Cell and Bioscience
·
2022
·Vol. 12
·期 1
·1-20
·
IF 9.584
Zhang Yufeng,Yang Min,Zhang Sheng,Yang Zhiqiang,Zhu Yufan,Wang Yi,Chen Zhe,Lv Xuan,Huang Zan,Xie Yuanlong,Cai Lin
Background Dysregulated osteoclast activity due to altered osteoclast differentiation causes multiple bone diseases. Osteoclasts are multinucleated giant cells derived from hematopoietic stem cells and play a major role in bone absorption. However, the mechanisms underlying the tight regulation of osteoclast differentiation in multiple pathophysiological status remain unknown. Results We showed that Bhlhe40 upregulation is tightly associated with osteoclast differentiation and osteoporosis. Functionally, Bhlhe40 promoted osteoclast differentiation in vitro, and Bhlhe40 deficiency led to increased bone mass and decreased osteoclast differentiation in vivo. Moreover, Bhlhe40 deficient mice resisted estrogen deficiency and aging-induced osteoporosis. Mechanism study showed that the increase in bone mass due to Bhlhe40 deficiency was a cell intrinsic defect in osteoclast differentiation in these mice. BHLHE40 upregulated the gene expression of Fos and Nfatc1 by directly binding to their promoter regions. Notably, inhibition of Fos/Nfatc1 abrogated the enhanced osteoclast differentiation induced by BHLHE40 overexpression. Conclusions Our research reveals a novel Bhlhe40/c-Fos/Nfatc1 axis involved in regulating osteoclastogenesis and shows that osteoporosis caused by estrogen deficiency and aging can be rescued by regulating Bhlhe40 in mice. This may help in the development of a new strategy for the treatment of osteoporosis.
研究领域:
骨骼生物学
·
分子生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LABORATORY INVESTIGATION
·
2021
·Vol. 101
·期 9
·1118-1129
·
IF 5.662
Wang Xin,Li Xing-Liang,Qin Li-Jie
Myocardial injury is a severe complication of sepsis and contributes substantially to the death of critically ill patients. Long non-coding RNAs (lncRNAs) participate in the pathogenesis of sepsis-induced myocardial injury. In this study, we investigated the role of lncRNA X-inactive specific transcript (XIST) in septic myocardial injury and explored its mechanism. Lipopolysaccharide (LPS)-stimulated H9C2 cells and rats subjected to cecal ligation and puncture (CLP) were used as the in vitro and in vivo models. After exposure to LPS, XIST and c-Fos levels were upregulated, but miR-150-5p was downregulated in H9C2 cardiomyocytes and myocardial tissues. XIST affected viability, apoptosis, and pyroptosis in LPS-challenged H9C2 cells. Moreover, XIST knockdown attenuated LPS-induced injury in H9C2 cells by targeting the miR-150-5p/c-Fos axis. c-Fos could bound to the promoter of the TXNIP/XIST gene and enhanced TXNIP/XIST expression. Silencing of XIST improved cardiac function and survival rate and reduced apoptosis and pyroptosis by regulating the miR-150-5p/c-Fos axis in septic rats in vivo. Taken together, our data show that XIST/miR-150-5p/c-Fos axis affected septic myocardial injury, which may indicate a novel therapeutic strategy for sepsis-induced myocardial injury.
研究领域:
分子生物学
·
心脏病学
·
传染病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ULTRASOUND IN MEDICINE AND BIOLOGY
·
2020
·
IF 2.514
Yao Liu,Yijin Fan,Huajun Tang,Chengzhi Li
The purpose of this study was to investigate the therapeutic effects of focused ultrasound on the expression of notch1, c-fos and transforming growth factor-β3 (TGF-β3) in genital skin of SD rats with vulvar lichen simplex chronicus (LSC). Fifty-six female SD rats with LSC were randomly divided into therapy and sham groups. The therapy group was exposed to focused ultrasound. The sham group received the same therapy with an instrument that had no power output. Four wk after a singly focused ultrasound therapy, histologic analyses revealed that recovered SD rats accounted for 75% of SD rats in the therapy group and 10.7% in the sham group. Total collagen fiber density in the superficial layer of dermis in the therapy group was significantly lower than that in the sham group. Notch1 and c-fos protein expression in the therapy group was significantly lower than that in the sham group, with the opposite effect present for TGF-β3. Focused ultrasound therapy may inhibit superficial collagen fibrosis in the dermis by affecting expression of notch1, c-fos and TGF-β3 in vulvar skin tissue and consequently reduce the recurrence rate of LSC.
研究领域:
皮肤病学
·
治疗超声
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ONCOLOGY
·
2022
·Vol. 60
·期 5
·1-14
·
IF 5.884
Hang Sun,Youjie Li,Xiao Wang,Xue Zhou,Simin Rong,Dongmin Liang,Guangbin Sun,Huizhen Cao,Hongfang Sun,Ranran Wang,Yunfei Yan,Shuyang Xie,Yunxiao Sun
Chronic myeloid leukemia (CML) is a hematological disease, and imatinib (IM) resistance represents a major problem for its clinical treatment. In the present study, the role of tribbles pseudokinase 2 (TRIB2) in IM resistance of CML and the possible mechanism were investigated. It was found that TRIB2 was highly expressed in IM‑resistant patients with CML through the Oncomine database and this conclusion was confirmed using reverse transcription‑quantitative PCR and western blot experiments. Knockdown of TRIB2 was found to increase the drug sensitivity of KG cells to IM using Cell‑Counting Kit‑8 (CCK‑8) assays, and the low‑expression TRIB2 mice were further found to be more sensitive to the IM and have a higher survival rate in leukemia model mice. Moreover, using western blot and luciferase experiments, it was found that TRIB2 could regulate c‑Fos through the ERK signaling pathway, and c‑Fos suppressed the transcriptional activity and the expression of miR‑33a‑5p. Further investigation identified that the binding site for c‑Fos to function on miR‑33a‑5p was the ‑958‑965 region. Finally, CCK‑8 assays and western blot experiments demonstrated that miR‑33a‑5p could inhibit the proliferation of KG cells and reduce IM resistance by suppressing the expression of HMGA2. In conclusion, it was demonstrated that TRIB2 regulates miR‑33a‑5p to reverse IM resistance in CML, which may help identify novel targets and therapeutic strategies for the clinical treatment of IM resistance.
研究领域:
肿瘤学
·
血液学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2024
·
IF 6.1
Wenxuan Liu,Runlin Gui,Yang Li,Man Li,Zhen Lei,Yanyan Jin,Yi Yu,Yujia Li,Lu Qian,Yuyan Xiong
Insulin resistance (IR) is a central pathophysiological process underlying numerous chronic metabolic disorders, including type 2 diabetes and obesity. Lycii Cortex, a widely used traditional Chinese herb, has demonstrated potential benefits in preventing and managing diabetes and IR. Whereas, the specific bioactive compounds responsible for these protective effects and their underlying mechanisms of action remain elusive. This study aimed to identify the bioactive components within Lycii Cortex that contribute to its anti-diabetic effects and to elucidate the molecular mechanisms underlying its beneficial actions on insulin resistance. Network pharmacology and molecular docking analyses were employed to identify the potential active compounds in Lycii Cortex and their corresponding target proteins. An in vitro model of IR was established using palmitic acid (PA)-treated HepG2 cells. Cell viability was assessed using the CCK-8 assay, while glucose uptake was evaluated by 2-NBDG staining and extracellular glucose measurement. To validate the in vitro findings, an in vivo model of obesity-induced IR was established using high-fat diet (HFD)-fed mice. The network pharmacology analysis preliminarily identified 13 candidate chemicals and 10 hub LyC and IR-related genes (LIRRGs). Molecular docking analysis demonstrates that Linarin as the potential active component exhibits the greatest potential to target c-FOS for preventing obesity-induced IR. Enrichment analysis suggested that Linarin-targeted pathways are correlated with inflammation. In vitro experimental validation demonstrated that Linarin was capable of protecting against PA-induced IR in HepG2 cells evidenced by improving glucose uptake ability and reducing extracellular glucose content. Additionally, we found that Linarin ablated PA-induced increase in the expression of c-FOS and inflammatory cytokines. Furthermore, in PA-treated cells, silencing c-FOS markedly improved glucose consumption, and reduced inflammation and Arginase 2 (ARG2) expression. Similarly, as exposure to PA, silencing ARG2 also ameliorated glucose uptake and inflammation, while not affecting c-FOS expression. In vivo experiments further showed that Linarin administration remarkably improved glucose tolerance and insulin sensitivity, and reduced the fat mass and body weight in HFD-induced obese mice. In this study, Linarin has been identified as the bioactive compound of Lycii Cortex to ameliorate obesity-related IR and inflammation through the c-FOS/ARG2 signaling cascade. These findings underscore the therapeutic potential of Linarin and provide valuable insights into developing novel intervention strategies for type 2 diabetes therapy.
研究领域:
药理学
·
分子生物学
·
内分泌学
·
代谢性疾病
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Lipids in Health and Disease
·
2026
·Vol. 25
·期 1
·116
·
IF 6.9
Wang Binqi,Zhang Ruikai,Wu Mengting,Cai Tiantian,Gao Chan,Wang Luping,Jin Taian,Xu Zhiyong,Jin Juan,He Qiang
Background Germacrone, a major bioactive component of Curcuma zedoaria , exhibits promising anticancer activity across various preclinical models. However, its molecular mechanisms in renal cell carcinoma (RCC), particularly regarding metabolic regulation, remain largely unexplored. This study aimed to investigate the therapeutic potential and underlying mechanisms of germacrone in RCC, specifically focusing on lipid metabolic reprogramming. Methods This study integrated network pharmacology and RNA sequencing transcriptomics to identify potential molecular targets of germacrone in 786-O and Caki-1 cells. In vivo antitumor efficacy was evaluated using the subcutaneous xenograft tumor model in BALB/c nude mice. In vitro, cell proliferation, apoptosis, migration, and cell cycle distribution were assessed using CCK-8, flow cytometry, transwell, and colony formation assays. To elucidate the underlying mechanism, de novo fatty acid synthesis was examined by quantifying intracellular triglyceride (TG) and total cholesterol (TC) levels. Interactions between germacrone and the c-Fos/SREBP1 signaling axis were analyzed using Western blot analysis, cellular thermal shift assays (CETSA), and molecular docking. Functional validation was performed using c-Fos overexpression plasmids to assess the extent to which germacrone’s effects were reversible. Results Germacrone significantly inhibited RCC growth in vivo, as evidenced by reduced tumor volume and weight, without detectable systemic toxicity. In vitro, germacrone suppressed proliferation, migration, and invasion in 786-O and Caki-1 cells, while promoting apoptosis and cell cycle arrest. Transcriptomic and molecular analyses indicated that germacrone targets the c-Fos transcription factor, leading to the downregulation of the SREBP1 signaling pathway and key lipogenic genes ( FASN and ACC1 ). This regulation resulted in a marked reduction in intracellular fatty acid and cholesterol biosynthesis. Notably, c-Fos overexpression significantly reversed the germacrone-induced suppression of lipid metabolism and cell viability, confirming that germacrone functions primarily by modulating the c-Fos/SREBP1 axis. Conclusion Germacrone serves as a novel modulator of the c-Fos/SREBP1 pathway, effectively inhibiting the growth of renal cancer by disrupting c-Fos-mediated lipid metabolism. These findings identify c-Fos as a potential therapeutic target and highlight germacrone as a promising candidate for RCC treatment strategies targeting metabolic reprogramming.
✓ 已验证
DOI
高影响因子
Cell Death & Disease
·
2026
·
IF 12.2
Ao Liyan,Chen Zhiqiang,Zhang Jingliang,Wang Qi,Luo Jin,Li Zhuoran,Jiao Qilong,Ning Bobin,Peng Shiyuan,Hu Wenhao,Jia Yuqi,Ci Weimin,Wang Baojun,Dong Zhouhuan,Zhang Xu,Niu Shaoxi
Prostate cancer is a highly heterogeneous malignancy, with distinct subtypes displaying unique molecular and metabolic profiles. This study identifies a compensatory shift in α-ketoglutarate (α-KG) metabolism in prostate cancer, where the tumor relies on IDH1 to incorporate citrate into the TCA cycle. IDH1 inhibition, leads to lower α-KG levels. Since α-KG is required for HIF-1α hydroxylation, IDH1 inhibition stabilizes HIF-1α, which subsequently upregulates c-Fos. C-Fos enhances GLUD1 transcription, promoting the conversion of glutamate to α-KG as a compensatory mechanism. Additionally, c-Fos upregulates downstream effectors, including FOXC1 and SOX2, driving neuroendocrine differentiation in prostate cancer. Targeting α-KG-metabolizing enzymes, such as IDH1 or GLUD1, presents promising therapeutic strategies for prostate cancer subtypes by inhibiting tumor proliferation and inducing oxidative stress, thus sensitizing tumors to ferroptosis. Overall, these findings uncover a metabolic adaptation in response to IDH1 inhibition and highlight the pivotal role of c-Fos in mediating this compensatory pathway, offering new insights into potential metabolic targets for prostate cancer treatment and ferroptosis-based therapies.
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
·
2012
·
IF 2.532
Haichen Niu,Yingwei Zheng,Tanzeel Huma,Joshua D. Rizak,Ling Li,Guimei Wang,He Ren,Liqi Xu,Jianzhen Yang,Yuanye Ma,Hao Lei
Previous studies have shown that olfactory impairment by disrupting the olfactory epithelium prior to morphine administration attenuated the development addiction-related behaviors . However, it is unclear whether olfactory impairment will affect the expression of already established addiction-related behaviors. To address this issue, mice were conditioned with morphine to induce behavioral sensitization and condition placed preference (CPP). After an abstinence period, the animals were subjected to either an intranasal ZnSO 4 effusion (ZnE) or sham treatment with saline. Behavioral sensitization and CPP reinstatement were evaluated 24 h later, as well as the expression of c-Fos protein, a marker of activated neural sites, in brain regions of interest. It was found that ZnE treatment attenuated morphine-induced behavioral sensitization and reinstatement of CPP. Compared to the saline-treated ones, the ZnE-treated animals showed reduced c-Fos expression in the nucleus accumbens (NAc) associated with behavioral sensitization, and in the NAc, cingulate cortex , dentate gyrus , amygdala , lateral hypothalamus and ventral tegmental area associated with CPP reinstatement. Together, these results demonstrated that acute olfactory impairment could attenuate already established addiction-related behaviors and expression of c-Fos in drug addiction related brain regions, perhaps by affecting the coordination between reward and motivational systems in the brain.
研究领域:
神经科学
·
药理学
✓ 已验证
DOI
高影响因子
Cell Reports
·
2026
·Vol. 45
·期 3
·
IF 7.7
Chao Li,Han Zhao,Jingjing Wang,Chenfei Liu,Shiqing He,Jingchao Zhou,Liangyu Li,Yiyao Liu,Qingping Wang,Xiaojing Shen,Junjie Wu,Guangquan Chen,Yu Wang,Liang Yang,Bin Du
Tumor-resident microbiota are identified as a critical modulator in the carcinogenesis and progression of cervical malignancies. However, the mechanisms linking these microbiota to cervical cancer remain poorly understood. In this study, we find that patients with cervical cancer exhibit increased microbiota diversity, characterized by eight distinct bacterial species that distinguish them from control subjects. Intratumoral or intravenous administration of an isolated strain, Gordonia polyisoprenivorans GP-2, derived from tumor-resident microbiota, significantly promotes the growth and metastasis of cervical cancer in mice. Further investigation reveals that GP-2 metabolizes host-derived choline to produce the bacterial metabolite lysophosphatidylcholine (lysoPC). We propose and validate the biosynthetic pathway for lysoPC in strain GP-2 and demonstrate that lysoPC activates the classical tumorigenic genes c-Jun / c-Fos using cervical tumor organoids derived from patients. These findings elucidate the mechanisms underlying microbiota-host crosstalk in cervical cancer and highlight a potential therapeutic target for intervening in tumor-resident bacteria.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2020
·
IF 3.37
Zuotian Wu,Gaohua Wang,Huiling Wang,Ling Xiao,Yanyan Wei,Can Yang
Background Recent studies indicate that antidepressants treatment restores neuronal plasticity. In contrast, some researchers claim that serotonergic antidepressants, including fluoxetine (FLU), may exacerbate neuronal plasticity, which is contradictory and rarely studied. Since almost those studies exposed cells with drugs for 1–2 days as treatment models of antidepressants, it is possible that FLU exposure for longer periods would have opposite effects on neuronal plasticity. Results In the present study, we examined the effects of FLU exposure (up to 3 days) on the neuronal plasticity in differentiated PC12 cells. The cell viability shown a slight decrease at day 2 (93.5 ± 3.5 %), followed by a highly significant decrease at day 3(71.4 ± 4.4 %). As previously reported, neuronal plasticity was significantly upregulated by FLU exposure at day 1. However, the neurite length, activity-regulated cytoskeleton-associated protein (Arc) and c-Fos mRNA were inhibited with FLU exposure at day 3. Similarly, the expression of tubulin, which play important roles in the neuronal plasticity, was the same result. Furthermore, we found α-tubulin interacted with collapsing response mediator protein 2(CRMP2), which is related to neuronal plasticity, and the regulation of CRMP2 activity influenced the neurite length, Arc, c-Fos and tubulin expression. Conclusions The results demonstrated that neuronal plasticity was increased by FLU exposure at day 1, but exposure with FLU for more than 2 days had opposite effect on it. The reduction in neuronal plasticity with FLU exposure for more than 2 days might be involved in some aspects of the therapeutic effect of antidepressant on depression.
研究领域:
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Xin-Yao Li,Bang-Yin Tan,Yue Zhang,Yan-Lin Lv,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Stemona sessilifolia (Miq.) Miq. has been employed in traditional medicine for its potential renal benefits, including anti-edema, diuretic, and anti-jaundice properties. However, the renoprotective effects related to these traditional uses remain to be fully elucidated. Aim of the study : To investigate the therapeutic efficacy of S . sessilifolia against hyperuricemic nephropathy and elucidate its underlying signaling pathway. Materials and methods A hyperuricemic nephropathy mouse model, induced by potassium oxonate and hypoxanthine, was employed to evaluate the renal protection of the extract of S. sessilifolia through biochemical tests and histopathological observation. Transcriptomic analysis was applied to explore potential signaling pathways. Subsequently, bioassay-guided isolation was conducted during phytochemical investigation. Uric acid-induced HK-2 cells were then employed to validate the renal cytoprotective effects of the isolated compounds. Results Treatment with S. sessilifolia extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels by 65.15%, 47.95%, and 49.1%, respectively. Additionally, it decreased urinary protein excretion, and ameliorated renal injury and fibrosis in mice. The protective effects might be exerted by inhibiting the c-Myc/c-Fos/MAPK signaling pathway to maintain the homeostasis of renal tissue. Moreover, the bioactive compound stemoninine protected HK-2 cells against uric acid-induced oxidative stress, inflammatory response, proliferation, migration, and apoptosis. Conclusion The S. sessilifolia extract and its major bioactive compound, stemoninine, protected against hyperuricemic nephropathy by suppressing the c-Myc/c-Fos/MAPK signaling pathway.
研究领域:
民族药理学
·
肾病学
·
植物化学
·
分子生物学
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2025
·
IF 2
Xiao Li,Hui Yang,Ming Qian,Hang Liu,Shuang Zuo,Jin-Chun Liu,Wei-Hong Ge,Lin Zhou
Vincristine (VCR) is a commonly used clinical anti-cancer drug, but it can also induce neurotoxicity and cause vincristine-induced neuropathic pain (VINP). The metabotropic glutamate receptor 5 (mGluR5) within spinal dorsal horn neurons regulates the transmission of pain mediated by glutamate. In this study, we investigated for the first time the role of mGluR5 in the transmission of noxious information in VINP. Expression of mGluR5 protein was significantly increased in the spinal cord from days 6 to 14 after VCR injection. Immunofluorescence double staining showed that mGluR5 colocalized with the neuron-specific marker NeuN. The intrathecal administration of MPEP (a specific antagonist of mGluR5) or DHPG (an agonist of mGluR5) influenced the pain threshold and mGluR5 protein expression in VINP mice. The expression of c-Fos protein was also affected by MPEP. Furthermore, simulated blockade of intracellular mGluR5 site by intrathecal injection of small interfering RNA (siRNA) of the excitatory amino acid transporter 3 (EAAT3) reduced mechanical allodynia and thermal hyperalgesia and suppressed the expression of mGluR5 and c-Fos proteins. The results collectively indicate that mGluR5 site in spinal dorsal horn neurons may be involved in the regulation of intracellular nociceptive signal transmission in VINP, and the expression of c-Fos largely depends on the intracellular mGluR5.
研究领域:
神经科学
·
药理学
·
疼痛研究
✓ 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）