Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Zhang Shuo,Gao Peichao,Wang Qunxin,Liu Shuhui,Okoth Sheila,Zhang Meihua,Ji Helong,Yan Liping,Fan Wentao,Song Suquan
Fatty liver hemorrhagic syndrome (FLHS) has become a common and serious disease in intensive laying hen farming, seriously endangering the productivity and health of laying hens. Although probiotics have been recognized as an emerging candidate therapeutic strategy for liver disease, their effective substances and mechanisms for alleviating FLHS remain to be elucidated. In this study, corticosterone (Cort) was applied to induce FLHS in laying hens, and Lactobacillus plantarum ( L. plantarum 1–2-3) was used for the intervention. The results showed that L. plantarum 1–2-3 treatment significantly ameliorated Cort-induced hepatic steatosis and liver damage in laying hens, as evidenced by decreased levels of triglyceride (TG), total cholesterol (TC), aspartate aminotransferase, and alanine aminotransferase. Importantly, we found that L. plantarum 1–2-3 could biosynthesize gamma-aminobutyric acid (GABA) by expressing glutamic acid decarboxylase. Surprisingly, feeding GABA to laying hens replicated the effect of L. plantarum 1–2-3 in alleviating Cort-induced FLHS. GABA significantly down-regulated the mRNA expression of Acc , Fasn , Cd36 , and Gpam while upregulating the levels of Ppara and Cpt1a . An in vitro verification study showed that GABA decreased TG and TC content in Leghorn male hepatoma cells. Moreover, GABA significantly enhanced antioxidant enzyme activity, inhibited oxidative stress in hepatocytes, regulated the AMPK/NLRP3 signaling pathway, and reduced the protein expression of NF-κB, TNFα, and IL-1β. In conclusion, our study demonstrated that L. plantarum 1–2-3 could effectively alleviate FLHS in laying hens, while GABA was an important postbiotic for L. plantarum 1–2-3 to exert lipid-lowering and anti-inflammatory effects.
研究领域:
微生物学
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兽医学
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肝脏病学
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营养生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Han Yan,Wenting Cheng,Siyuan Qin,Jing Zuo,Lei Li,Jing Zhang,Qinxia Chang,Yonghao Yan,Shiqi Wang,Canhua Huang,Haiyuan Zhang
The blood–brain barrier (BBB) caused limited drug accumulation and programmed death-ligand 1 (PD-L1) compromised immunosuppressive microenvironment are bottlenecks in glioblastoma multiforme (GBM) treatment. Herein, we bioengineered a human heavy chain nanoferritin (HTE NPs) for GBM-specific delivery and efficient immunotherapy. To achieve targeted mitochondrial metabolic regulation, we connected triphenylphosphonium (TPP) with the photosensitive agent IR780 to form T780, which self-assembles with esomeprazole magnesium (EM) and human H-ferritin (HFn) to obtain HTE NPs. HFn endows HTE NPs with BBB penetration and specific site-targeting capabilities, thereby enhancing tumor accumulation and pH-responsive release within GBM cells. T780 subsequently induces mitochondrial damage, activating the AMP-dependent protein kinase (AMPK) pathway and blocking the transmission of T-cell inhibitory signals through the phosphorylation of PD-L1, thereby promoting T-cell activation. Moreover, EM inhibits the release of extracellular vesicles (EVs), reducing the inhibitory effect of PD-L1 on circulating T cells. Furthermore, mitochondrial impairment-induced mitochondrial DNA (mtDNA) leakage activates the cGAS-STING signaling pathway, inducing the maturation of dendritic cells (DCs), recruiting supportive immune cells to clear GBM cells, and improving the immunosuppressive microenvironment. Therefore, HTE NPs not only achieve efficient tumor accumulation but also facilitate the activation immune response, providing a promising strategy for the clinical treatment of GBM.
研究领域:
肿瘤学
·
神经科学
·
纳米技术
·
免疫学
✓ 已验证
DOI
高影响因子
Frontiers in Aging Neuroscience
·
2024
·
IF 4.1
Xue Weikang,Lei Ziyi,Liu Bin,Guo Hanxin,Yan Weiyi,Jin Youngnam N.,Yu Yanxun V.
Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integrate molecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Aβ1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Aβ1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Aβ1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calcium responses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Aβ1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Aβ in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches.
研究领域:
神经科学
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分子生物学
·
神经退行性疾病
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模式生物
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DOI
PubMed
高影响因子
Aging and Disease
·
2024
·Vol. 16
·期 3
·1652
·
IF 7
Cheng Zhuang,Ruiqi Sun,Yuchen Zhang,Qing Zou,Jianxin Zhou,Naijun Dong,Xuyu Zhao,Wenjun Fu,Xiaoke Geng,Jiao Wang,Qian Li,Robert Chunhua Zhao
Rheumatoid arthritis (RA) is an autoimmune disease that affects the living quality of patients, especially the elderly population. RA-related morbidity and mortality increase significantly with age, while current clinical drugs for RA are far from satisfactory and may have serious side effects. Therefore, the development of new drugs with higher biosafety and efficacy is demanding. Black phosphorus nanosheets (BPNSs) have been widely studied because of their excellent biocompatibility. Here, we focus on the inherent bioactivity of BPNSs, report the potential of BPNSs as a therapeutic drug for RA and elucidate the underlying therapeutic mechanism. We find that BPNSs inhibit autophagy at an early stage via the AMPK-mTOR pathway, switch the energy metabolic pathway to oxidative phosphorylation, increase intracellular ATP levels, suppress apoptosis, reduce inflammation and oxidative stress, and down-regulate senescence-associated secretory phenotype (SASP)-related genes in rheumatoid arthritis synovial fibroblasts (RA-SFs). Further, BPNSs induce the apoptosis of macrophages and promote their transition from the M1 to the M2 phenotype by regulating related cytokines. Significantly, the administration of BPNSs can alleviate key pathological features of RA in mice, revealing great therapeutic potential. This study provides a novel option for treating RA, with BPNSs emerging as a promising therapeutic candidate.
研究领域:
纳米医学
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免疫学
·
药理学
·
细胞生物学
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生物医学工程
·
风湿病学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2026
·
IF 6.2
Hong-Wang Dong,Xi-Han Sun,Wen-Ting Peng,Ge Song,Zheng-Yu Huang,Wen-Tao Qi,Wei Fang
Dietary fiber mediated modulation of gut microbiota represents a promising strategy for managing metabolic disorders. Wheat bran, a major by-product of global wheat production, is rich in insoluble dietary fiber. However, the host-microbe interactions through which wheat insoluble dietary fiber (WIDF) influences metabolism remain incompletely characterized. In this study, concurrent WIDF supplementation attenuated high fat diet (HFD) induced metabolic dysfunction, reducing body weight by 14% ( P < 0.05) at week 12 and ameliorating liver steatosis and obesity. It also significantly improved blood and liver lipid profiles (serum and liver TC reduced by 29.4% and 29.9%, respectively; serum and liver TG reduced by 23.7% and 45.7%, respectively; P < 0.05), alleviated oxidative stress by reducing MDA content and raising GSH levels, and enhanced glucose tolerance ( P < 0.05). Multiple bacterial genera including norank_f_ Muribaculaceae, Romboutsia , and Candidatus_Saccharimonas , were correlatived with these metabolic improvements. Correlative metabolomic profiling identified microbiota-associated L-leucine and L-valine, two branched-chain amino acids (BCAAs), as candidate metabolites. In vitro HepG2 experiments suggested that L-leucine and L-valine were associated with changes in AMPK related signaling at supraphysiological concentrations and with reduced oleic acid induced lipid accumulation. Antibiotic depletion and fecal microbiota transplantation experiments supported the involvement of gut microbiota in the metabolic effects of WIDF. The observed association among WIDF related gut microbiota changes, BCAA availability, and AMPK related signaling provides a hypothesis that requires further in vivo validation. Download: Download high-res image (397KB) Download: Download full-size image
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DOI
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-13
·
IF 4.6
Liang Chenchen,Gao Siyuan,Gao Jianpeng,Xu Yanwen,Li Qilong
To investigate the effects and potential mechanisms of human umbilical cord mesenchymal stem cells, exosomes, and their conditioned media on lipid storage in oleic acid (OA) and palmitic acid (PA) treated hepatocytes and high-fat methionine- choline deficient diet (HFMRCD) induced non-alcoholic steatohepatitis (NASH) mice. AML12 cells were stimulated with OA and PA to establish the lipid storage cell model. HucMSCs, exosomes, and culture medium were then co-cultured. At the same time, C57BL/6 mice were fed an HFMRCD for 6 or 8 weeks to establish a NASH mouse model. The effect of HucMSCs, exosomes, and culture medium on lipid droplet repair of hepatocytes or NASH mice was then assessed. The weight of hepatocytes or liver tissue, Oil Red O, hematoxylin–eosin staining, Masson staining, Western blot, and qPCR were used to detect the related IL-6, TNF-α, TGF-β1 andEI24/AMPK/mTOR pathway expression in hepatocytes and liver tissue. Compared with the model group, the effect of HucMSCs-Ex on inhibiting the accumulation of lipid droplets was more obvious at the cell level. In vivo study showed that HucMSCs-Ex reduces activity scores in NASH mice and improves liver tissue morphology by reducing vacuolar degeneration, fat deposition, and collagen deposition of liver tissue. Western blot and qPCR results showed that inflammatory factors and AMPK/mTOR or EI24-related autophagy pathways were altered before and after treatment. HucMSCs, HucMSC-Ex, and CM can promote autophagy in hepatocytes or NASH mice through the AMPK/mTOR or EI24-related autophagy pathway and alleviate injury associated with lipid deposition, collagen deposition or inflammation, reversing the progression of NASH.
研究领域:
细胞生物学
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分子生物学
·
肝病学
·
干细胞研究
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Meng Yang,Shengquan Wu,Qihui Dai,Weihong Qin,Yujie Zhang,Yiting Lei,Haochang Song,Tingting Zheng,Min Guan,Gonghua Huang,Xinguang Liu
Excessive lipid accumulation often occurs in the early stage of chronic kidney disease (CKD) which is prone to induce oxidative stress and mitochondrial damage, promoting the progression of kidney fibrosis. Andrographolide (AP), a multifunctional natural terpenoids derived from Andrographis paniculate , has been suggested to play beneficial roles in metabolic disorders-associated disease. Here, we reported that AP effectively counteracts tubule injury and interstitial fibrosis in mice fed with a long-term high-fat diet (HFD). AP treatment decreased HFD-induced lipid accumulation in kidney parenchyma and attenuated lipotoxicity-mediated oxidative stress and mitochondrial dysfunction, resulting in a marked decrease in tubular cell senescence. Importantly, AP inhibited senescence-associated secretory phenotype (SASP) secretion by senescent tubular cells, and in turn suppressed proliferation and activation of fibroblasts in a paracrine effect. Furthermore, we revealed that AP functions as an AMP-activated protein kinase (AMPK) activator to ameliorate renal lipid accumulation through coordinately modulating AMP-activated protein kinase AMPK target genes. By stimulation of AMPK activity, AP protects injured kidney against tubular cell senescence and fibroblast activation. These results suggest the potential therapeutic application of AP in the prevention and treatment of CKD, highlighting the promising drug strategy of targeting the lipotoxicity-mediated premature senescence in tubular cells.
研究领域:
肾病学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2021
·
IF 7.376
Wen-Qiao Qiu,Wei Ai,Feng-Dan Zhu,Yue Zhang,Min-Song Guo,Betty Yuen-Kwan Law,Jian-Ming Wu,Vincent Kam-Wai Wong,Yong Tang,Lu Yu,Qi Chen,Chong-Lin Yu,Jian Liu,Da-Lian Qin,Xiao-Gang Zhou,An-Guo Wu
Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yuhuan Li,Jiayin Lv,Shuchen Liu,Zhuoran Wang,Yu Gao,Zheyuan Fan,Lei Huang,Jing Cui,Boya Zhang,Xinchen Liu,Zhuo Zhang,Te Liu,Daowei Li,Modi Yang
The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.
研究领域:
免疫学
·
药理学
·
风湿病学
·
炎症
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
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