INTERNATIONAL JOURNAL OF HYPERTHERMIA
·
2024
·
IF 3
Yijin Fan,Xi Wang,Yao Liu,Huajun Tang,Chengzhi Li
Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL).Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment.Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05).Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
研究领域:
肿瘤学
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妇科
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医学影像学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
XiaoMing Zhou,ChenXi Zhang,Wen Shen,RuiFei Zhuang,ShenLin Liu,JinDi Liu
Background Curzerene, a bioactive compound from Curcuma zedoaria, exhibits anticancer effects, but its role in gastric precancerous lesions remains poorly understood. This study investigates the potential of Curzerene in inhibiting gastric precancerous lesions progression by regulating the long non-coding RNA (LncRNA) AFAP1-AS1 and the Hippo/YAP signaling pathway. Methods In vitro, a gastric precancerous cell model (MC cells) was established by treating GES-1 cells with MNNG. The effects of Curzerene on cell proliferation, migration, and EMT were assessed using CCK-8, scratch assays, RT-PCR, and Western blot. In vivo, a gastric precancerous mouse model was induced by MNU, and the therapeutic effects of Curzerene (14 mg/kg and 28 mg/kg) were evaluated through histological and molecular analysis. Results Curzerene treatment significantly inhibited MC cell proliferation, migration, and EMT, downregulating LncRNA AFAP1-AS1 and YAP while upregulating E-cadherin and downregulating N-cadherin. In vivo, Curzerene alleviated gastric mucosal damage, reduced cancer markers (P53 and CD133), and improved histopathology. Transcriptomic analysis identified the Hippo/YAP pathway as a key mediator of Curzerene’s effects. YAP activation reversed Curzerene’s inhibitory effects on EMT, confirming the involvement of this pathway. Conclusion Curzerene effectively inhibits gastric precancerous lesion progression by targeting the YAP signaling and the following LncRNA AFAP1-AS1 to suppress EMT. These findings suggest Curzerene’s novel potential as a promising therapeutic agent for early intervention and prevention of gastric cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-13
·
IF 6.1
Li Jing,Wang Xiaochen,Bai Jie,Wei Huangzhao,Wang Wenbo,Wang Shuai
Background Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. Methods The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Results NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. Conclusions SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.
研究领域:
医学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2023
·
IF 4.1
Qichang Liu,Mei Zuo,Yi Song,Shuzhong He,Jian Huang,Yang Chen
BACKGROUND Phytopathogens cause various diseases by parasitizing crops, reducing crop yield and resulting in substantial economic losses in agricultural production. A novel type isolated from the perennial herbaceous Peganum harmala L. seeds, β -carboline alkaloids pegaharine A ( PA ), has become a hot topic in developing plant-originated green pesticides owing to their significant physiological activities. RESULTS A scalable bioinspired total synthesis of PA is accomplished in the present work. The systematical biological assay study showed that PA exhibited moderate inhibitory activity against nine tested plant pathogenic fungi and showed significant inhibitory activity in vitro against the three tested plant pathogenic bacteria. Most noteworthy is the inhibitory rates of PA on Xanthomonas oryzae pv. oryzae ( Xoo ), X. oryzae pv. oryzicola ( Xoc ) and X. axonopodis pv. citri ( Xac ) of 93.6%, 92.1% and 86.1%, respectively, which are better than the control drug, bismerthiazol (63.4%, 61.2% and 53.7% at 100 μg mL −1 concentration). Furthermore, the EC 50 value of PA against Xoo , Xoc and Xac was 52.2, 60.0 and 65.1 μg mL −1 , respectively, superior to 72.9, 64.2 and 70.1 μg mL −1 of the control drug. Moreover, the anti- Xoo mechanistic studies revealed that PA exerted its antibacterial effects by increasing the permeability of the bacterial membrane, reducing the extracellular polysaccharide content and inducing morphological changes in bacterial cells. CONCLUSION A novel β -carboline alkaloid, PA , was prepared by biomimetic total synthesis. Its significant antibacterial activity was closely related to the permeation of bacterial cell membranes, which was confirmed by anti- Xoo mechanistic studies. More importantly, the structure could be regarded as a model for developing novel bactericides. © 2023 Society of Chemical Industry.
研究领域:
植物化学
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植物病理学
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有机合成
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微生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2025
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IF 3.2
Daxian Li,Yan Wu,Lirong Chang,Yizhi Song,Xiaoqiang Du,Fenqin Xue,Yang Liu,Jie Wu,Tianlong Wang
Introduction: As a taxane-based cytostatic agent, paclitaxel holds a broad spectrum of life-saving properties. However, its use is frequently limited by painful neuropathy in the extremities, which severely hinders the ultimate prognosis of cancer survivors. While bee venom therapy has shown promise in alleviating chemotherapy-induced neuropathic pain, the analgesic potential of its primary bioactive components, such as melittin and phospholipase A2 (bvPLA2), remains uncharacterized. This study investigated the ameliorative effects of melittin against paclitaxel-induced peripheral neuropathy in rats through integrated behavioral, in vivo electrophysiological, and neuropharmacological approaches.Methods: Paclitaxel was administered intraperitoneally (i.p.) at a total dose of 8 mg/kg. Cold and mechanical allodynia and hyperalgesia were quantified using the acetone drop and von Frey filament tests. To compare the therapeutic properties of bee venom ingredients, either melittin (0.5 mg/kg) or bvPLA2 (0.12 mg/kg) was administered subcutaneously at ST36 (Zusanli acupoint). In vivo extracellular recordings of wide dynamic range (WDR) neurons were performed in the spinal dorsal horn. Noradrenaline depletion was induced by the i.p. treatment with N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg), and serotonin depletion was conducted by the i.p. administration of para-chlorophenylalanine (PCPA, 450 mg/kg).Results: ST36 treatment with melittin, but not bvPLA2, markedly impeded mechanical and cold hypersensitivity. Electrophysiological analysis revealed that paclitaxel induced spontaneous and stimulus-evoked hyperexcitation of spinal WDR neurons. Melittin selectively suppressed evoked neuronal activities (i.e., acute responses and after-discharges) without modulating the spontaneous firing of WDR neurons. Neuropharmacological investigation demonstrated that the effects of melittin were fully reversed by noradrenaline depletion, whereas serotonin depletion had no effect.Discussion: Our findings establish that melittin treatment at ST36 could ease paclitaxel-induced neuropathic pain by partially attenuating the hyperexcitable state of spinal WDR neurons. Furthermore, these ameliorative actions were mediated by the specific recruitment of the endogenous noradrenergic system. This study provides novel evidence supporting melittin as a targeted symptomatic agent for paclitaxel-induced peripheral neuropathy, which would advance the development of promising analgesic strategies in oncological care.
研究领域:
药理学
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神经科学
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肿瘤学
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生物医学
✓ 已验证
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 11
·e70667
·
IF 4.2
Tao Zhang,Qianhan Yang,Jun Chen,Jiyu Jiang,Jingnan Han,Yun Zhou
Diabetic retinopathy (DR), the leading cause of adult blindness, has its risk increased by excessive endoplasmic reticulum stress (ERS). Nuclear receptor subfamily 2 group f member 2 (NR2F2) is an orphan nuclear receptor with essential roles in angiogenesis. However, its roles in DR remain unknown. Notably, NR2F2 protein expression was upregulated in streptozotocin-induced diabetic mice retina and the retinal endothelial cells characterized by endothelial marker CD31. Retinal NR2F2 expression was knocked down in diabetic mice using adeno-associated virus serotype 2. NR2F2 knockdown increased retinal thickness, decreased acellular capillary formation and FITC-labeled dextran leakage, and increased tight junction (TJ) protein ZO-1 expression in vivo. Additionally, NR2F2 knockdown inhibited reactive oxygen species generation and the ERS marker CHOP expression in vivo. In high glucose (HG)-induced human retinal microvascular endothelial cell (HRMEC) monolayers, NR2F2 knockdown inhibited FITC-dextran flux, increased transendothelial electrical resistance, reduced VEGFA secretion and restored expression and continuous distribution of TJ proteins. NR2F2 knockdown also reduced ERS markers expression and inhibited ERS-related signaling pathways in vitro. mRNA-seq analysis in NR2F2-knockdown HRMECs exposed to HG showed that NR2F2 inhibition upregulated CYB5R2 mRNA level. NR2F2 was bound directly to the CYB5R2 promoter for transcriptional repression in HRMECs. CYB5R2 overexpression inhibited ERS-related protein expressions and barrier dysfunction in HRMEC monolayers, and CYB5R2 knockdown reversed the endothelial protective effect of NR2F2 inhibition. In conclusion, NR2F2 knockdown attenuates vascular dysfunction by alleviating ERS in retinal microvascular endothelial cells and alleviates disease progression in DR mice. This may be achieved by reducing CYB5R2 transcriptional repression. Graphical Nuclear receptor subfamily 2 group f member 2 (NR2F2) knockdown increased the NADH-Cytochrome b5 reductase 2 (CYB5R2) expression in human retinal microvascular endothelial cells by reducing CYB5R2 transcriptional repression. The upregulation of CYB5R2 attenuated vascular dysfunction by inhibiting endoplasmic reticulum stress (ER Stress)-related pathways including PERK, IRE1, and ATF6 pathways in retinal microvascular endothelial cells, thereby inhibiting disease progression in diabetic retinopathy mice.
研究领域:
医学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-26
·
IF 3.9
Xiao Tian Hao,Zhu Bao Ting
Formic acid, a toxic one-carbon metabolite formed from methanol and formaldehyde in the body, can cause neuronal dysfunctions. It was recently hypothesized that metabolic formation of toxic one-carbon metabolites (particularly formic acid) under hyperglycemic conditions may contribute to the pathogenesis of diabetic complications in humans. The present study aims to investigate the mechanism of formic acid-induced neurotoxicity using immortalized HT22 mouse hippocampal neurons as an in-vitro model. We found that treatment of cells with sodium formate (SF, a salt form of formic acid) causes a concentration-dependent loss of cell viability (based on MTT assay), whereas the cell number is reduced to a lesser degree when SF is present at lower concentrations. In addition, SF at the lower concentrations decreases cell proliferation by suppressing DNA synthesis, but at higher concentrations, SF induces cell death through apoptosis. SF can preferentially cause accumulation of mitochondrial ROS, disruption of mitochondrial structure, and suppression of mitochondrial functions (including ATP production). SF-induced mitochondrial ROS accumulation subsequently leads to the depletion of cellular glutathione, along with the buildup of cellular ROS and lipid-ROS. These changes jointly lead to increased permeability of both cytoplasmic and mitochondrial membranes, and ultimately the induction of apoptotic cell death. Analysis of the cellular transcriptomics revealed that the expression of genes for the relevant enzymes and proteins involved in mitochondrial function, energy metabolism and other cellular processes is altered in SF-treated cells. These findings highlight mitochondria as a crucial target in mediating SF-induced cytotoxicity, and also shed mechanistic lights on how formic acid accumulation may contribute to the pathogenesis of diabetic neuropathy and other diabetic complications.
研究领域:
神经科学
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糖尿病研究
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毒理学
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细胞生物学
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线粒体生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Jiahua Li,Yafeng Hao,Huizhuo Pan,Yingying Zhang,Guohui Cheng,Baona Liu,Jin Chang,Hanjie Wang
Vascular endothelial growth factor (VEGF) is the key regulator in neovascular lesions. The anti-VEGF injection is a major way to relieve retinal neovascularization and treat these diseases. However, current anti-VEGF therapeutics show significant drawbacks. The reason is the inability to effectively control its therapeutic effect. Therefore, how to controllably inhibit the VEGF target is a key point for preventing angiogenesis. Here, a CRISPR-dCas9 optogenetic nanosystem was designed for the precise regulation of pathologic neovascularization. This system is composed of a light-controlled regulatory component and transcription inhibition component. They work together to controllably and effectively inhibit the target gene’s VEGF. The opto-CRISPR nanosystem achieved precise regulation according to individual differences, whereby the expression and interaction of gene was activated by light. The following representative model laser-induced choroid neovascularization and oxygen-induced retinopathy were taken as examples to verify the effect of this nanosystem. The results showed that the opto-CRISPR nanosystem was more efficacious in the light control group (NV area effectively reduced by 41.54%) than in the dark control group without light treatment. This strategy for the CRISPR-optogenetic gene nanosystem led to the development of approaches for treating severe eye diseases. Besides, any target gene of interest can be designed by merely replacing the guide RNA sequences in this system, which provided a method for light-controlled gene transcriptional repression.
研究领域:
分子生物学
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光遗传学
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纳米技术
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眼科学
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基因治疗
✓ 已验证
产品关联
DOI
PubMed
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·
IF 1.6
Jianghong Wang,Xiaoyuan Wang,Yanru Song,Zilin Huang,Han Wu,Liang Chang,Bingjie Huo,Guanwei Fan
Background: The Precancerous Lesion of Gastric Cancer (PLGC) is an early stage in the development of gastric cancer. The clinical application of HPXLD has been found to be effective in treating PLGC, but the mechanism of how HPXLD acts on PLGC is still unclear. Objective: The objectives of this study were to reveal the molecular mechanism of how HPXLD can be used to treat PLGC and investigate this mechanism through bioinformatics and experimental validation. Methods: PLGC-associated target genes were identified through bioinformatics analysis. A rat model of PLGC was induced using N-methyl-N'-nitro-N-nitrosoquanidine (MNNG) in combination with ranitidine, hot saline, ethanol, and intermittent fasting, with interventions by HPXLD. The pathological alterations in gastric mucosa were assessed through Hematoxylin-eosin staining (HE). Immunohistochemistry (IHC) and Western blot analyses were employed to evaluate the changes in expression levels of inflammation-related proteins. Results: After conducting bioinformatics analysis, it was found that there were 23 HPXLDPLGC crossover genes, which were significantly enriched in the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. The results of HE showed that HPXLD was effective in improving gastric mucosal histopathological changes. Additionally, the IHC results demonstrated that HPXLD was able to downregulate the expression of IL-6, COX-2, MCP- 1, and MMP-9. Furthermore, Western blot analysis revealed that HPXLD was able to downregulate the expressions of IL-6, IL-17RA, ACT1, NF-κB, and TNF-α. Conclusion: HPXLD has been shown to improve PLGC by reducing the expression of inflammation- related proteins. This suggests that HPXLD may potentially be a treatment option for PLGC.
研究领域:
肿瘤学
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中医药学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yu Wang,Haojie Yu,Li Wang,Lei Zhang,Jian Yang,Chenguang Ouyang,Jian Hu,Jingyi Feng,Zheng Deng,Chang Chen
Efficient glycemic control serves as the cornerstone of diabetes and its complication treatments, necessitating additional symptomatic medications or nutritional supplements tailored to various complications. However, different diseases and medications require specific treatment regimens and drug delivery methods. For instance, conventional subcutaneous insulin injections suffer from uncontrollable release rates and onset times. This study has developed a segmented microneedle array that integrates two controlled-release mechanisms within a single array. Different drugs are loaded into distinct regions, allowing for modular and simultaneous timed-release therapies. The posterior segment of the microneedle tip releases insulin via a glucose-sensitive mechanism, enabling real-time intelligent glycemic regulation and effective glycemic control for up to 43.7 h, which is nearly 8 times longer than subcutaneous injections. The anterior segment releases vitamin B9 via a sustained-release mechanism, which has potential preventive and reparative effects on diabetic neuropathy, providing a gentler and more sustained nutrient supply. The regionalized design of the microneedles significantly enhances drug delivery efficiency and the intelligent customization of drug release, especially in managing diabetic neuropathy.
研究领域:
生物医学工程
·
药剂学
·
糖尿病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2023
·
IF 3
Yike Wu,Mingyu Hao,Weifeng Li,Yun Xu,Dewen Yan,Yong Xu,Wenlan Liu
Given the increasing morbidity of diabetes mellitus type 2 (T2DM) with peripheral neuropathy (PN), efficient screening for T2DM-PN is of great significance. Altered N-glycosylation is closely associated with T2DM progression, whereas its association with T2DM-PN remains uncharacterized. In this study, N-glycomic profiling was performed to identify the N-glycan features between T2DM patients with (n = 39, T2DM-PN) and without PN (n = 36, T2DM-C). Another independent set of T2DM patients (n = 29 for both T2DM-C and T2DM-PN) were utilized to validate these N-glycomic features. There were 10 N-glycans varied significantly between T2DM-C and T2DM-PN ( p < 0.05 and 0.7 < AUC < 0.9), of which T2DM-PN was associated with increased oligomannose and core-fucosylation of sialylated glycans, and decreased bisected mono-sialylated glycan. Notably, these results were validated by an independent set of T2DM-C and T2DM-PN. This is the first profiling for N-glycan features in T2DM-PN patients, which reliably differentiates them from T2DM controls, thus providing a prospective profile of glyco-biomarkers for the screening and diagnosis of T2DM-PN.
研究领域:
医学
·
分子生物学
·
代谢组学
·
糖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Molecular Pharmacology
·
2024
·Vol. 17
·期 1
·e18761429267000
·
IF 2.4
Fengyan Tang,Bo Zhao,Li Zhang,Faisal Raza,Hajra Zafar,Shao Zhong,Lin Li,Wenhua Zhu,Lingna Fang,Bing Lu,Liwen Shen,Ping Guo,Nengxing Yu,Quanmin Li
Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated. Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques. Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert anti-oxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin. Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.
研究领域:
药理学
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内分泌学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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