Journal of Essential Oil Bearing Plants
·
2022
·
IF 1.971
Chunlian Li,Xiaobin Lin,Qiuyang Cai,Weicheng Zhang,Xianyi Wu,Zekai Tan,Lewen Yao,Shiyuan Huang,Yanghe Yuan,Lanyue Zhang
The perennial herb Alpinia oxyphylla Miq. (Zingiberaceae) is an important traditional medicinal plant in China. The present study evaluated the chemical composition of A. oxyphylla essential oil (AOEO) using GC-MS. The AOEO contained 55 compounds, including nootkatone (20.12%), valencene (12.26%), and ethyl-p-methoxycinnamate (5.00%). Previous studies have shown that AOEO possesses significant antioxidant and antibacterial activities. However, the anti-inflammatory effect of AOEO on tissue plasminogen activator (TPA)-induced ear edema is yet to be reported. In this study, TPA-induced ear edema was used to investigate the anti-inflammatory activity of AOEO. Hematoxylin and eosin staining of mouse tissue sections indicated that AOEO reduced the degree of edema, and immunohistochemistry experiments revealed that AOEO inhibited the expression of tumor necrosis factors, such as cyclooxygenase 2 (COX-2), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB). A. oxyphylla is a commonly used traditional Chinese medicine with good biological activity. Analysis of the species potential geographical distribution and diversity indicated that the species can be rationally protected and exploited. Based on the chemical composition and biological activity of AOEO, further research and development should effectively promote the development of medicine, food, and cosmetics industries. The potential distribution of A. oxyphylla under current climatic conditions was predicted using DIVA-GIS and geographic information from herbarium specimens and other documents. The species predicted distribution spanned more than 12 provinces in China and was the most extensive in Hainan. Under current climatic conditions, A. oxyphylla is suitable for growing and expanding its population in the warm, humid regions of southern China.
研究领域:
植物学
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药理学
·
生物化学
✓ 已验证
DOI
高影响因子
RESPIRATORY RESEARCH
·
2025
·
IF 5
De-zhi Sun,Xi-ru Yang,Cong-shu Huang,Zhi-jie Bai,Pan Shen,Zhe-xin Ni,Chao-ji Huang-fu,Yang-yi Hu,Ning-ning Wang,Xiang-lin Tang,Yong-fang Li,Yue Gao,Wei Zhou
Background High altitude pulmonary edema (HAPE) poses a significant medical challenge to individuals ascending rapidly to high altitudes. Hypoxia-induced cellular morphological changes in the alveolar-capillary barrier such as mitochondrial structural alterations and cytoskeletal reorganization, play a crucial role in the pathogenesis of HAPE. These morphological changes are critical in understanding the cellular response to hypoxia and represent potential therapeutic targets. However, there is still a lack of effective and valid drug discovery strategies for anti-HAPE treatments based on these cellular morphological features. This study aims to develop a pipeline that focuses on morphological alterations in Cell Painting images to identify potential therapeutic agents for HAPE interventions. Methods We generated over 100,000 full-field Cell Painting images of human alveolar adenocarcinoma basal epithelial cells (A549s) and human pulmonary microvascular endothelial cells (HPMECs) under different hypoxic conditions (1%~5% of oxygen content). These images were then submitted to our newly developed segmentation network (SegNet), which exhibited superior performance than traditional methods, to proceed to subcellular structure detection and segmentation. Subsequently, we created a hypoxia scoring network (HypoNet) using over 200,000 images of subcellular structures from A549s and HPMECs, demonstrating outstanding capacity in identifying cellular hypoxia status. Results We proposed a deep neural network-based drug screening pipeline (CPHNet), which facilitated the identification of two promising natural products, ferulic acid (FA) and resveratrol (RES). Both compounds demonstrated satisfactory anti-HAPE effects in a 3D-alveolus chip model (ex vivo) and a mouse model (in vivo). Conclusion This work provides a brand-new and effective pipeline for screening anti-HAPE agents by integrating artificial intelligence (AI) tools and Cell Painting, offering a novel perspective for AI-driven phenotypic drug discovery. Supplementary Information The online version contains supplementary material available at 10.1186/s12931-025-03173-1.
研究领域:
医学
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生物信息学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Forensic Science Medicine and Pathology
·
2015
·Vol. 11
·期 4
·570-576
·
IF 1.983
Zhang Lin,Ma Jinghong,Li Shangxun,Xue Rui,Jin Ming,Zhou Yiwu
Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 µg/ml in heart blood, 39 µg/ml in femoral vein blood, 141 µg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.
研究领域:
法医学
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毒理学
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临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 3.8
Ya Xu,Huiyang Li,Nan Sun,Bingmei Yao,Wenjin Dai,Jian Wang,Sujia Si,Shuo Liu,Liqun Jiang
Background High Altitude Pulmonary Edema (HAPE) seriously threatens the health of people at high altitudes. There are drug treatments for HAPE, and dry powder formulations (DPFs) represent a rapid and accessible delivery vehicle for these drugs. However, there are presently no reports on the inhalability of DPFs in low-pressure environments. Given the reduced atmospheric pressure typical at high altitudes, conventional DPFs might not be suitable for inhalation. Therefore, it is necessary to elucidate the deposition behaviors of dry powder in the respiratory tract at low pressure, as well as to improve their pulmonary deposition efficiency via adjustments to their formulation and design. Methods The effect of air pressure, inspiratory velocity, and particle properties (such as size, density, and aerodynamic diameter) on pulmonary deposition of DPFs was calculated by a computational fluid dynamics (CFD)-coupled discrete phase model. DPFs of various aerodynamic diameters were prepared by spray drying, and the inhalability of these DPFs in a low-pressure environment was evaluated in mice. Finally, a mouse model of HAPE was established, and the treatment of HAPE by nifedipine-loaded DPFs with small aerodynamic diameter was validated. Results CFD results showed that low pressure decreased the deposition of DPFs in the lungs. At 0.5 standard atmosphere, DPFs with aerodynamic diameter of ∼2.0 μm could not enter the lower respiratory tract; however, a decrease in the physical diameter, density, and, consequently, the aerodynamic diameter of the DPFs was able to enhance pulmonary deposition of these powders. To validate the CFD results, three kinds of dry powder with aerodynamic diameters of 0.66, 0.98, and 2.00 μm were prepared by spray drying. Powders with smaller aerodynamic diameter could be inhaled into the lungs of mice more effectively, and, consequently could ameliorate the progression of HAPE more effectively than conventional powders. These results were consistent with the CFD results. Conclusions Low atmospheric pressure can prevent the pulmonary deposition of DPFs at high altitudes. Compared with conventional DPFs, powders with smaller aerodynamic diameter can be effectively inhaled at these pressures and thus might be more suitable for the treatment the HAPE.
研究领域:
药剂学
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呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxics
·
2022
·Vol. 10
·期 6
·299
·
IF 4.472
Guoqiang Fan,Tianzhu Shen,Kun Jia,Xiaoping Xiao,Zhanfeng Wu,Fanghua Gong,Huiqiang Lu
Pentachloronitrobenzene (PCNB) is an organochlorine protective fungicide mainly used as a soil and seed fungicide. Currently, there are few reports on the toxicity of PCNB to zebrafish embryo. Here, we evaluated the toxicity of PCNB in aquatic vertebrates using a zebrafish model. Exposure of zebrafish embryos to PCNB at concentrations of 0.25 mg/L, 0.5 mg/L, and 0.75 mg/L from 6 hpf to 72 hpf resulted in abnormal embryonic development, including cardiac malformation, pericardial edema, decreased heart rate, decreased blood flow velocity, deposition at yolk sac, shortened body length, and increased distance between venous sinus and arterial bulb (SV-BA). The expression of genes related to cardiac development was disordered. However, due to the unstable embryo status in the 0.75 mg/L exposure concentration group, the effect of PCNB on the expression levels of cardiac-related genes was not concentration-dependent. We found that PCNB increased reactive oxygen species stress levels in zebrafish, increased malondialdehyde (MDA) content and catalase (CAT) activity, and decreased superoxide dismutase (SOD) activity. The increased level of oxidative stress reduced the proliferation ability of zebrafish cardiomyocytes, and the expressions of zebrafish proliferation-related genes such ascdk-2,cdk-6,ccnd1, andccne1were significantly down-regulated. Astaxanthin (AST) attenuates PCNB-induced reduction in zebrafish cardiomyocyte proliferation by reducing oxidative stress levels. Our study shows that PCNB can cause severe oxidative stress in zebrafish, thereby reducing the proliferative capacity of cardiomyocytes, resulting in zebrafish cardiotoxicity.Keywords:pentachloronitrobenzene;pericardial edema;reactive oxygen species;proliferation of cardiomyocytes;zebrafish
研究领域:
毒理学
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水生生物学
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心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2025
·
IF 3.8
Xianduo Sun,Gaosheng Hu,Yuting Li,Wenjing Li,Yong Wang,Hui Yan,Guoqing Long,Long Zhao,Anhua Wang,Jingming Jia
Gut microbiota have been found to promote hypoxia-induced intestinal injury. However, the role of gut microbiota in high-altitude pulmonary edema (HAPE), the preventive effect of synbiotic on HAPE, and the mechanisms by which they might work remain unknown. In this study, we aimed to investigate the role of gut microbiota in the pathogenesis of HAPE and to explore the underlying mechanisms involved. We performed a fecal microbiome analysis and found a significant decrease in intestinal Klebsiella and Escherichia-Shigella, along with a notable increase in intestinal Bifidobacterium and Lactobacillus, as volunteers recovered from acute mountain sickness (AMS). Gavage colonization with Klebsiella pneumoniae and Escherichia coli induced plasma inflammation, increased plasma lysophosphatidylcholine (LPC) levels, and contributed to HAPE in rats at a simulated altitude of 6,500 m. Conversely, a synbiotic containing Bifidobacterium, Lactiplantibacillus, fructooligosaccharides, and isomaltose-oligosaccharides significantly reduced the severity of HAPE. Cellular experiments and molecular dynamics simulations revealed that LPCs can cause damage and permeability to human pulmonary microvascular endothelial cell (HPMEC) and human pulmonary alveolar epithelial cell (HPAEpiC) monolayers under hypoxic conditions by disrupting cell membrane integrity. In addition, tail vein injection of LPCs promoted HAPE in mice at a simulated altitude of 6,500 m. In conclusion, this study describes a gut microbiota-LPCs/inflammation-HAPE axis, an important new insight into HAPE that will help open avenues for prevention and treatment approaches.
研究领域:
医学
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微生物学
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生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Nanoscience
·
2024
·Vol. 21
·期 4
·757-765
·
IF 1.4
Zirui Liu,Dan Li,Baofeng Zhao,Xifan Mei
BackgroundGouty arthritis, characterized by excruciating pain and discomfort, poses a significant burden on patients. While nanomedicines have shown promise in addressing this ailment, their complicated synthesis processes often involve potentially toxic procedures, contributing to adverse side effects in disease management.MethodsIn this study, we introduce a straightforward and elegant solution by utilizing easily prepared gold platinum (AuPt) nanoparticles for the treatment of gouty arthritis. The synthesis of these nanoparticles involves the use of gold and platinum precursors in conjunction with NaBH4, simplifying the manufacturing process. Experimental models of gout were established in both in vivo and in vitro settings through lipopolysaccharide and monosodium urate crystal induction.ResultsOur findings revealed that AuPt nanoparticles exhibited potent anti-inflammatory effects against gout. This effect was attributed to their ability to activate the Nrf2/HO-1 pathway, resulting in pain alleviation and the inhibition of inflammation, ultimately leading to the reduction of joint edema. With their uncomplicated synthesis and promising therapeutic potential, these simply prepared AuPt nanoparticles emerge as a compelling candidate for pharmaceutical intervention in the treatment of gouty arthritis.ConclusionThis approach not only holds the promise of delivering effective relief to patients but also minimizes the risk of unwanted side effects associated with complex nanomedicine synthesis processes.
研究领域:
药理学
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纳米医学
·
炎症研究
✓ 已验证
DOI
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Jin Li,Tongjie Cheng,Qiang Tian,Ying Cheng,Lixia Zhao,Xingzhen Zhang,Yi Qu
As a leading cause of vision impairment of the retina, macular edema (ME) has one of the highest clinical demands for treatment. Current treatment of ME relies heavily on invasive techniques resulting in complications and poor patient compliance. To enhance the efficiency of triamcinolone acetonide as eye drop to the posterior segment of the eye, we developed and characterized a novel formulation, namely, triamcinolone acetonide chitosan-coated liposomes (TA-CHL), prepared by the calcium acetate gradient method with some modifications. TA-CHL provided the mean particle size of 135.46 ± 4.49 nm and high entrapment efficiency (90.66 ± 3.21%), exhibited a sustained release profile, excellent physical stability, and no significant toxicity on cornea, conjunctiva, and retina. Optical coherence tomography system (OCT) was used to detect pharmacokinetics of CHL in vivo, indicating that CHL had good potency for drug delivery. Cellular uptake experiments showed CHL had the higher transduction efficiency into HCEC and ARPE-19 than liposomes. TA-CHL was shown to be potentially effective eye drop to contribute to the posterior segment of the eye.
研究领域:
药剂学
·
眼科医学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2016
·
IF 2.429
Li-Hua Peng,Wei Wei,Ying-Hui Shan,Yee-Song Chong,Lian Yu,Jian-Qing Gao
This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.
研究领域:
药剂学
·
药理学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Letters in Drug Design & Discovery
·
2020
·Vol. 17
·期 4
·502-511
·
IF 1.169
Song Mingxia,Liu Bing,Yu Shengwang,He Shihui,Liang Yuqiu,Li Sifan,Chen Qiuyan,Deng Xianqing
Background: Several series of hydrazone derivatives of pyrazole-4-carboxaldehydes (4- 11) were designed and synthesized to screen their inflammatory activity. Methods: The products were characterized by 1H NMR, 13C NMR and HRMS. In vitro LPS-induced TNF-α model and in vivo
xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Results and Conclusion: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF-α at the concentration of 10 μg/mL. Compounds 7b and 11c, two of the most potent
compounds, exhibited TNF-α inhibitory ability in a dose-dependent manner with IC50 values of 5.56 and 3.69 μM, respectively. In vivo, intraperitoneal administration with 7b and 11c markedly inhibited the ear edema at the doses of 20 and 50 mg/kg. Compound 11c, inhibited edema by 49.59
% at the dose of 20 mg/kg, was comparable to the reference drug dexamethasone at the same dose (with an inhibition of 50.49 %). To understand the binding pattern, molecular docking of representative 7b and 11c was performed, which demonstrated that both compounds have a forceful binding with
the TNF-α, and that the phenyl and hydrazide moieties of them play a significant role in binding with the target site.
研究领域:
药物化学
·
炎症研究
·
分子生物学
✓ 已验证
DOI
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Yizhou Zhong,Bingli Zhang,Yuji Huang,Jiaxin Du,Boxuan Liang,Zhiming Li,Rongyi Ye,Bo Wang,Hongyi Xian,Xifei Yang,Weifeng Rong,Xiang Guo,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water . Brain edema is the primary pathological consequence of 1,2-DCE overexposure. We found that microRNA (miRNA)-29b dysregulation after 1,2-DCE exposure can aggravate brain edema by suppressing aquaporin 4 (AQP4). Moreover, circular RNAs (circRNAs) can regulate the expression of downstream target genes through miRNA , and affect protein function. However, circRNAs’ role in 1,2-DCE-induced brain edema via miR-29b-3p/AQP4 axis remains unclear. To address the mechanism’s bottleneck, we explored the circRNA-miRNA-mRNA network underlying 1,2-DCE-driven astrocyte swelling in SVG p12 cells by circRNA sequencing, electron microscopy and isotope 3 H labeling combined with the 3-O-methylglucose uptake method. The results showed that 25 and 50 mM 1,2-DCE motivated astrocyte swelling, characterized by increased water content, enlarged cell vacuoles, and mitochondrial swelling. This was accompanied by miR-29b-3p downregulation and AQP4 upregulation. We verified that AQP4 were negatively regulated by miR-29b-3p in 1,2-DCE-induced astrocyte swelling. Also, circRNA sequencing highlighted that circBCL11B was upregulated by 1,2-DCE. This was manifested as circBCL11B overexpression playing an endogenous competitive role via upregulating AQP4 by binding to miR-29b-3p, thus leading to astrocyte swelling. Conversely, circBCL11B knockdown reversed the 1,2-DCE-motivated AQP4 upregulation and alleviated the cell swelling. Finally, we demonstrated that the circBCL11B was targeted to miR-29b-3p by fluorescence in situ hybridization and dual-luciferase reporter assay. In conclusion, our findings indicate that circBCL11B acts as a competing endogenous RNA to facilitate 1,2-DCE-caused astrocyte swelling via miR-29b-3p/AQP4 axis. These observations provide new insight into the epigenetic mechanisms underlying 1,2-DCE-induced brain edema.
研究领域:
毒理学
·
神经科学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2017
·
IF 5.012
Zhenzhou Lin,Hua Huang,Yong Gu,Kaibin Huang,Yafang Hu,Zhong Ji,Yongming Wu,Shengnan Wang,Tingting Yang,Suyue Pan
Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders . This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group received a loading dose of 10 μg/kg of GBC, followed by 1.2 μg/6 h for 3 days, while same dose of vehicle was used as control. The 28-day survival rate in the GBC group (11/23) was significantly higher than that in the vehicle group (8/36). In addition, the frequency and duration of spontaneous recurrent seizures in SE rats were profoundly reduced by GBC but not by vehicle treatment. Moreover, cognitive impairment was observed in the SE rats at day 28, which was reversed by GBC treatment. Meanwhile, cerebral edema , as well as neuronal loss, was decreased in several brain areas in the GBC group. Additionally, on the molecular basis, the subunits of sulfonylurea receptor 1/transient receptor potential M4 (SUR1-TRPM4) heterodimer were both strongly upregulated after SE but partly suppressed by GBC treatment. Furthermore, gene knockdown of Trpm4 in SE rats reduced BBB disruption and neuronal loss, similar to the inhibitory effects with GBC treatment. Taken together, GBC treatment markedly improved survival and neurologic outcomes after SE. The salutary effects of GBC were correlated to the alleviation of cerebral edema and reduction in neurological injury via down-regulation of SUR1-TRPM4 channel.
研究领域:
神经病学
·
药理学
·
神经科学
✓ 已验证
DOI
PubMed
高影响因子
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