
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