JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
·
2018
·Vol. 41
·期 5
·706-718
·
IF 1.441
L. Zhang,Y. Li,Y. Wang,A. Sajid,S. Ahmed,X. Li
The aims of this study were to establish optimal doses of doxycycline (dox) against Haemophilus parasuis on the basis of pharmacokinetic–pharmacodynamic (PK-PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes for PK studies. The area under the concentration 0- to 24-hr curve (AUC 0–24 ), elimination half-life ( T ½ke ), and mean residence time (MRT) of dox in healthy and H. parasuis -infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40 H. parasuis isolates was conducted through broth microdilution method, the corresponding MIC 50 and MIC 90 were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration-dependent killing mechanism. Based on the observed AUC 24 hr /MIC values by modeling PK-PD data in H. parasuis -infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects for H. parasuis over 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90% TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity against H. parasuis .
研究领域:
兽医学
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微生物学
·
药理学
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DOI
高影响因子
Science Advances
·
2022
·Vol. 8
·期 48
·
IF 14.957
Changwei Yang,Tao Sheng,Wenhui Hou,Juan Zhang,Li Cheng,Hao Wang,Wei Liu,Shiqi Wang,Xinmin Yu,Yuqi Zhang,Jicheng Yu,Zhen Gu
Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).
研究领域:
生物医学工程
·
药学
·
糖尿病研究
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DOI
PubMed
高影响因子
Science Translational Medicine
·
2020
·Vol. 12
·期 558
·
IF 16.304
Xiayi Xu,Xianfeng Xia,Kunyu Zhang,Aliza Rai,Zhuo Li,Pengchao Zhao,Kongchang Wei,Li Zou,Boguang Yang,Wai-Ki Wong,Philip Wai-Yan Chiu,Liming Bian
Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here, we report the development of a hydrogel based on thiourea-catechol reaction to enhance the bioadhesion. Compared with classical bioadhesive hydrogels, our hydrogels show enhanced mechanical properties, exceedingly short curing time, and pH-independent gelation with a much lower oxidant concentration. We further report the robust adhesion of our hydrogels to acidic gastric tissues and easy delivery to the porcine stomach via endoscopy. The delivered hydrogels adhered to ulcer sites in vivo for at least 48 hours. Hydrogel treatment of gastric ulcers in rodent and porcine models accelerated ulcer healing by suppressing inflammation and promoting re-epithelization and angiogenesis. The improved retention of proregenerative growth factors and reduced exposure to external catabolic factors after hydrogel application may contribute to the observed therapeutic outcomes. Our findings reveal a promising biomaterial-based approach for treating gastrointestinal diseases.
研究领域:
生物材料学
·
医学
·
药剂学
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DOI
高影响因子
Frontiers in Veterinary Science
·
2021
·
IF 3.412
Ahmad Salah Uddin,Sun Jichao,Cheng Fusheng,Li Bing,Arbab Safia,Zhou Xuzheng,Zhang Jiyu
A comparative study on pharmacokinetics of four long-acting enrofloxacin injectable formulations was investigated in 36 healthy pigs after intramuscular injection according to the recommended single dose @ 2.5 mg/kg body weight. The drug concentrations in the plasma were computed using high-performance liquid chromatography (HPLC) with fluorescence detection. WinNonLin5.2.1 software was used to analyze the experimental data and compared it under one-way ANOVA using SPSS software with a 95% confidence interval (CI). The main pharmacokinetic parameters, that is, the maximum plasma concentrations (Cmax), the time to maximum concentration (Tmax), area under the time curve concentration (AUCall) and Terminal half-life (T1/2) were 733.84 ± 129.87, 917.00 ± 240.13, 694.84 ± 163.49, 621.98 ± 227.25 ng/ml, 2.19 ± 0.0.66, 1.50 ± 0.37, 2.89 ± 0.24, 0.34 ± 0.13 h, 7754.43 ± 2887.16, 8084.11 ± 1543.98, 7369.42 ± 2334.99, 4194.10 ± 1186.62 ng h/ml, 10.48 ± 2.72, 10.37 ± 2.38, 10.20 ± 2.81, and 10.61 ± 0.86 h for 10% enrofloxacin (Alkali), 20% enrofloxacin (Acidic), Yangkang and control drug Nuokang® respectively. There were significant differences among Cmax, Tmax, and AUCall of three formulations compare with that of the reference formulation. No significant differences were observed among the T1/2 for tested formulations compare with the reference formulation. The pharmacokinetic parameters showed that the tested formulations were somewhat better compared to the reference one. The calculated PK/PD indices were effective for bacteria such as Actinobacillus pleuropneumoniae and Pasteurella multocida with values higher than the cut-off points (Cmax/MIC90≥10–12 and AUC/MIC90 ≥ 125). However, they were not effective against bacteria like Haemophilus parasuis, Streptococcus suis, E. coli, and Bordetella bronchiseptica where lower values were obtained.
研究领域:
药理学
·
兽医学
·
动物科学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 8
·2924-2934
·
IF 6.6
Zhaoyi Wang,Wangbei Cao,Fanghui Wu,Xiurong Ke,Xinyu Wu,Tong Zhou,Jun Yang,Guojing Yang,Cheng Zhong,Zhongru Gou,Changyou Gao
Osteochondral tissue involves cartilage, calcified cartilage and subchondral bone. These tissues differ significantly in chemical compositions, structures, mechanical properties and cellular compositions. Therefore, the repairing materials face different osteochondral tissue regeneration needs and rates. In this study, we fabricated an osteochondral tissue-inspired triphasic material, which was composed of a poly(lactide-co-glycolide) (PLGA) scaffold loaded with fibrin hydrogel, bone marrow stromal cells (BMSCs) and transforming growth factor-β1 (TGF-β1) for cartilage tissue, a bilayer poly(L-lactide-co-caprolactone) (PLCL)-fibrous membrane loaded with chondroitin sulfate and bioactive glass, respectively, for calcified cartilage, and a 3D-printed calcium silicate ceramic scaffold for subchondral bone. The triphasic scaffold was press-fitted into the osteochondral defects in rabbit (cylindrical defects with a diameter of 4 mm and a depth of 4 mm) and minipig knee joints (cylindrical defects with a diameter of 10 mm and a depth of 6 mm). The μ-CT and histological analysis showed that the triphasic scaffold was partly degraded, and significantly promoted the regeneration of hyaline cartilage after they were implanted in vivo. The superficial cartilage showed good recovery and uniformity. The calcified cartilage layer (CCL) fibrous membrane was in favor of a better cartilage regeneration morphology, a continuous cartilage structure and less fibrocartilage tissue formation. The bone tissue grew into the material, while the CCL membrane limited bone overgrowth. The newly generated osteochondral tissues were well integrated with the surrounding tissues too.
研究领域:
组织工程学
·
再生医学
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DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 20
·3316
·
IF 4.7
Xiaonian Cao,Yunfei Hou,Qingqing Liu,Qian Yang,Min Liu,Haixu Lin,Qingxi Ren,Jian Mao
The unique flavour contribution of higher alcohols in alcoholic beverages has received growing attention; however, there is a dearth of information on their in vivo metabolic kinetics. In this study, the composition and content of higher alcohols in different alcoholic beverages from ChineseBaijiuandLujiuwere studied via in vivo analysis using Bama pigs to elucidate the mechanisms for intoxication of alcohol in vitro and in drinkers. Direct injection combined with gas chromatography–mass spectrometry (GC-MS) were used to accurately quantify a total of 14 higher alcohols in five alcoholic beverages. Based on the external standard method, a total content of 289.37–938.33 mg/L was detected, mainly 1-butanol, 3-methyl-1-butanol, 1-hexanol, 2-methyl-1-propanol and 2-butanol. Then, headspace solid-phase microextraction (HS-SPME) and solid-phase extraction (SPE) combined with GC-MS analysis strategy, respectively, were adopted to continuously monitor the changes in the concentrations of ethanol and 11 higher alcohols in the blood within 24 h after gavage of different alcoholic beverages, and the key pharmacokinetic parameters were analysed. The peak concentration (Cmax) and area under curve (AUC) of blood higher alcohols were significantly lower than those of ethanol (p <0.05), accompanied by a later peak time (Tmax) and a larger apparent clearance rate (CL_F), and there were certain differences between the same higher alcohols in different alcoholic beverages and between different higher alcohols in the same alcoholic beverage. This work provides valuable insights into the metabolism of alcoholic beverages.
研究领域:
食品科学
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动物生理学
·
代谢组学
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产品关联
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
Animals
·
2024
·Vol. 14
·期 7
·999
·
IF 2.7
Xiangyun Zhai,Liping Dang,Shiyu Wang,Wenyuan Li,Chao Sun
Simple SummarySuccinate is an important product of the fermentative metabolism of dietary fiber, and similar to propionate, high levels of succinate in the gut modulate the body’s inflammatory response, glucose tolerance, and lipid metabolism. Our study showed that the addition of 1% succinate to pig diets promoted growth and fat deposition capacity without affecting feed intake, remodeled the fatty acid content of the longissimus dorsi muscle, and consequently improved meat quality. Further, we isolated and cultured primary porcine preadipocytes. The results showed that succinate increased the expression of genes related to adipogenic differentiation while decreasing the levels of genes related to lipolysis and promoting the formation of cellular lipid droplets. Mechanistically, dietary supplementation with succinate increases succinylation modification in adipose tissue to promote facilitated lipogenesis. This suggests that it is feasible and important to improve fatty acids and meat quality in porcine muscle through dietary succinate supplementation.AbstractSuccinate, one of the intermediates of the tricarboxylic acid cycle, is now recognized to play a role in a broad range of physiological and pathophysiological settings, but its role in adipogenesis is unclear. Our study used Bama miniature pigs as a model to explore the effects of succinate on performance, meat quality, and fat formation. The results showed that adding 1% succinate significantly increased the average daily gain, feed/gain ratio, eye muscle area, and body fat content (p< 0.05), but had no effect on feed intake. Further meat quality analysis showed that succinate increased the marbling score and intramuscular fat content of longissimus dorsi muscle (LM), while decreasing the shear force and the cross-sectional area of LM (p< 0.05). Metabolomics analysis of LM revealed that succinate reshaped levels of fatty acids, triglycerides, glycerophospholipids, and sphingolipids in LM. Succinate promotes adipogenic differentiation in porcine primary preadipocytes. Finally, dietary succinate supplementation increased succinylation modification rather than acetylation modification in the adipose tissue pool. This study elucidated the effects of succinate on the growth and meat quality of pigs and its mechanism of action and provided a reference for the role of succinate in the nutrition and metabolism of pigs.
研究领域:
动物营养
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代谢
·
分子生物学
·
食品科学
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产品关联
DOI
PubMed
高影响因子
Microbiome
·
2023
·Vol. 11
·期 1
·1-24
·
IF 15.5
Hu Jun,Chen Jianwei,Hou Qiliang,Xu Xiaojian,Ren Jing,Ma Libao,Yan Xianghua
Background Gut fungi are increasingly recognized as important contributors to host physiology, although most studies have focused on gut bacteria. Post-translational modifications (PTMs) of proteins play vital roles in cell metabolism. However, the contribution of gut fungi to host protein PTMs remains unclear. Mining gut fungi that mediate host protein PTMs and dissecting their mechanism are urgently needed. Results We studied the gut fungal communities of 56 weaned piglets and 56 finishing pigs from seven pig breeds using internal transcribed spacer (ITS) gene amplicon sequencing and metagenomics. The results showed that Kazachstania slooffiae was the most abundant gut fungal species in the seven breeds of weaned piglets. K. slooffiae decreased intestinal epithelial lysine succinylation levels, and these proteins were especially enriched in the glycolysis pathway. We demonstrated that K. slooffiae promoted intestinal epithelial glycolysis by decreasing lysine succinylation by activating sirtuin 5 (SIRT5). Furthermore, K. slooffiae -derived 5′-methylthioadenosine metabolite promoted the SIRT5 activity. Conclusions These findings provide a landscape of gut fungal communities of pigs and suggest that K. slooffiae plays a crucial role in intestinal glycolysis metabolism through lysine desuccinylation. Our data also suggest a potential protective strategy for pigs with an insufficient intestinal energy supply.
Video Abstract
研究领域:
微生物学
·
分子生物学
·
动物科学
✓ 已验证
DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
·
2024
·
IF 1.2
Yushu Tang,Ning Hao
Bacillus licheniformis and bacitracin have a huge application market and value in the fields of medicine, chemistry, aquaculture, agricultural, and sideline products. Therefore, the selection of B. licheniformis with high production of bacitracin is of great importance. In this experimental protocol, Bacillus with a high yield of bacitracin was isolated, purified, and identified from the fresh feces of healthy pigs. The inhibitory effect of secondary metabolite bacitracin on Micrococcus luteus was also tested. Thin-layer chromatography and high-performance liquid chromatography were used for the qualitative and quantitative detection of bacitracin. The physiological and biochemical characteristics of B. licheniformis were determined by relevant kits. The phylogenetic relationships of B. licheniformis were determined and constructed using gene sequence detection. This protocol describes and introduces the standard isolation, purification, and identification process of B. licheniformis from animal fresh feces from multiple perspectives, providing a method for the large-scale utilization of B. licheniformis and bacitracin in factories.
研究领域:
微生物学
·
药理学
·
农业科学
·
水产养殖
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 8
·3685
·
IF 5.6
Chen Zhu,Kun Fu,Hu Wen,Guangqi Chen,Henggui Zhang
The global spread of COVID-19 led to the rapid authorization of remdesivir as the first antiviral therapy. However, accumulating clinical evidence has linked its use to cardiac adverse effects. Understanding the mechanisms underlying remdesivir-induced cardiotoxicity is critical for optimizing its clinical use and ensuring patient safety. This study investigates the electrophysiological and molecular features underlying remdesivir-induced cardiac toxicity in male and female guinea pigs, aiming to elucidate the sex-dependent differences in cardiac dysfunction and the role of mitochondria in mediating these effects. A cardiac injury model was established via intraperitoneal administration of remdesivir. In vivo telemetry and ex vivo electrocardiography were used for continuous monitoring of cardiac electrical activity, while optical mapping enabled the assessment of action potential parameters and conduction properties. The histopathological alterations and mitochondrial ultrastructure were examined by hematoxylin–eosin staining and transmission electron microscopy. ELISA and Western blot analyses were performed to explore the inflammatory signaling, apoptosis, and mitochondrial dynamics. Remdesivir induced distinct sex-specific patterns of cardiac toxicity. Compared with female guinea pigs, male guinea pigs had significantly more severe myocardial injury, which was characterized by extensive inflammatory cell infiltration, marked mitochondrial disruption, and a higher incidence of sustained ventricular tachyarrhythmia. Overall, remdesivir was associated with sex-dependent cardiac toxicity, accompanied by mitochondrial impairment and inflammatory activation. Male guinea pigs were more susceptible to electrophysiological instability and mitochondrial dysfunction. These findings highlight the importance of carefully evaluating remdesivir’s cardiac effects and support the need for individualized, sex-specific considerations in its clinical administration.
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yajun Shuai,Tao Yang,Meidan Zheng,Li Zheng,Jie Wang,Chuanbin Mao,Mingying Yang
Assembling natural proteins into large, strong, bone-mimetic scaffolds for repairing bone defects in large-animal load-bearing sites remain elusive. Here this challenge is tackled by assembling pure silk fibroin (SF) into 3D scaffolds with cortical-bone-like lamellae, superior strength, and biodegradability through freeze-casting. The unique lamellae promote the attachment, migration, and proliferation of tissue-regenerative cells (e.g., mesenchymal stem cells [MSCs] and human umbilical vein endothelial cells) around them, and are capable of developing in vitro into cortical-bone organoids with a high number of MSC-derived osteoblasts. High-SF-content lamellar scaffolds, regardless of MSC inoculation, regenerated more bone than non-lamellar or low-SF-content lamellar scaffolds. They accelerated neovascularization by transforming macrophages from M1 to M2 phenotype, promoting bone regeneration to repair large segmental bone defects (LSBD) in minipigs within three months, even without growth factor supplements. The bone regeneration can be further enhanced by controlling the orientation of the lamella to be parallel to the long axis of bone during implantation. This work demonstrates the power of oriented lamellar bone-like protein scaffolds in repairing LSBD in large animal models.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）