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Animal models that are susceptible to SARS-CoV-2 infection and develop clinical signs like human COVID-19 are desired to understand viral pathogenesis and develop effective medical countermeasures. The golden Syrian hamster is important for the study of SARS-CoV-2 since hamsters are naturally susceptible to SARS-CoV-2. However, infected hamsters show only limited clinical disease and resolve infection quickly. In this study, we describe development of human angiotensin-converting enzyme 2 (hACE2) transgenic hamsters as a model for COVID-19. During development of the model for SARS-CoV-2, we observed that different hACE2 transgenic hamster founder lines varied in their susceptibility to SARS-CoV-2 lethal infection. The highly susceptible hACE2 founder lines F0F35 and F0M41 rapidly progress to severe infection and death within 6 days post-infection (p.i.). Clinical signs included lethargy, weight loss, dyspnea, and mortality. Lethality was observed in a viral dose-dependent manner with a lethal dose as low as 1 × 100.15 CCID50. In addition, virus shedding from highly susceptible lines was detected in oropharyngeal swabs on days 2–5 p.i., and virus titers were observed at 105.5−6.5 CCID50 in lung and brain tissue by day 4 p.i.. Histopathology revealed that infected hACE2-hamsters developed rhinitis, tracheitis, bronchointerstitial pneumonia, and encephalitis. Mortality in highly susceptible hACE2-hamsters can be attributed to neurologic disease with contributions from the accompanying respiratory disease. In contrast, virus challenge of animals from less susceptible founder lines, F0M44 and F0M51, resulted in only 0–20% mortality. To demonstrate utility of this SARS-CoV-2 infection model, we determined the protective effect of the TLR3 agonist polyinosinic-polycytidylic acid (Poly (I:C)). Prophylactic treatment with Poly (I:C) significantly improved survival in highly susceptible hACE2-hamsters. In summary, our studies demonstrate that hACE2 transgenic hamsters differ in their susceptibility to SARS-CoV-2 infection, based on the transgenic hamster founder line, and that prophylactic treatment with Poly (I:C) was protective in this COVID-19 model of highly susceptible hACE2-hamsters. [ABSTRACT FROM AUTHOR]

Nonhuman primate (NHP) studies that utilize simian immunodeficiency virus (SIV) to model human immunodeficiency virus (HIV-1) infection have proven to be powerful, highly informative research tools. However, there are substantial differences between SIV and HIV-1. Accordingly, there are numerous research questions for which SIV-based models are not well suited, including studies of certain aspects of basic HIV-1 biology, and pre-clinical evaluations of many proposed HIV-1 treatment, prevention, and vaccination strategies. To overcome these limitations of NHP models of HIV-1 infection, several groups have pursued the derivation of a minimally modified HIV-1 (mmHIV-1) capable of establishing pathogenic infection in macaques that authentically recapitulates key features of HIV-1 in humans. These efforts have focused on three complementary objectives: (1) engineering HIV-1 to circumvent species-specific cellular restriction factors that otherwise potently inhibit HIV-1 in macaques, (2) introduction of a C chemokine receptor type 5 (CCR5)-tropic envelope, ideally that can efficiently engage macaque CD4, and (3) correction of gene expression defects inadvertently introduced during viral genome manipulations. While some progress has been made toward development of mmHIV-1 variants for use in each of the three macaque species (pigtail, cynomolgus, and rhesus), model development progress has been most promising in pigtail macaques (PTMs), which do not express an HIV-1-restricting tripartite motif-containing protein 5 α (TRIM5α). In our work, we have derived a CCR5-tropic mmHIV-1 clone designated stHIV-A19 that comprises 94% HIV-1 genome sequence and replicates to high acute-phase titers in PTMs. In animals treated with a cell-depleting CD8α antibody at the time of infection, stHIV-A19 maintains chronically elevated plasma viral loads with progressive CD4+ T-cell loss and the development of acquired immune-deficiency syndrome (AIDS)-defining clinical endpoints. However, in the absence of CD8α+ cell depletion, no mmHIV-1 model has yet displayed high levels of chronic viremia or AIDS-like pathogenesis. Here, we review mmHIV-1 development approaches, the phenotypes, features, limitations, and potential utility of currently available mmHIV-1s, and propose future directions to further advance these models. [ABSTRACT FROM AUTHOR]

Objective To summarize the existing animal models of cholelithiasis, and to explore a pathological model that can better reflect the characteristics of clinical syndromes of traditional Chinese and western medicine and meet the needs of the development of clinical and basic research of traditional Chinese medicine. Methods The animal models for experimental research on cholelithiasis at home and abroad were collected and sorted out by searching CNKI, Wanfang, VIP, SinoMed, PubMed and other databases. The animal types, modeling methods, modeling cycles, detection indicators and positive drugs of the models were statistically analyzed. Results Among the 128 articles included, the animal types of cholelithiasis models were mainly guinea pigs, rabbits and C57BL/6J mice. The most used modeling method is high-fat diet, and the feeding cycle takes eight weeks to complete. High-frequency detection indicators were stone formation rate, total cholesterol, phospholipids, total bilirubin, total bile acid, etc. The commonly used intervention methods are traditional Chinese medicine compound, western medicine and single Chinese medicine or extract. Ursodeoxycholic acid (UDCA) is mainly used for western medicine intervention, whereas the intervention of traditional Chinese medicine mainly includes traditional Chinese medicine compound, acupuncture, exercise, diet and other methods. The positive control drug in the experiment was mostly UDCA. Conclusion With the continuous improvement and development of cholelithiasis animal model, there are many kinds of modeling methods to simulate the clinical manifestations of cholelithiasis in Chinese and western medicine, but there are also some limitations. This paper aims to provide reference for the selection, application and improvement of cholelithiasis model through data mining and characteristic analysis. [ABSTRACT FROM AUTHOR]

Objective To establish an animal model of dampness-syndrome in mice (single model) and evaluate its characteristics of dampness-syndrome. The above-mentioned mice with dampness syndrome were used to construct mice model of ischemic stroke (double model) and observe the effect of dampness-pathogenic on the outcome of stroke. Methods Healthy C57BL/6J male mice were randomly divided into dampness-syndrome (including sham-surgery group and ischemic stroke group, with 10 mice in each group) and non dampness- syndrome groups (including sham-surgery group and ischemic stroke group, with 10 mice in each group). The dampness-syndrome group was fed with high-fat diet and the non dampness-syndrome group was fed with normal diet for 12 weeks. After the mice model of dampness-syndrome was successfully established, transient middle cerebral artery occlusion/reperfusion (tMCAO/R) surgery was used to replicate an ischemic stroke mice model. Evaluation indicators for dampness-syndrome mice model: the general status including body weight, morphology, posture, activity status, and physical characteristics, the histopathological observation of the aorta (oil red O staining, Masson-trichrome staining) and liver (HE staining, oil red O staining), electron microscopic observation of the tongue tissue (scanning electron microscopy, electron microscopy), blood lipid levels [total cholesterol (TC),triglycerides (TG)] and liver coefficient. Evaluation indicators for ischemic stroke mice model: neurological function score and the cerebral infarction volume ratio. Results Compared with the non dampness- syndrome group, the mice in the dampness-syndrome group showed an increased in body weight, poor hair color, sparse hair, fatigue and laziness, mental atrophy, anorexia and lethargy. It was observed that the aortic lumen was narrowed, the intima was significantly thickened, lipid plaque deposition was increased, and foam cells were visible. A large amount of red lipid droplets appeared in liver cells. There were obvious lipid infiltration and diffuse steatosis. Increased keratosis of the mucosal layer of tongue tissue, the thicker stratum corneum, lipofuscin, and bacteria on the tongue surface were found. Serum TG and TC levels significantly increased (P＜0.01), and the liver coefficient significantly decreased (P＜0.001). Compared with non dampness-syndrome group (sham-surgery group), neurological function score and the cerebral infarction volume ratio in dampness-syndrome ischemic stroke group obviously increased (P＜0.001). Conclusion High-fat feeding for 12 weeks combined with tMCAO/R modeling can successfully establish a mice model with dampness-syndrome ischemic stroke, and the neurological function score and cerebral infarction volume in the dampness-syndrome ischemic stroke group was more severe than that in the non dampness-syndrome ischemic stroke group. [ABSTRACT FROM AUTHOR]

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions, expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet, a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment, and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass, food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions, PASI score, the value of transdermal water loss (TEWL), and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index, changes in the histopathological morphology of liver tissue under HE staining, changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR, and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group, the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P＜0.001), significantly lower food intake (P＜0.005), and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur, mental fatigue, etc. appeared. The TWEL were significantly increased (P＜0.001), and the PASI scores also significantly increased (P＜0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+ neutrophil subpopulation, CD11binLy6Chigh monocyte subpopulation, CD11binCD11chigh classical dendritic cell subpopulation, F4/80-CD11c+ dendritic cell subpopulation was significantly increased (P＜ 0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration, and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P＜ 0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated (P＜0.005, P＜0.001), while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P＜0.05, P＜ 0.01). ABCA1 protein level in skin increased (P＞0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern, which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern. [ABSTRACT FROM AUTHOR]

Treating flexor tendon injuries within the digital flexor sheath (commonly referred to as palmar hand zone 2) presents both technical and logistical challenges. Success hinges on striking a delicate balance between safeguarding the surgical repair for tendon healing and initiating early rehabilitation to mitigate the formation of tendon adhesions. Adhesions between tendon slips and between tendons and the flexor sheath impede tendon movement, leading to postoperative stiffness and functional impairment. While current approaches to flexor tendon repair prioritize maximizing tendon strength for early mobilization and adhesion prevention, factors such as pain, swelling, and patient compliance may impede postoperative rehabilitation efforts. Moreover, premature mobilization could risk repair failure, necessitating additional surgical interventions. Pharmacological agents offer a potential avenue for minimizing inflammation and reducing adhesion formation while still promoting normal tendon healing. Although some systemic and local agents have shown promising results in animal studies, their clinical efficacy remains uncertain. Limitations in these studies include the relevance of chosen animal models to human populations and the adequacy of tools and measurement techniques in accurately assessing the impact of adhesions. This article provides an overview of the clinical challenges associated with flexor tendon injuries, discusses current on‐ and off‐label agents aimed at minimizing adhesion formation, and examines investigational models designed to study adhesion reduction after intra‐synovial flexor tendon repair. Understanding the clinical problem and experimental models may serve as a catalyst for future research aimed at addressing intra‐synovial tendon adhesions following zone 2 flexor tendon repair. [ABSTRACT FROM AUTHOR]

The dura mater is a barrier between the brain and the surrounding environment. Injuries to the dura can lead to serious complications, therefore, ensuring a hermetic closure of the dura is a primary task for a neurosurgeon. The aim of the study is to compare the effectiveness of applying the newly developed ViscollDURA collagen membrane (VDCM), with the commercially available Durepair (xenogeneic collagen) in animal model. A dural tear model was utilized in rats with membrane implantation using an application method. The sample size consisted of 24 rats. Group I underwent VDCM implantation, while Group II underwent Durepair implantation. Results were evaluated at 30, 60, and 90 days. The study was assessed using magnetic resonance imaging, histology, electron scanning microscopy, and immunohistochemistry. The obtained results underwent statistical analysis. In the clinical presentation, there were no difference between groups. Histologically, Group 1 showed comparable results to Group 2. The integration process of the membrane statistically differed between the groups. In Group 1, neovascularization and tissue replacement showed better results than in Group 2. Magnetic resonance imaging differences were observed at later stages, with group 2 showing adhesion and brain deformation in the implantation area. Both membranes showed safety and compatibility. The collagen membrane produced under sterile conditions demonstrated better regeneration with minimal inflammatory reaction. The study suggests that VDCM exhibits biocompatibility comparable to Durepair, providing prospects for potential applications in neurosurgery. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, affecting up to 30% of the population, with approximately 20% of cases occurring in non-obese individuals. The recent shift to the term metabolic dysfunction-associated steatosis liver disease (MASLD) highlights the disease's heterogeneity. However, there are no well-established animal models replicating non-obese NAFLD (NO-NAFLD). This study aimed to evaluate the relevance of the high-fat diet (HFD) combined with the propylthiouracil (PTU)-induced rat model in mimicking the histopathology and pathophysiology of NO-NAFLD. We first analyzed metabolic and clinical parameters between NO-NAFLD patients (Average BMI = 21.96 kg/m2) and obese NAFLD patients (Average BMI = 29.7 kg/m2). NO-NAFLD patients exhibited significantly higher levels of carnitines, phospholipids, and triglycerides. In the animal model, we examined serum lipid profiles, liver inflammation, histology, and transcriptomics. Hepatic steatosis in the HFD+PTU model at week 4 was comparable to that of the HFD model at week 8. The HFD+PTU model showed higher levels of carnitines, phospholipids, and triglycerides, supporting its relevance for NO-NAFLD. Additionally, the downregulation of lipid synthesis-related genes indicated differences in lipid accumulation between the two models. Overall, the HFD+PTU-induced rat model is a promising tool for studying the molecular mechanisms of NO-NAFLD. [ABSTRACT FROM AUTHOR]

For many years, the significance of cardiac lymphatic vessels was largely overlooked in clinical practice, with little consideration given to their role in the pathophysiology or treatment of cardiac diseases. However, recent research has brought renewed attention to these vessels, progressively illuminating their function and importance within the realm of cardiovascular science. Experimental studies, particularly those utilizing animal models of cardiac disease, have demonstrated a clear relationship between cardiac lymphatic vessels and both the pathogenesis and progression of these conditions. These findings have prompted a growing interest in potential therapeutic applications that specifically target the cardiac lymphatic system. Conversely, while clinical investigations into cardiac lymphatics remain limited, recent studies have begun to explore their identification through specific surface markers, as well as the expression dynamics of lymphangiogenic factors. These studies have increasingly highlighted associations of lymphatic dysfunction with inflammation and fibrosis, both of which negatively impact cardiac function and remodeling across various pathological states. Despite these advances, comprehensive reviews of the current knowledge regarding the cardiac lymphatic vasculature, particularly within specific disease contexts, remain scarce. This review aims to address this gap by providing a detailed synthesis of existing reports, encompassing both animal model research and studies on human clinical specimens, with a special focus on the role of cardiac lymphatic vessels in different disease states. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non‐human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents. Methods: Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF‐Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann–Whitney statistical analyses were done when indicated. Results: NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro‐muscular block at equivalent doses to clinical doses in humans. The rocuronium‐induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count. Conclusion: These results support the use of non‐human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA‐reversal agents. [ABSTRACT FROM AUTHOR]

This study comprehensively validated the bleomycin (BLEO) induced mouse model of IPF for utility in preclinical drug discovery. To this end, the model was rigorously evaluated for reproducible phenotype and TGFβ‐directed treatment outcomes. Lung disease was profiled longitudinally in male C57BL6/JRJ mice receiving a single intratracheal instillation of BLEO (n = 10–12 per group). A TGFβR1/ALK5 inhibitor (ALK5i) was profiled in six independent studies in BLEO‐IPF mice, randomized/stratified to treatment according to baseline body weight and non‐invasive whole‐body plethysmography. ALK5i (60 mg/kg/day) or vehicle (n = 10–16 per study) was administered orally for 21 days, starting 7 days after intratracheal BLEO installation. BLEO‐IPF mice recapitulated functional, histological and biochemical hallmarks of IPF, including declining expiratory/inspiratory capacity and inflammatory and fibrotic lung injury accompanied by markedly elevated TGFβ levels in bronchoalveolar lavage fluid and lung tissue. Pulmonary transcriptome signatures of inflammation and fibrosis in BLEO‐IPF mice were comparable to reported data in IPF patients. ALK5i promoted reproducible and robust therapeutic outcomes on lung functional, biochemical and histological endpoints in BLEO‐IPF mice. The robust lung fibrotic disease phenotype, along with the consistent and reproducible lung protective effects of ALK5i treatment, makes the spirometry‐confirmed BLEO‐IPF mouse model highly applicable for profiling novel drug candidates for IPF. [ABSTRACT FROM AUTHOR]

Rabbits have played a significant role in both livestock production and the advancement of reproductive scientific research. Their unique biological traits, including induced ovulation and a reproductive process that closely mirrors that of humans, have been pivotal in their use as a model. Moreover, their body size is perfectly aligned with the 3Rs principles: Replacement, Reduction, and Refinement. Consequently, techniques for gamete collection and embryo recovery, followed by their use in artificial insemination or embryo transfer, are characterized by being minimally invasive. However, refining in vitro fertilization and embryo culture techniques continues to present challenges. The incorporation of cutting‐edge genomic editing tools, such as CRISPR/Cas9, has reestablished rabbits as essential models in genetic and biomedical research, driving scientific progress. This review aims to describe the most effective reproductive biotechnologies for both male and female rabbits and how these methodologies are in line with the 3Rs principles—Replacement, Reduction, and Refinement—highlighting their significance in conducting ethical research. [ABSTRACT FROM AUTHOR]

Purpose: Parastomal hernia poses a challenging problem in the field of hernia surgery. The high incidence and recurrence rates of parastomal hernia necessitate surgeons to enhance surgical techniques and repair materials. This study aimed to develop a rat model of parastomal hernia by inducing various types of defects on the abdominal wall with colostomy. This established method has potential for future studies on parastomal hernia. Methods: In this study, 32 male rats were included and randomly divided into four groups: the oblique abdominis excision (OE), oblique abdominis dissection (OD), rectus abdominis excision (RE), and rectus abdominis dissection (RD) groups. In each group, colostomy was performed and an abdominal wall defect was induced. The rats were observed for 28 days following surgery. The survival rate, body weight, parastomal hernia model scores, abdominal wall adhesion and inflammation, and collagen level in the hernial sac were compared. Results: No significant differences in survival rate and weight were observed among the four groups. The parastomal hernia model scores in the RE and RD groups were significantly higher than those in the OE and OD groups. The ratio of collagen I/III in the RE and RD groups was significantly lower than that in the OE and OD groups. Adhesion and inflammation levels were lower in the RE group than in the RD group. Conclusion: Based on a comprehensive comparison of the findings, RE with colostomy emerged as the optimal approach for establishing parastomal hernia models in rats. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the chicken femur as a laboratory model for the human metacarpal by comparing the bone microarchitecture and mechanical properties of chicken femurs to human cadaveric metacarpals. Methods: Sixteen fresh chicken femora and 20 fresh frozen cadaveric human metacarpals were imaged using a micro computed tomography scanner. The bones were then mechanically tested using four-point-bending and torsional testing. Results: There were no significant differences in macroscopic features between chicken femora and human metacarpals, including overall length, external radius, internal radius, cortical width and cross-sectional area of the diaphyseal cortex (p > 0.05). There were no significant differences in the trabecular number and spacing in the distal metaphysis of both groups (p > 0.05). The diaphysis and proximal metaphysis did not share any microarchitectural similarities. Four-point bending tests resulted in significantly higher yield forces, ultimate force, failure points and stiffness in human metacarpals (p < 0.05). Torsion tests resulted in significant higher ultimate torque and torsional rigidity in human metacarpals (p < 0.05). Conclusions: The chicken femur has structural and biomechanical differences to the fresh frozen human metacarpal despite the similarity in their macroscopic features. [ABSTRACT FROM AUTHOR]

Exposure to infectious or non‐infectious immune activation during early development is a serious risk factor for long‐term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic‐polyribocytdilic acid), a synthetic analogue of double‐stranded RNA, during gestation, which robustly induces an acute viral‐like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)‐treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non‐rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)‐exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non‐exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring. [ABSTRACT FROM AUTHOR]

Summary: Antibiotic resistance is now deemed a worldwide problem that puts public health at risk. The potential of Murraya (Murraya koenigii (L.) Spreng. and Murraya paniculata (L.) Jacq.) leaves and stems as antibacterial agents against multidrug‐resistant Acinetobacter baumannii (MDRAB) was assessed in our study. First, screening was performed by disc diffusion assay, and minimum inhibitory concentration values were then determined as compared to tigecycline. A. baumnii mouse model of infection was established to substantiate the antibacterial activity of Murraya species. Results revealed high antimicrobial activity for stem of both plants where leaves showed moderate to weak activity. Phytochemical characterisation revealed the identification of 129 metabolites belonging to different classes of compounds viz. coumarins, carbazole alkaloids, flavonoids, phenolic acids, and miscellaneous. In vivo data from the animal model supported the high efficiency of M. paniculata stems as promising extract for lead candidates against MDRAB pulmonary infections. Inhibition of its essential MurF (UDP‐N‐acetylmuramoyl‐tripeptide‐D‐alanyl‐d‐alanine ligase) protein has been reported as a potential target for broad‐spectrum drugs. In silico results after molecular docking to MurF from Acinetobacter baumannii (PDB ID: 4QF5) showed competitive binding mode to ATP ligand at the active site predicting antibacterial activity of the tested compounds. Furthermore, chlorogenic acid, caffeic acid, sinapic acid, feruloyl agmatine, and mahanimbidine were detected as the key discriminatory metabolites correlated with antibacterial activity. To our knowledge, this is the first in vivo anti‐MDRAB study for the investigated plant. Murraya plants have enormous possibility for the discovery of novel bioactive compounds which could combat against resistant microorganisms. [ABSTRACT FROM AUTHOR]

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. Methods: Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. Results: Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5–200 mg/kg with an intervention time of 7–28 days were relatively effective. Conclusions: Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC. [ABSTRACT FROM AUTHOR]

Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models. Methods: Seventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed. Results: Our findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage. Conclusion: We have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors. [ABSTRACT FROM AUTHOR]

Background: An overlooked factor in the efficacy of topical antibiotics to treat bacterial keratitis is the state of the corneal epithelium. Recently, we evaluated topical cefiderocol for the treatment of extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) keratitis in eyes with the corneal epithelium abraded. The goal of this study was to use the same model with the corneal epithelium left intact to evaluate the efficacy of cefiderocol and other antibiotics and compare the results to those of the previous study. Methods: NZW rabbit corneas with intact epithelium were inoculated with XDRPA. After 16 h, the rabbits were topically treated with cefiderocol 50 mg/mL, ciprofloxacin 0.3%, tobramycin 14 mg/mL, or saline. Following 8 h of treatment, the corneas were harvested for CFU determinations and cefiderocol concentrations. Results: Only cefiderocol significantly decreased CFU of the XDRPA strain compared with saline. The CFU in the cefiderocol and tobramycin-treated corneas for the XDRPA strain with initially intact epithelium were 1.83–1.4 Log10 greater than those produced in corneas with the abraded epithelium (p < 0.05). Cefiderocol concentrations were 5.02× less in corneas with initially intact epithelium. Conclusions: The efficacy of cefiderocol and tobramycin to treat experimental XDRPA keratitis is dependent on the state of the corneal epithelium. [ABSTRACT FROM AUTHOR]

This study evaluated changes over time in skeletal muscle atrophy, expressions of skeletal muscle anabolic and catabolic genes, and mitochondrial activity by skeletal muscle type in an adenine-induced chronic kidney disease (CKD) model. A CKD model was successfully established by feeding male Wistar rats a 0.75% adenine diet for 4 weeks starting at 8 weeks of age. Control and CKD groups were sacrificed at 12 and 20 weeks of age. The back muscles were analyzed histologically, and succinate dehydrogenase (SDH) staining was performed to evaluate mitochondrial activity. Gene expressions of myogenic determination gene number 1 and myogenin as indicators of muscle anabolism, atrogin-1 and muscle RING-finger protein-1 (MuRF1) as indicators of muscle catabolism, and peroxisome proliferator-activated receptor-γ coactivator-1-α as a marker of mitochondrial biogenesis were assessed. Type I and type II muscle cross-sectional areas (CSAs) were decreased at 12 weeks, but type I muscle CSA was recovered at 20 weeks. SDH staining was lower in CKD than in control rats at 12 weeks, but no significant difference was observed at 20 weeks. Increased expressions of myogenin, atrogin-1, and MuRF-1 were observed only at 12 weeks, but no differences were observed at 20 weeks. The adenine-induced CKD rat model appears to show changes in muscle atrophy over time. [ABSTRACT FROM AUTHOR]

Heart failure is a clinical syndrome that has become a leading public health problem worldwide. Globally, nearly 64 million individuals are currently affected by heart failure, causing considerable medical, financial, and social challenges. One therapeutic option for patients with advanced heart failure is mechanical circulatory support (MCS) which is widely used for short-term or long-term management. MCS with various ventricular assist devices (VADs) has gained traction in end-stage heart failure treatment as a bridge-to-recovery, -decision, -transplant or -destination therapy. Due to limitations in studying VADs in humans, animal studies have substantially contributed to the development and advancement of MCS devices. Large animals have provided an avenue for developing and testing new VADs and improving surgical strategies for VAD implantation and for evaluating the effects and complications of MCS on hemodynamics and organ function. VAD modeling by utilizing rodents and small animals has been successfully implemented for investigating molecular mechanisms of cardiac unloading after the implantation of MCS. This review will cover the animal research that has resulted in significant advances in the development of MCS devices and the therapeutic care of advanced heart failure. [ABSTRACT FROM AUTHOR]

One of the frequent causes of low back pain is intervertebral disc degeneration (IDD), which is followed by discogenic pain. Some significant risk factors that have been linked to the onset and progression of IDD include age, mechanical imbalance, changes in nutrition and inflammation. According to recent studies, five types of animal models are established for producing IDD: the spontaneous models, the puncture models, the biomechanical models, the chemical models and the hybrid models. These models are crucial in studying and understanding IDD's natural history and identifying potential treatment targets for IDD. In our study, we'll talk about the technical aspects of these models, the time between model establishment and the apparition of observable degradation, and their potential in various research. Each animal model should be compared to the human natural IDD pathogenesis to guide future research efforts in this area. By improving knowledge and appropriate application of various animal models, we seek to raise awareness of this illness and further translational research. [ABSTRACT FROM AUTHOR]

Background/Objectives: Type 1 diabetes affects cytokines as potential inducers of NFκB signalling involved in inflammation and neuronal survival. Our goal was to assess the expression of NFκB p65 and its negative regulator, Nrf2, in myenteric neurons and adjacent smooth muscle of different gut segments after chronic hyperglycaemia and immediate insulin treatment. Methods: After ten weeks of hyperglycaemia, intestinal samples of control, streptozotocin-induced diabetic and insulin-treated diabetic rats were prepared for fluorescent immunohistochemistry, immunogold electron microscopy, ELISA and qPCR. Results: In the diabetic rats, the proportion of NFκB p65-immunoreactive myenteric neurons decreased significantly in the duodenum and increased in the ileum. The density of NFκB p65-labelling gold particles increased in the ileal but remained unchanged in the duodenal ganglia. Meanwhile, both total and nuclear Nrf2 density increased in the myenteric neurons of the diabetic duodenum. In smooth muscle, NFκB p65 and Nrf2 density increased in the small intestine of diabetic rats. While on the mRNA level, NFκB p65 and Nrf2 were induced, on the protein level, NFκB p65 increased and Nrf2 decreased in muscle/myenteric plexus homogenates. Insulin treatment had protective effects. Conclusions: Our findings reveal a segment-specific NFκB and Nrf expression in myenteric neurons and ganglionic muscular environments, which may contribute to regional neuronal survival and motility disturbances in diabetes. [ABSTRACT FROM AUTHOR]

Generating animal models can explore the role of new candidate genes in causing diseases and the pathogenicity of a specific mutation in the underlying genes. These animals can be used to identify new pharmaceutical or genetic therapeutic methods. In the present experiment, we developed a rpe65a knock out (KO) zebrafish as a retinitis pigmentosa (RP) disease model. Using the CRISPR/Cas9 system, the rpe65a gene was KO in zebrafish. Two specific single-guide RNAs (sgRNAs) were designed for the zebrafish rpe65a gene. SgRNAs were cloned into the DR274 plasmid and synthesized using in vitro transcription method. The efficiency of Ribonucleoprotein (synthesized sgRNA and recombinant Cas9) was evaluated by in vitro digestion experiment. Ribonucleoprotein complexes were microinjected into one to four-celled eggs of the TU zebrafish strain. The effectiveness of sgRNAs in KO the target gene was determined using the Heteroduplex mobility assay (HMA) and Sanger sequencing. Online software was used to determine the percent of mosaicism in the sequenced samples. By examining the sequences of the larvae that showed a mobility shift in the HMA method, the presence of indels in the binding region of sgRNAs was confirmed, so the zebrafish model for RP disease established. Zebrafish is an ideal animal model for the functional study of various diseases involving different genes and mutations and used for evaluating different therapeutic approaches in human diseases. This study presents the production of rpe65a gene KO zebrafish models using CRISPR/Cas9 technology. This model can be used in RP pathophysiology studies and preclinical gene therapy experiments. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to investigate the alterations in the microbial community of KK-Ay mice following antibiotic treatment. A comparative analysis of the gut microbiota was conducted between KK-Ay mice treated with antibiotics and those without treatment. The microbial community dynamics in antibiotic-treated KK-Ay mice were meticulously assessed over an eight-week period using 16S rDNA sequencing analysis. Simultaneously, dynamic renal function measurements were performed. The results demonstrated a marked decrease in bacterial DNA abundance following antibiotic intervention, coupled with a substantial reduction in bacterial diversity and a profound alteration in microbial composition. These observed microbiota changes persisted in the KK-Ay mice throughout the eight-week post-antibiotic treatment period. Particularly noteworthy was the reemergence of bacterial populations after two weeks or more, resulting in a microbiota composition resembling that of untreated KK-Ay mice. This transition was characterized by a significant increase in the abundance of clostridia at the class level, Lachnospirales and Oscillospirales at the order level, and Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Concurrently, there was a notable decrease in Clostridia_UCG-014. The observed alterations in the gut microbiota of antibiotic-treated KK-Ay mice suggest a dynamic response to antibiotic intervention and subsequent restoration towards the original untreated state. [ABSTRACT FROM AUTHOR]

Objective: Current laryngeal injection models rely on the transoral route and are suboptimal due to limited view, narrowed working space, and the need to sacrifice animals for investigation of the injectables. In the present study, a novel surgical model for laryngeal intervention therapy utilizing an ultra‐high frequency ultrasound imaging system was proposed. Based on this system, we developed a systemic evaluation approach, from guidance of the injection process, documentation of the injection site of the material, to in vivo longitudinal follow‐up on the augmentation and medialization effect by analyzing the ultrasonography data. Study Design: In vivo animal study. Setting: Academic institution. Methods: Injection laryngoplasty with hyaluronic acid under ultrasonography guidance was performed on Sprague‐Dawley rats one week after induced unilateral vocal paralysis. Ultrasonography was performed at preinjection, immediately postinjection, on Day 2, Day 7 and then weekly for 4 weeks to obtain measurements, including the glottic area, angle between bilateral folds, and vocal fold width ratio. Laryngoscopic and histologic studies were also performed. Results: Unilateral injections to the paralyzed fold were successfully performed as demonstrated by ultrasonographic, laryngoscopic, and histologic studies. The width ratio was significantly increased after injection for 4 weeks, while the glottic airway area was unchanged. Conclusion: Here, a novel surgical model for laryngeal injection utilizing ultrasonography in rats was established. In addition to providing visual guidance for precise localization of the injection, robust documentation of the treatment effect was also demonstrated. This methodology could be beneficial for screening therapeutic agents for treatment of glottic insufficiency. [ABSTRACT FROM AUTHOR]

Background and Objectives: Empty nose syndrome (ENS) is a debilitating condition that often results from traumatic or iatrogenic causes, such as nasal surgery. There are various conservative and surgical treatments for ENS, but their effectiveness remains uncertain. Therefore, the development of animal models that accurately mimic human ENS is essential for advancing effective treatment strategies. Materials and Methods: To investigate ENS development, turbinoplasty was performed in the nasal cavity of swine, entailing partial removal of the ventral turbinate using turbinectomy scissors followed by electrocauterization. After 56 days, samples were obtained for histological and morphological analyses. Results: A significant reduction in the volume of the ventral turbinate in the ENS model led to an expansion of the nasal cavity. Histological analysis revealed mucosal epithelial changes similar to those observed in ENS patients, including squamous cell metaplasia, goblet cell metaplasia, submucosal fibrosis, and glandular atrophy. Biomarkers related to these histopathological features were identified, and signals potentially contributing to squamous cell metaplasia were elucidated. Conclusions: The swine ENS model is anticipated to be instrumental in unraveling the pathogenesis of ENS and may also be useful for evaluating the effectiveness of various treatments for ENS. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine needle biopsy is an effective method for obtaining tissue samples from various organs; however, challenges such as inadequate specimens persist. This study compared a newly designed Tricore needle with a Franseen needle for endoscopic ultrasound-guided fine needle biopsy of porcine liver. Both needles were tested on four male Yorkshire pigs. Specimens were obtained with an 100% (36/36) success rate with no procedure-related adverse effects. The Tricore needle experienced significantly less resistance during puncture than Franseen needle (3.83 vs. 5.97 N, P < 0.001) and better ultrasound visibility (168.97 vs. 125.04, P = 0.004). The Tricore needle also achieved faster specimen acquisition time (48.94 vs. 59.90 s, P = 0.038), larger total specimen area (6.67 vs. 4.68 mm2, P = 0.049), fewer fragments (23.94 vs. 31.94, P = 0.190), lager fragment area (0.28 vs. 0.15 mm2, P < 0.001), and more the number of complete portal tracts (15.44 vs. 9.33, P = 0.017) compared to the Franseen needle. The newly designed Tricore needle showed enhanced procedural performance and specimen quantity and quality compared to commercially available Franseen needle. Although further clinical studies are required, the Tricore needle may represent a favorable option for endoscopic ultrasound-guided fine-needle biopsy procedures. [ABSTRACT FROM AUTHOR]

Restoration of the abdominal wall defects due to herniation or other complications represents a challenging task of the reconstructive surgery. Synthetic grafts or crosslinked animal-derived grafts, are utilized, followed by significant adverse reactions. This study aimed to evaluate primarily the production of a decellularized abdominal wall scaffold and secondly its biocompatibility upon transplantation in an animal model.Full-thickness abdominal wall samples were harvested from Wistar Rats and then decellularized utilizing a three-cycle process. To evaluate the decellularization efficacy, histological, biochemical and biomechanical analyses were performed. The biocompatibility assessment involved the implantation of the produced scaffolds to Sprague Dawley rats. The grafts remained for a total period of 4 weeks, followed by immunohistochemistry for the detection of CD11b+, CD4+ and CD8+ cells.Histological, biochemical and biomechanical results, indicated the production of compatible acellular full-thickness abdominal wall samples. After 4 weeks of implantation, a minor presence of immunity cells was observed.The data of this study indicated the successful production of a full-thickness abdominal wall scaffold. Biologically derived full-thickness abdominal wall scaffolds may have greater potential in restoration of the abdominal wall defects, bringing them one step closer to their clinical utility. [ABSTRACT FROM AUTHOR]

Aims: The primary objective of this investigation is to establish an animal model that accurately represents skeletal muscle injury as a consequence of decompression sickness. Additionally, this study aims to delineate the potential mechanisms underlying the development and progression of skeletal muscle damage associated with decompression sickness. Materials and methods: (1) In this research, rats were utilized as experimental models and subjected to 600 kPa pressure in an air medium for a duration of 60 min, followed by decompression at a consistent rate of 1.5 min to reach atmospheric pressure in order to establish an animal model for decompression injury. Assessment of decompression injury involved the observation of general symptoms and signs, as well as histopathological examination of lung tissue to determine the extent of damage in the pulmonary system of rats. (2) Building on the rat decompression injury model, we conducted pathological and serological examinations to assess the status of rat skeletal muscle. Additionally, we investigated the signaling mechanism of the TLR9-MyD88 pathway in mediating alterations in rat skeletal muscle resulting from decompression injury, and evaluated the effects of decompression injury on apoptosis in rat skeletal muscle. Results: Repeated decompression induces significant damage to skeletal muscle tissue, characterized by edema, fiber rupture, and atrophy. This process also leads to a transient elevation in creatine kinase (CK-MM) levels in rat serum, as well as an upregulation of proteins such as TLR9, MyD88, p38, and ERK in rat skeletal muscle tissue. Furthermore, repeated decompression results in a temporary increase in the transcription levels of Atrogen-1mRNA and MuRF-1mRNA in rat skeletal muscle tissue. Discussion: The decompression protocol applied in this study successfully induced decompression sickness in a rat model, leading to skeletal muscle damage that was consistent with the expected pathology of decompression injury. Despite the initial injury, the rats showed evidence of adaptation following prolonged exposure to decompression conditions. [ABSTRACT FROM AUTHOR]

Although significant progress has been made in developing preclinical models for metabolic dysfunction‐associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English‐language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction‐associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light–dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease. [ABSTRACT FROM AUTHOR]

Background: Salvianolic acid B is the most abundant water-soluble component in the traditional Chinese medicine Danshen and can reduce myocardial ischemia-reperfusion (MI/R) injury through multiple targets and pathways. However, the role of SalB in protecting the myocardium from ischemia/reperfusion injury remains unclear. Purpose: To perform a preclinical systematic review and meta-analysis to assess the efficacy of Sal B in an animal model of myocardial infarction/reperfusion (MI/R) and to summarize the potential mechanisms of Sal B against MI/R. Methods: Studies published from inception to March 2024 were systematically searched in PubMed, Web of Science, Embase, China National Knowledge Infrastructure Wanfang, and VIP databases. The methodological quality was determined using the SYRCLE RoB tool. The R software was used to analyze the data. The potential mechanisms are categorized and summarized. Results: 32 studies containing 732 animals were included. The results of the meta-analysis showed that Sal B reduced myocardial infarct size (p < 0.01), and the cardiological indices of CK-MB (p < 0.01), CK (p < 0.01), LDH (p < 0.01), and cTnI (p < 0.01) compared to the control group. In addition, Sal B increased cardiac function indices, such as LVFS (p < 0.01), -dp/dt max (p < 0.01), +dp/dt max (p < 0.01), and cardiac output (p < 0.01). The protective effects of Sal B on the myocardium after I/R may be mediated by attenuating oxidative stress and inflammation, promoting neovascularization, regulating vascular function, and attenuating cardiac myocyte apoptosis. Publication bias was observed in all the included studies. Further studies are required to elucidate the extent of the cardioprotective effects of SalB and the safety of its use. Conclusion: To the best of our knowledge, this is the first meta-analysis of Sal B in the treatment of MI/R injury, and Sal B demonstrated a positive effect on MI/R injury through the modulation of key pathological indicators and multiple signaling pathways. Further studies are needed to elucidate the extent to which SalB exerts its cardioprotective effects and the safety of its use. [ABSTRACT FROM AUTHOR]

Background: The development of therapies and vaccines for various diseases often necessitates the analysis of cellular immunity. However, unlike other rodents, the limited availability of reagents for Syrian hamsters restricts immunological analysis, particularly in the determination of serum effector molecules such as cytokines. In this study, we aim to produce and characterize the cytokines IFN-γ, TGF-β, IL-6, IL-10, and TNF-α from Syrian hamsters in recombinant form and to generate polyclonal antibodies against them in rats. Methods and results: Cytokine transcript sequences were cloned into expression vectors in E. coli. Recombinant proteins were produced, purified through affinity chromatography, and characterized by Western blot using an anti-6xHis monoclonal antibody. Rats were immunized with the recombinant proteins to generate polyclonal antibodies (pAbs). These pAbs were characterized by Western blot and titrated by indirect ELISA. The recombinant cytokines rTNF-α, rIL-10, rIFN-γ, rTGF-β, and rIL-6 were produced and specifically recognized at their expected molecular weights of 22.3 kDa, 19.8 kDa, 18.9 kDa, 11.8 kDa, and 22.9 kDa. pAbs were produced and demonstrated the ability to specifically recognize their target proteins with titers of 409,600 (rIL-10), 204,800 (rTNF-α), 102,400 (rIL-10), 51,200 (rTGF-β), and 25,600 (rIFN-ɣ). Conclusions: The reagents produced represent a starting point for developing immunoassays to detect hamster cytokines, facilitating the analysis of cellular immunity in this biomodel. [ABSTRACT FROM AUTHOR]

BACKGROUND: Establishing an objective and standard animal model of bone nonunion is essential for experimental studies and treatment of nonunion. OBJECTIVE: To establish an objective animal model for experimental studies of nonunion. METHODS: Specific pathogen-free male Wistar rats were selected and prepared by cutting off a 5 mm bone defect in the middle femur, peeling off a large periosteum and removing bone marrow. Animal models were fixed with a 1.2 mm Kirschner wire. At 1, 4 and 8 weeks, bone nonunion was observed by gross specimen observation, X-ray examination and histopathological examination. RESULTS AND CONCLUSION: The gross specimen, X-ray film and histopathological examination showed that there was no callus formation in the bone defect area, the broken end was filled with fiber tissue, and the bone callus was rare or even invisible. To conclude, the rat model of nonunion can be successfully established by osteotomy of the middle femur, large periosteum peeling and bone marrow removal. This modeling method is simple, reliable and effective. [ABSTRACT FROM AUTHOR]

BACKGROUND: “Tendon off-position” is a disease name included in the International Classification of Diseases 11th Revision, and also a clinical indication of manipulation, acupuncture and other treatments. However, its specific mechanism is still unclear. It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of “tendon off-position,” so as to further study the mechanism of effective clinical treatments. OBJECTIVE: To establish an animal model of “tendon off-position” in rats based on isometric contraction of skeletal muscles, and to explore the changes of skeletal muscle function and morphological phenotype after “tendon off-position.” METHODS: Sixty rats were randomly divided into control group, static-loading group and extra loading group, with twenty rats in each group. Rats in the control group were kept normally without treatment. In the latter two groups, the rats were fixed by the self-made static-loading modeling device and a static-loading (the body mass of each rats was applied as the static-loading) was applied to cause sustained isometric contraction of the upper limb muscles. Then, animal models of “tendon off-position” were successfully established. In the extra loading group, 50% of the body mass was added to the ankle joint after modeling. The skeletal muscle samples were harvested at 2 and 4 weeks after modeling. The changes of limb grip strength, wet mass of skeletal muscle, and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured, and the changes of skeletal muscle histomorphology and ultrastructure were observed. RESULTS AND CONCLUSION: At 2 weeks after modeling, the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass, significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A, and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers. Electron microscopy results showed that the structure of myofibrils was disordered, the Z-line was distorted, and the light and dark boundaries were blurred. At 4 weeks after modeling, the grip strength of the model rats was increased compared with that at 2 weeks, the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased, and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees. It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of “tendon off-position” at 2 weeks, and can be used to study the mechanism of acupuncture and manipulation in the treatment of “tendon off-position.” [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as an alternative term to NAFLD. MASLD is a globally recognized chronic liver disease that poses significant health concerns and is frequently associated with obesity, insulin resistance, and hyperlipidemia. To better understand its pathogenesis and to develop effective treatments, it is essential to establish suitable animal models. Therefore, attempts have been made to establish modelling approaches that are highly similar to human diet, physiology, and pathology to better replicate disease progression. Here, we reviewed the pathogenesis of MASLD disease and summarised the used animal models of MASLD in the last 7 years through the PubMed database. In addition, we have summarised the commonly used animal models of MASLD and describe the advantages and disadvantages of various models of MASLD induction, including genetic models, diet, and chemically induced models, to provide directions for research on the pathogenesis and treatment of MASLD. [ABSTRACT FROM AUTHOR]

Heart weight is a routine measurement at post-mortem examination. An increased heart weight is associated with pre-existing heart disease and sudden cardiac death. However, during decomposition, the heart weight measured at post-mortem examination may not reflect the weight at the time of death. A previous study showed that heart dimensions can be used to estimate heart weight. This study documents the changes in heart dimensions during decomposition using porcine and ovine animal models. It shows that, in contrast to heart weight, which decreases in the post-mortem interval, the heart dimensions increase. Heart width increases and subsequently plateaus at the end of the 18 days to a mean of 6 and 8 mm in ovine and porcine hearts, whereas the length continues to increase. Using the results of this study, in conjunction with previous published literature, the heart width may be used as a parameter to estimate heart weight and determine cardiac hypertrophy at the time of death in decomposed hearts. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27‐hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model.Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C‐C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme‐linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un‐operated rats receiving high‐fat/high‐cholesterol diet (HFHCD) or normal diet (ND). Micro‐computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene.Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (p < .05 versus the ND group). Lesion size, infiltration of CD68+ cells, and iNOS+ monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro‐inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (p < .05 versus the vehicle control group).Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action. [ABSTRACT FROM AUTHOR]

Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund's adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has not been validated with currently used drugs. Here we tested the effects of the adjuvant analgesic/antiepileptic voltagegated Na+ channel blocker complex mechanism of action topiramate in comparison with the gold standard antimigraine serotonin 5-HT1B/D receptor agonist sumatriptan in this model. CFA was injected subcutaneously into the right whisker pad of male Sprague-Dawley rats (250-300 g), then mechanonociceptive threshold values were investigated with von Frey filaments (3, 5, and 7 days after CFA injection). Effects of topiramate (30 mg/kg per os) and sumatriptan (1 mg/kg subcutaneous) on the adjuvantinduced chronic inflammatory orofacial allodynia were investigated 60, 120, and 180 min after the treatments each day. To determine the optimal concentration for drug effect analysis, we tested the effects of two different CFA-concentrations (1 and 0.5 mg/mL) on mechanonociceptive thresholds. Both concentrations of CFA induced a chronic orofacial allodynia in 60% of all rats. Although, higher CFA concentration induced greater allodynia, much more stable threshold reduction was observed with the lower CFA concentration: on day 3 the thresholds decreased from 18.30 g to approximately 11 g (low) and 5 g (high), respectively, however a slight increase was observed in the case of higher CFA concentration (on days 5, 7, and 11). In all investigation days, topiramate showed significant anti-allodynic effect comparing the pre and post drug dose and comparing the vehicle treated to the drug treated groups. Sumatriptan also caused a significant threshold increase compared to pre dose thresholds (day 3) and also showed a slight anti-allodynic effect compared to the vehicle-treated group (day 3 and 5). In the present study CFA-induced chronic orofacial allodynia was reversed by topiramate in rats validating the model with the adjuvant analgesic. Other than establishing a validated orofacial pain-related syndrome model in rats, new ways are opened for the repurposing of topiramate. [ABSTRACT FROM AUTHOR]

Background: Phenotype alterations of nociceptive neurons have been shown to be a key step in the pathogenesis of many pain‐related diseases. However, it is unclear if the characteristic changes of temporomandibular joint (TMJ) primary afferent neurons are related to the pathogenesis of temporomandibular joint osteoarthritis (TMJOA) chronic pain. This study aimed to determine the morphological and neurochemical changes in trigeminal ganglion (TG) neurons innervating the TMJ in TMJOA chronic pain rats. Materials and Methods: Monosodium iodoacetate (MIA)‐induced TMJOA chronic pain rat model was established (n = 6), and saline was injected in rats of the control group (n = 6). TMJ primary afferent neurons were labeled with retrograde tracing (Dil). The spatial distribution and the expression of calcitonin gene‐related peptide (CGRP), isolectin B4 (IB4), and neurofilament 200 (NF200) of TMJ primary afferent neurons in TG were investigated using immunofluorescence. Intracellular calcium signaling was recorded by calcium imaging (n = 20). Results: TMJ primary afferent neurons were located only in the V3 region of the TG from both saline‐ and MIA‐injected rats. The number of TG neurons innervating the TMJ was increased in MIA‐injected rats. Elevated number and intracellular calcium concentration of small‐ and medium‐sized instead of large‐sized Dil+ TG neurons were found in MIA‐injected rats. The upregulated expression of CGRP and IB4, but not NF200, in TG neurons innervating the rat TMJs was accompanied by TMJOA chronic pain. Conclusion: This study suggests that sensitization of small‐ to medium‐sized Dil+ TG neurons and CGRP‐ and IB4‐positive Dil+ TG neurons might contribute to the development of TMJOA chronic pain in rats. This will provide valuable information for more efficient control of TMJOA chronic pain. [ABSTRACT FROM AUTHOR]

Introduction Despite the significant need for mechanical ventilation in- and out-of-hospital, mechanical ventilators remain inaccessible in many instances because of cost or size constraints. Mechanical ventilation is especially critical in trauma scenarios, but the impractical size and weight of standard mechanical ventilators restrict first responders from carrying them in medical aid bags, leading to reliance on imprecise manual bag-mask ventilation. This is particularly important in combat-related injury, where airway compromise and respiratory failure are leading causes of preventable death, but medics are left without necessary mechanical ventilation. To address the serious gaps in mechanical ventilation accessibility, we are developing an Autonomous, Modular, and Portable Ventilation platform (AMP-Vent) suitable for austere environments, prolonged critical care, surgical applications, mass casualty incidents, and stockpiling. The core system is remarkably compact, weighing <2.3 kg, and can fit inside a shoebox (23.4 cm × 17.8 cm × 10.7 cm). Notably, this device is 65% lighter than standard transport ventilators and astoundingly 96% lighter than typical intensive care unit ventilators. Beyond its exceptional portability, AMP-Vent can be manufactured at less than one-tenth the cost of conventional ventilators. Despite its reduced size and cost, the system's functionality is uncompromised. The core system is equipped with closed-loop sensors and advanced modes of ventilation (pressure-control, volume-control, and synchronized intermittent mandatory ventilation), enabling quality care in a portable form factor. The current prototype has undergone preliminary preclinical testing and optimization through trials using a breathing simulator (ASL 5000) and in a large animal model (swine). This report aims to introduce a novel ventilation system and substantiate its promising performance through evidence gathered from preclinical studies. Materials and Methods Lung simulator testing was performed using the ASL 5000, in accordance with table 201.105 "pressure-control inflation-type testing" from ISO 80601-2-12:2020. Following simulations, AMP-Vent was tested in healthy 10-kg female domestic piglets. The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee approved all animal procedures. Swine received 4-min blocks of alternating ventilation, where AMP-Vent and a conventional anesthesia ventilator (GE AISYS CS2) were used to titrate to varied end-tidal carbon dioxide (EtCO2) goals with the initial ventilator switching for each ascending target (35, 40, 45, 50, 55 mmHg). Results During ASL 5000 simulations, AMP-Vent exhibited consistent performance under varied conditions, maintaining a coefficient of variation of 2% or less within each test. In a large animal study, AMP-Vent maintained EtCO2 and SpO2 targets with comparable performance to a conventional anesthesia ventilator (GE AISYS CS2). Furthermore, the comparison of minute ventilation (V e) distributions between the conventional anesthesia ventilator and AMP-Vent at several EtCO2 goals (35, 40, 45, 50, and 55 mmHg) revealed no statistically significant differences (p  = 0.46 using the Kruskal–Wallis rank sum test). Conclusions Preclinical results from this study highlight AMP-Vent's core functionality and consistent performance across varied scenarios. AMP-Vent sets a benchmark for portability with its remarkably compact design, positioning it to revolutionize trauma care in previously inaccessible medical scenarios. [ABSTRACT FROM AUTHOR]

Introduction While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current behind armor blunt trauma standard. The purpose of this study was to report on the methods, procedures, and data collected from swine. Materials and Methods Live swine tests were conducted after obtaining approvals from the local institution and the Army Care and Use Review Office of the U.S. Department of Defense. Trachea tubes and an intravenous line were introduced before administering anesthesia. Pressure transducers were inserted into the lungs and aorta. An indenter simulating the backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers was used to deliver impact loading to the liver region. A triaxial accelerometer was included in the indenter design. The animals were monitored for 6 hours, necropsies were performed, and injuries were identified. Biomechanical data of the energy, velocity, deflection, viscous criterion, force, and impulse variables were obtained for each test. Results Peak accelerations, velocities, deflections, forces, impulse, and energies ranged from 897 to 5,808 g, 21 to 59 m/s, 1.96 to 8.87 cm, 2.3 to 13.1 kN, 1.1 to 7.1 Ns, and 58 to 387 J, respectively. The peak viscous criterion ranged from 0.8 to 5.8 m/s. All animals survived the 6-hour survival period. Three animals responded with liver lacerations while the remaining 4 did not have any injuries. Conclusion The experimental design based on parallel tests with whole body human cadavers and cadaver swine was found to be successful in delivering controlled impacts to the liver region of live swine and reproducing liver injuries. Previously used biomechanical measures as potential candidates for injury criteria development were obtained. Using this proven model, tests with additional samples are needed to develop injury risk curves for liver impacts and obtain regional (liver) injury criteria. [ABSTRACT FROM AUTHOR]

Introduction Auditory injuries induced by repeated exposures to blasts reduce the operational performance capability and the life quality of military personnel. The treatment for blast-induced progressive hearing damage is lacking. We have recently investigated the therapeutic function of liraglutide, a glucagon-like peptide-1 receptor agonist, to mitigate blast-induced hearing damage in the animal model of chinchilla, under different blast intensities, wearing earplugs (EPs) or not during blasts, and drug-treatment plan. The goal of this study was to investigate the therapeutical function of liraglutide by comparing the results obtained under different conditions. Materials and Methods Previous studies on chinchillas from two under-blast ear conditions (EP/open), two blast plans (G1: 6 blasts at 3–5 psi or G2:3 blasts at 15–25 psi), and three treatment plans (blast control, pre-blast drug treatment, and post-blast drug treatment) were summarized. The auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) recorded within 14 days after the blasts were used. Statistical analysis was performed to evaluate the effect of liraglutide under different conditions Results ABR threshold shifts indicated that the conditions of the EP and open ears were substantially different. Results from EP chinchillas indicated that the pre-blast treatment reduced the acute ABR threshold elevation on the day of blasts, and the significance of such an effect increased with the blast level. Liraglutide-treated open chinchillas showed lower ABR threshold shifts at the later stage of the experiment regardless of the blast levels. The DPOAE was less damaged after G2 blasts compared to G1 when pre-blast liraglutide was administrated. Lower post-blast MLR amplitudes were observed in the pre-blast treatment groups. Conclusions This study indicated that the liraglutide mitigated the blast-induced auditory injuries. In EP ears, the pre-blast administration of liraglutide reduced the severity of blast-induced acute damage in ears with EP protection, especially under G2. In animals with open ears, the effect of liraglutide on the restoration of hearing increased with time. The liraglutide potentially benefits post-blast hearing through multiple approaches with different mechanics. [ABSTRACT FROM AUTHOR]

Introduction Non-compressible torso hemorrhagic (NCTH) shock is the leading cause of potentially survivable trauma on the battlefield. New hypotensive drug therapies are urgently required to resuscitate and protect the heart and brain following NCTH. Our aim was to examine the strengths and limitations of permissive hypotension and discuss the development of small-volume adenosine, lidocaine, and Mg2+ (ALM) fluid resuscitation in rats and pigs. Materials and Methods For review of permissive hypotension, a literature search was performed from inception up to November 2023 using PubMed, Cochrane, and Embase databases, with inclusion of animal studies, clinical trials and reviews with military and clinical relevance. For the preclinical study, adult female pigs underwent laparoscopic liver resection. After 30 minutes of bleeding, animals were resuscitated with 4 mL/kg 3% NaCl ± ALM bolus followed 60 minutes later with 4 h 3 mL/kg/h 0.9% NaCl ± ALM drip (n  = 10 per group), then blood transfusion. Mean arterial pressure (MAP) and cardiac output (CO) were continuously measured via a left ventricular pressure catheter and pulmonary artery catheter, respectively. Systemic vascular resistance (SVR) was calculated using the formula: 80 × (MAP − CVP)/CI. Oxygen delivery was calculated as the product of CO and arterial oxygen content. Results Targeting a MAP of ∼50 mmHg can be harmful or beneficial, depending on how CO and SVR are regulated. A theoretical example shows that for the same MAP of 50 mmHg, a higher CO and lower SVR can lead to a nearly 2-fold increase in O2 supply. We further show that in animal models of NCTH, 3% NaCl ALM bolus and 0.9% NaCl ALM drip induce a hypotensive, high flow, vasodilatory state with maintained tissue O2 supply and neuroprotection. ALM therapy increases survival by resuscitating the heart, reducing internal bleeding by correcting coagulopathy, and decreasing secondary injury. Conclusions In rat and pig models of NCTH, small-volume ALM therapy resuscitates at hypotensive pressures by increasing CO and reducing SVR. This strategy is associated with heart and brain protection and maintained tissue O2 delivery. Translational studies are required to determine reproducibility and optimal component dosing. ALM therapy may find wide utility in prehospital and far-forward military environments. [ABSTRACT FROM AUTHOR]

Introduction Disease and non-battle injury (DNBI) has historically been the leading casualty type among service members in warfare and a leading health problem confronting military personnel, resulting in significant loss of manpower. Studies show a significant increase in disease burden for DNBI when compared to combat-related injuries. Understanding the causes of and trends in DNBI may help guide efforts to develop preventive measures and help increase medical readiness and resiliency. However, despite its significant disease burden within the military population, DNBI remains less studied than battle injury. In this review, we aimed to evaluate the recently published literature on DNBI and to describe the characteristics of these recently published studies. Materials and Methods This systematic review is reported in the Prospective Register of Systematic Reviews database. The systematic search for published articles was conducted through July 21, 2022, in Cumulative Index of Nursing and Allied Health, Cochrane Library, Defense Technical Information Center, Embase, and PubMed. Guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses, the investigators independently screened the reference lists on the Covidence website (covidence.org). An article was excluded if it met any of the following criteria: (1) Published not in English; (2) published before 2010; (3) data used before 2001; (4) case reports, commentaries, and editorial letters; (5) systematic reviews or narrative reviews; (6) used animal models; (7) mechanical or biomechanical studies; (8) outcome was combat injury or non-specified; (9) sample was veterans, DoD civilians, contractors, local nationals, foreign military, and others; (10) sample was U.S. Military academy; (11) sample was non-deployed; (12) bioterrorism study; (13) qualitative study. The full-text review of 2 independent investigators reached 96% overall agreement (166 of 173 articles; κ = 0.89). Disagreements were resolved by a third reviewer. Study characteristics and outcomes were extracted from each article. Risk of bias was assessed using the Newcastle-Ottawa Scale. Meta-analysis of pooled estimates of incidence rates for disease (D), non-battle injury (NBI), and combined DNBI was created using random-effects models. Results Of the 3,401 articles, 173 were included for the full review and 29 (16.8%) met all inclusion criteria. Of the 29 studies included, 21 (72.4%) were retrospective designs, 5 (17.2%) were prospective designs, and 3 (10.3%) were surveys. Across all studies, the median number of total cases reported was 1,626 (interquartile range: 619.5-10,203). The results of meta-analyses for 8 studies with reported incidence rates (per 1,000 person-years) for D (n  = 3), NBI (n  = 7), and DNBI (n  = 5) showed pooled incidence rates of 22.18 per 1,000 person-years for D, 19.86 per 1,000 person-years for NBI, and 50.97 per 1,000 person-years for combined DNBI. Among 3 studies with incidence rates for D, NBI, and battle injury, the incidence rates were 20.32 per 1,000 person-years for D, 6.88 per 1,000 person-years for NBI, and 6.83 per 1,000 person-years for battle injury. Conclusions DNBI remains the leading cause of morbidity in conflicts involving the U.S. Military over the last 20 years. More research with stronger designs and consistent measurement is needed to improve medical readiness and maintain force lethality. Level of Evidence Systematic Review and Meta-Analysis, Level III. [ABSTRACT FROM AUTHOR]

Rabbits are routinely used as a natural model of fetal growth restriction (FGR); however, no studies have confirmed that rabbits have FGR. This study aimed to characterize the fetoplacental unit (FPU) in healthy pregnant rabbits using diffusion-weighted MRI and stereology. A secondary objective of the study was to describe the associations among findings from diffusion-weighted MRI (DW-MRI), fetal weight measurement and histological analysis of the placenta. Pregnant rabbits underwent DW-MRI under general anesthesia on embryonic day 28 of pregnancy. MR imaging was performed at 3.0 T. The apparent diffusion coefficient (ADC) values were calculated for the fetal brain, liver, and placenta. The placenta was analyzed by stereology (volume density of trophoblasts, the maternal blood space and fetal vessels). Each fetus and placenta were weighed. Two groups of fetuses were defined according to the position in the uterine horn (Cervix group versus Ovary group). We analyzed 20 FPUs from 5 pregnant rabbits. Fetuses and placentas were significantly lighter in the Cervix group than in the Ovary group (34.7 ± 3.7 g vs. 40.2 ± 5.4 g; p = 0.02). Volume density analysis revealed that the percentage of fetal vessels, the maternal blood space and trophoblasts was not significantly affected by the position of the fetus in the uterine horn. There was no difference in ADC values according to the position of the fetus in the uterine horn, and there was no correlation between ADC values and fetal weight. The findings of a multimodal evaluation of the placenta in a rabbit model of FGR suggested is not a natural model of fetal growth restriction. • In rabbits, the fetus closest to the ovary is heavier than the one near the cervix. • It is possible to use DW-MRI to assess placental function in rabbits. • Rabbits do not appear to be a natural model for intrauterine growth restriction. [ABSTRACT FROM AUTHOR]