Animal Models and Experimental Medicine最新文献

Background: Diabetes-induced oxidative stress can have adverse effects on sperm and its DNA integrity. The Ashrasi date palm (ADP) has potent antioxidant properties. The aim of this study was to evaluate the antioxidant effect of ADP hydroalcoholic extract on sperm parameters and sperm DNA fragmentation in diabetic rats.

Methods: Forty male rats were randomly divided into five groups (n = 7): 1, control; 2, diabetic; 3-5, diabetic + ADP (30, 90 and 270 mg/kg for groups 3, 4 and 5, respectively). After preparation of ADP extract and its phytochemical screening, it was administered orally to rats, once a day for 5 weeks. At the end of the study, sperm parameters and sperm DNA fragmentation in all groups were investigated.

Results: At doses of 90 and 270 mg/kg, ADP extract significantly increased the sperm viability compared to diabetic group 2 (p = 0.04 and p = 0.03, respectively) and resulted in a significant decrease in immotile sperm (p = 0.002 and p = 0.006, respectively). At a dose of 270 mg/kg, a considerable enhancement of forward sperm motility was observed (p = 0.04) and there was a significant decrease in sperm DNA fragmentation (p = 0.04).

Conclusions: The findings of the present study show for the first time that the hydroalcoholic extract of ADP has protective and antioxidant effects against diabetes-induced oxidative stress and can improve sperm parameters and protect sperm DNA integrity.

Pulmonary hypertension (PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular (RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: non-invasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

Background: Hypertension and dyslipidemia are considered reversible risk factors for cardiovascular disease. The purpose of this study was to explore the impact of traditional and nontraditional blood lipid profiles on the risk of left ventricular hypertrophy (LVH) and to explore the superposition effect of dyslipidemia combined with hypertension.

Methods: Data on 9134 participants (53.5 ± 10.3 years old) from the Northeast China Rural Cardiovascular Health Study (NCRCHS) were statistically analyzed. The blood lipid profile was measured by total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total glyceride (TG), and calculated nontraditional blood lipid indices including non-HDL-C, atherosclerosis index (AI), TC/HDL-C, and residual cholesterol (RC).

Results: After the adjustment of age and gender, the odds ratios (ORs) of LVH in patients with hypertension, high LDL-C, high non-HDL-C, high AI, and high TC/HDL-C were 3.97 (3.31-4.76), 1.27 (1.02-1.59), 1.21 (1.04-1.39), 1.33 (1.15-1.53), and 1.42 (1.22-1.65), respectively. After full adjustment of potential confounding factors, high AI and TC/HDL-C were associated with LVH rather than traditional blood lipid indices. The combination of hypertension and nontraditional dyslipidemia (defined by high AI and TC/HDL-C) was associated with the highest risk of LVH, especially in participants under 45 years of age. The risk was more significant in men, 5.09-fold and 6.24-fold, respectively, compared with 3.66-fold and 4.01-fold in women.

Conclusions: People with dyslipidemia defined by nontraditional blood lipid indices (high AI and high TC/HDL-C) and hypertension were more likely to develop LVH.

Object: Early-life neglect has irreversible emotional effects on the central nervous system. In this work, we aimed to elucidate distinct functional neural changes in medial prefrontal cortex (mPFC) of model rats.

Methods: Maternal separation with early weaning was used as a rat model of early-life neglect. The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.

Results: Glutamatergic and GABAergic neurons of mPFC were distinguished by typical electrophysiological properties. The excitation of mPFC glutamatergic neurons was significantly increased in male groups, while the excitation of mPFC GABAergic neurons was significant in both female and male groups, but mainly in terms of rest membrane potential and amplitude, respectively.

Conclusions: Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect, which can contribute to distinct mechanisms for emotional and cognitive manifestations.

Background: Liqoseal consists of a watertight layer of poly(ester)ether urethane and an adhesive layer containing polyethylene glycol-N-hydroxysuccinimide (PEG-NHS). It is designed to prevent cerebrospinal fluid (CSF) leakage after intradural surgery. This study assessed the safety and biodegradability of Liqoseal in a porcine craniotomy model.

Methods: In 32 pigs a craniotomy plus durotomy was performed. In 15 pigs Liqoseal was implanted, in 11 control pigs no sealant was implanted and in 6 control pigs a control dural sealant (Duraseal or Tachosil) was implanted. The safety of Liqoseal was evaluated by clinical, MRI and histological assessment. The degradation of Liqoseal was histologically estimated.

Results: Liqoseal, 2 mm thick before application, did not swell and significantly was at maximum mean thickness of 2.14 (±0.37) mm at one month. The foreign body reaction induced by Liqoseal, Duraseal and Tachosil were comparable. Liqoseal showed no adherence to the arachnoid layer and was completely resorbed between 6 and 12 months postoperatively. In one animal with Liqoseal, an epidural fluid collection containing CSF could not be excluded.

Conclusion: Liqoseal seems to be safe for intracranial use and is biodegradable. The safety and performance in humans needs to be further assessed in clinical trials.

Background: Multiple mitochondrial dysfunction syndromes (MMDS) presents as complex mitochondrial damage, thus impairing a variety of metabolic pathways. Heart dysplasia has been reported in MMDS patients; however, the specific clinical symptoms and pathogenesis remain unclear. More urgently, there is a lack of an animal model to aid research. Therefore, we selected a reported MMDS causal gene, Isca1, and established an animal model of MMDS complicated with cardiac dysplasia.

Methods: The myocardium-specific Isca1 knockout heterozygote (Isca1 HET) rat was obtained by crossing the Isca1 conditional knockout (Isca1 cKO) rat with the α myosin heavy chain Cre (α-MHC-Cre) rat. Cardiac development characteristics were determined by ECG, blood pressure measurement, echocardiography and histopathological analysis. The responsiveness to pathological stimuli were observed through adriamycin treatment. Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.

Results: ISCA1 expression in myocardium exhibited a semizygous effect. Isca1 HET rats exhibited dilated cardiomyopathy characteristics, including thin-walled ventricles, larger chambers, cardiac dysfunction and myocardium fibrosis. Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organizational levels. Meanwhile, HET rats exhibited typical MMDS characteristics, including damaged mitochondrial morphology and enzyme activity for mitochondrial respiratory chain complexes Ⅰ, Ⅱ and Ⅳ, and impaired ATP production.

Conclusion: We have established a rat model of MMDS complicated with cardiomyopathy, it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy. This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases, as well as research and development of drugs.

We emphasize the importance of studying the primate brain in cognitive neuroscience and suggest a new mind-set in primate experimentation within the boundaries of animal welfare regulations. Specifically, we list the advantages of investigating both genes and neural mechanisms and processes in the emergence of behavioral and cognitive functions, and propose the establishment of an open field of primate research. The latter may be conducted by implementing and harmonizing experimental practices with ethical guidelines that regulate (1) management of natural parks with free-moving populations of target nonhuman primates, (2) establishment of indoor-outdoor labs for both system genetics and neuroscience investigations, and (3) hotel space and technologies which remotely collect and dislocate information regarding primates geographically located elsewhere.

Oxygen plays a pivotal role in the metabolism and activities of mammals. However, oxygen is restricted in some environments-subterranean burrow systems or habitats at high altitude or deep in the ocean-and this could exert hypoxic stresses such as oxidative damage on organisms living in these environments. In order to cope with these stresses, organisms have evolved specific strategies to adapt to hypoxia, including changes in physiology, gene expression regulation, and genetic mutations. Here, we review how mammals have adapted to the three high-altitude plateaus of the world, the limited oxygen dissolved in deep water habitats, and underground tunnels, with the aim of better understanding the adaptation of mammals to hypoxia.

Background: Hematopoietic stem cells (HSC) maintain the hematopoietic system homeostasis through self-renewal and multilineage differentiation potential. HSC are regulated by the microenvironment, cytokine signaling, and transcription factors. Recent results have shown that lipid pathways play a key role in the regulation of HSC quiescence, proliferation, and division. However, the mechanism by which lipid metabolism regulates HSC proliferation and differentiation remains to be clarified. Lipoprotein lipase (LPL) is an essential enzyme in the anabolism and catabolism of very low-density lipoprotein, chylomicrons, and triglyceride-rich lipoproteins.

Methods: The percentage of hematopoietic stem/progenitor cells and immune cells were determined by fluorescence-activated cell sorting (FACS). The function and the mechanism of HSCs were analyzed by cell colony forming assay and qPCR analysis. The changes in LPL^+/- HSC microenvironment were detected by transplantation assays using red fluorescent protein (RFP) transgenic mice.

Results: To explore the function of LPL in HSC regulation, heterozygous LPL-knockout mice (LPL^+/-) were established and analyzed by FACS. LPL^+/- mice displayed decreased hematopoietic stem/progenitor cell compartments. In vitro single-cell clonogenic assays and cell-cycle assays using FACS promoted the cell cycle and increased proliferation ability. qPCR analysis showed the expression of p57^KIP2 and p21^WAF1/CIP1 in LPL^+/- mice was upregulated.

Conclusions: LPL^+/- mice exhibited HSC compartment impairment due to promotion of HSC proliferation, without any effects on the bone marrow (BM) microenvironment.