FASEB JOURNAL
·
2025
·Vol. 39
·期 8
·e70510
·
IF 4.2
Songlun Jiang,Xu Zhang,Fanfan Chen,Zifan Zhao,Chenglong Zhang,Yuchun Sun
Bone organoids offer potential for bone regeneration and in vitro organ models. Current limitations in bone organoid culture systems include low efficiency in construction and functionality, as well as increased apoptosis in prolonged cultures of larger sizes. The ketone body 3-hydroxybutyrate (3HB), synthesized in the liver, addresses these challenges effectively. Our findings suggest that 3HB increases intracellular calcium ion (Ca 2+ ) levels in human bone marrow-derived mesenchymal stem cells (hBMSCs) by activating the hydroxycarboxylic acid receptor 2 (HCAR2). This activation initiates the cAMP/PKA/CREB pathway, which elevates the expression of anti-apoptotic genes such as myeloid cell leukemia 1 (MCL1) and B cell lymphoma 2-related protein A1 (BCL2A1), thereby reducing apoptosis. Furthermore, this pathway boosts the expression of osteogenic proteins, including Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2), facilitating osteogenesis in bone organoids. Consequently, 3HB may enhance the construction of bone organoids that are more mature, larger, and have longer viability. Graphical Our study demonstrates that 3-Hydroxybutyrate (3HB) activates the HCAR2 receptor in hBMSCs, leading to an increase in intracellular calcium levels and subsequent activation of the cAMP/PKA/CREB signaling pathway. This pathway upregulates the expression of the anti-apoptotic molecule MCL1 and early osteogenic factors RUNX2 and BMP2. These dual effects of 3HB, promoting osteogenesis and inhibiting apoptosis, provide a promising strategy for constructing more viable and mature bone organoids with higher efficiency.
研究领域:
再生医学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2022
·Vol. 19
·期 1
·1-14
·
IF 9.587
Lan Tian,Wu Yuhan,Zhang Yulei,Li Shuhan,Zhu Zhanpeng,Wang Liyan,Mao Xueqin,Li Ye,Fan Cuiqin,Wang Wenjing,Yu Shu Yan
Background Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder.
Methods Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Results Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. Conclusion Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine. Graphical Abstract
研究领域:
神经科学
·
药理学
·
分子生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2023
·Vol. 28
·期 5
·93
·
IF 3.1
Chenglong Sun,Wenhao Zheng,Linjie Wang,Quan Du
Background: Gastrodin (Gas) exhibits anti-inflammatory properties against diseases associated with the central nervous system (CNS). This study aimed to investigate the potential neuroprotective role of Gas in traumatic brain injury (TBI). Methods: A rat TBI model was established in male adult Sprague-Dawley (SD) rats by controlled cortical impingement (CCI), and lipopolysaccharide (LPS) was applied to induce the activation of BV2 microglia and HT22 hippocampal neurons. Neurological deficits, motor function and brain water content were evaluated in TBI rats. TUNEL and Nissl’s staining were applied to measure neuronal degeneration and apoptosis. Microglial activation, the mRNA and protein profiles of pro-inflammatory cytokines were tested by immunohistochemistry (IHC), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: Gas significantly reduced neurological deficits, cerebral edema, and neuronal apoptosis and improved motor function in TBI mice. In addition, Gas inactivated microglia and blocked the production of pro-inflammatory cytokines on the damaged side of the TBI rat brain. In vitro, Gas attenuated BV2 microglia inflammation and reduced HT22 hippocampal neuronal apoptosis. On the other hand, Gas activated the PKA/CREB/BDNF pathway both in vivo and in vitro. Conclusions: Gas blocks microglial activation-mediated inflammation through the PKA/CREB/BDNF pathway, thereby improving neurobehavioral function after TBI, which provides a potential therapeutic benefit for treating TBI.
研究领域:
神经科学
·
药理学
·
神经病学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Le Wang,Zhaobin Lei,Guanjie Zhang,Yang Cheng,Mingwei Zhong,Guangyong Zhang,Sanyuan Hu
The escalating incidence of metabolic pathologies such as obesity and diabetes mellitus underscores the imperative for innovative therapeutics targeting lipid metabolism modulation. Within this context, augmenting thermogenic processes in adipose cells emerges as a viable therapeutic approach. Given the limitations of previous β3-adrenergic receptor (β3-AR) agonist treatments in human diseases, there is an increasing focus on therapies targeting the β2-adrenergic receptor (β2-AR). Olodaterol (OLO) is a potent β2-AR agonist that is a potential novel pharmacological candidate in this area. Our study explores the role and underlying mechanisms of OLO in enhancing brown adipose thermogenesis, providing robust evidence from in vitro and in vivo studies. OLO demonstrated a dose-dependent enhancement of lipolysis, notably increasing the expression of Uncoupling Protein 1 (UCP1) and raising the rate of oxygen consumption in primary brown adipocytes. This suggests a significant increase in thermogenic potential and energy expenditure. The administration of OLO to murine models noticeably enhanced cold-induced nonshivering thermogenesis. OLO elevated UCP1 expression in the brown adipose tissue of mice. Furthermore, it promoted brown adipocyte thermogenesis by activating the β2-AR/cAMP/PKA signaling cascades according to RNA sequencing, western blotting, and molecular docking analysis. This investigation underscores the therapeutic potential of OLO for metabolic ailments and sheds light on the intricate molecular dynamics of adipocyte thermogenesis, laying the groundwork for future targeted therapeutic interventions in human metabolic disorders.
研究领域:
药理学
·
代谢学
·
内分泌学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jingyuan Mo,Weiguo Liao,Jinyan Du,Xiaoling Huang,Yaxin Li,Anyu Su,Lanying Zhong,Mingyu Gong,Pengcheng Wang,Zai Liu,Huizhen Kuang,Lisheng Wang
Ethnopharmacological relevance Ischemic stroke is an acute central nervous system disease that poses a threat to human health. It induces a series of severe pathological mechanisms, ultimately leading to neuronal cell death in the brain due to local ischemia and hypoxia. Buyang Huanwu decoction (BYHWD), as a representative formula for treating ischemic stroke, has shown good therapeutic effects in stroke patients. Aim of the study This study aimed to explore the mechanism of BYHWD in promoting neural remodeling after ischemic stroke from the perspective of neuronal synaptic plasticity, based on the cAMP/PKA/CREB signaling pathway. Materials and methods A modified suture technique was employed to establish a rat model of MCAO. The rats were divided into sham, model, and BYHWD (20 g/kg) groups. After the corresponding intervention, rat brains from each group were collected. TMT quantitative proteomics technology was employed for the research. Following proteomics studies, we investigated the mechanism of BYHWD in the intervention of ischemic stroke through animal experiments and cell experiments. The experimental animals were divided into sham, model, and BYHWD (5 g/kg, 10 g/kg, and 20 g/kg) groups. Infarct volume and severity of brain injury were measured by TTC staining. HE staining was utilized to evaluate alterations in tissue morphology. The Golgi staining was used to observe changes in cell body, dendrites, and dendritic spines. Transmission electron microscopy was used to observe the ultrastructure of synapses in the cortex and hippocampus. TUNEL staining was conducted to identify apoptotic neurons. Meanwhile, a stable and reliable (OGD/R) SH-SY5Y cell model was established. The effect of BYHWD-containing serum on SH-SY5Y cell viability was measured by CCK-8 kit. The apoptosis situation of SH-SY5Y cells was determined by Annexin V-FITC/PI. Immunofluorescence was employed to measure the fluorescence intensity of synaptic-related factors Syt1, Psd95, and Syn1. Synaptic plasticity pathways were assessed by using RT-qPCR and Western blot to determine the expression levels of cAMP, Psd95, Prkacb, Creb1/p-Creb1, BDNF, Shank2, Syn1, Syt1, Bcl-2, Bcl-2/Bax mRNA and proteins. Results After treatment with BYHWD, notable alterations were detected in the signaling pathways linked to synaptic plasticity and the cAMP signaling pathway-related targets among the intervention targets. This trend of change was also reflected in other bioinformatics analyses, indicating the important role of synaptic plasticity changes before and after modeling and drug intervention. The results of vivo and vitro experiments showed that BYHWD improved local pathological changes, and reduced cerebral infarct volume, and neurological function scores in MCAO rats. It increased dendritic spine density, improved synaptic structural plasticity, and had a certain neuroprotective effect. BYHWD increased the postsynaptic membrane thickness, synaptic interface curvature, and synaptic quantity. 10% BYHWD-containing serum was determined as the optimal concentration for treatment. 10% BYHWD-containing serum significantly reduced the overall apoptotic rate of (OGD/R) SH-SY5Y cells. Immunofluorescence experiments demonstrated that 10% BYHWD-containing serum could improve synaptic plasticity and increase the relative expression levels of synaptic-related proteins Syt1, Psd95, and Syn1. BYHWD and decoction-containing serum upregulated the mRNA and protein expression levels in (OGD/R) SH-SY5Y cells and MCAO rats, suggesting its ability to improve damaged neuronal synaptic plasticity and enhance transmission efficiency, which might be achieved through the regulation of the cAMP/PKA/CREB pathway. Conclusions This study may provide a basis for clinical medication by elucidating the underlying experimental evidence for the promotion of neural plasticity after ischemic stroke by BYHWD.
研究领域:
神经药理学
·
药理学
·
神经科学
·
分子生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2019
·
IF 3.261
Qiwen Du,Weichen Jia,Jingyu Dai,Chao Du,Aiyun Shao,Rongmin Zhang,Yuefei Ji
Natural organic matter (NOM) contains a large number of aromatic ketones and quinones, which can produce reactive oxygen species (ROS), such as 1 O 2 and HO·, through photosensitization. These ROS play important roles in the attenuation of organic pollutants in sunlit surface water. The NOM components fractionated with XAD-8 resin at different pH influence the photo-generation of ROS, which may be related to the degree of dissociation of functional groups. In this study, probe chemicals were used to investigate the effect of dissociation degree (p K a ) of NOM model compounds on ROS production under 254 nm UV irradiation. Experimental results showed that six model compounds with similar molecular weights and structures but different p K a values have different ROS production abilities in a pH 7.0 reaction system. The ability for DHB 2,5 (2.97), DHB 3,4 (4.48), and GUA (9.99) to photo-generate 1 O 2 increased with increasing dissociation. The ability for DHB 3,4 and GUA to photo-generate HO· followed the same trend. The correlation between NOM dissociation constant and ROS generation is preliminary established, which explains the influence of functional groups. Our results may provide some basic information for understanding the correlation between NOM structural features and ROS generation.
研究领域:
环境化学
·
光化学
·
水处理
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF OBESITY
·
2025
·
IF 3.8
Peng Zhou,Gao Jianfang,Xu Liling,Huang Shan,Wang Rui,Du Juan,Zhang Zhongxiao,Zhang Ling,Feng Lei,Wang Xingyun,Guo Xirong
Background/Objectives Emerging evidence suggests that extracellular vesicles (EVs) in breast milk may serve as an abundant source of candidates for regulating metabolism. Our study aims to identify phospholipids derived from human milk EVs (mEVs) that can benefit people with obesity. Methods Infant mice were either fed with formula milk or breastfed to investigate whether mEVs affect adipose tissue physiology in infants. Human milk samples were collected from nursing mothers who had given birth at Shanghai Tongren Hospital. UPLC-MS/MS was used to characterize lipidomic profile of human colostrum and mature milk. Body weight changes, H&E staining, blood lipid test, GTT and ITT test were measured to evaluate physiology changes of phospholipid administrated high-fat-diet (HFD) mice. Infrared measurement, western blot, qPCR and IHC analysis were measured to evaluate thermogenesis. RNA-seq and qPCR were used to evaluate the cluster of genes and pathways. Seahorse, electron microscope observation and qPCR were measured to evaluate mitochondrial remodeling of adipocyte. PKA inhibitor (H89) was used to evaluate signal axis of mitochondrial coupling respiration in adipocyte. Results Lipidomic analyses of mEVs identified phosphatidylethanolamine (PE) as a signature molecule, whose abundance remains consistent between colostrum and mature milk. PE significantly enhanced brown adipocyte thermogenic respiration in vivo, activated mitochondrial biogenesis transcriptionally, and suppressed mitochondrial clearance. These results led to an increased number of mitochondria and promotes the beiging process. RNA sequencing revealed that PE potentially remodels mitochondria through the PKA signaling pathway, which may influence thermogenesis and lipolysis. The activation mechanism of PE in adipocytes was confirmed by a reduction in thermogenesis phenotype. Conclusions mEVs-derived PE serves as a universal cellular adjustor, regulating mitochondrial efficiency via PE/PKA signaling in response to shifts in demand of energy. mEVs serve as a tool for mother-to-child signaling bridge, which maintain a long-time health of adipose tissue.
研究领域:
分子生物学
·
生物化学
·
细胞生物学
·
代谢研究
·
营养学
·
信号转导
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yan Cao,Jinpeng Lv,Yan Tan,Ruolin Chen,Xiaoxue Jiang,Duo Meng,Kun Zou,Min Pan,Liming Tang
Ethnopharmacological relevance Tribuloside, a natural flavonoid extracted from Chinese medicine Tribulus terrestris L., has shown potent efficacy in treating various diseases. In China, the fruits of Tribulus terrestris L. have long been utilized for relieving headache, dizziness , itchiness, and vitiligo . Water-based extract derived from Tribulus terrestris L. can enhance melanogenesis in mouse hair follicle melanocytes by elevating the expression of α-melanocyte stimulating hormone (α-MSH) and melanocortin-1 recepter (MC-1R). Nevertheless, there is a lack of information regarding the impact of tribuloside on pigmentation in both laboratory settings and living organisms. Aim of the study The present research aimed to examine the impact of tribuloside on pigmentation, and delve into the underlying mechanism. Materials and methods Following the administration of tribuloside in human epidermal melanocytes (HEMCs), we utilized microplate reader, Masson-Fontana ammoniacal silver stain, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to measure melanin contents, dendrite lengths, melanosome counts; L-DOPA oxidation assay to indicate tyrosinase activity, Western blotting to evaluate the expression of melanogenic and associated phosphodiesterase (PDE)/cyclic adenosine monophosphate (cAMP)/cyclic-AMP dependent protein kinase A (PKA) pathway proteins. A PDE-Glo assay to verify the inhibitory effect of tribuloside on PDE was also conducted. Additionally, we examined the impact of tribuloside on the pigmentation in both zebrafish model and human skin samples. Results Tribuloside had a notable impact on the production of melanin in melanocytes, zebrafish, and human skin samples. These functions might be attributed to the inhibitory effect of tribuloside on PDE, which could increase the intracellular level of cAMP to stimulate the phosphorylation of cAMP-response element binding (CREB). Once activated, it induced microphthalmia-associated transcription factor (MITF) expression and increased the expression of tyrosinase, Rab27a and cell division cycle protein 42 (Cdc42), ultimately facilitating melanogenesis, melanocyte dendricity, and melanin transport. Conclusion Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity, and melanosome transport; meanwhile, tribuloside does not have any toxic effects on cells and may be introduced into clinical prescriptions to promote pigmentation.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 19
·10406
·
IF 4.9
Yan Zhang,Yaping Yang,Huicong Liang,Yuerun Liang,Guixin Xiong,Fang Lu,Kan Yang,Qi Zou,Xiaomin Zhang,Guanhua Du,Ximing Xu,Jiejie Hao
Asthma is a chronic airway inflammation that is considered a serious public health concern worldwide. Nobiletin (5,6,7,8,3′,4′-hexamethyl flavonoid), an important compound isolated from several traditional Chinese medicines, especially Citri Reticulatae Pericarpium, is widely used for a number of indications, including cancer, allergic diseases, and chronic inflammation. However, the mechanism by which nobiletin exerts its anti-asthmatic effect remains unclear. In this research, we comprehensively demonstrated the anti-asthmatic effects of nobiletin in an animal model of asthma. It was found that nobiletin significantly reduced the levels of inflammatory cells and cytokines in mice and alleviated airway hyperresponsiveness. To explore the target of nobiletin, we identified PDE4B as the target of nobiletin through pharmacophore modeling, molecular docking, molecular dynamics simulation, SPR, and enzyme activity assays. Subsequently, it was found that nobiletin could activate the cAMP-PKA-CREB signaling pathway downstream of PDE4B in mouse lung tissues. Additionally, we studied the anti-inflammatory and anti-airway remodeling effects of nobiletin in LPS-induced RAW264.7 cells and TGF-β1-induced ASM cells, confirming the activation of the cAMP-PKA-CREB signaling pathway by nobiletin. Further validation in PDE4B-deficient RAW264.7 cells confirmed that the increase in cAMP levels induced by nobiletin depended on the inhibition of PDE4B. In conclusion, nobiletin exerts anti-asthmatic activity by targeting PDE4B and activating the cAMP-PKA-CREB signaling pathway.
研究领域:
药理学
·
免疫学
·
分子生物学
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
THERIOGENOLOGY
·
2024
·
IF 2.4
Wenjiao Liu,Han wang,Qi Mu,Ting Gong
Taste receptor type 1 subunit 3 (T1R3) is a G protein-coupled receptor encoded by the TAS1R3 gene that can be specifically activated by certain sweeteners or umami agents for sweet/umami recognition. T1R3 is a potential target for regulating male reproduction. However, studies on the impact of non-nutritive sweeteners on reproduction are limited. In the present study, we evaluated the impact of the non-nutritive sweeteners (saccharin sodium, sucralose and acesulfame-K) on testosterone synthesis in testicular Leydig cells of Xiang pigs by comparing the relative abundance of mRNA transcripts and protein expression of T1R3, steroidogenic related factors, and intracellular cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), as well as testosterone levels using Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). To clarify the specific mechanism, a dual luciferase assay was used to uncover the relationship between the transcription factors and steroidogenic enzyme. The acute intratesticular injection of a typical non-nutritive sweeteners was conducted to verify this impact in mouse. The results showed that saccharin sodium not only enhanced T1R3 expression in Leydig cells of Xiang pigs, but also caused significant increases in testosterone, cAMP, PKA, phosphorylation of specificity protein 1 (p-SP1), total protein of specificity protein 1 (SP1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) ( P <0.05). Similarly, treatment of Leydig cells with sucralose and acesulfame-K also increased testosterone level, protein expression of T1R3, 17-α-hydroxylase/17, 20-lyase (CYP17A1), and 3β-HSD1 ( P <0.05). Treatment with SQ22536 (an adenylate cyclas inhibitor) or H89 (a PKA inhibitor) significantly reduced saccharin sodium-induced protein levels of p-SP1, StAR, CYP17A1, and 3β-HSD1 ( P <0.05). In addition, a dual luciferase assay further demonstrated that SP1 significantly increased the promoter activity of CYP17A1 ( P <0.05). When mouse testes were injected with saccharin sodium, T1R3, p-SP1, CYP17A1, and 3β-HSD1 were upregulated, leading to a significant testicular increase in testosterone and cAMP levels ( P <0.05). These results suggest a mechanism by which the taste receptor T1R3 regulates testosterone production, and this mechanism may be linked to the cAMP-PKA pathway. Understanding the interrelationship between T1R3 and the cAMP-PKA-SP1 pathway contributes to clarify the regulatory mechanisms of male reproduction.
研究领域:
生殖生物学
·
内分泌学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2016
·Vol. 37
·期 4
·889-900
·
IF 2.348
Jieqiong He,Chao Wang,Yunpeng Sun,Bo Lu,Jinjin Cui,Nana Dong,Maomao Zhang,Youbing Liu,Bo Yu
Exendin-4 (ex-4) is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist which exerts beneficial effects on glycemic control and promotes cell viability. In the present study, we investigated the anti-apoptotic effects of ex-4, as well as the potential mechanisms responsible for these effects in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) under conditions of oxygen, glucose and serum deprivation (OGD). The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. The MSCs were pre-conditioned with ex-4 for 12 h prior to being subjected to OGD conditions, and the expression levels of an apoptotic marker (cleaved caspase-3), endoplasmic reticulum (ER) stress markers [phosphorylated (p-)protein kinase RNA-like endoplasmic reticulum kinase (PERK), PERK, binding immunoglobulin protein (BIP), activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP)], as well as those of a survival marker (Bcl-2) were measured by western blot analysis. Furthermore, the mRNA levels of ATF-4 and CHOP were determined by RT-qPCR. ELISA was used to examine the activity of intracellular cAMP. Moreover, the GLP-1R antagonist, exendin9-39 (ex9-39), the protein kinase A (PKA) inhibitor, H89, and small interfering RNA (siRNA) targeting rat ATF-4 and CHOP were co-incubated with the MSCs. The apoptotic rate was markedly diminished following pre-conditioning with ex-4 in a dose‑dependent manner (P<0.05). The ER stress markers, p-PERK, BIP, ATF-4 and CHOP, were upregulated in the cells subjected to OGD conditions. Ex-4 pre-conditioning significantly decreased the mRNA and protein levels of ATF-4 and CHOP (P<0.05), and increased the activity of intracellular cAMP (P<0.05). Furthermore, the anti-apoptotic effects of ex-4 were almost reversed by treatment with either H89 or ex9-39 (P<0.05); transfection with siRNA-CHOP significantly reduced the apoptotic rate of the MSCs and did not impair the cytoprotective effects of ex-4. Taken together, these findings suggest that ex-4 protects rat BM-MSCs from OGD-induced apoptosis through the activation of the PKA/cAMP pathway and the attenuation of the ER stress signaling pathway. Ex-4 may thus prove to be a therapeutic agent with the potential to improve the viability of MSCs in the ischemic milieu, and consequently, to optimize the therapeutic effects of MSC therapy in acute myocardial infarction.
研究领域:
干细胞生物学
·
药理学
·
细胞信号传导
·
心血管疾病
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Jian Chen,Lishan Li,Afang Zhang,Xuetong Zhang
Despite significant advancements in aerogels science, the fabrication of high-performance aerogels with their plastic processability remains unexplored owing to their inherent trade-off between skeletal rigidity and transformable processability. Herein, a universal solubility-pKa coupling-effect to engineer high-performance thermoplastic nylon aerogel family with excellent thermomechanical processing performance is proposed. By modulating solubility parameters and acid dissociation constants in nylon-solvent systems, it is precisely control crystallization to assemble interlaced 1D nanofiber skeletons, yielding nylon aerogels that integrate a high specific surface area (226 m 2 g −1 ), exceptional compressive modulus (12.6 MPa), and ultralow thermal conductivity (0.034 W m −1 K −1 ). Notably, beyond achieving performance comparable to aramid and other high-performance aerogels, these nylon aerogels uniquely incorporate thermoplastic properties enabling multiple thermomechanical processing for aerogel functionalization, including protective barrier via thermal encapsulating, reassembly of aerogel unmanned aerial vehicle through thermal cutting and welding, and biomimetic hydrophobic surfaces with lotus and petal effects through precise thermal imprinting. Surprisingly, thermomechanical processing also induces fluorescence of aerogels, suggesting applications in thermal-recording, anti-counterfeiting, etc. This research overcomes the critical skeletal rigidity-transformable processability trade-off in aerogels, enabling novel manufacturing approaches and broader engineering applications.
研究领域:
材料科学
·
高分子化学
·
纳米材料
·
热功能材料
·
先进制造
✓ 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）