Frontiers in Physiology
·
2019
·
IF 3.201
Shentu Xuping,Wang Xiaolong,Xiao Yin,Yu Xiaoping
Yeast-like symbiotes (YLS), harbored in the abdomen fat-body cells of the rice brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae), are vital to the growth and reproduction of their host. It is feasible to manipulate BPH infestation on rice by inhibiting YLS using fungicide. In this study, the fungicide propiconazole was injected into the hemolymph of BPH thorax via microinjection to investigate its effect on YLS, especially the dominant species, Hypomyces chrysospermus, and their host BPH. Propiconazole markedly reduced the total number of YLS and H. chrysospermus in BPH hemolymph and fat body, thereby leading to an obvious higher mortality and lower fecundity of BPH than the negative control (PBS, phosphate buffer solution). After microinjecting propiconazole, the survival rate of BPH nymphs at the 5th instar was significantly lower than that obtained after PBS treatment. Eight days after propiconazole microinjection, the BPH survival rate dropped to 40%, only half of BPH survival rate treated with PBS microinjection. For female adults (1-day-old), there were significant differences in the survival rates between BPHs treated with propiconazole and those treated with PBS at days 5–8. The fecundity of BPH decreased significantly by microinjecting propiconazole and averaged only 229 eggs per female, which was 20% less than that of the negative control. Furthermore, we reared BPH on the susceptible variety TN1 sprayed with propiconazole to prove the feasibility manipulating field occurrence of BPH by inhibiting YLS using fungicides. The number of YLS and H. chrysospermus in BPH obviously declined. Subsequently, the survival rate and fecundity of BPH significantly decreased after feeding on rice treated with propiconazole. Meanwhile, the propiconazole residue was detected in the hemolymph and gut of BPH by HPLC analysis within 1 day of feeding. Inhibiting YLS using fungicides was a novel and effective way to control BPH infestation.
研究领域:
昆虫学
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植物保护
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微生物学
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PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Tingting Yang,Jiayu Yuan,Yuting Peng,Jiale Pang,Zhen Qiu,Shangxiu Chen,Yuhan Huang,Zhenzhou Jiang,Yilin Fan,Junjie Liu,Tao Wang,Xueyan Zhou,Sitong Qian,Jinfang Song,Yi Xu,Qian Lu,Xiaoxing Yin
The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated DHT had a significant positive relationship with the clinical characteristics of BPH patients. Activation of AMPK by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated YAP1-TEAD4 heterodimers. Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
研究领域:
泌尿学
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内分泌学
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药理学
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细胞生物学
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2015
·Vol. 22
·期 21
·16914-16926
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IF 2.828
Wang Sheng,Bai Naling,Wang Bing,Feng Zhuo,Hutchins William C.,Yang Ching-Hong,Zhao Yuhua
Commonly used flame retardants, such as polybrominated diphenyl ethers, are extremely persistent in the environment, causing serious environmental risks. Certain strains of bacteria are able to degrade several low brominated congeners of PBDEs aerobically. However, the aerobic degradation pathway is not yet well understood, particularly at the genetic level. In this study, we isolated Cupriavidus sp. WS from the environment that could degrade diphenyl ether (DE), 4-bromodiphenyl ether, and 4,4′-bromodiphenyl ether. DE was completely degraded in 6 days without any detectable end-product. Using transposon mutagenesis, several DE degradation-deficient mutants were obtained. Knocking out bphA1 , bphA2 , and bphA3 eliminated the ability of the Cupriavidus sp. WS bacterium to degrade DE, indicating that the bph genes play a crucial role in DE degradation by this strain. The specific roles of bphA , bphB , and bphC were identified by systematically expressing these genes in Escherichia coli . The dihydrodiol product of BphA was dehydrogenated into 2,3-dihydroxydiphenyl ether by BphB. 2,3-Dihydroxydiphenyl ether was then decomposed into phenol and 2-pyrone-6-carboxylic acid by BphC. Thus, BphA, BphB, and BphC act sequentially in the aerobic degradation of DE, 4-bromodiphenyl ether, and 4,4′-dibromodiphenyl ether by the Cupriavidus sp. WS bacterium.
研究领域:
环境微生物学
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分子生物学
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污染治理
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PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Xiao Qing,Liu Qi-Meng,Jiang Ru-Chao,Chen Kai-Feng,Zhu Xiang,Ma Lei,Li Wei-Xi,He Fei,Huang Jun-Jun
Previous studies have indicated that α1D/1A antagonist naftopidil (NAF) suppresses prostate growth by decreasing cell proliferation without affecting apoptosis and prostate volume in benign prostatic hyperplasia (BPH). A NAF-derived α1D/1A antagonist 1- benzyl-N-(3-(4-(2-methoxyphenyl) piperazine-1-yl) propyl)-1H-indole-2- carboxamide (HJZ-12) has been reported from our laboratory, which exhibits high subtype-selectivity to both α1D- and α1A- AR (47.9- and 19.1- fold, respectively) with respect to a1B-AR in vitro. However, no further study was conducted. In the present study, a pharmacological evaluation of HJZ-12 in BPH was performed on an estrogen/androgen-induced rat BPH model and human BPH-1 cell line. In vivo, HJZ-12 exhibited better performance than NAF in preventing the progression of rat prostatic hyperplasia by not only decreasing prostate weight and proliferation (similar to NAF) but also, shrinking prostate volume and inducing prostate apoptosis (different from NAF). In vitro, HJZ-12 exhibited significant cell viability inhibition and apoptotic induction in BPH-1 cell line, without presenting cell anti-proliferation properties. Intriguingly, the role of HJZ-12 on cell viability and apoptosis was an α1-independent action. Furthermore, RNA-Seq analysis was applied to screen out six anti-apoptotic genes (Bcl-3, B-lymphoma Mo-MLV insertion region 1 [Bmi-1], ITGA2, FGFR3, RRS1, and SGK1). Amongst them, Bmi-1 was involved in the apoptotic induction of HJZ-12 in BPH-1. Overall, HJZ-12 played a remarkable role in preventing the progression of prostatic hyperplasia through α1-independent apoptotic induction, indicating that it will be a multi-target effective candidate for BPH treatment.
研究领域:
药理学
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泌尿学
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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
ASIAN JOURNAL OF ANDROLOGY
·
2025
·
IF 2.7
Zheng Cheng-Hao,Wang Wen-Hao,Ji Shi-Yu,Jing Yi-Feng,Han Bang-Min,Xia Shu-Jie,Wang Xing-Jie
Postoperative wound repair after transurethral resection of the prostate (TURP) in benign prostatic hyperplasia (BPH) patients is crucial for reducing complications and promoting recovery. Androgens, particularly dihydrotestosterone (DHT), influence prostatic development and wound healing, with type II 5α-reductase (5αR2) playing a key role in DHT synthesis. In this study, the effects of type II 5α-reductase inhibitors (5-ARIs) on postoperative healing, inflammation control, and fibrosis reduction were evaluated. A double-blinded randomized clinical trial was performed to assess 87 BPH patients treated with type II 5-ARIs (n = 47) or placebo (n = 42) over six months. The type II 5-ARIs group presented a 55.0% lower complication rate (P = 0.002), with reduced hematuria (0 vs 7.1%, P = 0.046) and catheter reintroduction (0 vs 9.5%, P = 0.025). An animal study using 12 beagles was performed, and molecular markers were analyzed via single-cell RNA sequencing, enzyme-linked immunosorbent assay (ELISA), and histology. 5αR2 inhibition accelerated urothelial regeneration, decreased inflammation, and reduced myofibroblast activation by 42.0% while increasing the expression of the urothelial marker uroplakin 3A (UPK3A) by 67.0%. Organoid experiments confirmed increased urothelial differentiation and reduced glandular epithelial expansion with type II 5-ARI treatment. These findings suggest that 5αR2 inhibition promotes TURP postoperative recovery in BPH patients by reducing inflammation, inhibiting fibrosis, and promoting wound repair. These findings support the use of type II 5-ARIs as potential adjuvant therapies for optimizing BPH patient postoperative outcomes.
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高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Xiangpeng Kong,Haiqin Ren,Ke Pei,Yajun Yao,Zhigang Liang,Yunfeng Xue,Shuang Liang,Tongtong Li,Jing Zhang,Yuxia Guo,Miaorong Pei,Huifeng Li
Benign prostatic hyperplasia (BPH) is a common disease affecting male urinary system function and quality of life, with its incidence increasing due to population ageing and unhealthy lifestyles. Modern medicine mainly adopts symptomatic treatments such as 5-alpha reductase inhibitors and alpha1 adrenergic receptor blockers. However, due to the complex pathogenesis of BPH, these drugs can only partially alleviate symptoms and have shortcomings such as high treatment costs and significant side effects. BPH is similar to the descriptions of “Jīng Lóng” and “Lóng Bì” in traditional Chinese medicine (TCM), and its onset is closely related to liver and kidney dysfunction. Kidney insufficiency and blood stasis are common clinical syndromes of BPH. Compared with modern medicine, treatment based on syndrome differentiation of TCM can achieve good results in treating this subtype of BPH. Therefore, guided by the holistic view of TCM, adopting a holistic and systematic research approach to explore therapeutic targets and potential therapeutic components for BPH with a specific syndrome can provide new ideas for the clinical treatment of BPH. This study integrated clinical metabolomics and network pharmacology to identify therapeutic targets for kidney insufficiency and blood stasis-type BPH. Serum analysis of BPH patients and healthy controls for testosterone, estradiol, SRD5α2, NF-κB p65, and TGF-β levels, alongside metabolomics and network pharmacology, revealed hormonal imbalance, increased inflammatory/fibrotic markers, and 58 differential metabolites in BPH. Pathway enrichment analysis identified 6 key metabolic pathways, while network pharmacology constructed four compound-reaction-enzyme-gene networks and pinpointed 178 potential targets, including 23 core targets. Reverse screening against the Yaozh Database-Natural Product AI Engine Platform matched 11 druggable targets with 49 interacting components, and target-component fitting analysis confirmed the reliability of 8 core targets. This combined approach validated the findings of hormonal imbalance and significant metabolic pathway changes and provided valuable insights for BPH treatment and drug development.
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高影响因子
ENVIRONMENTAL RESEARCH
·
2022
·
IF 8.431
Qihua Lin,Xinru Zhou,Shusheng Zhang,Junliang Gao,Mengqi Xie,Linqin Tao,Faqian Sun,Chaofeng Shen,Muhammad Zaffar Hashmi,Xiaomei Su
Most functional microorganisms cannot be cultivated due to entering a viable but non-culturable (VBNC) state, which limits the characterization and application of polychlorinated biphenyl (PCB)-degrading strains. Resuscitating VBNC bacteria could provide huge candidates for obtaining high-efficient PCB degraders. However, limited studies have focused on the ability of resuscitated strains for PCBs degradation. In the present study, whole-genome analysis of a resuscitated strain SPC0, and its performances in degradation of three prevalent PCB congeners (PCBs 18, 52 and 77) were investigated. The results indicate that the strain SPC0 belonged to the genus Streptococcus , possessed the degradation potential for aromatic xenobiotics . The SPC0 could effectively degrade PCBs 18 and 52, but exhibited lower degradation efficiency of PCB 77. Degradation of PCBs 18 and 52 could be fitted well by zero-order model, whereas the fittest model for PCB 77 degradation was pseudo second-order kinetics. The bph genes expression, chloride ions release and degradation metabolites identification, suggest that SPC0 possessed the capability of oxidative dehalogenation and mineralization of PCBs. Interestingly, SPC0 can degrade PCBs via the bph -encoded biphenyl pathway, and further mineralize metabolite dichlorobenzoate via protocatechuate pathway. This study is the first to show that a strain belonging to genus Streptococcus possessed PCB-degrading capability, which uncovered the powerful potential of resuscitated strains for bioremediation of PCB-contaminated sites.
研究领域:
环境微生物学
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生物修复
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基因组学
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生物降解
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2024
·
IF 6.8
Yunfu Shen,You Yang,Zi Wang,Wanjun Lin,Na Feng,Meina Shi,Jiachen Liu,Wenzhe Ma
Background and Purpose Triple-negative breast cancer (TNBC) has a poor prognosis due to limited therapeutic options. Recent studies have shown that TNBC is highly dependent on mitochondrial oxidative phosphorylation. The aim of this study was to investigate the potential of coptisine, a novel compound that inhibits the complex I of the mitochondrial electron transport chain (ETC), as a treatment for TNBC. Experimental Approach In this study, mitochondrial metabolism in TNBC was analysed by bioinformatics. In vitro and in vivo experiments (in mice) were conducted to evaluate the potential of coptisine as an ETC complex I-targeting therapeutic agent and to investigate the molecular mechanisms underlying coptisine-induced mitochondrial dysfunction. The therapeutic effect of coptisine was assessed in TNBC cells and xenograft mouse model. Key Results We demonstrated that mitochondrial ETC I was responsible for this metabolic vulnerability in TNBC. Furthermore, a naturally occurring compound, coptisine, exhibited specific inhibitory activity against this complex I. Treatment with coptisine significantly inhibited mitochondrial functions, reprogrammed cellular metabolism, induced apoptosis and ultimately inhibited the proliferation of TNBC cells. Additionally, coptisine administration induced prominent growth inhibition that was dependent on the presence of a functional complex I in xenograft mouse models. Conclusion and Implications Altogether, these findings suggest the promising potential of coptisine as a potent ETC complex I inhibitor to target the metabolic vulnerability of TNBC. Graphical
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Yun Zhao,Guobin Zheng,Shu Yang,Shangjing Liu,Yifan Wu,Yaodong Miao,Zhen Liang,Yunqing Hua,Jing Zhang,Jia Shi,Dan Li,Yanfei Cheng,Yunsha Zhang,Yuanli Chen,Guanwei Fan,Chuanrui Ma
Background and purpose Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS ( Panax notoginseng saponins ), containing the main active ingredients of Panax notoginseng , exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). Experimental approach The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE −/− mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2 −/− macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2 −/− mice treated with high-fat diet (HFD) and AAV-PCSK9. Key results PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. Conclusion and implications PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS. Graphical
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Huilin Liu,Chao Huang,Zhenni Liu,Yuhan Li,Yanan Zhu,Min Gao,Jing Chen,Hui Zhang,Zhengtao Xiao,Wei Zhao
Background and Purpose Cardiac glycosides (CGs), traditionally prescribed for heart failure and arrhythmias, show anticancer potential. However, their mechanisms for preferential inhibition of tumour tissue and constituent malignant cells are not fully elucidated. This study aims to elucidate the therapeutic benefits of CGs in targeting specific tumours and dissect their multi-targeting mechanisms that confer their cytotoxicity against malignant cells. Experimental Approach We designed an integrated workflow to identify therapeutic CGs with high toxicity to certain cancers, investigating their multi-target effects, assessing their toxicity to malignant cells and analysing the prognostic relevance of CGs' target genes. The computational findings were confirmed through gene knockdown, cell viability assays, reactive oxygen species (ROS) measurements and so forth. Key Results CGs modulate multiple genes crucial for ion homeostasis, oxidative stress and apoptosis, with a particularly strong inhibitory effects on uveal melanoma (UVM). Notably, digitoxin suppresses UVM cell proliferation and induces ROS levels by simultaneously targeting STAT3 and KLF5. Single-cell transcriptomic analysis revealed that malignant cells are likely more vulnerable to CGs due to their higher expression of CG target genes compared with surrounding cells in the UVM microenvironment. Conclusions and Implications Given UVM's limited options, our study highlights the potential of digitoxin as a promising novel therapeutic agent for this aggressive and rare ocular cancer. Our comprehensive approach is effective in identifying the potent, cancer-specific therapeutic agents from herbal plants.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
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2024
·
IF 6.8
Chang Di,Tong Wu,Kai Gao,Na Li,Huifang Song,Lili Wang,Haojie Sun,Jingyun Yi,Xinran Zhang,Jiexin Chen,Mala Shah,Yuwu Jiang,Zhuo Huang
Background and Purpose KCNT1 encodes a sodium-activated potassium channel (Slack channel), and its mutation can cause several forms of epilepsy. Traditional antiepileptic medications have limited efficacy in treating patients with KCNT1 mutations. Here, we describe one heterozygous KCNT1 mutation, M267T, in a patient with EIMFS. The pathological channel properties of this mutation and its effect on neuronal excitability were investigated. Additionally, this study aimed to develop a medication for effective prevention of KCNT1 mutation-induced seizures. Experimental Approach Wild-type or mutant KCNT1 plasmids were expressed heterologously in Xenopus laevis oocytes, and channel property assessment and drug screening were performed based on two-electrode voltage-clamp recordings. The single-channel properties were investigated using the excised inside-out patches from HEK293T cells. Through in utero electroporation, WT and M267T Slack channels were expressed in the hippocampal CA1 pyramidal neurons in male mice, followed by the examination of the electrical properties using the whole-cell current-clamp technique. The kainic acid-induced epilepsy model in male mice was used to evalute the antiseizure effects of carvedilol. Key Results The KCNT1 M267T mutation enhanced Slack channel function by increasing single-channel open probability. Through screening 16 FDA-approved ion channel blockers, we found that carvedilol effectively reversed the mutation-induced gain-of-function channel properties. Notably, the KCNT1 M267T mutation in the mouse hippocampal CA1 pyramidal neurons affected afterhyperpolarization properties and induced neuronal hyperexcitability, which was inhibited by carvedilol. Additionally, carvedilol exhibited antiseizure effects in the kainic acid-induced epilepsy model. Conclusion and Implication Our findings suggest carvedilol as a new potential candidate for treatment of epilepsies. Graphical
研究领域:
神经科学
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药理学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2024
·
IF 6.8
Siyue Chen,Yuming Liu,Yutian Zhang,Xu Guo,Tinghui Bai,Kai He,Yanfang Zhu,Yi Lei,Mei Du,Xiaohong Wang,Qiang Liu,Hua Yan
Background and Purpose Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Experimental Approach Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1 -knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. Key Results BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. Conclusion and Implications BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis. Graphical
研究领域:
眼科学
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免疫学
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药理学
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分子生物学
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PubMed
高影响因子
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