Animal models and experimental medicine最新文献

Background: Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation. Although dual innervation approaches using two neurotizers have shown promise, there is a lack of evidence-based comparison in the literature. Furthermore, no animal model of dual reinnervation has yet been published. This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats.

Methods: Fifteen Wistar rats were divided into four experimental groups and one control group. The sural nerve was exposed and used as a cross-face nerve graft (CFNG), which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead. The CFNG, the masseteric nerve (MN), and the recipient nerve were coapted in one or two stages. The length and width of the utilized structures were measured under an operating microscope. Return of whisker motion was visually confirmed.

Results: Nine out of the eleven rats that underwent surgery survived the procedure. Whisker motion was observed in all experimental animals, indicating successful reinnervation. The mean duration of the surgical procedures did not differ significantly between the experimental groups, ensuring similar conditions for all groups.

Conclusions: Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible, with a high success rate, and shows good prospects for future experiments.

Human herpesvirus, a specific group within the herpesvirus family, is responsible for a variety of human diseases. These viruses can infect humans and other vertebrates, primarily targeting the skin, mucous membranes, and neural tissues, thereby significantly impacting the health of both humans and animals. Animal models are crucial for studying virus pathogenesis, vaccine development, and drug testing. Despite several vaccine candidates being in preclinical and clinical stages, no vaccines are current available to prevent lifelong infections caused by these human herpesviruses, except for varicella-zoster virus (VZV) vaccine. However, the strict host tropism of herpesviruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases. This makes it challenging to evaluate vaccines and antivirals against human herpesvirus comprehensively. Herein, we summarize the current animal models used to study the human herpesviruses including α-herpesviruses (herpes simplex virus type 1(HSV-1), HSV-2, VZV), β-herpesviruses (human cytomegalovirus (HCMV), γ-herpesviruses (Epstein-Barr virus (EBV)) and Kaposi's sarcoma herpesvirus (KSHV)). By providing concise information and detailed analysis of the potential, limitations and applications of various models, such as non-human primates, mice, rabbits, guinea pigs, and tree shrews, this summary aims to help researchers efficiently select the most appropriate animal model, offering practical guidance for studying human herpesvirus.

Glaucoma, a visual thief, is characterized by elevated intraocular pressure (IOP) and the loss of retinal ganglion cells (RGCs). Selecting suitable animals for preclinical models is of great significance in research on the prevention, early screening, and effective treatments of glaucoma. Rabbit eyeballs possess similar vascularity and aqueous humor outflow pathways to those of humans. Thus, they are among the earliest in vivo models used in glaucoma research. Over the years, rabbit models have made substantial contributions to understanding glaucomatous pathophysiology, surgical adaptations, biomedical device development, and drug development for reducing IOP, protecting RGCs, and inhibiting fibrosis. Compared to other animals, rabbits fit better with surgical operations and cost less. This review summarizes the merits and demerits of different ways to produce glaucomatous rabbit models, such as intracameral injection, vortex vein obstruction, Trendelenburg position, laser photo-coagulation, glucocorticoid induction, limbal buckling induction, retinal ischemia-reperfusion models, and spontaneous models. We analyzed their mechanisms in the hope of providing more references for experimental design and promoting the understanding of glaucoma treatment strategies.

Background: Liver diseases are a major contributor to both morbidity and mortality. Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal. The use of floxed rat resource has rapidly increased, but the liver-specific Cre rat lines for studying liver diseases and interested genes are limited, especially in a spatially and temporally restricted manner.

Methods: RNA sequencing and real-time polymerase chain reaction (PCR) were used to screen and confirm the presence of liver-specific genes. Apoa4-Cre rats and Cyp2c11-Cre rats were produced by CRISPR/Cas9 knockin. Rosa26-imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4-Cre/Rosa26-imCherry and Cyp2c11-Cre/Rosa26-imCherry rats. The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tissue sections. Hematoxylin-eosin stain was used to evaluate the liver histopathologic changes. The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.

Results: Apoa4 and Cyp2c11 were identified as two liver-specific genes. Apoa4-Cre and Cyp2c11-Cre rats were produced and hybridized with Rosa26-imCherry rats. The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats. All the blood biochemical parameters except low-density lipoprotein (LDL) did not change significantly in the Cre rats. No histological alterations were detected in the livers of the Cre rats.

Conclusions: Liver-specific Apoa4-Cre and Cyp2c11-Cre rats have been established successfully and could be used to study gene knockout, specifically in juvenile and adult liver.

The mortality rate of patients with abdominal aortic aneurysm (AAA) after rupture is extremely high, and this disease has become an important disease endangering the health of the Chinese population. Methods used to model AAA include intraluminal pressurized elastase infusion, chronic infusion of angiotensin II (Ang II) via an osmotic pump, periarterial application of calcium chloride, vascular grafting, and gene modification. AAA models induced by elastase and Ang II are the two most widely used animal models. In the elastase-induced model, because intraluminal infusion is transient, with the cessation of initial stimulation, the aneurysm lesion tends to be stable and rarely ruptures. The model induced by Ang II infusion often presents with a typical aortic dissection with a false lumen, whereas clinical AAA patients do not necessarily have dissection. Currently, the treatment of AAA in clinical practice remains endovascular, and there is a lack of pharmacological therapy, which is also related to the fact that the pathogenic mechanism has not been fully elucidated. Smoking, old age, male sex, and hypertension are the main risk factors for AAA, but these risk factors have not been fully investigated in the current modeling methods, which may affect the clinical translational application of research results based on animal models. Therefore, this article reviews the most commonly used AAA modeling methods, comments on their applications and limitations, and provides a perspective on the development of novel animal models.

Dear Colleagues,

It is my distinct honor to serve as the Honorary Chief Editor of AMEM, an international open-access journal, dedicated to serve as a platform for international exchange, and the translation of research outcomes in the field of life sciences. AMEM strives to establish itself as a high-level international academic exchange platform that brings together scientific wisdom from around the world and offers a prestigious journal for presenting research findings, and disseminating state of the art knowledge in the vibrant fields of life sciences.

AMEM's strong academic foundation and extensive international influence are evident from its inclusion in esteemed databases, such as ESCI, MEDLINE, Scopus, PMC, and DOAJ, with a Q2 ranking in JCI and JCR, and widespread indexing by academic search engines including Google Scholar. The articles published in AMEM cover various frontier areas of animal model preparation, laboratory animal science, and experimental medicine, featuring special columns on medical artificial intelligence, stem cells and regenerative medicine, neurodegenerative diseases, and cardiovascular and cerebrovascular disease research, making it one of the key platform for dissemination of new and novel research, and developments to global readers. I am sure the untiring and sincere efforts of the Editorial team and contributing authors will help the AMEM to leap forward to greater heights.

Here, I sincerely invite researchers in various fields of life sciences to contribute original articles to AMEM. Whether you specialize in the development and utilization of experimental animal resources or are focused on experimental medical research on cancers, neurodegenerative diseases, and more, AMEM is an ideal choice for showcasing your research findings and promoting academic excellence. We greatly appreciate that your scholarly contributions will play a pivotal role in advancing experimental animal, and experimental medicine fields.

I sincerely hope that researchers worldwide will join hands with the AMEM team in our shared mission of showcasing the latest research findings and academic excellence from the platform of AMEM. Our team will make sure that your research breakthroughs reach every corner of the world.

Finally, I wish all of you continued success, and look forward to witnessing the sustained growth in the stature and outreach of the AMEM.

Thank you all!

AMEM Honrary Editor-in-Chief

Background: Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation (ECC). To evaluate the hemodynamic impact of ECC on atheromatous plaques, an atherosclerosis animal model, which is also eligible for ECC, is required.

Methods: Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet (group diet, n = 10), a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury (group BI, n = 9), or served as controls (n = 10). After 3 or 6 months, aortic explants were analyzed by (immuno-)histology and RT-PCR.

Results: Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls (3 months: p = 0.03 each, 6 months: p < 0.0001 each). Aortic inflammatory infiltration was significantly enhanced in groups diet (CD3 at 3 months: p < 0.0001, 6 months: p = 0.02; CD68 at 3 months: p = 0.01) and BI (CD3 at 3 months: p < 0.0001, 6 months: p = 0.03; CD68 at 3 months: p = 0.04, 6 months: p = 0.02). Increased intima hyperplasia occurred in both groups (p < 0.0001 each). Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques. Calcification of the intima and media was increased in groups diet (intima: p < 0.0001 at 3 and 6 months; media at 3 months: p < 0.0001, 6 months: p = 0.01) and BI (intima: p < 0.0001 at 3 and 6 months; media at 3 months: p < 0.0001, 6 months: p = 0.02). Extensive lipid accumulation was found in the intima in both treatment groups (p < 0.0001 each).

Conclusions: A rabbit model with high aortic calcific plaque burden-diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome-exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized. It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.

Cerebral ischemia/reperfusion (I/R) injury is an important pathophysiological condition of ischemic stroke that involves a variety of physiological and pathological cell death pathways, including autophagy, apoptosis, necroptosis, and phagoptosis, among which autophagy is the most studied. We have reviewed studies published in the past 5 years regarding the association between autophagy and cerebral I/R injury. To the best of our knowledge, this is the first review article summarizing potential candidates targeting autophagic pathways in the treatment of I/R injury post ischemic stroke. The findings of this review may help to better understand the pathogenesis and mechanisms of I/R events and bridge the gap between basic and translational research that may lead to the development of novel therapeutic approaches for I/R injury.

Background: China is a high-burden country for multidrug-resistant tuberculosis/rifampin-resistant tuberculosis (MDR/RR-TB). Fluoroquinolones (FQs) are key drugs for the treatment of patients with MDR/RR-TB. However, research on the resistance of FQs in Beijing is limited.

Methods: We collected clinical isolates from all patients with pulmonary TB in Beijing from January 2016 to December 2021, conducted drug-sensitivity tests and sequencing for levofloxacin (LFX) and moxifloxacin (MFX), and collected the treatment plans and outcomes of the patients.

Results: A total of 8512 clinical isolates were collected from patients with pulmonary TB, and 261 RR-TB strains were screened. The proportions of drug-sensitive and drug-resistant strains significantly differed by age group and treatment history. The rates of LFX and MFX resistance were 27.6% (72/261) and 36.4% (95/261), respectively. The detection rates of MDR-TB and pre-extensively drug-resistant TB (pre-XDR-TB) were 73.2% (191/261) and 36.4% (95/261), respectively, and the trends were significant (χ² trend = 9.995, p = 0.002; χ² trend = 12.744, p = 0.026). Among the 261 RR-TB strains, 14.9% (24/261) were sensitive to LFX but resistant to MFX. Among the four patients with LFX-resistant TB who received LFX treatment failed in three patients(Fisher's exact test, p = 0.009). The common mutation sites were 94 and 90 in gyrA. A novel mutation Ala90Ser was discovered.

Conclusions: FQs resistance trends in RR-TB patients in Beijing are striking. Strains showed incomplete cross-resistance to LFX and MFX. Testing for FQs resistance and developing a reasonable treatment plan are recommended. Attention should be given to the changing trends in MDR-TB and pre-XDR-TB.