EXPERIMENTAL CELL RESEARCH
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2023
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IF 3.7
Jinpeng Lv,Ximei Zhang,Xiaohong An,Yan Cao,Duo Meng,Kun Zou,Rongyin Gao,Ruzhi Zhang
The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane , which plays critical roles in many physiological processes . Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis , dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions , which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation . Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants , highlighting their potential as a therapeutic strategy for skin pigmentation disorders.
研究领域:
细胞生物学
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分子生物学
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皮肤生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2023
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IF 5
Mo-li Zhu,Jie Zhang,Li-juan Guo,Rui-zhu Yue,Shan-shan Li,Bao-yue Cui,Shuang Guo,Qian-qian Niu,Ya-nan Yu,Huan-huan Wang,Lin Yang,Ya-ling Yin,Shuang-xi Wang,He-qin Zhan,Zhi-tao Gao,Peng Li
Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze , Transcranial Doppler TCD, hematoxylin–eosin (HE) staining , Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2021
·Vol. 28
·期 4
·319-329
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IF 1.978
Lu Yan,Yang Mei-ling,Shen A-ling,Lin Shan,Peng Mei-zhong,Wang Tian-yi,Lu Zhu-qing,Wang Yi-lian,Peng Jun,Chu Jian-feng
Objective To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. Methods Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. Results KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl 2 in Ca 2+ -free solutions containing K + or NE. In addition, KXA pretreatment inhibited accumulation of Ca 2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. Conclusion KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Yanan Wang,Deyao Qian,Xinyuan Wang,Xue Zhang,Zerui Li,Xinlei Meng,Liangmin Yu,Xuefeng Yan,Zhiyu He
Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin’s ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs’ skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.
研究领域:
纳米医学
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药学
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生物医学工程
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分子生物学
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炎症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Yi Chen,Hongjin Qian,Dandan Peng,Yan Jiang,Qiaolin Liu,Yan Tan,Longbao Feng,Biao Cheng,Guilan Li
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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药学
✓ 已验证
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）