ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Caihua Ye,Meng Cheng,Lin Ma,Tianzhu Zhang,Zuhao Sun,Chunshui Yu,Junping Wang,Yan Dou
Prevention of Alzheimer’s disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aβ deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
研究领域:
神经科学
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药理学
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神经炎症
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药物递送系统
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阿尔茨海默病研究
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
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IF 7.5
Ruisi Zhou,Yanting You,Zhiqiang Zha,Jie Chen,Yanchun Li,Xiaohu Chen,Xiaomei Chen,Xuefeng Jiang,Jinxiang Chen,Hiu Yee Kwan,Xiaoshan Zhao,Liping Huang,Yanyan Liu
Ovarian cancer (OC) stands as the second most prominent factor leading to cancer-related fatalities, characterized by a notably low five-year survival rate. The insidious onset of OC combined with its resistance to chemotherapy poses significant challenges in terms of treatment, emphasizing the utmost importance of developing innovative therapeutic agents. Despite its remarkable anti-tumor efficacy, celastrol (CEL) faces challenges regarding its clinical utilization in OC due to its restricted water solubility and notable side effects. In this study, celastrol (CEL) was encapsulated into Zeolitic imidazolate framework-8(ZIF-8) nanoparticle and grafted with biotin-conjugated polyethylene glycol (CEL@ZIF-8@PEG-BIO). Comprehensive comparisons of the physicochemical properties and anticancer activities of CEL and CEL@ZIF-8@PEG-BIO were conducted. Our findings revealed that CEL@ZIF-8@PEG-BIO exhibited favorable characteristics, including hydrodynamic diameters of 234.5 nm, excellent water solubility, high drug loading (31.60% ± 2.85), encapsulation efficiency (60.52% ± 2.79), and minimal side effects. Furthermore, CEL@ZIF-8@PEG-BIO can release chemicals in response to an acidic micro-environment, which is more likely a tumor micro-environment. In vitro, studies showed that CEL@ZIF-8@BIO inhibited cell proliferation, led to mitochondrial membrane potential (MMP) decline, and generated reactive oxygen species in OC cells. Both in vitro and in vivo experiments indicated that CEL@ZIF-8@PEG-BIO enhanced anti-tumor activity against OC via up-regulated apoptosis-promoting biomarkers and rendered cancer cell apoptosis via the P38/JNK MAPK signaling pathway. In conclusion, we have successfully developed a novel drug delivery system (CEL@ZIF-8@PEG-BIO), resulting in significant improvements in both water solubility and anti-tumor efficacy thereby providing valuable insights for future clinical drug development.
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
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免疫学
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分子生物学
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基因组学
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Meilan Xue,Xuehan Zhang,Yifan Zhou,Jiayi Yan,Haiqi Gao,Yixian Bai,Jing Shi,Yuhan Liu,Yan Xu,Nan Zhang,Lu Li,Shaobo Shi,Hui Liang
This study was aimed to reveal the neuroprotective effect of sulfated fucooligosaccharides (FOS) in an aging mouse model induced by d-galactose. The results showed that FOS treatment ameliorated inflammation, improved behavioral decline in memory and cognition, and exerted neuroprotective effects. FOS reduced microglia activation by decreasing the expression of P38 mitogen-activated protein kinase (P38 MAPK), cyclic-AMP response binding protein (CREB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, FOS improved intestinal mucosal barrier damage and reduced the release of lipopolysaccharide. FOS increased the diversity of the gut flora and promoted a significant enrichment of the Akkermansia genus. FOS also increased the butyric acid level and reduced the expression of histone deacetylase 3 (HDAC3), Toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB). Fecal microbiota transplantation from the FOS-treated mice showed a similar effect to FOS treatment in inhibiting neuroinflammation and reduced d-galactose-induced cognitive dysfunction. The results suggested that FOS supplementation ameliorated d-galactose-induced neuron damage and exerted neuroprotective effects through the gut–brain axis.
研究领域:
神经科学
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衰老研究
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免疫学
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胃肠病学
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微生物学
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药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
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IF 4.831
Hengke Guo,Siyu Guo,Hongmei Liu
The bioactive peptides and trace element selenium (Se) both have good antioxidant activity. However, whether combined Se and bioactive peptides have more excellent antioxidant activity remain unknown. The aim of this study is to prepare a Se-rich peptide fraction containing both Se and peptides from Se-rich yeast protein hydrolysate and investigated its antioxidant activity and effect on ultraviolet B (UVB) radiation-induced skin oxidative damage. The peptide fractions with different molecular weight (MW) and Se content were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins followed by a filtration process. In vitro free radical scavenging and lipid peroxidation inhibition assays showed that Se-rich peptides fraction with lower MW of <1 kDa (sSeP) had the highest antioxidant activity compared with Se-rich peptide fractions with higher MW of <3 kDa or normal peptide fractions. Oral administration of sSeP significantly decreased the level of malonaldehyde (MDA) in liver and serum, and increased the activity of glutathione peroxidase (GPx) in liver and serum in normal mice. When topically applied on the dorsal skin of mice, sSeP effectively alleviate UVB radiation-induced skin damage and oxidative stress by increasing GPx and catalase activities and glutathione content in skin or serum. Furthermore, sSeP showed a protective effect against H 2 O 2 -induced cytotoxicity in cultured human epidermal keratinocytes (HaCaT) cells probably by increasing aquaporin-3 expression and attenuating the phosphorylation of p38 MAPK. Overall, the results showed that Se-rich yeast peptide fraction containing Se and bioactive peptides could be a promising antioxidant nutrient used as food additive to enhance the body’s antioxidant ability or as cosmeceutical product to minimize the skin oxidative damage.
研究领域:
生物化学
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药理学
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化妆品
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营养补充剂
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENDODONTICS
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2019
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IF 2.833
Jing Zhang,Cheng Fei Zhang,Quan Li Li,Chun Hung Chu
Introduction Stem cells from the apical papilla (SCAPs) possess strong odonto/osteogenic differentiation potential. This study investigated the effect of cyclic adenosine monophosphate (cAMP) on odonto/osteogenic differentiation of SCAPs and the underlining interplay between cAMP and transforming growth factor beta 1 (TGF-β1). Methods SCAPs were stimulated with an activator of cAMP (forskolin) in the presence of either TGF-β1 or a TGF-β1 inhibitor. The amounts of calcium mineral deposition and alkaline phosphatase activity were determined. Quantitative real-time polymerase chain reaction was performed to elucidate cAMP on the TGF-β1–mediated odonto/osteogenic differentiation of SCAPs. The effect of cAMP on the phosphorylation of Smad2/Smad3 and extracellular-regulated kinase (ERK)/P38 induced by TGF-β1 was analyzed by Western blotting . Results Cotreatment with forskolin and a TGF-β1 inhibitor enhanced alkaline phosphatase activity and deposition of calcium minerals in SCAPs. Moreover, the TGF-β1 inhibitor synergized the effect of forskolin on the expression of type I collagen and runt-related transcription factor 2. The results of Western blotting revealed that forskolin attenuated the unregulated expression of the phosphorylation of Smad3 and ERK induced by TGF-β1, and a cAMP inhibitor (H89) antagonized this effect. Conclusions This study showed that cAMP signaling exerts its up-regulating effects on the odonto/osteogenic differentiation of SCAPs by interfering with TGF-β1 signaling via inhibiting Smad3 and ERK phosphorylation.
研究领域:
口腔科学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Wei Xia,Zhu Qingfen,Liu Na,Xu Lihua,Wei Sheng,Fan Zhiyun,Sun Changhua,Zhao Yan,Qiao Mingqi,Wu Jibiao,Hu Defu,Wang Yang,Sun Peng
Zhenlong Xingnao Capsule (ZXC) is a Tibetan medicine used to treat ischemic stroke. In this study, we determined the in vitro and in vivo effects of ZXC on reactive oxygen species (ROS) in a mouse BV-2 microglial cell hypoxia-reoxygenation and rat middle cerebral artery occlusion infarction models. We aimed to clarify the role of ZXC in cerebral ischemia protection; reveal amino acid neurotransmitter changes in the frontal cortex after drug intervention; determine mRNA and protein expression changes in Bcl-2, Bax, caspase-3, P38, and nuclear factor (NF)-кB in the frontal cortex and changes in antioxidant indices in the brain; and elucidate the mechanisms underlying ZXC action. After hypoxia-reoxygenation, ROS levels were significantly increased in BV-2 cells, and their levels decreased after treatment with ZXC. ZXC had protective effects on ischemic/anoxic injury in vitro and in vivo by downregulating the expressions of caspase-3 and NF-кB mRNA during ischemia and reperfusion and that of p38 and caspase-3 during acute ischemia and reperfusion as well as the steady-state levels of excitatory amino acids/inhibitory amino acids and by improving the total antioxidant capacity and total superoxide dismutase activities during ischemia. These findings provide new molecular evidence for the mechanisms underlying ZXC action.
研究领域:
药理学
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神经科学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2019
·
IF 3.197
Yanbei Tu,Kai Wang,Jian-Bo Wan,Chengwei He
Glycine tabacina (Labill.) Benth, a renowned Chinese medicinal herb, has been used for treatment of rheumatoid arthritis (RA) and joint infection. This study aimed to investigate inhibitory effect of its ethanol extract (GTE) on RA-associated inflammation. Nine isoflavonoids of twelve ones which were found in G. tabacina roots were identified by UHPLC-DAD-MS/MS. GTE treatment suppressed lipopolysaccharide-stimulated overproduction of nitric oxide, TNF-α and IL-6, and iNOS expression in macrophages. GTE blocked the activation of NF-κB and MAPK pathways, as indicated by reduced levels of phosphorylation of IKKα/β, IκBα, p38, ERK and JNK, and the suppressed nuclear translocation of NF-κB p65. Additionally, GTE administration decreased swelling of arthritic paw and serum TNF-α and IL-1β levels in collagen-induced arthritis (CIA) mice. These results demonstrated that GTE exhibited strong anti-inflammatory and anti-arthritic activities through suppressing NF-κB and MAPK pathways activation in activated macrophages and CIA mice, suggesting the potential applications of this species in RA prevention and treatment as functional food or therapeutic agent.
研究领域:
药理学
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免疫学
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炎症研究
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风湿病学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2015
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IF 2.912
Chuanyang Su,Xiaomin Xia,Qiong Shi,Xiufang Song,Juanli Fu,Congxue Xiao,Hongjun Chen,Bin Lu,Zhiyin Sun,Shanmei Wu,Siyu Yang,Xuegang Li,Xiaoli Ye,Erqun Song,Yang Song
Neohesperidin dihydrochalcone (NHDC), a sweetener derived from citrus, belongs to the family of bycyclic flavonoids dihydrochalcones. NHDC has been reported to act against CCl4-induced hepatic injury, but its mechanism is still unclear. We first discovered that NHDC showed a strong ability to scavenge free radicals. In addition, NHDC induces the phase II antioxidant enzymes heme oxygenase 1 (HO-1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) through the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) signaling. Further assays demonstrated that NHDC induces accumulation of Nrf2 in the nucleus and augmented Nrf2-ARE binding activity. Moreover, NHDC inhibits the ubiquitination of Nrf2 and suggests the modification of Kelch-like ECH-associated protein 1 (Keap1) and the disruption of the Keap1/Nrf2 complex. c-Jun N-terminal kinase (JNK) and p38 but not extracellular signal-regulated protein kinase (ERK) phosphorylations were up-regulated by NHDC treatment. Taken together, NHDC showed its protective antioxidant effect against CCl4-induced oxidative damage via the direct free radical scavenging and indirect Nrf2/ARE signaling pathway.
研究领域:
药理学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Jiale Chen,Zhixiang Mu,Dongfan Chen,Chen Huang,Ting Jin,Lin Li,Youyun Zeng,Qiang Zhou,Yanmei Zhang,Hongli Mao,Hui Deng,Xinkun Shen,Hong Yang,Xiaojun Cai
Smart hydrogel dressings capable of simultaneously highly effective antimicrobial, anti-inflammatory, and promoting re-epithelialization and angiogenesis are urgently needed for the management of diabetic wounds. Herein, a H 2 S-releasing multifunctional hydrogel was developed by utilizing the dynamic Schiff base reaction between carboxymethyl chitosan (CMC) and polyhexamethylene guanidine (PHMG)-modified aldehyde F108 (PFC). Diallyl trisulfide (DATS) was encapsulated into the PFC nanoparticles. Apart from possessing the essential properties necessary for an idealized hydrogel dressing, such as excellent injectability, tissue adhesion, self-healing, and stimulus–response degradation, the [email protected] &CMC also utilized the synergistic effect of the PHMG and DATS to provide an efficient antimicrobial effect; the H 2 S was slowly released from the DATS under the action of GSH and exerted excellent anti-inflammatory effects, by inhibiting the expression of p-ERK and p-STAT3 in activated macrophages, and promoting macrophage polarization to the M2 phenotype. Strikingly, following the completion of the efficient antimicrobial and anti-inflammatory effects, the continuously generated H 2 S further significantly accelerated the proliferation, migration, and vascularization of endothelial cells by extending the activation of the p-p38 and p-ERK1/2. Owing to superior performances, [email protected] &CMC significantly promoted the healing of diabetic wounds induced by streptozotocin with good biocompatibility. This study demonstrates that [email protected] &CMC is a versatile hydrogel dressing with great potential for the management of diabetic wounds.
研究领域:
生物医学工程
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材料科学
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药剂学
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伤口愈合
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糖尿病管理
✓ 已验证
产品关联
DOI
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Yeye Hu,Xueting Guan,Ziliang He,Yuan Xie,Zhiqiang Niu,Wei Zhang,Aoran Wang,Ji Zhang,Chuanling Si,Fu Li,Weicheng Hu
Apigenin-7-O-glucoside (AG), a flavonoid glycoside, has been shown in vitro anti-inflammatory activities. To date, the mechanism of AG against colitis has not been reported. In this study, we investigated the role of AG in relieving colitis and explored its potential mechanisms in dextran sulfate sodium (DSS)-induced colitis mice. The results indicated oral administration of AG increased colon length and improved colonic histopathology. Besides, it dramatically restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers such as ZO-1, occludin, claudin-1, and claudin-3. The mitogen-activated protein kinases (MAPKs) including ERK, JNK, and p38 were significantly inhibited. Moreover, 16S rDNA sequencing revealed that AG improved the abundance of Akkermansia , and reduced that of Bacteroides and Desulfovibrio . Taken together, AG supplementation relieved DSS-induced colitis by protecting the intestinal barrier, inhibiting the MAPK pathway, and modulating gut microbiota, which indicated that AG may be a good candidate therapeutic compound for sustaining gut health to lower the risk of colitis.
研究领域:
药理学
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免疫学
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胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
Bioengineered
·
2022
·
IF 6.832
Kun Xiao,Pengfei Liu,Peng Yan,Yanxin Liu,Licheng Song,Yuhong Liu,Lixin Xie
Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.
研究领域:
分子生物学
·
细胞生物学
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免疫学
·
移植医学
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DOI
PubMed
高影响因子
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