WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
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2013
·Vol. 30
·期 4
·1251-1260
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IF 1.262
Zhou Gang,Shi Qing-shan,Ouyang You-sheng,Chen Yi-ben
Isothiazolones are used as preservatives in various modern industrial products. Although microorganisms that exhibit resistance towards these biocides have been identified, the underlying resistance mechanisms are still unclear. Therefore, we investigated the resistance properties of the following Burkholderia cepacia strains to Kathon (a representative of isothiazolones): a wild-type (WT) strain; a laboratory resistance strain (BC-IR) induced from WT; and an isolated strain (BC-327) screened from industrial contamination samples. The bacterial cell structure was disrupted by 50 μg ml −1 Kathon treatment. BC-IR and BC-327 did not display resistance in the presence of 1 ml L −1 Tween 80, 1 ml L −1 Triton X-100, 0.1 % sodium dodecyl sulfate or 1 mmol L −1 EDTA-2Na. Additionally, BC-IR and BC-327 exhibited lower relative conductivity from 10 to 180 min. The types as well as the levels of outer-membrane proteins (OMPs) were altered among WT, BC-IR and BC-327. Finally, the two Kathon-resistance strains BC-IR and BC-327 presented higher resistance capacity to H 2 O 2 . We measured the levels of peroxide-sensor genes and observed that the transcriptional activator oxyR , superoxide dismutase sod1 , sod2 , catalase cat1 and cat3 were all up-regulated under oxidative conditions for all strains. Taken together, OMPs and peroxide-sensor genes in B. cepacia contributed to isothiazolone resistance; However, the laboratory strain BC-IR exhibited a different resistance mechanism and properties compared to the isolated strain BC-327.
研究领域:
微生物学
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分子生物学
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工业生物技术
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PubMed
高影响因子
PHYTOMEDICINE
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2025
·
IF 8.3
Mengxin Li,Jun Wang,Zihan Xu,Yue Lin,Jingquan Dong
Background Obstructive sleep apnea syndrome (OSAS), a chronic disorder affecting approximately 10% of adults worldwide with heightened prevalence in males and obese populations, induces irreversible neurocognitive impairment. Atraric Acid (AA), a natural depside compound derived from lichens, exhibits dual functional properties through its molecular groups capable of free radical scavenging and metal chelation. However, its therapeutic potential in OSAS-related pathologies remains unexplored. Objective This study aims to investigate the neuroprotective effects and molecular mechanisms of AA against CIH-induced neuronal damage. Methods CIH mouse models and hypoxic injury models in HT22 neurons were established. AA was administered to mice at doses of 5, 10, and 20 mg/kg (selected based on literature references and preliminary experiments), and to cells at an optimal concentration of 20 μM (determined by CCK-8 assays). Therapeutic efficacy was evaluated through behavioral tests including the Morris Water Maze, Elevated Plus Maze, and Open Field Test. Neuroprotective effects were assessed via histopathological examination (e.g., neuronal survival in hippocampal CA3 and DG sub-regions) and detection of oxidative stress/ferroptosis markers (e.g., MDA levels, GPX4 expression, and related biomarkers). Transcriptomic sequencing and molecular docking analyses were employed to investigate differentially expressed genes, pathway enrichment, and underlying mechanisms. Results In vivo and in vitro experiments demonstrated that AA significantly alleviated neuronal damage in CIH mice and enhanced HT22 cell viability. AA down-regulated oxidative stress- and ferroptosis-related gene expression. Transcriptomic sequencing identified AMPK signaling as a key target. Combined AMPK inhibitor (Compound C) and nuclear-cytoplasmic fractionation experiments confirmed that AA synergistically regulates dual antioxidant pathways (Nrf2/HO-1 and FoxO3a/SOD2) via AMPK activation. Conclusion AA mitigates CIH-induced neurocognitive impairment by AMPK-dependent activation of the Nrf2/HO-1 and FoxO3a/SOD2 axes, establishing a dual antioxidant-ferroptosis defense barrier. This study is the first to systematically elucidate AA's molecular mechanisms using transcriptomics data integrated with computational simulations, providing novel therapeutic targets and a translational paradigm for developing natural compound-based therapies for OSAS.
研究领域:
神经生物学
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睡眠医学
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分子药理学
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氧化应激
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信号转导
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转化医学
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天然产物药理学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
·
IF 3.322
Ting Zhou,Bao Yang
Prenylated resveratrols are drug candidates presented in many natural sources. They possess multiple pharmacological activities. Due to the limited abundance in nature and disadvantage of chemical synthesis, it is required to produce prenylated resveratrols by biological strategy. In this work, a prenyltransferase iacE from Pestalotiopsis fici was prepared by heterologous overexpression. It could catalyze 2- C -prenylation of resveratrol efficiently. Dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP) could serve as prenyl donor. Glu97, Thr114 and Tyr413 were proved to be important residues in the active site by site-directed mutagenesis. The product was purified and identified to be 2- C -prenyl resveratrol by NMR . 2- C -prenyl resveratrol exerted neuroprotective activity through inhibiting ROS overproduction and improving the activities of antioxidant enzymes in HT22 cell. The genes involved in antioxidant defense were regulated, including upregulated CAT , SOD2 , NFE2L2 , GPx4 , and downregulated PTGS2 and ACSL4 . These results supplied a novel technique for prenylated resveratrols production.
研究领域:
生物技术
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药理学
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神经科学
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PubMed
高影响因子
TISSUE & CELL
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2025
·
IF 2.5
Yujie Ma,Runqiang Liu,Juan Zhan,Yihan Lai,Sicheng Li,Wei Wang,Yisen Shao,Lin Jiang
The incidence of tongue squamous cell carcinoma (TSCC) has been increasing annually. Type 2 diabetes mellitus (T2DM) is one of the risk factors for TSCC, with hyperglycemia being a hallmark of T2DM that promotes the development of oral cancer and results in poorer prognoses for TSCC patients who also have T2DM. Oleic acid (OA), a component of Brucea javanica oil emulsion, exhibits both anti-cancer and anti-diabetic properties. However, the precise regulatory mechanisms of OA on tongue squamous cell carcinoma (TSCC) under high glucose conditions have yet to be fully elucidated. Our findings demonstrated that high glucose significantly enhanced the migratory, invasive, and proliferative capabilities of TSCC cells. Notably, OA treatment effectively reversed these high glucose-induced enhancements in TSCC cellular activities. Furthermore, our research revealed that OA exerted its anti-tumor effects by stabilizing its binding with S100A9, which modulated the glycolytic pathway. Ultimately, we confirmed that the anti-tumor mechanism of OA in TSCC patients with T2DM was associated with the inactivation of the S100A9-HK2/PKM2-SOD2 pathway. In summary, OA inhibited the proliferation, migration, and invasion of TSCC cells under high glucose conditions through the regulation of the S100A9-HK2/PKM2-SOD2 pathway.
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高影响因子
JOURNAL OF PINEAL RESEARCH
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2023
·
IF 10.3
Chao Gu,Quan Zhou,Xiayu Hu,Xiaoyang Ge,Mingzhuang Hou,Wenhao Wang,Hao Liu,Qin Shi,Yong Xu,Xuesong Zhu,Huilin Yang,Xi Chen,Tao Liu,Fan He
Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 μM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2 , underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.
研究领域:
药理学
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干细胞生物学
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骨再生
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组织工程
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骨质疏松
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PubMed
高影响因子
Advanced Science
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2024
·
IF 14.3
Xia Zhang,Lijia Liang,Fengxian Wang,Pedro A. Jose,Ken Chen,Chunyu Zeng
Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.
研究领域:
纳米技术
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药学
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肾脏生理学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
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2024
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IF 3.4
Jiawen Chen,Xiaozhi Xu,Yuru Shao,Xiaohong Bian,Ruiyan Li,Yubin Zhang,Yibei Xiao,Meiling Lu,Qizhou jiang,Yuan Zeng,Fangrong Yan,Junmei Ye,Zhe Li
Doxorubicin (DOX), a widely used chemotherapy agent in cancer treatment, encounters limitations in clinical efficacy due to associated cardiotoxicity. This study aims to explore the role of AKT serine/threonine kinase 2 (AKT2) in mitigating DOX-induced oxidative stress within the heart through both intracellular and extracellular signaling pathways. Utilizing AKT2 knockout (KO) and NRF2 KO murine models, alongside neonatal rat cardiomyocytes (NRCMs), we systematically investigate the impact of AKT2 deficiency on DOX-induced cardiac injury. Our findings reveal that DOX administration induces significant oxidative stress, a primary contributor to cardiac injury. Importantly, Akt2 deficiency exhibits a protective effect by alleviating DOX-induced oxidative stress. Mechanistically, Akt2 deficiency facilitates nuclear translocation of NRF2, thereby suppressing intracellular oxidative stress by promoting the expression of antioxidant genes. Furthermore, We also observed that AKT2 inhibition facilitates superoxide dismutase 2 (SOD2) expression both inside macrophages and SOD2 secretion to the extracellular matrix, which is involved in lowering oxidative stress in cardiomyocytes upon DOX stimulation. The present study underscores the important role of AKT2 in mitigating DOX-induced oxidative stress through both intracellular and extracellular signaling pathways. Additionally, our findings propose promising therapeutic strategies for addressing DOX-induced cardiomyopathy in clinic.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2019
·Vol. 29
·期 36
·1904056
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IF 15.621
Jing Zhu,Chengchao Chu,Dongsheng Li,Xin Pang,Huili Zheng,Junqing Wang,Yesi Shi,Yang Zhang,Yi Cheng,En Ren,Jingliang Cheng,Xiaoyuan Chen,Gang Liu
To address the urgent need for effective sonodynamic therapy (SDT), a facile and efficient strategy is developed for fabricating a new class of sonotheranostics. Herein, a Fe(III)-porphyrin nano-sonosensitizer is prepared by a one-step coordination synthesis, and then anchored with Bis(DPA-Zn)-RGD and manganese superoxide dismutase (SOD2) siRNA. Benefiting from the delicate interactions of the Fe(III)-coordinated nanoformulations, a highly potent sono/gene combinational therapy guided by fluorescence/magnetic resonance imaging is achieved. Importantly, this sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer-targeted delivery capability and enhanced reactive oxygen species production via triple-regulated approaches, including down-regulation of SOD2, depletion of glutathione, and generation of Fenton reaction. This work opens up new perspectives for developing versatile sonotheranostics to overcome the clinical challenges of SDT.
研究领域:
纳米技术
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癌症研究
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诊疗学
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生物医学工程
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分子生物学
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高影响因子
Food & Function
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2021
·Vol. 12
·期 10
·4582-4590
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IF 5.396
Xue-Yan Dai,Yi Zhao,Jing Ge,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.
研究领域:
毒理学
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药理学
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分子生物学
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免疫学
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PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
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2019
·
IF 3.082
Zhengqi Liu,Lingyi Dong,Kaiying Jia,Hui Zhan,Zhihong Zhang,Nagendra P. Shah,Xueying Tao,Hua Wei
ABSTRACT Exopolysaccharide (EPS) of Lactobacillus plantarum WLPL04 and its sulfated EPS were systematically investigated for their antioxidant activities and effects on protecting the oxidative damage of Caco-2 cells from H 2 O 2 . Exopolysaccharide was successfully sulfonated from purified EPS as confirmed by Fourier-transform infrared spectroscopy, and the degree of sulfonation was 0.30. Both EPS and sulfated EPS showed antioxidant activities in vitro determined by 1,1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl radical scavenging tests, and those activities of sulfated EPS were significantly enhanced at 1,000 μg/mL. Cell viabilities of Caco-2 in the range of 1 to 100 μg/mL of EPS and sulfated EPS showed no significant difference. In H 2 O 2 -damaged Caco-2 cells models, EPS and sulfated EPS significantly inhibited the enhancement of reactive oxygen species and malondialdehyde levels, and sulfated EPS enhanced the effects by 40.86% and 61.11% when compared with the purified EPS at the same concentration of 100 μg/mL, respectively. For the activities of antioxidant-related enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and expression of genes ( SOD2 , GPX2 , MT1M ) on Caco-2 cells, strong protection abilities against the oxidative stress were displayed from both EPS and sulfated EPS, and sulfated EPS exhibited significant enhancement as compared with either EPS or control groups. In summary, sulfonation is an effective strategy for improving the antioxidant activities of EPS from L. plantarum WLPL04 in vitro and on Caco-2 cells.
研究领域:
微生物学
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生物化学
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细胞生物学
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药学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
·
IF 6.9
Lei Wang,Yufeng Tao,Xuesong Wang,Yuhan Gan,Yuting Zeng,Shasha Li,Qing Zhu
Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.
研究领域:
药理学
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医学
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生物化学
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分子生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng
Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.
研究领域:
药理学
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民族药理学
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分子生物学
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细胞生物学
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毒理学
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高影响因子
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