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1.
Acta Pharmacol Sin ; 45(4): 728-737, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38086898

ABSTRACT

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.


Subject(s)
Heart Failure , Myocardial Infarction , Humans , Mice , Animals , Rats , Chemokine CCL2/metabolism , Myocardial Infarction/metabolism , Myocytes, Cardiac , Heart Failure/metabolism , Regeneration , Mice, Inbred C57BL , Apoptosis , STAT3 Transcription Factor/metabolism
2.
Small ; 19(29): e2208174, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37026668

ABSTRACT

Ultrathin 2D organic nanosheets (2DONs) with high mobility have received tremendous attention due to thickness of few molecular layers. However, ultrathin 2DONs with high luminescence efficiency and flexibility simultaneously are rarely reported. Here, the ultrathin 2DONs (thickness: 19 nm) through the modulation of tighter molecular packing (distance: ≈3.31 Å) achievable from the incorporation of methoxyl and dipenylamine (DPA) groups into 3D spirofluorenexanthene (SFX) building blocks is successfully prepared. Even with closer molecular stacking, ultrathin 2DONs still enable the suppression of aggregation quenching to exhibit higher quantum yields of blue emission (ΦF  = 48%) than that on amorphous film (ΦF  = 20%), and show amplified spontaneous emission (ASE) with a mediate threshold (332 mW cm-2 ). Further, through drop-casting method, the ultrathin 2DONs are self-organized into large-scale flexible 2DONs films (1.5 × 1.5 cm) with the low hardness (H: 0.008 Gpa) and low Young's modulus (Er : 0.63 Gpa). Impressively, the large-scale 2DONs film can realize electroluminescence performances with a maximum luminance (445 cd m-2 ) and low turn on voltage (3.7 V). These ultrathin 2DONs provide a new avenue for the realization of flexible electrically pumping lasers and intelligent quantum tunneling systems.

3.
Zhen Ci Yan Jiu ; 43(10): 674-7, 2018 Oct 25.
Article in Chinese | MEDLINE | ID: mdl-30365266

ABSTRACT

Brain plasticity is referred to the ability of the brain to change in structure and functional activities from microscopic aspects (synapses) in individual neurons to larger-scale aspects such as cortical remapping, neuronal remodeling, etc. in response to injury. Acupuncture has a positive effect in the treatment of cerebral diseases, thus leading to an increasing research on its underlying mechanisms in regulating brain plasticity. The present paper reviewed recent development of studies on acupuncture treatment of Alzheimer's disease, vascular dementia, cerebral ischemia, bone cancer pain, autism, etc. from 1) regulating synaptic plasticity (up-regulating the proportion of hippocampal synapses, increasing synaptic curvature, post-synaptic density, and numerical density, areal density, and lowering synaptic cleft); 2) increasing hippocampal post-synaptic potential slop, peak and peak area of population spikes to evoke long-term potentiation (LTP) by regulating the expression of glutamate N-methyl-D-aspartate (NMDA) and alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, and growth associated protein (GAP-43); 3) down-regulating the expression of glial fibrillary acidic protein (GFAP) to suppress the activity of astrocytes in the ischemic cerebral area and hippocampus in cerebral ischemia rats, and in the spinal cord dorsal horns of bone cancer rats, etc. and promoting vimentin and connexin 43 expression; and 4) promoting neuronal remodeling, and repair and regeneration of the injured nerve in the central nervous system via regulating neuron-glia network, expression of nerve growth factor, brain derived neurotrophic factor, etc. The future studies should pay more attention to 1) the contribution of acupuncture intervention to the correlation between the initiation of the endogenous protective effect and the brain plasticity during the onset of nerve injury and repair of the injured nerve, and 2) standarization of stimulating quantity, manipulation and duration of acupuncture treatment, as well as the relationship between the stimulating quantity and efficacy.


Subject(s)
Acupuncture Therapy , Synapses , Animals , Brain , Hippocampus , Humans , Neuronal Plasticity , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate
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