Frontiers in Pharmacology
·
2024
·
IF 4.4
Zhang Yunxia,Wu Xiaoxiao,Li Ruoqi,Sui Mengru,Li Guoyin,Fan Shuhua,Yang Mingsheng,Liu Qiuping,Liu Xiaomeng,Wu Changjing,Li Lili
Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyHC1 and MyHC2a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.
研究领域:
药理学
·
肌肉生物学
·
代谢疾病
·
分子生物学
·
细胞生物学
·
动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Xinyu Wang,Yuhang Liu,Yeli Fan,Junjie Yan,Ge Yan,Qingfeng Liu,Qian Xu,Lizhen Wang,Donghui Pan,Yuping Xu,Chongyang Chen,Yu Chen,Min Yang
In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo-shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen-treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation-targeting prowess while sidestepping the release of pro-inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid-loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy “Trojan horse” in the battle against pneumonia-induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.
研究领域:
药理学
·
免疫学
·
生物医学工程
·
肺科学
✓ 已验证
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND MICROBIOLOGY
·
2024
·
IF 1
Zhu Y. B.,Zhang W.,Fan Y. L.,Chen Y. Y.,Zhu J. L.,Lu H. X.
Abstract Two immunochromatographic assays based on hematite (α-Fe 2 O 3 ) nanoparticles were developed for rapid detection of aflatoxin M1 (AFM1) and Escherichia coli O157:H7 in the milk. Hematite nanoparticles were prepared and utilized as colored signal labels. The competitive format was applied for AFM1 detection, while the sandwich format for E. coli O157:H7 determination. Under optimal conditions, the assay exhibited a visual detection limit of 0.10 ng/mL and quantitative determination limit of 0.017 ng/mL for AFM1. For E. coli O157:H7, a visual detection limit of 2.9 × 10 5 CFU/mL was achieved. The entire determination process could be accomplished within 15 min. Compared with traditional nanolabels, hematite nanoparticles showed advantages of facile preparation, high stability and easy bioconjugation. The developed assays provided effective and rapid screening strategies for AFM1 and E. coli O157:H7 in milk samples with high sensitivity and specificity.
研究领域:
食品安全
·
分析化学
·
纳米技术
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2022
·
IF 5.589
Tushuai Li,Zhihong Liu,Xiao Fu,Yongquan Chen,Shenglong Zhu,Jie Zhang
Chemo-immunotherapy has gained increasing attention as one of the most promising combination therapy strategies to battle cancer. In this study, the therapeutic nanoparticles (TNPs) co-delivering doxorubicin (DOX) and IL-12 (IL-12) were developed for chemo-immunotherapy combination therapy on liver cancer. TNPs were synthesized based on the ionic interactions between cationic chitosan (Ch) and anionic poly-(glutamic acid) (PGA). DOX and IL-12 loaded in TNPs presented prolonged circulation in blood, efficient accumulation in tumors, and internalization in tumor cells. After that, DOX and IL-12 were co-released in the tumor microenvironment . The locally responsive property of TNPs could subsequently re-educate macrophages. More significantly, TNPs with no obvious side effects can remarkably inhibit the H22 tumor growth in vivo. A low dosage of loaded IL-12 in TNPs can effectively polarize macrophages toward the M1 phenotype to reduce tumor burden, further enhancing the antitumor efficacy. Our results suggest that the self-stabilized TNPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Guo Ge,Tianlin Wang,Zihou Liu,Xiaomeng Liu,Tiange Li,Yuntang Chen,Jialin Fan,Erkigul Bukye,Xianqing Huang,Lianjun Song
Realizing the simultaneous speedy detection of multiple mycotoxins in contaminated food and feed is of great practical importance in the domain of food manufacturing and security. Herein, a fluorescent aptamer sensor based on self-assembled DNA double-crossover was developed and used for effective simultaneous quantitative detection of aflatoxins M 1 and B 1 by fluorescence resonance energy transfer (FRET). Fluorescent dye-modified aflatoxin M 1 and B 1 aptamers are selected as recognition elements and signal probes, and DNA double crosses are consistently locked by the aflatoxin aptamers, which results in a “turn-off” of the fluorescent signal. In the presence of AFM 1 and AFB 1 , the aptamer sequences are more inclined to form Apt-AFM 1 and Apt-AFB 1 complexes, and the fluorescent probes are released from the DNA double-crossing platform, leading to an enhanced fluorescent signal (Cy3: 568 nm; Cy5: 660 nm). Under the optimal conditions, the signal response of the constructed fluorescent aptamer sensor showed good linearity with the logarithm of AFM 1 and AFB 1 concentrations, with detection limits of 6.24 pg/mL and 9.0 pg/mL, and a wide linear range of 0.01–200 ng/mL and 0.01–150 ng/mL, respectively. In addition, the effect of potential interfering substances in real samples was analyzed, and the aptasensor presented a good interference immunity. Moreover, by modifying and designing aptamer probes, the sensor can be applied to high-throughput simultaneous screening of other analytes , providing a new approach for the development of fluorescent aptamer sensors.
研究领域:
食品科学
·
分析化学
·
生物技术
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2024
·Vol. 68
·期 3
·4034
·
IF 2.1
Lan Wang,Zhenyu Fan,Haijin Wang,Shougui Xiang
Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT ‒ qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
·
药理学
·
炎症
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Yi Zhang,Yuanxiang Huang,Zhenfeng Yue,Huajun Fan,Shaojing Wu
A novel, efficient and specific aptamer-functionalized sorbent was successfully synthesized and applied in the analysis of ultra-trace aflatoxin M1 (AFM1) and its analogues in milk. By using a gold nanoparticle-based colorimetric analysis tool, we could determine that the AFM1-aptamer (M1-aptamer) recognized and bound AFM1 to generate an aptamer-target complex. After analysis and verification, the M1-aptamer on the surface of the carboxyl microspheres were completely modified via EDC/NHs amide formation. The effects of extraction pH, extraction buffer, concentration of Mg 2+ and elution solvents were investigated by single-factor experiments to determine the most suitable analysis conditions. Using these conditions, the extraction performance of the M1-aptamer-functionalized sorbent could be studied and an analytical method for AFM1 and its analogues in milk could be established. The results of adsorption equilibrium as well as adsorption selectivity experiments indicated that the M1-aptamer offered a specific adsorption site to selectively adsorb aflatoxins exhibiting a dihydrofuran oxaphthalene scaffold. The adsorption capacity of the aptamer-functionalized sorbent was 233.1 μg/g. A studied method for the determination AFM1 in milk with low matrix effect demonstrated a good linear correlation in the range of 0 to 2.0 μg/L (R 2 = 0.9982) and high detection sensitivity (detection limits of 7 ng/kg in milk and 21 ng/kg in milk power). Furthermore, excellent spiked recovery and good repeatability were obtained. The method delivered specific, accurate and reproducible results for enriching and detecting ultra-trace AFM1 and its analogues in milk.
研究领域:
分析化学
·
食品科学
·
纳米技术
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Bolong Fang,Shaolan Xu,Youju Huang,Fengmei Su,Zhen Huang,Hao Fang,Juan Peng,Yonghua Xiong,Weihua Lai
In this study, we developed an indirect competitive plasmonic immunoassay using glucose oxidase (GOx)-induced redox reaction to etch Au nanorods (AuNRs) for qualitative and quantitative detection of aflatoxin M1 (AFM1) in milk. In this system, streptavidin (SA) was selected as a linker between biotinylated anti-AFM1-monoantibody (bio-mAb) and biotinylated GOx (bio-GOx) to form the immunocomplexes bio-mAb-SA-bio-GOx. After the oxidation of the glucose and I - , the resultant I 2 could etch cetytrimethylammonium bromide (CTAB)-stabilized AuNRs . This resulted in the blue shift of the longitudinal localized surface plasmon resonance (LSPR) extinction peak, with a color change from blue to pink. The linear range and limit of detection (LOD) of the plasmonic immunoassay were 0.25–10 ng mL −1 and 0.11 ng mL −1 , respectively. It displayed quantitative detection with high sensitivity, specificity, recovery, and accuracy, which is promising for qualitative and quantitative detection of AFM1 in food safety.
研究领域:
纳米技术
·
分析化学
·
食品科学
·
毒理学
✓ 已验证
DOI
高影响因子
Frontiers in Neuroscience
·
2024
·
IF 3.2
Shuo Li,Alhamdu Adamu,Yucai Ye,Fankai Gao,Rulin Mi,Guofang Xue,Zhaojun Wang
Objective: To investigate the effect of (+)-borneol on neuroinflammation and microglia phenotype polarization in epileptogenesis and its possible mechanism.Methods: Based on mouse models of status epilepticus (SE) induced by pilocarpine, and treated with 15 mg/kg (+)-borneol, western-blot was used to detect the expressions of NeuN, Iba-1, TLR4, p65 and p-p65 in the hippocampus. Immunofluorescence was used to detect the expression of apoptosis-related proteins Bax and Bcl-2. To explore the effect of (+)-borneol on microglia in vitro, we used the kainic acid-induced microglia model and the concentration of (+)-borneol was 25 μM according to CCK-8 results. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in the supernatant of each group was detected by ELISA. The nitric oxide (NO) content in the supernatant was detected by Griess method. The expressions of Iba-1 and TLR4-NFκB signaling pathway-related proteins (TLR4, p65, p-p65) were detected by Western-Blot. Immunofluorescence was used to detect microglia’s M1 and M2 phenotype polarization and the expression of Iba-1 and TLR4.Results: (+)-borneol reduced hippocampal neuronal injury, apoptosis, and microglia activation by inhibiting the TLR-NFκB signaling pathway in SE mice. TLR4 agonist LPS partially reversed the neuroprotective effect of (+)-borneol. In the KA-induced microglia model, (+)-borneol inhibited microglia activation, M1 phenotype polarization, and secretion of pro-inflammatory cytokines through the TLR4-NFκB signaling pathway. LPS treatment inhibited the therapeutic effects of (+)-borneol.Conclusion: (+)-borneol inhibits microglial neuroinflammation and M1 phenotype polarization through TLR4-NFκB signaling pathway and reduces neuronal damage and apoptosis in SE mice. Therefore, (+)-borneol may be a potential drug for epilepsy modification therapy.
研究领域:
神经科学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Pan Su,Mengdi Wu,Xiaoting Yin,Mengyuan Li,Yucheng Li,Ming Bai,Baoying Wang,Erping Xu
Ethnopharmacological relevance Modified Xiaoyao San (MXYS), a clinical empirical modified formula based on famous traditional Chinese herbal prescription Xiaoyao San, according to the “yu syndrome” theory of traditional Chinese medicine . MXYS has been shown to be an excellent effective therapy for depression patients in clinic, but the antidepressant mechanisms remain unclear. Aim of the study A growing body of evidence indicates the microglia autophagy and M1 polarized microglia (proinflammatory phenotype)-mediated neuroinflammation act critical roles in the pathogenesis of depression. This study aimed to investigate whether MXYS exerts antidepressant efficacy through inhibition of M1 polarized microglia-mediated neuroinflammation and modulation of autophagy involved in PI3K/Akt/mTOR pathway. Materials and methods In present research, the lipopolysaccharide (LPS)-induced depressive mice and LPS-stimulated N9 microglia cell line were utilized. Behavioral tests (sucrose preference, tail suspension and open field tests) were carried out to evaluate the antidepressant effect of MXYS. The neuronal damage was measured by Nissl's staining in LPS-treated mice. The proinflammatory cytokine levels, the autophagic markers, microglia M1 polarization as well as the PI3K/Akt/mTOR pathway related proteins of MXYS treatment were analyzed by ELISA kits, Western blot and immunofluorescence staining in vivo and vitro . Finally, the influence of autophagy antagonist (3-MA) on the protective effect of MXYS-containing serum in the LPS-stimulated N9 microglia was investigated. Results Treatment of LPS-induced depressive mice with MXYS significantly reversed depression-like behaviors, accompanied by reduction of proinflammatory cytokine levels (TNF-α, IL-1β) and amelioration of neuronal damage in prefrontal cortex. MXYS suppressed microglia M1 polarization and promoted autophagy in prefrontal cortex and LPS-stimulated N9 cells. Importantly, the remarkable inhibitory effect of the MXYS-medicated serum on microglia M1 polarization was blocked by autophagy antagonist 3-MA in LPS-stimulated N9 cells. Meanwhile, the MXYS treatment exhibited an excellent inhibition effect of PI3K/Akt/mTOR pathway in vivo and vitro . Conclusion Our research suggests that the antidepressant effect of MXYS in LPS-induced depressive mice may be related to alleviate neuroinflammation through suppression of microglia M1 polarization via enhancing autophagy involved in inactivation of the PI3K/Akt/mTOR pathway.
研究领域:
药理学
·
神经科学
·
中医
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Yu He,Ejun Peng,Xiaozhuo Ba,Jian Wu,Wen Deng,Qiu Huang,Yonghua Tong,Haojie Shang,Zichen Zhong,Xiao Liu,Yanlong Zhang,Tao Ye,Xiaoqi Yang,Kangyang Wang,Yabin Xie,Kehua Jiang,Ding Xia,Zhiqiang Chen,Kun Tang
Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO 2 /TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO 2 /TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO 2 /TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO 2 /TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO 2 /TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO 2 /TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.
研究领域:
纳米技术
·
药理学
·
肾脏生理学
·
炎症
·
氧化应激
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC NEUROSCIENCE
·
2023
·Vol. 24
·期 1
·1-12
·
IF 2.4
Cai Jimin,Yang Yang,Han Jiahui,Gao Yu,Li Xin,Ge Xin
Background Microglial polarization and the subsequent neuroinflammatory response and oxidative stress are contributing factors for traumatic brain injury (TBI) plus hemorrhagic shock (HS) induced brain injury. In the present work, we have explored whether Lysine (K)-specific demethylase 4 A (KDM4A) modulates microglia M1 polarization in the TBI and HS mice. Results Male C57BL/6J mice were used to investigate the microglia polarization in the TBI + HS model in vivo. Lipopolysaccharide (LPS)-induced BV2 cells were used to examine the mechanism of KDM4A in regulating microglia polarization in vitro. We found that TBI + HS resulted in neuronal loss and microglia M1 polarization in vivo, reflected by the increased level of Iba1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, malondialdehyde (MDA) and the decreased level of reduced glutathione (GSH). Additionally, KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. Similar to the results in vivo, KDM4A also highly expressed in LPS-induced BV2 cells. LPS-induced BV2 cells exhibited enhanced microglia M1 polarization, and enhanced level of pro-inflammatory cytokines, oxidative stress and reactive oxygen species (ROS), while this enhancement was abolished by the suppression of KDM4A. Conclusion Accordingly, our findings indicated that KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. The important role of KDM4A in TBI + HS-induced inflammatory response and oxidative stress was at least partially realized through regulating microglia M1 polarization.
研究领域:
神经科学
·
炎症
·
氧化应激
·
细胞生物学
✓ 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）