ACS Nano
·
2021
·
IF 15.881
Ming-Chen Sun,Xiao-Ling Xu,Yan Du,Xue-Fang Lou,Wei Wang,Yu-Chan You,Di Liu,Fei-Yang Jin,Jing Qi,Min-Xia Zhu,Lu-Wen Zhu,Jun Wang,Yong-Zhong Du
Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine–proline–valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP–tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.
研究领域:
药学
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皮肤科
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生物技术
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药理学
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DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Dun Liu,Runyan Niu,Siliang Wang,Lihua Shao,Xian Yang,Xuexue Liu,Xiaolong Ma,Zezhang Zhu,Jinping Zhang,Benlong Shi,Huanyu Ni,Xiao Du
Neural stem cell (NSCs) transplantation is a promising therapeutic strategy for spinal cord injury (SCI), but its efficacy is greatly limited by the local inhibitory microenvironment. In this study, based on l-arginine (l-Arg)-loaded mesoporous hollow cerium oxide (AhCeO2) nanospheres, we constructed an injectable composite hydrogel (AhCeO2-Gel) with microenvironment modulation capability. AhCeO2-Gel protected NSCs from oxidative damage by eliminating excess reactive oxygen species while continuously delivering Nitric Oxide to the lesion of SCI in a pathological microenvironment, the latter of which effectively promoted the neural differentiation of NSCs. The process was confirmed to be closely related to the up-regulation of the cAMP-PKA pathway after NO-induced calcium ion influx. In addition, AhCeO2-Gel significantly promoted the polarization of microglia toward the M2 subtype as well as enhanced the regeneration of spinal nerves and myelinated axons. The prepared bioactive hydrogel system also efficiently facilitated the integration of transplanted NSCs with host neural circuits, replenished damaged neurons, alleviated neuroinflammation, and inhibited glial scar formation, thus significantly accelerating the recovery of motor function in SCI rats. Therefore, AhCeO2-Gel synergized with NSCs transplantation has great potential as an integrated therapeutic strategy to treat SCI by comprehensively reversing the inhibitory microenvironment.
研究领域:
生物医学工程
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神经科学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
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IF 3.69
Wanwan Zhang,Yifang Wei,Xiaoxiao Cao,Kaixin Guo,Qiangqiang Wang,Xiaochun Xiao,Xufeng Zhai,Dingding Wang,Zebo Huang
Ethnopharmacological relevance Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence. Aim of the study Erectile dysfunction (ED) has become a major health problem for the global ageing population. The aim of this study is therefore to evaluate the effect of peptide-rich preparations from C. gigas oysters on ED and related conditions as increasing evidence suggests that peptides are important bioactive components of marine remedies and seafood. Materials and methods Crassostrea oyster peptide (COP) preparations COP1, COP2 and COP3 were obtained from C. gigas oysters by trypsin, papain or sequential trypsin-papain digestion, respectively. The contents of testosterone, cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) and the activity of nitric oxide synthase (NOS) in mice and/or cells were measured by enzyme-linked immunosorbent assays. Real-time PCR was used to assess the expression of genes associated with sex hormone secretion pathways. The model animal Caenorhabditis elegans was also used to analyze the gene expression of a conserved steroidogenic enzyme. In silico analysis of constituent peptides was performed using bioinformatic tools based on public databases. Results The peptide-rich preparation COP3, in which >95% peptides were <3000 Da, was found to increase the contents of male mouse serum testosterone and cAMP, both of which are known to play important roles in erectile function, and to increase the activity of mouse penile NOS, which is closely associated with ED. Further investigation using mouse Leydig-derived TM3 cells demonstrates that COP3 was able to stimulate the production of testosterone as well as NO, a pivotal mediator of penile erection. Real-time PCR analysis reveals that COP3 up-regulated the expression of Areg and Acvr2b , the genes known to promote sex hormone secretion, but not Fst , a gene involved in suppressing follicle-stimulating hormone release. Furthermore, COP3 was also shown to up-regulate the expression of let-767 , a well-conserved C. elegans gene encoding a protein homologous to human 17-β-hydroxysteroid dehydrogenases. Preliminary bioinformatic analysis using the peptide sequences in COP3 cryptome identified 19 prospective motifs, each of which occurred in more than 10 peptides. Conclusions In this paper, Crassostrea oyster peptides were prepared by enzymatic hydrolysis and were found for the first time to increase ED-associated biochemical as well as molecular biology parameters. These results may help to explain the ethnopharmacological use of oysters and provide an important insight into the potentials of oyster peptides in overcoming ED-related health issues.
研究领域:
药理学
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生物化学
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分子生物学
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民族药理学
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海洋生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2022
·Vol. 36
·期 11
·4278-4292
·
IF 6.388
Bei Bei Zhou,Dan Liu,Jia Cheng Qian,Ren Xiang Tan
Food-drug interaction is an important but overlooked issue. For example, little is known concerning whether or not the chemotherapy of cancers is affected by the well-defined dietary chemicals such as 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1) derived from daily consumed cruciferous vegetables. This work, inspired by the described melanogenesis reduction by certain indoles, presents that LTr1 mitigates the melanogenesis and thus potentiates the in vitro and in vivo anti-melanoma effectiveness of different chemotherapeutic agents including dacarbazine, vemurafenib, and sorafenib. In B16 melanoma cells, LTr1 was shown to inhibit the melanogenesis by acting towards the regulatory (R) subunit of protein kinase A (PRKAR1a) associated with the phosphorylation of cAMP-response element binding protein (CREB). This allows LTr1 to reduce the expression of melanogenesis-related enzymes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2). Furthermore, LTr1 was addressed to bind to the aryl hydrocarbon receptor (AhR) and up-regulate the expression of CYP1A1 encoding cytochrome P450 1A1, leading to the escalation of reactive oxygen species (ROS) level. The increased ROS generation promotes the cysteine-to-cystine transformation to inhibit the pheomelanogenesis in melanomas. Collectively, the work identifies LTr1 as a new melanogenesis inhibitor that modulates the PKA/CREB/MITF and AhR/CYP1A1/ROS pathways, thereby providing a new option for (re)sensitizing melanomas to chemotherapeutics.
研究领域:
癌症生物学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
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IF 5.8
Xiao Fu,Ting Lei,Cong Chen,Gan Fu
The recent “cell-based theory” of coagulation suggests that platelets serve as the site of coagulation factor reactions, making platelets an effective target for inhibiting membrane thrombosis. Unfortunately, there is limited research on how blood purification membranes affect platelet intracellular signaling . In this study, we modified polyethersulfone (PES) membranes with the platelet phosphodiesterase (PDE) inhibitor dipyridamole (DIP) and investigated the effects of the DIP/PES (DP) membranes on platelet adhesion, activation, aggregation, and secretion, as well as the role of the PDE-cyclic adenosine monophosphate (cAMP) intracellular signaling pathway. Additionally, we evaluated the hemocompatibility and preliminary in vivo safety of DP membranes. Our results demonstrate that the modified DP membranes effectively inhibited platelet adhesion, membrane CD62P expression, and plasma soluble P-selectin activation levels. Furthermore, we confirmed that DP membranes achieved platelet aggregation inhibition and reduced platelet factor 4 and β-thromoglobulin secretion levels by inhibiting platelet intracellular PDE-cAMP signaling. Moreover, the modified DP membranes exhibited good anticoagulant and red blood cell membrane stability and complement resistance and demonstrated preliminary biocompatibility in mouse experiments. Collectively, these findings highlight the potential application of DP dialysis membranes in blood purification for critically ill patients.
研究领域:
血液学
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生物医学工程
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药理学
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生物材料
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Chao Wang,Xiaoxin Liu,Junqiu Zhai,Chunfei Zhong,Haishen Zeng,Longkuan Feng,Yunyun Yang,Xinyan Li,Mei Ma,Tiangang Luan,Jiewei Deng
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of reactive oxygen species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O 2 .− and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O 2 .− and NO. In addition, transcriptome sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.
研究领域:
毒理学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
BMC Medical Genomics
·
2024
·Vol. 17
·期 1
·1-10
·
IF 2.1
Xu Kuishuai,Zhang Liang,Wang Tianrui,Yu Tengbo,Zhao Xia,Zhang Yingze
Objective There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the “gene profile” of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. Methods A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups’ DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. Results T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways ( p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. Conclusions Transcriptomics reveals dynamic changes in the“gene profiles”of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.
研究领域:
分子生物学
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基因组学
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糖尿病研究
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肌肉骨骼疾病
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产品关联
DOI
PubMed
高影响因子
Applied Physiology Nutrition and Metabolism
·
2018
·Vol. 44
·期 1
·
IF 2.518
Yu Qiao,Guoqiang Fan,Jun Guo,Shixing Gao,Ruqian Zhao,Xiaojing Yang
Zinc-α2-glycoprotein (ZAG) has been demonstrated to play a role in stimulating lipid mobilization under normal conditions. However, further studies are required to determine whether ZAG overexpression can alleviate the reduction in plasma lipid levels under stress conditions. In the present study, we investigated the effects of ZAG on lipometabolism in white adipose tissue (WAT) after dexamethasone (DEX) stimulation using C57BL/6 male mice as the experimental models. Transcript and protein levels of genes associated with the β-adrenoreceptor (β-AR)/cyclic adenosine monophosphate/protein kinase a (PKA) pathway, lipid mobilization, and energy metabolism were determined by quantitative real-time polymerase chain reaction and Western blotting. Plasma levels of nonesterified fatty acid (NEFA) were measured using an automatic biochemical analyzer. Results indicated that plasma NEFA levels were decreased in the DEX group, but NEFA levels were rescued by ZAG overexpression. ZAG overexpression resulted in the upregulation of β3-AR and phosphorylated PKA protein relative to those of the DEX group. Analysis of lipometabolism showed that protein levels of phosphorylated hormone-sensitive lipase was reduced upon DEX treatment but were restored by ZAG overexpression. For energy metabolism, ZAG significantly upregulated the protein expression of carnitine palmitoyltransferase1a and cytochrome c oxidase subunit 1 relative to those of the DEX group. In conclusion, ZAG could alleviate DEX-induced decrease in plasma NEFA levels and this could be associated with the promoting lipid mobilization in WAT.
研究领域:
药理学
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内分泌学
·
代谢
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Jing Zhang,Chengcheng Lv,Zhenyang Yu,Yangyuan Zhou
Reproductive toxicities of imidazolium- ([EMIM]X) and pyridinium-based ([APYR]X) ionic liquids (ILs) are essential to fully assess their hazards. Presently, effects of five ILs on the intricate processes of reproduction, including sperm-oocyte interactions, were explored in Caenorhabditis elegans . Results showed that 1-ethylpyridinium bromide ([EPYR]Br) stimulated oocytes, zygotes and total reproduction. 1-Octylpyyridinium bromide ([OPYR]Br) inhibited oocytes and stimulated zygotes, it inhibited the initial and total reproduction. 1-Dodecylpyridinium bromide ([DPYR]Br) inhibited oocytes and zygotes, but stimulated the initial and total reproduction. 1-Ethyl-3-methylimidazolium bromide ([EMIM]Br) inhibited oocytes, but stimulated zygotes and reproduction. 1-Ethyl-3-methylimidazolium iodide ([EMIM]I) inhibited germcells and oocytes but stimulated zygotes and reproduction. Regarding hormones and lipid metabolism, the ILs commonly reduced main sperm protein, sperm transmembrane protein 9 and spermatocyte protein 8. The qRT-PCR results showed that the ILs commonly down-regulated the expressions of mpk-1 , while up-regulated those of inx-14 , with influences on the expressions of vab-1 , unc-43 and rme-2 . These biochemicals and genes were directly connected with the sperm-oocyte interactions. Transcriptomic analysis results supported the involvement of cAMP and cGMP-PKG signaling pathways underlying the effects on the sperm-oocyte interactions. The results also implied ILs’ impacts on neural and immune diseases and even cancers that should be considered in the future.
研究领域:
毒理学
·
生殖生物学
·
分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
·
2023
·
IF 12.8
Lin Huang,Weixia Zhang,Difei Tong,Lingzheng Lu,Weishang Zhou,Dandan Tian,Guangxu Liu,Wei Shi
Recently, increased production and consumption of disinfectants such as triclosan (TCS) and triclocarban (TCC) have led to massive pollution of the environment, which draws global concern over the potential risk to aquatic organisms. However, the olfactory toxicity of disinfectants in fish remains elusive to date. In the present study, the impact of TCS and TCC on the olfactory capacity of goldfish was assessed by neurophysiological and behavioral approaches. As shown by the reduced distribution shifts toward amino acid stimuli and hampered electro-olfactogram responses, our results demonstrated that TCS/TCC treatment would cause deterioration of the olfactory ability of goldfish. Our further analysis found that TCS/TCC exposure suppressed the expression of olfactory G protein-coupled receptors in the olfactory epithelium, restricted the transformation of odorant stimulation into electrical responses by disturbing the cAMP signaling pathway and ion transportation, and induced apoptosis and inflammation in the olfactory bulb. In conclusion, our results demonstrated that an environmentally realistic level of TCS/TCC would weaken the olfactory capacity of goldfish by constraining odorant recognition efficiency, disrupting olfactory signal generation and transduction, and disturbing olfactory information processing.
研究领域:
环境科学
·
水生毒理学
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神经生物学
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鱼类生理学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Mengyi Yan,Xiayun Chen,Xiaotong Li,Qianqian Liu,Baixue Yu,Yi Cen,Wei Zhang,Yibin Liu,Xinxuan Li,Ying Chen,Tao Wang,Shiying Li
The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting β -catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between β -catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C–C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.
研究领域:
肿瘤学
·
免疫疗法
·
药理学
·
分子生物学
·
细胞信号传导
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）