JOURNAL OF PHARMACY AND PHARMACOLOGY
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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
Communications Biology
·
2020
·Vol. 3
·期 1
·1-15
·
IF 4.165
Ren Hongyan,Xiao Wei,Qin Xingliang,Cai Gangzhi,Chen Hao,Hua Zaidong,Cheng Cheng,Li Xinglei,Hua Wenjun,Xiao Hongwei,Zhang Liping,Dai Jiali,Zheng Xinmin,Zhu Zhe,Qian Chong,Yao Jie,Bi Yanzhen
Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.
研究领域:
动物遗传学
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分子生物学
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动物科学
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PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2021
·
IF 4.294
Shuwen Tan,Yi Zhou,Haiquan Zhao,Jinhua Wu,Hui Yu,Yin Yang,Yalan Yang,Huabin Zhao,Hua Li
XX sex reversal, also called XX disorders of sex development (XX-DSD), is a condition affecting the development of the gonads or genitalia, and is relatively common in pigs. However, its genetic etiology and transcriptional regulation mechanism in the hypothalamic-pituitary-gonadal axis (HPGA) remain mostly unknown. XX-DSD ( SRY -negative) pigs and normal sows were selected by external genitalia observation. The hypothalamus, which is the integrated center of the HPGA was sampled for whole-transcriptome RNA-seq. The role of DEmiRNA was validated by its overexpression and knockdown in vitro. A total of 1,258 lncRNAs, 1,086 mRNAs, and 61 microRNAs differentially expressed in XX-DSD pigs compared with normal female pigs. Genes in the hormone biosynthesis and secretion pathway significantly up-regulated, and the up-regulation of GNRH1 , KISS1 and AVP may associate with the abnormal secretion of GnRH. We also predicted the lncRNA-miRNA-mRNA co-expression triplets and constructed three competing endogenous RNA (ceRNA) potentially associated with XX-DSD. Functional enrichment studies suggested that TCONS_00340886 , TCONS_00000204 and miR-181a related to GnRH secretion. Further, miR-181a inhibitor up-regulated GNRH1 , PAK6 , and CAMK4 in the GT1-7 cells. Conversely, transfection of miR-181a mimics obtained the opposite trends. The expression levels of FSHR , LHR , ESR1 and ESR2 were significantly higher in XX-DSD gondas than those in normal sows. Taken together, we proposed that the balance of endocrine had broken in XX-DSD pigs. The current study is the first to examine the transcriptomic profile in the hypothalamus of XX-DSD pigs. It provides new insight into coding and non-coding RNAs that may be associated with DSD in pigs.
研究领域:
遗传学
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分子生物学
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动物科学
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内分泌学
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DOI
PubMed
高影响因子
Animals
·
2023
·Vol. 13
·期 3
·345
·
IF 3
Hulong Lei,Qian Du,Naisheng Lu,Xueyuan Jiang,Mingzhou Li,Dong Xia,Keren Long
Simple SummaryCopper sulfate and copper glycinate have been used as additives for copper supplementation and growth promotion in the swine feed industry. However, their effects on the gut microenvironment, especially for the fecal microbiota and metabolites, still remain unclear, which are the important indicators of gut health. As well as the nutrient digestibility and physiological and biochemical indices of pigs, the effects of copper sulfate and copper glycinate on fecal microbial communities and metabolic profiles were investigated to understand it better in the present study. Our results suggested that copper sulfate and copper glycinate could differentially affect fecal microbiota and metabolites, by which dietary copper glycinate exerted more beneficial effects on the gut health of pigs.AbstractThis study aims to compare the fecal microbiome-metabolome response to copper sulfate (CuSO4) and copper glycinate (Cu-Gly) in pigs. Twelve Meishan gilts were allocated into the CuSO4group and the Cu-Gly group (fed on a basal diet supplemented with 60 mg/kg copper from CuSO4or Cu-Gly) paired in litter and body weight. After a two-week feeding trial, the Cu-Gly group had a higher copper digestibility, blood hemoglobin, and platelet volume and higher levels of plasma iron and insulin-like growth factor-1 than the CuSO4group. The Cu-Gly treatment increased the abundance of theLachnospiraceaefamily and the generaLachnospiraceae XPB1014,Corprococcus_3,Anaerorhabdus_furcosa_group,Lachnospiraceae_FCS020_group, andLachnospiraceae_NK4B4_groupand decreased the abundance of theSynergistetesphylum andPeptostreptococcaceaefamily compared to the CuSO4treatment. Moreover, the Cu-Gly group had a lower concentration of 20-Oxo-leukotriene E4 and higher concentrations of butyric acid, pentanoic acid, isopentanoic acid, coumarin, and Nb-p-Coumaroyl-tryptamine than the CuSO4group. The abundance ofSynergisteteswas positively correlated with the fecal copper content and negatively correlated with the fecal butyric acid content. The abundance of theLachnospiraceae_XPB1014_groupgenus was positively correlated with the plasma iron level and fecal contents of coumarin and butyric acid. In conclusion, Cu-Gly and CuSO4could differentially affect fecal microbiota and metabolites, which partially contributes to the intestinal health of pigs in different manners.Keywords:copper sulfate;copper glycinate;microbiome;metabolome;pigs;copper source
研究领域:
动物科学
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营养学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Wei Wei,Yuanzhu Ma,Xianzhu Zhang,Wenyan Zhou,Hongwei Wu,Jingwei Zhang,Junxin Lin,Chenqi Tang,Youguo Liao,Chenglin Li,Xiaozhao Wang,Xudong Yao,Yi Wen Koh,Wenwen Huang,Hongwei Ouyang
Irregular partial-thickness cartilage defect is a common pathogenesis of osteoarthritis (OA) with no available treatment in clinical practice. Currently, cartilage tissue engineering is only suitable for a limited area of full-thickness cartilage defect. Here, we design a biomimetic joint paint for the intractable partial-thickness cartilage defect repair. The joint paint, composed of a bridging layer of chondroitin sulfate and a surface layer of gelatin methacrylate with hyaluronic acid, can quickly and tightly adhere to the cartilage defect by light activation. Being treated by the joint paint, the group of rabbit and pig models with partial-thickness cartilage defects showed a restoration of a smooth cartilage surface and the preservation of normal glycosaminoglycan content, whereas the untreated control group exhibited serious progressive OA development. This paint treatment functions by prohibiting chondrocyte apoptosis, maintaining chondrocyte phenotype, and preserving the content of glycosaminoglycan in the partial-thickness cartilage defects. These findings illustrated that the biomimetic joint paint is an effective and revolutionary therapeutics for the patients with noncurable partial-thickness cartilage defects.
研究领域:
组织工程
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骨科
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再生医学
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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
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-11
·
IF 4.122
Xiao Qiling,Zhou Qiongqiong,Yang Lu,Tian Zhongyuan,Wang Xiliang,Xiao Yuncai,Shi Deshi
Human carboxylesterases has been proven to be age and race-related and a sound basis of clinical medication. PLE involve in signal transduction and highly catalyze hydrolysis. Therefore, the expression level of PLE most probably exist age and breed difference and lead to significant differences of pharmacology and physiology. Four age groups of Tongcheng (TC) and Large White (LW) pigs were selected to explore PLE breed and age differences, and it was found that PLE mRNA was most abundant in liver in both breeds. In liver, PLE levels and hydrolytic activities increased with age, and PLE levels (except for 3 month) and the hydrolytic activities were higher in LW than in TC across all age groups. Abundance of PLE isoenzymes was obvious different between breeds and among age groups. The most abundant PLE isoenzyme in LW and TC pigs was PLE-A1 (all age groups) and PLE-B9 (three early age groups) or PLE-G3 (adult groups), respectively. 103 new PLE isoenzymes were found, and 55 high-frequency PLE isoenzymes were accordingly classified into seven categories (A-G). The results of this research provide a necessary basis not only for clinical medication of pigs but also for pig breeding purposes.
研究领域:
兽医学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD PROTECTION
·
2020
·
IF 1.581
Hongying Li,Qiujin Zhu,Rui Chang,Ke Hu,Xuling Zhu,Aqi Xu,Shitao Xu,Pengyu Tang
ABSTRACT In order to reduce the health risks associated with red meat as listed by the World Health Organization, the work presented in this article aimed to elucidate the interaction between 5′-CMP–supplemented feed and N -glycolylneuraminic acid (Neu5Gc) in experimental animals in vivo. 5′-CMP was added to the diet of 90-, 180-, and 270-day-old Xiang pigs, and after 30 days, the Neu5Gc contents, physicochemical parameters, and free amino acid contents of muscle and internal viscera were measured by high-performance liquid chromatography coupled with fluorescence detection. The mechanism by which 5′-CMP affects Neu5Gc contents was investigated using molecular docking. Results show that 5′-CMP significantly decreased the Neu5Gc content in 180-day-old Xiang pigs ( P < 0.05) but had no effect on the Neu5Gc contents in 90- and 270-day-old Xiang pigs. Umami amino acids were significantly increased in 180-day-old Xiang pigs. In the 90- and 270-day-old pigs, histidine increased by 10.38 and 17.87%, respectively. The other free amino acids were either reduced or not affected. Moreover, the 5′-CMP–supplemented diet did not affect the physicochemical parameters of the longissimus muscle in the Xiang pigs. 5′-CMP could occupy almost all the sialyltransferase active-site residues but not His302 and showed inhibition of the sialyltransferase activity. The results provided an experimental basis for the subsequent reduction of Neu5Gc in red meat before slaughter.
研究领域:
营养学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
·
2017
·Vol. 41
·期 2
·307-313
·
IF 1.202
Z. Ling,L. Yonghong,L. Junfeng,Z. Li,L. Xianqiang
The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae ( APP ) ( n = 2), Streptococcus suis ( S. suis ) ( n = 2), and Haemophilus parasuis ( HPS ) ( n = 2) were evaluated by chekerboard test and time-kill assays. The pharmacokinetics (PKs) of TIL- and FF-loaded hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP , S. suis and HPS with the fractional inhibitory concentration (FIC) ranging from 0.375 to 0.75. The time-kill assays showed that 1/2 minimum inhibitory concentration (MIC) TIL combined with 1/2 MIC FF had a stronger ability to inhibit the growth of APP , S. suis, and HPS than 1 MIC TIL or 1 MIC FF, respectively. After oral administration, plasma TIL and FF concentrations could maintain about 0.1 μg/ml for 192 and 176 hr. The SLN prolonged the last time point with detectable concentrations (T last ), area under the concentration–time curve (AUC 0-t ), elimination half-life (T ½ke ), and mean residence time (MRT) by 3.1, 5.6, 12.7, 3.4-fold of the active pharmaceutical ingredient (API) of TIL and 11.8, 16.5, 18.1, 12.1-fold of the API of FF, respectively. This study suggests that the TIL-FF-SLN could be a useful oral formulation for the treatment of APP , S. suis, and HPS infection in pigs.
研究领域:
兽医学
·
药剂学
·
微生物学
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-24
·
IF 10.6
Lai Huasheng,Yip Hon-Chi,Gong Yu,Chan Kai-Fung,Leung Kevin Kai-Chung,Chan Melissa Shannon,Xia Xianfeng,Chiu Philip Wai-Yan
Background Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGel MSC−Exo ) for the prevention of esophageal stenosis after ESD in a porcine model. Results Pigs were randomly assigned into (1) ChGel MSC−Exo treatment group, (2) ChGel PBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC–MS/MS) and small RNA sequencing. ChGel MSC−Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGel PBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFβ1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. Conclusions Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD. Graphical Abstract
研究领域:
胃肠病学
·
干细胞研究
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再生医学
·
外科手术
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产品关联
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
·
耳鼻喉科学
·
肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2024
·
IF 2.6
Xu Changzhi,Yang Xianshu,Sui Heming,Tong Xu,Zhang Dandan,Zheng Xianrui,Jiao Jun,Wang Chonglong,Cao Zubing,Zhang Yunhai
According to previous studies, the quality and fertilization rate of fresh sperm from boars of different ages were significantly different. However, the difference of freeze–thaw sperm quality and fertility in boars of different ages is unclear. In this study, boars of a Chinese native breed were assigned into two groups. Each group consisted of five boars aged aged either 2–3 years (young boars = YB) or 5–6 years (aging boars = AB) A total of 60 ejaculates for each group were collected and cryopreserved. Semen quality and in vitro fertility of post-thaw sperm was evaluated. The results showed that the concentration and motility of fresh sperm collected from AB were similar to YB, but their semen volume was higher than that in YB (p < 0.05). Frozen–thawed sperm of AB had lower viability than YB, and higher abnormal rate and reactive oxygen species (ROS) levels of YB (p < 0.05). There was no effect of the age on post-thaw sperm motility and time survival. Functional assessments indicated that increasing age markedly compromises the integrity of the sperm plasma membrane and acrosome, as well as mitochondrial functionality post-thaw, albeit without affecting DNA integrity. Furthermore, increasing age of boars reduces the ability of sperm to bind to the oocyte zona pellucida after thawing, delaying the time of the first embryo cleavage after fertilization. Finally, the early developmental efficiency of in vitro fertilized embryos progressing from 4-cell to blastocyst derived from post-thaw sperm in AB significantly decreased compared to those from YB (p < 0.05). Taken together, these results suggest that increasing age in boars impairs the quality and in vitro fertility of frozen thawed sperm.
研究领域:
动物科学
·
生殖生物学
·
兽医学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）