ACTA OTO-LARYNGOLOGICA
·
2024
·
IF 1.2
Nishan Chen,Tongxiang Diao,Jilei Zhang,Lisheng Yu
Backgrounds Due to the therapeutic needs of inner ear diseases, a simple method of inner ear drug delivery has been under exploration. Postauricular administration, which involves injecting the drug through the middle of the retroauricular groove, is a potential novel approach, but its mechanisms remain unclear.Objectives To investigate threshold shifts in the auditory brainstem response (ABR), as well as the morphology and quantity of hair cells on the bilateral inner ear of guinea pigs after postauricular neomycin administration.Material and Methods Thirty healthy guinea pigs were divided randomly into two groups and administered either neomycin 200 mg/kg or saline 1 ml via daily postauricular injection for 10 days. Auditory threshold-shifts were examined by tests of the ABR. The quantity and morphology of hair cells in the organ of Corti were assessed by confocal laser scanning microscopy.Results The ABR results showed that at a frequency of 16 kHz, the threshold shift was 21.00 ± 14.49 dB in the neomycin injection side, 10.00 ± 16.67 dB in the contralateral side, and 0.50 ± 3.69 dB in the saline group. At a frequency of 24 kHz, the threshold shift was 37.00 ± 16.36 dB in the neomycin injection side, 14.50 ± 9.26 dB in the contralateral side, and 1.00 ± 2.11 dB in the saline group. Histopathological analysis revealed that the outer hair cells (OHCs) in the neomycin injection side suffered significant morphological and numerical loss, while the OHC loss in the contralateral ear was less severe than in the injection side but greater than in the saline group.Conclusions and Significance This study confirms that postauricular administration is a novel method of local drug delivery to the inner ear, which has practical value in future experimental modeling and the treatment of inner ear diseases.
研究领域:
耳科学
·
药理学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Junrong Li,Shanli Zhu,Fangxiong Shi
Non-nutritive sweeteners (NNS) are widespread in the food industry, but their effects on reproductive endocrine function remain inadequately characterized within the current scientific literature. This study investigated NNS impacts on hypothalamic-pituitary-ovarian (HPO) axis function in guinea pigs. The results showed that the NNS groups exhibited significantly lower serum levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH) compared to controls, with rebaudioside A (RA) showing the lowest GnRH. Conversely, luteinizing hormone (LH) concentrations were significantly elevated in NNS groups. The RA group exhibited increased testosterone (T) levels, and all experimental groups showed more SS follicular cysts. T1R2 protein expression was highest in the sucralose (TGS) group, while gonadotropin-releasing hormone receptor (GnRHR) expression decreased significantly in NNS groups, particularly with RA. Luteinizing hormone receptor (LHR) protein expression increased significantly in NNS groups, with no changes in follicle-stimulating hormone receptor (FSHR) or T1R3 expression. Therefore, NNS supplementation affects HPO axis function in guinea pigs, as evidenced by decreased serum GnRH and FSH levels, increased LH content, inhibited GnRHR protein expression, and promoted LHR protein expression. The observed upregulation of T1R2 protein expression in the TGS group suggests a potential link between sweet taste receptor activation and reproductive hormone regulation.
研究领域:
内分泌学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Li Dafei,Zhao Haiyan,Xu Piao,Lin Qiongping,Zhao Tingting,Li Chubing,Cui Zhong-Kai,Tian Guangyong
Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the in vivo setting with guinea pigs, we have demonstrated that PD can reduce the threshold shift of auditory brainstem response (ABR) caused by cisplatin, promote the nuclear translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2), increase the expression of Nrf2 and heme oxygenase-1 (HO-1), and thus reduce the loss of outer hair cells (OHCs). PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.
研究领域:
药理学
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耳鼻喉科学
·
肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Neurology
·
2025
·
IF 2.8
Huan Lin,Xuanyi Li,Huiying Zhang,Yi Mu,Xi Wang,Naveena Konduru,Renlong Ji,Wen Liu,Zhao Fei,Wen Jiang,Yuehua Qiao
Background: Inner ear disorders, such as EH, commonly lead to hearing loss and vestibular dysfunction. EH is particularly prevalent in various inner ear diseases, including Meniere’s disease. We aimed to evaluate the effects of EH on WAI and OAEs.Objective: This study explores the potential of wideband acoustic immittance (WAI) and otoacoustic emissions (OAEs) for the early detection of changes in acoustic transmission associated with vasopressin-induced endolymphatic hydrops (EH) in a guinea pig model.Methods: We induced EH in guinea pigs via daily intraperitoneal injections of arginine vasopressin over 14 consecutive days. Auditory function was assessed using Auditory Brainstem Responses (ABR), while changes in sound energy transmission were measured using WAI and Distortion Products Otoacoustic Emissions (DPOAE).Results: Increased ABR thresholds in EH models were statistically significant (p < 0.05). After 14 days of EH induction, absorbance at 1 kHz significantly increased, whereas it significantly decreased at 4 kHz and 6 kHz (p < 0.05). DPOAE measures, both magnitude and phase, showed no significant changes (p > 0.05).Conclusion: WAI demonstrates greater sensitivity than DPOAE in the early detection of acoustic transmission alterations in EH models, suggesting its utility as a diagnostic tool in early-stage inner ear disorders.
研究领域:
听力学
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耳科学
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实验动物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2018
·Vol. 234
·期 4
·4291-4301
·
IF 3.923
Meng-Juan Lin,Lei Chen,Zhen-Peng Huang,Hu Qiu,Bao-Ping Yu
Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis.
研究领域:
胃肠病学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Pengfei Li,Jingkang Wang,Chunguo Wang,Long Cheng,Quantao Ma,Yaqi Li,Yongcheng An,Hongyu Dai,Yuhui Duan,Tieshan Wang,Xuan Ma,Minghui Zhang,Ting Wang,Baosheng Zhao
Ethnopharmacological relevance Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or “Nai-Zi-Lai” in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases . However, the pharmacological mechanisms of HCZP remain unrevealed. Aim of the study To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. Materials and methods A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Results Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. Conclusions HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.
研究领域:
药理学
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传统中药
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呼吸系统疾病
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE BIOLOGY
·
2017
·Vol. 250
·期 5
·483-492
·
IF 1.696
Chai Ran,Chen Yafei,Yuan Hongbo,Wang Xuzhao,Guo Shuai,Qi Jinlong,Zhang Hailin,Zhan Yong,An Hailong
Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Dysfunction of the CaCCs is implicated in many diseases. Drug discovery targeting at CaCCs has recently become possible with the determination that TMEM16A is the molecular identity of CaCCs. In this study, we demonstrated that resveratrol (RES), a Chinese traditional medicine compound, is a novel activator of TMEM16A. The yellow fluorescence protein quenching assay and measurement of intracellular calcium fluorescence intensity show that RES activates TMEM16A channels in an intracellular Ca 2+ -independent way. The data of inside-out patch clamp revealed that RES dose-dependently activates TMEM16A (EC 50 = 47.92 ± 9.35 μM). Furthermore, RES enhanced the contractions of the ileum of guinea pigs by activating the TMEM16A channel, which indicated that RES might be a promising drug for the treatment of gastrointestinal hypomotility. As RES was able to induce TMEM16A channel activation, TMEM16A can be added to the list of RES drug targets.
研究领域:
药理学
·
生理学
·
药物发现
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·956-968
·
IF 2.571
Wang Youpeng,Jing Weichao,Qu Wanying,Liu Zhiwei,Zhang Di,Qi Xiaoyu,Liu Lujia
ObjectivesThe aim of this study was to evaluate the effect of tectorigenin on treating allergic asthma model of guinea pigs and investigate the underlying mechanisms.MethodsAllergic asthma model of guinea pigs was established by sensitizing with ovalbumin (OVA). Then OVA-sensitized guinea pigs were injected with 10 mg/kg tectorigenin, 25 mg/kg tectorigenin or dexamethasone to investigate the effect of tectorigenin.Key findingsHigh dose of tectorigenin effectively decreased the number of coughs, the number of inflammatory cells and the levels of pro-inflammatory factors. Moreover, tectorigenin could inhibit pulmonary fibrosis in guinea pigs sensitized with OVA. In addition, the functions of tectorigenin were realized through downregulating profibrotic factors of transforming growth factor (TGF)-β1, phosphorylated (p)-Smad2/3 and Smad4, upregulating fibrosis-inhibitor of Smad7 and decreasing pro-inflammatory factors of vascular endothelial growth factor A (VEGFA), tumour necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-inhibitor of nuclear factor-kappa B (NF-κB) kinase β (p-IKKβ) and NF-κB.ConclusionsTectorigenin could inhibit pulmonary fibrosis and airway inflammation through TGF-β1/Smad signalling pathway and TLR4/NF-κB signalling pathway. Therefore, tectorigenin might be a promising medicine to treat allergic asthma.
研究领域:
药理学
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免疫学
·
呼吸医学
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DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Meng Shi,Ruihua Zhang,Qian Jin,Yalan Cui,Jingjing Shi,Xuejun Chen,Tong Shi,Yi Zhang,Siqing Zhu,Xingxing Zong,Jianfu Xu,Chen Wang,Liqin Li
Sarin was used as a chemical weapon due to its high neurotoxicity and mortality. Subacute sarin induced cognitive and behavioral disorder. However, the underlying mechanism is still unclear. Here we offered a multi-omic approach for the analysis of altered metabolites, lipids, and proteins to explore the neurotoxicity of subacute sarin. Guinea pigs were administered between the shoulder blades 16.8 μg/kg of sarin in a volume of 1.0 ml/kg body weight by subcutaneous injection once daily for 14 days. At the end of the final injection, guinea pigs were sacrificed, and striatum were dissected for analysis. A total of 138 different metabolites were identified in the metabolome analysis. Lipids and lipid-like molecules is the largest group (38.41%). For lipidomic analysis, a total of 216 lipids were identified. In proteomic study, over 4300 proteins were identified and quantified. By integrating these enriched components, we demonstrated that the joint pathways disturbed by subacute sarin mainly involving lipid, purine and pyrimidine metabolism in guinea pig striatum. Overall, this study highlights the powerfulness of omics platforms to deepen the understanding of nerve agents caused neurotoxicity.
研究领域:
毒理学
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神经科学
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生物化学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2018
·
IF 1.883
Juan Dai,Wei Long,Zhongping Liang,Lu Wen,Fan Yang,Gang Chen
Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.
研究领域:
药学
·
生物医学工程
·
药物递送系统
·
内耳治疗
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DOI
PubMed
高影响因子
JOURNAL OF ELECTROCARDIOLOGY
·
2017
·
IF 1.514
Yaoxu Chen,Chunxia Yin,Yingying Yang,Zhuo Fan,Jinling Shang,Wen Tan
Ischemia/reperfusion (I/R) induces prolongation of QT interval and action potential duration (APD), which is a major cardiac electrical disorder in patients with arrhythmias. However, the mechanism of QT interval prolongation induced by I/R remains unclear. In the present study, we hypothesized that the rapid component of delayed rectifier potassium ( I Kr ) channel plays an important role in I/R-induced QT interval prolongation. We observed a marked attenuation of I Kr and a significant prolongation of action potential duration (APD) in a simulated I/R system with sodium dithionite (Na 2 S 2 O 4 ) in ventricular myocytes of guinea pigs. The I Kr current density was inhibited by 64% and APD increased by 87% respectively. Moreover, the inhibition of I Kr is primarily ascribed to overproduction of reactive oxygen species (ROS) by I/R, which can be partly reversed by antioxidant vitamin E (100 μmol/L). The value of I Kr tail current density increased from 0.516 ± 0.040 pA/pF in I/R to 0.939 ± 0.091 pA/pF when treated with vitamin E. Moreover, we also demonstrated that QTc interval was increased by I/R and reversed by Vitamin E in isolated guinea pig hearts. In conclusion, the inhibition of I Kr is one of the underlying mechanisms of prolongation of QT interval and APD in I/R. Vitamin E might have a benefit in coronary reperfusion therapy .
研究领域:
心脏病学
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药理学
·
生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Gastrointestinal Surgery
·
2023
·
IF 2
Fan Ding,Run Guo,Fang Chen,Li-Ping Liu,Zheng-Yu Cui,Yi-Xing Wang,Gang Zhao,Hai Hu
BACKGROUND Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility. AIM To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. METHODS Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot. RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group. CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.
研究领域:
胃肠病学
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生理学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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