Biomolecules and Biomedicine
·
2025
·
IF 2.2
Tao Qin,Chenxia Rao,Yunsen Deng
Necrotizing enterocolitis (NEC) is a severe, often life-threatening gastrointestinal disease in neonates, predominantly affecting preterm infants, and is frequently complicated by intestinal stenosis—a condition whose nonspecific clinical manifestations make early diagnosis and timely intervention particularly challenging. We aimed to investigate the clinical characteristics of NEC intestinal stenosis and its correlation with the histone demethylase Jumonji domain-containing protein 3 (JMJD3). A total of 310 children with NEC treated between February 2021 and June 2024 were retrospectively enrolled, categorizing them into an NEC group (n=265) and a post-NEC intestinal stenosis group (n=45). General data and laboratory indicators were collected, and analyses were performed to identify factors influencing the development of post-NEC intestinal stenosis. Spearman correlation analysis was utilized to assess relationships between JMJD3 and clinical parameters. Results indicated that the post-NEC intestinal stenosis group exhibited significantly lower platelet counts (PLT) and elevated levels of serum C-reactive protein (CRP), procalcitonin (PCT), and JMJD3 in intestinal tissues (p<0.05). JMJD3 was significantly associated with the development of post-NEC intestinal stenosis (p<0.001), presenting a 3.114-fold increased risk. Furthermore, JMJD3 levels were negatively correlated with PLT levels and positively correlated with CRP and PCT levels (p<0.001). Receiver operating characteristic curve analysis demonstrated that the combination of CRP, PCT, and JMJD3 provided the highest predictive efficiency, with an area under the curve of 0.918, sensitivity of 86.67%, specificity of 86.42%, and a Youden index of 0.731 (p<0.05), all surpassing the performance of individual markers. In conclusion, levels of CRP, PCT, and JMJD3 were significantly elevated in NEC children with intestinal stenosis. Their combined assessment presents a highly effective approach for the early diagnosis of post-NEC intestinal stenosis.
研究领域:
儿科学
·
胃肠病学
·
分子生物学
·
免疫学
·
新生儿学
✓ 已验证
DOI
PubMed
高影响因子
eLife
·
2024
·
IF 6.4
Zeina Salloum,Kristin Dauner,Yun-feng Li,Neha Verma,David Valdivieso-González,Víctor Almendro-Vedia,John D Zhang,Kiran Nakka,Mei Xi Chen,Jeffrey McDonald,Chase D Corley,Alexander Sorisky,Bao-Liang Song,Iván López-Montero,Jie Luo,Jeffrey F Dilworth,Xiaohui Zha
Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the adenosine triphosphate (ATP) synthase in the inner mitochondrial membrane and changes the proton gradient in the mitochondria. This activates nuclear factor kappa-B (NF-κB) and Jmjd3 expression, which removes the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus lipopolysaccharide (M1), macrophages, either treated with statins in vitro or isolated from statin-fed mice, express lower levels proinflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL-4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
表观遗传学
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DOI
PubMed
高影响因子
ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 6
·1-11
·
IF 2.3
Zhuang Cuicui,Zhang Ruoqing,Bai Jiangang,Zhang Xinying,Zhao Jinhui
Escherichia coli ( E. coli ) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli -induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 μmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 μmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1β and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 μmol/L lycopene significantly increased E. coli -induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli -treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli -caused bovine mastitis, providing the new angle of the prevention and management of mastitis.
研究领域:
免疫学
·
微生物学
·
药理学
·
细胞生物学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2023
·
IF 3.2
Ruijun Qin,Ping Wang,Lingzhi Li
Chronic obstructive pulmonary disease (COPD), a heterogeneity of chronic respiratory disease pattern, presents considerable prevalence and mortality. We aimed to explore the role and mechanisms of Jumonji domain-containing protein-3 (JMJD3) in COPD. The viability and JMJD3 expression in human bronchial epithelial cell line BEAS-2B were respectively assayed by CCK-8 assay and Western blot following stepwise exposure to increasing concentrations of cigarette smoke extract (CSE). After JMJD3 was silenced and acyl-CoA synthetase long-chain family member 4 (ACSL4) was overexpressed in CSE-treated BEAS-2B cells, cell viability, cytotoxicity, oxidative stress and total iron level were estimated using kits. ELISA estimated inflammatory levels. DCFH-DA probe and BODIPY 581/591 C11 probe were exposed to assess ROS production and lipid peroxidation. Western blot tested the expressions of ferroptosis-associated proteins. Besides, H3K27me3 and ACSL4 expressions were tested by Western blot and immunofluorescence staining. In CSE-induced BEAS-2B cells, JMJD3 expression was increased and deletion of JMJD3 improved cell viability, reduced LDH release, mitigated inflammation, oxidative stress and inhibited ferroptosis. Moreover, JMJD3 interference raised H3K27me3 expression whereas lessened ACSL4 expression in CSE-treated BEAS-2B cells. CSE exposure reduced the abundance of ACSL4 in H3K27me3 antibody. Further ACSL4 elevation reversed the impacts of JMJD3 silencing on the damage of CSE-induced BEAS-2B cells. Collectively, JMJD3 depletion might suppress ferroptosis mediated by ACSL4 to alleviate CSE-triggered inflammation and oxidative stress in BEAS-2B cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 35
·13142-13152
·
IF 7.367
Jingxin Mo,Li Wang,Xiaojia Huang,Bing Lu,Changye Zou,Lili Wei,Junjun Chu,Paul K. Eggers,Shen Chen,Colin L. Raston,Jun Wu,Lee Yong Lim,Wei Zhao
Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics have show no significant developments over the last three decades, highlighting the fact that current therapeutic strategies require substantial improvements. In this study, we designed a novel folic acid-PEG-conjugated p-phosphonated calix[4]arene nanoparticle (Fp-PCN) for the simultaneous delivery of paclitaxel (PAC) and carboplatin (CAR) at an optimal ratio (5 : 1, mol : mol) to utilize their potential synergistic effect against OC cells. The Fp-PCNs loaded with PAC and CAR (Fp-PCNPAC+CAR) resulted in a remarkable efficacy in the suppression of OC, both in vitro and in vivo. Compared to free drugs, Fp-PCNPAC+CAR showed stronger apoptosis induction as well as invasion and self-renewal capacity suppression in SKOV-3 cells. The molecular mechanism to address the synergism is that Fp-PCNPAC+CAR downregulated JMJD3 expression to modulate the H3K27me3 epigenetic mark of the promoters of HER2 and MYCN. Furthermore, the expressions of JMJD3 and HER2 were significantly associated with poor outcomes for ovarian patients. Our study demonstrates that co-delivery of PAC and CAR can be achieved with the Fp-PCNs, and reveals a previously unrecognized and unexpected role of the JMJD3-HER2 signaling axis in PAC and CAR treatment of OC.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR THERAPY
·
2024
·
IF 12.1
Xiaoyuan Huang,Yanhua Lan,Jiahui Shen,Xiaomin Zhao,Yanyan Zhou,Wenzhi Wu,Jiajie Mao,Yuzhu Wu,Zhijian Xie,Zhuo Chen
Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.
研究领域:
免疫学
·
细胞生物学
·
代谢研究
·
骨骼研究
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Yang Bing,Liu Wenxu,Li Meiying,Mo Jingxin
Despite intensive research, ovarian cancer has the highest mortality rates among gynecological malignancies, partly because of its rapid acquisition of chemoresistance to platinum therapy. Hence, strategies are needed to effectively treat carboplatin-resistant ovarian cancer. In this study, we designed and prepared hyaluronic acid-decorated metal-organic frameworks for the targeted delivery of GSK-J1, a JMJD3 demethylase inhibitor (HA@MOF@GSK-J1) for the synergistic treatment of carboplatin-resistant ovarian cancer. HA@MOF@GSK-J1 showed outstanding effectiveness in the inhibition of ovarian cancer in vitro. Furthermore, HA@MOF@GSK-J1 demonstrated higher induction of apoptosis, reduced cell motility, and diminished cell spheroids by attenuating HER2 activity through the effectual activation of H3K27 methylation in its promoter area. Finally, our in vivo results confirmed that HA@MOF@GSK-J1 had better treatment efficacy for carboplatin-resistant ovarian tumor xenografts. Our results highlight the potential of HA@MOF@GSK-J1 as an effective strategy to improve the treatment of carboplatin-resistant ovarian cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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