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Aims: This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods: In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results: Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion: Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440.

Background: We compared rates of successful polyethylene glycol (PEG) nerve fusion between two epineural suture repairs (2SR) and five epineural suture repairs (5SR) in a rat sciatic nerve transection neurorrhaphy model. We hypothesise that the two and five epineural neural suture repair groups will achieve a similar rate of PEG fusion. Methods: Twenty-five Lewis rats underwent bilateral sciatic nerve transection. Primary neurorrhaphy (PN) consisting of 2SR in one hind limb and 5SR in the contralateral hind limb was performed utilizing PEG fusion. Successful PEG fusion was confirmed by a distal muscle twitch after nerve stimulation proximal to the nerve fusion site. Sciatic nerve conduction velocity (SNCV) across the repair site and the force generated by tibialis anterior muscle (TAM) contraction were also compared between the 2SR and 5SR groups. Results: Success rates were 100% for the 2SR and the 5SR groups. No statistically significant differences in SNCV (P = 0.444) or isometric tetanic TAM contractile force (P = 0.820) were observed between 2SR and 5SR in the setting of PEG fusion. Conclusion: These findings demonstrate no significant difference in successful PEG fusion between the 2SR and 5SR groups. In addition, the findings demonstrate no statistically significant differences in SNCV or isometric tetanic TAM contractile force following sciatic nerve transection when performing a 2SR or 5SR PN in the setting of PEG fusion. Successful PEG fusion can be achieved acutely with either a two or five-epineural suture repair in a rat model. [ABSTRACT FROM AUTHOR]

Aims: To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis. Methods: Empty adenovirus (EP) and a HDAC4 overexpression adenovirus were transfected into cultured human chondrocytes. The cell survival rate was examined by real-time cell analysis (RTCA) and EdU and flow cytometry assays. Cell biofunction was detected by Western blotting. The expression profiles of messenger RNAs (mRNAs) in the EP and HDAC4 transfection groups were assessed using whole-transcriptome sequencing (RNA-seq). Volcano plot, Gene Ontology, and pathway analyses were performed to identify differentially expressed genes (DEGs). For verification of the results, the A289E/S246/467/632 A sites of HDAC4 were mutated to enhance the function of HDAC4 by increasing HDAC4 expression in the nucleus. RNA-seq was performed to identify the molecular mechanism of HDAC4 in chondrocytes. Finally, the top ten DEGs associated with ribosomes were verified by quantitative polymerase chain reaction (QPCR) in chondrocytes, and the top gene was verified both in vitro and in vivo. Results: HDAC4 markedly improved the survival rate and biofunction of chondrocytes. RNA-seq analysis of the EP and HDAC4 groups showed that HDAC4 induced 2,668 significant gene expression changes in chondrocytes (1,483 genes upregulated and 1,185 genes downregulated, p < 0.05), and ribosomes exhibited especially large increases. The results were confirmed by RNA-seq of the EP versus mutated HDAC4 groups and the validations in vitro and in vivo. Conclusion: The enhanced ribosome pathway plays a key role in the mechanism by which HDAC4 improves the survival rate and biofunction of chondrocytes. Cite this article: Bone Joint Res 2023;12(7):433–446.

Introduction: Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millions of people worldwide and every year the incidence and prevalence increase substantially. The symptoms may start with mild manifestations of the disease such as increased albuminuria, serum creatinine levels, thickening of glomerular basement membrane, expansion of mesangial matrix to severe pathological symptoms such as glomerular lesions and tubulointerstitial fibrosis which may further proceed to cardiovascular dysfunction or end-stage renal disease. Perspective: Numerous therapeutic interventions are being explored for the management of DN, however, these interventions do not completely halt the progression of this disease and hence animal models are being explored to identify critical genetic and molecular parameters which could help in tackling the disease. Rodent models which mostly include mice and rats are commonly used experimental animals which provide a wide range of advantages in understanding the onset and progression of disease in humans and also their response to a wide range of interventions helps in the development of effective therapeutics. Rodent models of type 1 and type 2 diabetes induced DN have been developed utilizing different platforms and interventions during the last few decades some of which mimic various stages of diabetes ranging from early to later stages. However, a rodent model which replicates all the features of human DN is still lacking. This review tries to evaluate the rodent models that are currently available and understand their features and limitations which may help in further development of more robust models of human DN. Conclusion: Using these rodent models can help to understand different aspects of human DN although further research is required to develop more robust models utilizing diverse genetic platforms which may, in turn, assist in developing effective interventions to target the disease at different levels. [ABSTRACT FROM AUTHOR]

Objective To establish TMJ-OA rat models by occlusal disorder and forced open mouth, compare two TMJ-OA induction methods and assess their applicability by pathological changes in the cartilage, subchondral bone. Methods Twenty-one 8-week-old Sprague-Dawley ( SD) male rats were divided into four groups, namely control group, and three rats were conventional feeding. eighteen SD rats were randomly allocated to three groups using the randomization table; each group had the same number of SD rats. The Forced open mouth (OP), steady mouth opening was imposed to 20 mm daily (1 minute/day for 16 days). the occlusal disorder group (OD), an orthodontic ligation silk (0.25 mm diameter) revolved around the first molar, and a ligation knot was created on the first molar of the maxillary. The control group of occlusal disorder (ODS) use the same method, a ligation knot in the mesial of the first molar. Rat models were employed and followed for 4 weeks after experimental procedures, and TMJ joints in each group were harvested. The TMJ changes were evaluated by micro-CT, HE staining, and Safranin-O/Fast green staining. Results We found apparent histological phenotypes of TMJ-OA in the OP and OD groups, and observed a pronounced drop in bone volume fraction, BV/TV and Tb.Th between OD and OP groups had no significant difference (P > 0.05), and a substantial increase in the modified Mankin score was found, there was no significant difference in the two groups (P > 0.05), but two samples of OP group didn't present apparent histological phenotypes of TMJ-OA. Conclusions Osteoarthritis-like pathological changes in the cartilage and subchondral bone can be observed in both of the two methods. The occlusal disorder is a stable TMJOA model, forced open mouth caused osteoarthritis-like changes, but it's unstable and inefficient. [ABSTRACT FROM AUTHOR]

Background/Aim: Gastric acid reflux into the esophagus can cause irritation and inflammation of the esophagus and progress to reflux esophagitis (RE). Vitamin D3 (VitD3) has anti-inflammatory effects and plays an important regulatory role in adaptive and innate immunity. We hypothesized that VitD3 may play a protective role in RE. Materials and Methods: Seventy male Sprague-Dawley rats were used, and acute RE (n=35) or chronic RE (n=35) were surgically induced. The effects of different doses of VitD3 on morphological changes and alteration of pro-inflammatory cytokine levels were examined in the rat models. Western blot analysis was performed to determine protein expression levels of IL-1ß, IL-6, and IL-8 in esophageal tissues. Serum levels of VitD3 and calcium were determined using enzyme-linked immunosorbent assays. Results: The protein expression of proinflammatory cytokines IL-1ß, IL-6, and IL-8 was found significantly increased in RE. VitD3 treatment significantly reduced the levels of these pro-inflammatory cytokines in both the low-dose and high-dose VitD3 groups compared to control groups in acute RE, but not chronic RE. Macrographic and histopathological examination revealed various degrees of esophageal impairment in rats following surgical induction of acute or chronic RE in rats. These impairments were not improved by VitD3. Morphological grading of esophageal mucosa showed no significant differences between acute and chronic RE. Elevated serum levels of calcium were observed after VitD3 treatment. Conclusion: IL-1ß, IL-6, and IL-8 levels were significantly elevated in RE. The abnormal increase in these important pro-inflammatory cytokines was suppressed by VitD3 in the rat models of acute RE. These novel findings suggest a potential protective role of VitD3 in early-stage RE. [ABSTRACT FROM AUTHOR]

Objective To compare the effects and characteristics of cigarette smoke exposure (CSE) alone and CSE combined with airway instillation of bacterial lipopolysaccharide (LPS) in chronic obstructive pulmonary disease (COPD).Methods Male SD rats were randomly divided into control, CSE, and CSE+LPS groups, with 10 rats in each group. After 24 weeks, the models were established and the lung function of the rats was measured. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in the airway and lung tissue. The ELISA method was used to detect the level of serum interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) in peripheral blood.Results Airway resistance (RI), functional residual capacity (FRC), and chord compliance (Cchord) of the CSE and LPS+CSE groups were higher than those of the control group (all P < 0.05), while the tidal volume (TV), minute volume (MV), and forced expiratory volume in 50 ms (FEV50) / forced vital capacity (FVC) of the CSE and LPS+CSE groups were lower than those of the control group (all P < 0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of the small airway walls were higher in the CSE and LPS+CSE groups than those in the control group. Compensatory enlargement was evident in the alveolar cavity of the CSE and CSE+LPS groups, and the alveolar septum widened, with a fusion of pulmonary alveoli in the CSE+LPS group. The levels of IL-8 and TNF-α in serum of the CSE and CSE+LPS groups were higher than those of the control group (all P < 0.05). The level of TNF-α in serum of the CSE+LPS group was higher than that of the CSE group (P < 0.05).Conclusion The CSE combined with LPS method is superior to CSE alone for establishing the COPD rat model, and the combined model is closer to clinical manifestations.

Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma n-6/n-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.

Introduction: The diversity of dairy products and the increasing consumption levels have led to a growing interest in goat and sheep milk, which are rich in essential nutrients and functional components. The study aims to explore the nutritional composition, growth performance, digestibility, and serum metabolic differences of milk powders from cow, goat, and sheep using LC-MS/MS-based metabolomics in rat models., Methods: Sixty male Sprague-Dawley rats were fed with whole cow, goat, and sheep milk powder samples , and their feces and urine were analyzed for fat and protein content. LC/MS analysis was conducted using a Dionex UltiMate 3000 UHPLC system coupled with a Thermo Q EXACTIVE mass spectrometer, with data processed using Wekemo Bioincloud for quality control, normalization, comparisons with the KEGG database, statistical analyses, and selection of differential metabolites., Results: The sheep milk powder showed highest protein and fat content level, while cow and goat milk powders separately demonstrated higher lactose and carbohydrate levels. Each milk powder had a unique mineral profile, with sheep milk powder containing the highest calcium content. All groups exhibited consistent growth in body weight and high rates of protein and fat digestibility. Metabolomics analysis revealed distinct metabolic profiles, with goat milk powder linked to steroid hormone biosynthesis and sheep milk powder associated with hormone regulation and bile acid pathways., Conclusion: This study offers valuable insights into the metabolic implications of different milk powder sources, informing dietary choices and facilitating the development of targeted public health strategies to optimize nutritional intake and promote overall well-being., Competing Interests: JP, SP, XZ, and LS are employed by Feihe Research Institute, Heilongjiang Feihe Dairy Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Pan, Pang, Hu, Liu, Zhang, Song, Ren and Wang.)

Aims: To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods: A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results: The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. Conclusion: Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714–722.

Abstract Objectives Periodontal bacteria that have been studied show a strong connection to various vascular diseases. Among the many kinds of periodontal bacteria, Porphyromonas gingivalis (Pg) is well examined in the general aspects and in a rat model. However, whether other periodontal bacteria work or react differently is not studied well. Material and methods We chose Aggregatibacter actinomycetemcomitans (Aa) and Prevotella intermedia (Pi) as different types of periodontal bacteria. Low‐density and high‐density bacterial solutions were injected in the small artery of rats' groins using our rat model. Eighteen limbs of 9 SD male rats (500–650 g) were used. After 7 days, 14–18 days, and 28 days, the rats were sacrificed. A pathological and an immuno‐histochemical study was conducted and reported on the low‐density group with 12 limbs because the Pi group lacked a high‐density study. Immuno‐histochemical staining of live Pg was performed on three limbs of three rats at 1 h, 3 h, and 1 week after injection. Results The appearances from the acute, at 7 days, to chronic phases, at 28 days, were observed. The differences of the species were certainly observed in the internal elastic lamina (IEL), and immuno‐histochemical reactions. The inflammatory reactions, such as cellular distribution or intra‐thrombus materials, were similar in all. One week later, we could not see any living bacteria in the specimen or immunological observation. Conclusions The three species were essentially the same, except for Aa's stronger disruption of IEL, and more CD3 (Pan T cell) in Pi and more CD79a (Pan B cell) in Pg. We propose a new concept of a possible mechanism of vascular diseases, in which the work of LPS (lipopolysaccharides) and a toll‐like receptor (TLR) is emphasized.

Background: Pressure injuries (PIs) generally result from prolonged ischemia through localized skin compression, and ischemia persists and exacerbates damage even post-decompression. The mechanisms of ischemia post-decompression are still unclear, and appropriate methods for detection are lacking. Methods: We used blanchable erythema (BE) and early PI rat models. We assessed the perfusion using Evans Blue (EB) and thrombus formation under a light microscope. Furthermore, we performed a capillary refill time test (CRTT) to detect ischemia after depression coupled with the transparent disk method using a spectrophotometer. Results: Compared with the BE group, the early PI group showed significantly slow and insufficient perfusion, as determined by EB staining (p < 0.001). Histological observations revealed that ischemia during post-decompression of early PI was caused by a greater amount of thrombi. The CRTT results showed that although both groups exhibited varying degrees of insufficient refilling volume, the early PI group had significantly slower refilling than the BE group (p < 0.001), which persisted during the deterioration or disappearance of erythema. Conclusions: Our results showed that persistent ischemia caused by thrombi is an important cause of early PI deterioration post-decompression. Therefore, the performance of CRTT coupled with the transparent disc method may become a promising method for detecting ischemia post-decompression. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) has become a global problem. With the increasing prevalence of MetS worldwide, understanding its pathogenesis and treatment modalities are essential. Animal models should allow an appropriate representation of the clinical manifestations of human conditions. Rats are the most commonly used experimental animals for the study. The development of a proper MetS model using rats will contribute to the successful application of research findings to the clinical setting. Various intervention methods are used to induce MetS through diet induction with various compositions, chemicals, or a combination of both. This review will provide a comprehensive overview of several studies on the development of rat MetS models, along with the characteristics of the clinical manifestations resulting from each study.

There are few reliable biomarkers for gastrointestinal toxicity, and the further identification of such markers can improve the accuracy and speed of toxicological evaluations. This study aimed to evaluate the effectiveness of several recently proposed biomarkers—plasma citrulline, fecal calprotectin, fecal bile acid, and plasma miRNAs (miR-194 and -215)—in detecting intestinal toxicity. To this end, cysteamine hydrocholoride (cysteamine, 600 or 900 mg/kg, PO), indomethacin (10 mg/kg, PO), or 2,4-Dinitrobenzenesulfonic acid hydrate (DNBS, 20 mg/kg, IR) were administered to male Wistar rats to establish models of gastric/duodenal, jejunum/ileum, or colonic damage, respectively. Both novel biomarkers and traditional toxicological parameters were evaluated in these rat models. Standard in-life observations, such as fecal properties or body weight, were inadequate for monitoring intestinal toxicity, as there were few observable changes indicative of intestinal injury, especially in the cysteamine and indomethacin models. Plasma citrulline drastically decreased in cysteamine or indomethacin-treated rats, with a milder decrease in DNBS-treated animals. Fecal total bile acids and calprotectin levels increased only in rats treated with indomethacin or DNBS, but not with cysteamine. While plasma miR-194 remained unchanged across all models, miR-215 levels decreased after cysteamine treatment. Together, these results suggest that plasma citrulline and fecal calprotectin may be effective biomarkers for monitoring intestinal injury. Fecal TBA and plasma miR-215 also show potential as useful biomarkers, but further research is needed to confirm their efficacy. Specifically, plasma citrulline is indicative of damage from the stomach to the ileum, fecal total bile acids and calprotectin are indicative of damage from the jejunum to the rectum, and plasma miR-215 is indicative of damage from the stomach and the duodenum. Integrating these novel biomarkers with standard toxicological parameters will help in predicting actual intestinal sites of damage. This integration has the potential to improve the quality of toxicological evaluations. Our findings support the use of these biomarkers in clinical settings. • The study evaluates citrulline, calprotectin, bile acid, and miRNAs for detecting intestinal toxicity. • Plasma citrulline decreased drastically in cysteamine or indomethacin-treated rats. • Fecal total bile acids and calprotectin levels increased in indomethacin or DNBS-treated rats. • Plasma miR-215 levels decreased in cysteamine-treated rats. • These new biomarkers may enhance the monitoring and the predictability of damage sites within the intestine. [ABSTRACT FROM AUTHOR]

In this study, after optimizing the extraction process of CPP (Codonopsis pilosula polysaccharides), CPPM (CPP microcapsules) were prepared. Subsequently, the structural characteristics and physicochemical properties were studied. The results showed that CPPM is a hollow sac-like structure with rough folds and protuberances and comes in spherical or ellipsoidal shapes with uniform particle size. CPPM has certain swelling degree, low hardness, good adhesion, and stability. Then, the effect of CPPM on wounds repair was investigated by a rat model. The results showed that CPPM could improve the wound healing rate. Histological evaluation showed CPPM could promote neovascularization and fibroblast proliferation. By investigating the healing mechanism, it was found that CPPM increased the hydroxyproline content in granulation tissue and had an excellent antioxidant ability, and then inhibited lipid peroxidation, in addition, it significantly increased the transcript levels of VEGF and miRNA-21 genes, indicating that CPPM play an influential role in vascular remodeling during wound healing by up-regulating the expression of VEGF and miRNA-21 genes. [ABSTRACT FROM AUTHOR]

The difference between brain age predicted from MRI and chronological age (the so-called BrainAGE) has been proposed as an ageing biomarker. We analyse its cross-species potential by testing it on rats undergoing an ageing modulation intervention. Our rat brain age prediction model combined Gaussian process regression with a classifier and achieved a mean absolute error (MAE) of 4.87 weeks using cross-validation on a longitudinal dataset of 31 normal ageing rats. It was then tested on two groups of 24 rats (MAE = 9.89 weeks, correlation coefficient = 0.86): controls vs. a group under long-term environmental enrichment and dietary restriction (EEDR). Using a linear mixed-effects model, BrainAGE was found to increase more slowly with chronological age in EEDR rats (p = 0.015 for the interaction term). Cox regression showed that older BrainAGE at 5 months was associated with higher mortality risk (p = 0.03). Our findings suggest that lifestyle-related prevention approaches may help to slow down brain ageing in rodents and the potential of BrainAGE as a predictor of age-related health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To review treatment methods using natural extracts applied in rat models of periodontitis to establish a direction for the design of future experiments. Methods: An electronic search of PubMed was carried out using the keywords “periodontitis,” “natural”, “extracts”, “herb∗”, “plants” and “rats.” Articles were screened against inclusion and exclusion criteria by two independent researchers. Data describing the characteristics of rats, method of periodontitis inducement, extract administration, and outcome measures were extracted and analyzed by more than two authors manually. Results: Of the 864 articles identified, 33 studies were included. The use of Sprague–Dawley rats (51.2%) and male rats (90.9%) was preferred. The most common experimental methods were ligature placement (72.7%) and oral administration (66.7%). Alveolar bone loss was evaluated mainly by photography (51.5%) and micro-computed tomography (39.4%). Factors related to bone remodeling and inflammatory processes, such as interleukin-1β, tumor necrosis factor-α, receptor activator of nuclear factor-κB, and osteoprotegerin, were also measured. Conclusion: Many diverse experimental periodontitis models have been used. However, few articles observed bone formation, immune responses, antibacterial effects, and toxicity. Future studies to assess natural extracts for the treatment of periodontitis should be robust and well-designed.

Objective: An increasing number of studies indicate that autophagy plays an important role in the pathogenesis of spinal cord injury, and that regulating autophagy can enhance recovery from spinal cord injury. However, the effect of regulating autophagy and whether autophagy is detrimental or beneficial after spinal cord injury remain unclear. Therefore, in this study we evaluated the effects of autophagy regulation on spinal cord injury in rats by direct and indirect comparison, in an effort to provide a basis for further research. Data source: Relevant literature published from inception to February 1, 2018 were included by searching Wanfang, CNKI, Web of Science, MEDLINE (OvidSP), PubMed and Google Scholar in English and Chinese. The keywords included “autophagy”, “spinal cord injury”, and “rat”. Data selection: The literature included in vivo experimental studies on autophagy regulation in the treatment of spinal cord injury (including intervention pre- and post-spinal cord injury). Meta-analyses were conducted at different time points to compare the therapeutic effects of promoting or inhibiting autophagy, and subgroup analyses were also conducted. Outcome measure: Basso, Beattie, and Bresnahan scores. Results: Of the 622 studies, 33 studies of median quality were included in the analyses. Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 1.80, 95% CI: 0.81–2.79, P = 0.0004), 3 days (MD = 0.92, 95% CI: 0.72–1.13, P < 0.00001), 1 week (MD = 2.39, 95% CI: 1.85–2.92, P < 0.00001), 2 weeks (MD = 3.26, 95% CI: 2.40–4.13, P < 0.00001), 3 weeks (MD = 3.13, 95% CI: 2.51–3.75, P < 0.00001) and 4 weeks (MD = 3.18, 95% CI: 2.43–3.92, P < 0.00001) after spinal cord injury with upregulation of autophagy compared with the control group (drug solvent control, such as saline group). Basso, Beattie, and Bresnahan scores were higher at 1 day (MD = 6.48, 95% CI: 5.83–7.13, P < 0.00001), 2 weeks (MD = 2.43, 95% CI: 0.79–4.07, P = 0.004), 3 weeks (MD = 2.96, 95% CI: 0.09–5.84, P = 0.04) and 4 weeks (MD = 4.41, 95% CI: 1.08–7.75, P = 0.01) after spinal cord injury with downregulation of autophagy compared with the control group. Indirect comparison of upregulation and downregulation of autophagy showed no differences in Basso, Beattie, and Bresnahan scores at 1 day (MD = −4.68, 95% CI: –5.840 to −3.496, P = 0.94644), 3 days (MD = −0.28, 95% CI: −2.231–1.671, P = 0.99448), 1 week (MD = 1.83, 95% CI: 0.0076–3.584, P = 0.94588), 2 weeks (MD = 0.81, 95% CI: −0.850–2.470, P = 0.93055), 3 weeks (MD = 0.17, 95% CI: −2.771–3.111, P = 0.99546) or 4 weeks (MD = –1.23, 95% CI: −4.647–2.187, P = 0.98264) compared with the control group. Conclusion: Regulation of autophagy improves neurological function, whether it is upregulated or downregulated. There was no difference between upregulation and downregulation of autophagy in the treatment of spinal cord injury. The variability in results among the studies may be associated with differences in research methods, the lack of clearly defined autophagy characteristics after spinal cord injury, and the limited autophagy monitoring techniques. Thus, methods should be standardized, and the dynamic regulation of autophagy should be examined in future studies.

In treating patients with obstetric brachial plexus palsy, we noticed that denervated intrinsic muscles of the hand become irreversibly atrophic at a faster than denervated biceps. In a rat model of obstetric brachial plexus palsy, denervated intrinsic musculature of the forepaw entered the irreversible atrophy far earlier than denervated biceps. In this study, isobaric tags for relative and absolute quantitation were examined in the intrinsic musculature of forepaw and biceps on denervated and normal sides at 3 and 5 weeks to identify dysregulated proteins. Enrichment of pathways mapped by those proteins was analyzed by Kyoto Encyclopedia of Genes and Genomes analysis. At 3 weeks, 119 dysregulated proteins in denervated intrinsic musculature of the forepaw were mapped to nine pathways for muscle regulation, while 67 dysregulated proteins were mapped to three such pathways at 5 weeks. At 3 weeks, 27 upregulated proteins were mapped to five pathways involving inflammation and apoptosis, while two upregulated proteins were mapped to one such pathway at 5 weeks. At 3 and 5 weeks, 53 proteins from pathways involving regrowth and differentiation were downregulated. At 3 weeks, 64 dysregulated proteins in denervated biceps were mapped to five pathways involving muscle regulation, while, five dysregulated proteins were mapped to three such pathways at 5 weeks. One protein mapped to inflammation and apoptotic pathways was upregulated from one pathway at 3 weeks, while three proteins were downregulated from two other pathways at 5 weeks. Four proteins mapped to regrowth and differentiation pathways were upregulated from three pathways at 3 weeks, while two proteins were downregulated in another pathway at 5 weeks. These results implicated inflammation and apoptosis as critical factors aggravating atrophy of denervated intrinsic muscles of the hand during obstetric brachial plexus palsy. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Fudan University, China (approval No. DF-325) in January 2015.

A quantitative method for the evaluation of facial swelling in rats with middle cerebral artery occlusion (MCAO) was established using a mathematical method for the first time. The rat model of MCAO was established via bilateral common carotid artery ligation. Three groups of rats with the same baseline were selected (model group, positive drug group, and control group) according to their behavioral score and body weight 24 h after surgery. Drug administration was initiated on post-MCAO day 8 and was continued for 28 days. Mobile phones were used to collect facial images at different time points after surgery. In facial image analysis, the outer canthi of both eyes were used as the facial dividing line, and the outer edge of the rat's face was framed using the marking method, and the framed part was regarded as the facial area (S) of the rats. The histogram created with Photoshop CS5 was used to measure the face area in pixels. The distance between the outer canthi of both eyes (Le) and vertical line from the tip of the nose to the line joining the eyes was recorded as H1, and the line from the tip of the nose to the midpoint of the line joining the eyes was recorded as H2. The facial area was calibrated based on the relationship between H1 and H2. The distance between the eyes was inversely proportional to the distance between the rats and mobile phone such that the face area was calibrated by unifying Le. The size of Le between the eyes was inversely proportional to the distance between the rats and mobile phone. This was used to calibrate the face area. When compared with the control group, the facial area of the model group gradually increased from postoperative day 1 to day 7, and there was a significant difference in the facial area of the model group on postoperative day 7. Hence, positive drugs exhibited the effect of improving facial swelling. H1 and H2 can reflect the state of turning the head and raising the head of the rats, respectively. Facial area was calibrated according to the relationship between H1 and H2, which had no obvious effect on the overall conclusion. Furthermore, mobile phone lens was used to capture the picture of rat face, and the distance between the eyes and H1 and H2 was used to calibrate the facial area. Hence, this method is convenient and can be used to evaluate subjective judgment of the human eyes via a quantitative method.

Objectives: Periodontal bacteria that have been studied show a strong connection to various vascular diseases. Among the many kinds of periodontal bacteria, Porphyromonas gingivalis (Pg) is well examined in the general aspects and in a rat model. However, whether other periodontal bacteria work or react differently is not studied well. Material and methods: We chose Aggregatibacter actinomycetemcomitans (Aa) and Prevotella intermedia (Pi) as different types of periodontal bacteria. Low‐density and high‐density bacterial solutions were injected in the small artery of rats' groins using our rat model. Eighteen limbs of 9 SD male rats (500–650 g) were used. After 7 days, 14–18 days, and 28 days, the rats were sacrificed. A pathological and an immuno‐histochemical study was conducted and reported on the low‐density group with 12 limbs because the Pi group lacked a high‐density study. Immuno‐histochemical staining of live Pg was performed on three limbs of three rats at 1 h, 3 h, and 1 week after injection. Results: The appearances from the acute, at 7 days, to chronic phases, at 28 days, were observed. The differences of the species were certainly observed in the internal elastic lamina (IEL), and immuno‐histochemical reactions. The inflammatory reactions, such as cellular distribution or intra‐thrombus materials, were similar in all. One week later, we could not see any living bacteria in the specimen or immunological observation. Conclusions: The three species were essentially the same, except for Aa's stronger disruption of IEL, and more CD3 (Pan T cell) in Pi and more CD79a (Pan B cell) in Pg. We propose a new concept of a possible mechanism of vascular diseases, in which the work of LPS (lipopolysaccharides) and a toll‐like receptor (TLR) is emphasized. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) has become a global problem. With the increasing prevalence of MetS worldwide, understanding its pathogenesis and treatment modalities are essential. Animal models should allow an appropriate representation of the clinical manifestations of human conditions. Rats are the most commonly used experimental animals for the study. The development of a proper MetS model using rats will contribute to the successful application of research findings to the clinical setting. Various intervention methods are used to induce MetS through diet induction with various compositions, chemicals, or a combination of both. This review will provide a comprehensive overview of several studies on the development of rat MetS models, along with the characteristics of the clinical manifestations resulting from each study. [ABSTRACT FROM AUTHOR]

Background: Pressure injuries (PIs) generally result from prolonged ischemia through localized skin compression, and ischemia persists and exacerbates damage even post-decompression. The mechanisms of ischemia post-decompression are still unclear, and appropriate methods for detection are lacking. Methods: We used blanchable erythema (BE) and early PI rat models. We assessed the perfusion using Evans Blue (EB) and thrombus formation under a light microscope. Furthermore, we performed a capillary refill time test (CRTT) to detect ischemia after depression coupled with the transparent disk method using a spectrophotometer. Results: Compared with the BE group, the early PI group showed significantly slow and insufficient perfusion, as determined by EB staining (p < 0.001). Histological observations revealed that ischemia during post-decompression of early PI was caused by a greater amount of thrombi. The CRTT results showed that although both groups exhibited varying degrees of insufficient refilling volume, the early PI group had significantly slower refilling than the BE group (p < 0.001), which persisted during the deterioration or disappearance of erythema. Conclusions: Our results showed that persistent ischemia caused by thrombi is an important cause of early PI deterioration post-decompression. Therefore, the performance of CRTT coupled with the transparent disc method may become a promising method for detecting ischemia post-decompression.

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy. [ABSTRACT FROM AUTHOR]

Abstract Physical exercise and fitness may serve as resilience factors to stress exposure. However, the extreme range in human exercise performance suggests that genetic variation for exercise capacity could be a confounding feature to understanding the connection between exercise and stress exposure. To test this idea, we use laboratory rat models selectively bred for a low and high gain in aerobic running capacity in response to training to examine whether an inherent capacity to respond to physical exercise reflects how stress changes neurobiological functioning and regulates fear‐associated memory processing. Utilization of this contrasting rat model system of low and high responders has the potential to guide the interpretation of the reported association with exercise involvement and the reduction of stress‐induced anxiety disorders. Our data show that aerobic fitness may be linked to the ability to regulate fear‐associated memories. We also show that acquired exercise capacity may play a key role in regulating responses to an acute stressor. Exercise sensitivity plays a significant role in the activation of the plasticity‐associated molecule extracellular signal‐regulated kinase, changes in stress hormone activity, and anatomical modifications to the noradrenergic locus coeruleus. These data identify a unique operational mechanism that may serve as translational targets for lessening symptoms of stress and anxiety.

Physical exercise and fitness may serve as resilience factors to stress exposure. However, the extreme range in human exercise performance suggests that genetic variation for exercise capacity could be a confounding feature to understanding the connection between exercise and stress exposure. To test this idea, we use laboratory rat models selectively bred for a low and high gain in aerobic running capacity in response to training to examine whether an inherent capacity to respond to physical exercise reflects how stress changes neurobiological functioning and regulates fear‐associated memory processing. Utilization of this contrasting rat model system of low and high responders has the potential to guide the interpretation of the reported association with exercise involvement and the reduction of stress‐induced anxiety disorders. Our data show that aerobic fitness may be linked to the ability to regulate fear‐associated memories. We also show that acquired exercise capacity may play a key role in regulating responses to an acute stressor. Exercise sensitivity plays a significant role in the activation of the plasticity‐associated molecule extracellular signal‐regulated kinase, changes in stress hormone activity, and anatomical modifications to the noradrenergic locus coeruleus. These data identify a unique operational mechanism that may serve as translational targets for lessening symptoms of stress and anxiety. [ABSTRACT FROM AUTHOR]

Objective: Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 nd transmembrane (TM) helix of Adcy3 in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior., Methods: We used CRISPR-SpCas9 to mutate the TM domain of Adcy3 in WKY rats (Adcy3 mut/mut ). We also created a heterozygous knockout rat in the same strain (Adcy3 +/- ). Wild-type (WT), Adcy3 +/- , and Adcy3 mut/mut rats were fed a high-fat diet for 12 weeks. We measured body weight, fat mass, glucose tolerance, food intake, metabolism, emotion-like behaviors, and memory., Results: Adcy3 +/- and Adcy3 mut/mut rats weighed more than WT rats due to increased fat mass. There were key sex differences: adiposity was driven by increased food intake in males but by decreased energy expenditure in females. Adcy3 mut/mut males displayed increased passive coping and decreased memory while Adcy3 mut/mut females displayed increased anxiety-like behavior., Conclusions: These studies show that the ADCY3 TM domain plays a role in protein function, that Adcy3 may contribute to the relationship between obesity and MDD, and that sex influences the relationships between Adcy3 , metabolism, and behavior., Competing Interests: Disclosure The authors declared no conflict of interest.

Research Question: What are the long-term effects of different models of polycystic ovary syndrome (PCOS), and which model could be used in future research?, Design: PCOS models induced by letrozole, letrozole plus high-fat diet (LE+HFD), testosterone propionate (TP) or testosterone propionate plus HFD (TP+HFD) were established in rats. Body weight, energy intake, blood glucose, sex hormone concentrations, lipid profiles and the oestrus cycle were observed. Histology of ovaries, large intestine and fat was displayed. Protein and mRNA levels relating to hormone synthesis, oocyte maturation, the gut barrier, lipid metabolism and inflammation were evaluated using western blotting, immunohistochemistry and PCR. The composition of the microbial community was measured using 16S RNA sequencing., Results: Letrozole treatment induced hyperandrogenaemia, polycystic ovarian morphology, a disrupted oestrus cycle and impaired ovarian function, which could be restored within 42 days. Concurrently, letrozole disturbed glucose, fat, and energy metabolism, affected the inflammatory state and compromised intestinal homeostasis. HFD could amplify the disturbances in the metabolism and intestinal microenvironment, and the pituitary-ovarian axis was more efficiently and consistently affected by testosterone propionate. Testosterone propionate and TP+HFD treatment also disturbed the intestinal microenvironment. Although the metabolic effects of testosterone propionate were not as profound as those of letrozole, they were enhanced by HFD., Conclusions: Letrozole is useful for studies on metabolic disturbances in PCOS, and LE+HFD treatment is suitable for investigations on PCOS metabolic abnormalities and the gut-PCOS link. Testosterone propionate injection is appropriate for studying reproductive abnormalities in PCOS, while TP+HFD treatment is the most comprehensive for studying PCOS reproductive abnormalities, metabolic disturbances and the gut-PCOS link., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Disruption of estrogen receptor beta (ESR2) dysregulates granulosa cell genes essential for follicle maturation and ovulation. The datasets presented in this article depict gonadotropin-induced genes, which are differentially expressed in Esr2-null rat granulosa cells. Synchronized follicle development was initiated in four-week-old wildtype and Esr2-null female rats by administration of PMSG. Forty-eight hours after PMSG injection, further maturation of ovarian follicles was induced by hCG treatment. Granulosa cells were collected from the ovaries before gonadotropin administration, 48 h after PMSG treatment, and 4 h after hCG injection to the PMSG-treated rats. Total RNA was purified from granulosa cells and whole transcriptome was assessed by RNA-sequencing on an Illumina HiSeq X platform. RNA-seq data of wildtype and Esr2-null granulosa cells were analyzed and differentially expressed genes were identified by CLC Genomics Workbench. Gonadotropin-induced genes were identified by comparing the transcriptome data of PMSG- or hCG-induced wildtype granulosa cells with those without gonadotropin treatment. Furthermore, differentially expressed genes in Esr2-null granulosa cells were determined by comparing the transcriptome data with that of wildtype granulosa cells. These datasets can be used to recognize the gonadotropin-induced genes in granulosa cells that are Esr2-regulated and important for ovarian follicle maturation.

Contrast-induced nephropathy (CIN) is an iatrogenic disease caused by the parenteral administration of iodinated contrast media (CM). A number of agents are currently being assessed to minimise or prevent CIN. Such agents are typically assessed using rat models. The aim of this study was to provide a comprehensive review of the rat models of CIN used in pre-clinical research. The MEDLINE, EMBASE, Web of Science and Cochrane databases were systematically searched. Articles reporting rat models of CIN were included for assessment. Study designs, contrast agents and outcome measures were assessed. Of the assessed studies, a majority report a requirement for pre-existing renal impairment prior to the administration of CM. Outcome measures are heterogenous between studies, but typically include assessment and quantification of serum biochemical markers, cellular oxidative stress and histopathological changes. The significant variation in methodology reported in the current literature highlights the lack of consensus. The use of a reliable pre-contrast insult appears critical to result in the development of contrast nephropathy. The use of acceptable outcome measures appears to include serum laboratory markers, quantification of reactive oxygen species (ROS) and objective histopathological outcomes.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS), a common mental health disturbance associated with several periodic psychological symptoms in women. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMS/PMDD patients; however, side effects are inevitable, especially in long-term treatment. In previous studies, the natural compound paeonol in Moutan Cortex was found to play effective roles in central nervous system disorders with its anti-inflammatory, anti-oxidant, and neuroprotective effects. Consequently, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD. In this study, the open-field test (OFT) and elevated plus maze (EPM) and light dark box (LDB) tests were performed in mice to determine the optimal dose of paeonol for treating anxiety. Then, paeonol was used to treat the progesterone withdrawal (PWD) and resident intruder paradigm (RIP) rat models of PMDD. Using these two reliable models, the OFT and EPM, LDB, and composite aggressive tests were performed to evaluate the effect of the drug on behavioural symptoms of PMDD. From the dosage screening results, the optimal anti-anxiety dose of paeonol was identified as 17.5 mg/kg/d for 7 days. With regard to the effect of paeonol on PMDD rat models, a significantly improvement was found in the behavioural symptoms, but the effective dose varied in different models. For the PWD model rats, treatment with 6.05 mg/kg paeonol could significantly improve anxiety and irritability, while that with 24.23 mg/kg paeonol resulted in anxiety-like effects in behavioural tests. In RIP model rats, treatment with 12.11 mg/kg paeonol demonstrated excellent effects in improving anxiety, particularly irritable emotional behaviour. In conclusion, our study indicates that paeonol is a potential therapeutic compound for PMS/PMDD; it is a drug option that helps establish dosage guidance for treatment of this condition.

Background/Aims: Numerous studies have highlighted the activation of NF-κB in the esophageal mucosa during the early stages of gastroesophageal reflux disease (GERD). The present study aimed to investigate the role of the TLR4/NF-κB signaling pathway in GERD rat models. Methods: Wistar rats (n = 60) were recruited to establish a GERD animal model. Distal esophageal pH was assessed, followed by determination of the contents of thiobarbituric acid-reactive species (TBARS) and reactive oxygen species (ROS) in esophageal mucosa homogenate. ELISA was employed to detect the levels of inflammatory factors (IL-6, IL-8, IL-10 and TNF-α) in esophageal mucosa. The expression of MMP-3, MPP-9, Cldn1 and Cldn4 was determined by immunohistochemistry. RT-qPCR and western blot analysis were applied to evaluate the protein expressions in TLR4/NF-κB signaling pathway, while TUNEL staining was utilized to examine the apoptosis rate in the esophageal mucosal tissues. Results: Distal esophageal pH of the rats was higher in the GERD + PDTC group than in other groups. Levels of inflammatory factors in esophageal mucosal tissues were downregulated with the inhibition of NF-κB, which was determined to be associated with the decreased contents of TBARS and ROS. Moreover, decreased MMP-3 and MPP-9 in addition to elevated Cldn1 and Cldn4 were detected in the esophageal mucosa as a result of the inactivation of NF-κB. The TLR4/NF-κB signaling pathway-related proteins (TLR4, NF-κB and IκBα); the rate of apoptosis was demonstrated to be suppressed in the GERD + PDTC group, while inactivating NF-κB was found to alleviate the tissue damage observed in the esophageal mucosa. Conclusion: The key findings of the current study demonstrate that the inactivation of the TLR4/NF-κB signaling pathway alleviates oxidative stress injury and promotes the repair of esophageal mucosal injury among rats with GERD, highlighting a potential novel GERD mechanism.

Background/Aims: Chronic compression of the spinal cord causes the loss of motor neurons in the anterior horn, but the precise and extensive mechanism for the loss is not completely determined. Therefore, this study aims to explore the role of microRNA-494 (miR-494) in the proliferation of astrocytes and in the synaptic remodeling in the spinal cord of a rat model of chronic spinal cord injury (SCI) by regulating the Nogo/NgR signaling pathway. Methods: A rat model of chronic, compressive SCI was established, and the spinal cord state, blood supply changes, and astrocyte apoptosis were observed. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect expression of miR-494 and the Nogo/NgR signaling pathway-related genes. Fluorescence in situ hybridization (FISH) was used for detecting miR-494 expression and distribution. Results: Higher miR-494 expression was accompanied by the inhibition of astrocyte proliferation and synaptic remodeling. In addition, CDK6 could be regulated by miR-494 and was shown to be one of the target genes of miR-494. Positive expression of miR-494 detected by FISH was consistent with the results from RT-qPCR that miR-494 could downregulate CDK6 gene expression. Moreover, the direct miR-494 target CDK6 plays important inhibitory roles in chronic SCI by suppressing the Nogo/ NgR signaling pathway. Conclusions: The results demonstrated that miR-494 inhibition can promote astrocyte proliferation and synaptic remodeling by suppressing the Nogo/NgR signaling pathway in a rat model of chronic SCI.

Purpose: Obesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most effectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague–Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more effective in reverting the microbiota modifications caused by the high-fat diet when compared to either of the two factors alone. Methods: Using next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated different biological parameters with the genera exhibiting the highest variation in abundance between the groups. Results: The high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These effects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-affected genera were correlated with obesity-related parameters. Conclusions: The dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fiber control diet. Bariatric surgery contributed significantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same effects as when combined. [ABSTRACT FROM AUTHOR]

Oil spills can result in significant damage to marine estuaries, rivers, lakes, wetlands, and shorelines. Electrospun nanofibers containing biosurfactant (ENFs) can be used to clean oil spills up and protect the environmental biology. Present work aimed to study the side-effects of prepared nanofibers on animal models. Screening of the prepared ECNFs on animals showed that three of them (PVA-5, PEO-1, and PEO-5) are safe to hepatic tissues and liver functions. Furthermore, oxidative stress did not change after using these nanofibers. The PVA-1 nanofibers, however, were found to cause major pathological changes in the liver tissue. In addition, PVA-1 nanofibers were proved to alter the total white blood count and the neutrophil percentages significantly in comparison to the control. In conclusion, PVA-5, PEO-1, and PEO-5 are safe to hepatic tissues and liver functions. [ABSTRACT FROM AUTHOR]

Fluoroacetate (FA) is a tasteless, odorless, water‐soluble metabolic poison with severe toxicological effects. Characterized in the mid‐1900s, it has been used as a rodenticide but is comparably lethal to all mammals. Many countries have restricted its use, and modern‐day accidental human exposures are rare, but recently, concerns have been raised about its application as a chemical weapon with no known antidote. A combined treatment of methylene blue (MB), an antioxidant, and monosodium glutamate (MSG), a precursor of the citric acid cycle substrate alpha‐ketoglutarate, has been recommended as an effective countermeasure; however, no peer‐reviewed articles documenting the efficacy of this therapy have been published. Using a rodent model, we assessed the effects of MB and MSG on the neurologic, cardiac, and pulmonary systems. Transcriptomic analysis was used to elucidate inflammatory pathway activation and guide bioassays, which revealed the advantages and disadvantages of these candidate countermeasures. Results show that MB and MSG can reduce neurologic signs observed in rats exposed to sodium FA and improve some effects of intoxication. However, while this strategy resolved some signs of intoxication, ultimately it was unable to significantly reduce lethality. [ABSTRACT FROM AUTHOR]

The results of genetic studies suggest a possible role for SNAP-25 polymorphism in the development of autism spectrum disorders (ASDs); however, there are no data available on whether changes in SNAP-25 expression also affect animals in rodent models of ASD. The aim of the present study was to explore this issue. The studies included 1-month-old rats representing valproic acid (VPA)- and thalidomide (THAL)-induced models of autism. Their mothers received single doses of VPA (800 mg/kg) or THAL (500 mg/kg) per os on the 11th day of gestation. SNAP-25 protein content in the cerebellum, hippocampus, and frontal lobe was determined using Western blotting, while changes of mRNA levels of Snap25 gene were determined using real-time polymerase chain reaction. Compared to controls, SNAP-25 content was decreased by approximately 35% in all brain structures tested, in both males and females, exclusively in the VPA group. In contrast to this, Snap25 expression, studied in males, was increased in the hippocampus and cerebellum in both, VPA- and THAL-treated rats. We discuss the compliance of these results with the hypothesized role of SNAP-25 in the pathophysiology of ASD and the adequacy of the experimental models used. [ABSTRACT FROM AUTHOR]

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS), a common mental health disturbance associated with several periodic psychological symptoms in women. Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMS/PMDD patients; however, side effects are inevitable, especially in long-term treatment. In previous studies, the natural compound paeonol in Moutan Cortex was found to play effective roles in central nervous system disorders with its anti-inflammatory, anti-oxidant, and neuroprotective effects. Consequently, we assume that paeonol might produce positive effects in the treatment of PMS/PMDD. In this study, the open-field test (OFT) and elevated plus maze (EPM) and light dark box (LDB) tests were performed in mice to determine the optimal dose of paeonol for treating anxiety. Then, paeonol was used to treat the progesterone withdrawal (PWD) and resident intruder paradigm (RIP) rat models of PMDD. Using these two reliable models, the OFT and EPM, LDB, and composite aggressive tests were performed to evaluate the effect of the drug on behavioural symptoms of PMDD. From the dosage screening results, the optimal anti-anxiety dose of paeonol was identified as 17.5 mg/kg/d for 7 days. With regard to the effect of paeonol on PMDD rat models, a significantly improvement was found in the behavioural symptoms, but the effective dose varied in different models. For the PWD model rats, treatment with 6.05 mg/kg paeonol could significantly improve anxiety and irritability, while that with 24.23 mg/kg paeonol resulted in anxiety-like effects in behavioural tests. In RIP model rats, treatment with 12.11 mg/kg paeonol demonstrated excellent effects in improving anxiety, particularly irritable emotional behaviour. In conclusion, our study indicates that paeonol is a potential therapeutic compound for PMS/PMDD; it is a drug option that helps establish dosage guidance for treatment of this condition. [ABSTRACT FROM AUTHOR]

Contrast-induced nephropathy (CIN) is an iatrogenic disease caused by the parenteral administration of iodinated contrast media (CM). A number of agents are currently being assessed to minimise or prevent CIN. Such agents are typically assessed using rat models. The aim of this study was to provide a comprehensive review of the rat models of CIN used in pre-clinical research. The MEDLINE, EMBASE, Web of Science and Cochrane databases were systematically searched. Articles reporting rat models of CIN were included for assessment. Study designs, contrast agents and outcome measures were assessed. Of the assessed studies, a majority report a requirement for pre-existing renal impairment prior to the administration of CM. Outcome measures are heterogenous between studies, but typically include assessment and quantification of serum biochemical markers, cellular oxidative stress and histopathological changes. The significant variation in methodology reported in the current literature highlights the lack of consensus. The use of a reliable pre-contrast insult appears critical to result in the development of contrast nephropathy. The use of acceptable outcome measures appears to include serum laboratory markers, quantification of reactive oxygen species (ROS) and objective histopathological outcomes. [ABSTRACT FROM AUTHOR]

Background: To explore blood–brain barrier disruption in hypertensive posterior reversible encephalopathy syndrome.Methods: The hypertension rat models were successfully established and scanned on 7T micro-MRI. MRI parameter maps including apparent diffusion coefficient, T1 value, and perfusion metrics such as cerebral blood volume, cerebral blood flow, mean transit time and time to peak maps, were calculated.Results: The ADC values of the experimental group were higher than those of the control group both in cortical (P < 0.01) and subcortical (P < 0.05) regions. Voxel-wise analysis of ADC maps localized vasogenic edema primarily to the posterior portion of the brain. The increase in cerebral blood volume and cerebral blood flow values were found in the cortical and subcortical regions of rats with acute hypertension. No correlation was found between perfusion metrics and mean arterial pressure. The Evans blue dye content was higher in the posterior brain region than the anterior one (P < 0.05).Conclusions: Cerebral vasogenic edema resulting from acute hypertension supports the hypothesis of posterior reversible encephalopathy syndrome as the result of blood–brain barrier disruption, which maybe the potential therapeutic target for intervention.

Animal models of neurodegenerative diseases have helped us to better understand the pathogenesis of neurodegenerative diseases. However, recent failure to translate pre-clinical model studies to the clinic urges us to develop more rigorous and faithful animal models in neurodegenerative diseases. As genetic manipulation of rats becomes much more accessible due to availability of CRISPR-Cas9 and other genomic editing toolboxes, rats have been emerging as a new model system for neurodegenerative diseases. Even though mouse models have been dominant over the last decades, rats may provide advantages over mice. Rats are more genetically and physiologically closer to humans than to mice. Also, certain rat models can represent deposition of tau, which is one of the key pathological features of Alzheimer's diseases and tauopathies. However, there is an unmet need for standardized, rigorous testing in rat models. We adopted two commonly used biochemical and immunofluorescence methods from mice and human postmortem brains to measure tau aggregation. Due to the intrinsic differences between mice and rats, e.g., size of rat brains, certain equipment is required for rat models to study tau pathologies. Along with specific tools, here we describe the detailed methods for rat models of neurodegenerative diseases., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To explore blood–brain barrier disruption in hypertensive posterior reversible encephalopathy syndrome. Methods: The hypertension rat models were successfully established and scanned on 7T micro-MRI. MRI parameter maps including apparent diffusion coefficient, T1 value, and perfusion metrics such as cerebral blood volume, cerebral blood flow, mean transit time and time to peak maps, were calculated. Results: The ADC values of the experimental group were higher than those of the control group both in cortical (P < 0.01) and subcortical (P < 0.05) regions. Voxel-wise analysis of ADC maps localized vasogenic edema primarily to the posterior portion of the brain. The increase in cerebral blood volume and cerebral blood flow values were found in the cortical and subcortical regions of rats with acute hypertension. No correlation was found between perfusion metrics and mean arterial pressure. The Evans blue dye content was higher in the posterior brain region than the anterior one (P < 0.05). Conclusions: Cerebral vasogenic edema resulting from acute hypertension supports the hypothesis of posterior reversible encephalopathy syndrome as the result of blood–brain barrier disruption, which maybe the potential therapeutic target for intervention. [ABSTRACT FROM AUTHOR]

Rodent studies of bone in chronic kidney disease have primarily relied on end-point examinations of bone microarchitecture. This study used longitudinal in vivo microcomputed tomography (in vivo μCT) to characterize the onset and progression of bone loss, specifically cortical porosity, in the Cy/+ rat of model of CKD. Male CKD rats and normal littermates were studied. In vivo μCT scans of the right distal tibia repeated at 25, 30, and 35 weeks were analyzed for longitudinal changes in cortical and trabecular bone morphometry. In vitro μCT scans of the tibia and femur identified spatial patterns of bone loss across distal, midshaft and proximal sites. CKD animals had reduced BV/TV and cortical BV at all time points but developed cortical porosity and thinning between 30 and 35 weeks. Cortical pore formation was localized near the endosteal surface. The severity of bone loss was variable across bone sites, but the distal tibia was representative of both cortical and trabecular changes. The distal tibia was found to be a sensitive suitable site for longitudinal imaging of both cortical and trabecular bone changes in the CKD rat. CKD trabecular bone loss progressed through ~30 weeks followed by a sudden acceleration in cortical bone catabolism. These changes varied in timing and severity across individuals, and cortical bone loss and porosity progressed rapidly once initiated. The inclusion of longitudinal μCT in future studies will be important for both reducing the number of required animals and to track individual responses to treatment. Unlabelled Image • The distal tibia is a sensitive site for longitudinal μCT of cortical and trabecular bone changes in the CKD rat. • CKD trabecular bone loss largely precedes the initial formation of cortical porosity. • CKD cortical porosity formation is initially concentrated near the endosteal surface. • CKD cortical bone loss varies in timing and severity across individuals but porosity progresses rapidly once initiated. [ABSTRACT FROM AUTHOR]

This study investigated the expression of programmed cell death protein 4 (PDCD4) in rat models of coronary atherosclerosis (AS) and analyzed its role and mechanism. A total of 80 Wistar rats were selected and divided into the control group (n=40) and research group (n=40) according to the principle of similar body weight, of which coronary AS models were established in rats in the research group. PDCD4 expression in coronary artery tissues was detected using western blotting, and the expression of interleukin-6 (IL-6) and IL-8 in the coronary artery tissues were measured by means of reverse transcription-polymerase chain reaction (RT-PCR). The apoptotic rate of coronary artery smooth muscle cells was determined via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The relative expression of PDCD4 in coronary artery tissues in the research group was obviously higher than that in the control group, and the difference was statistically significant (t=6.121, P<0.01). In terms of the relative expression of messenger ribonucleic acid (mRNA) of IL-6 in the coronary artery tissues, the research group had a remarkably higher level than the control group, with a statistically significant difference (t=21.03, P<0.01). The difference in the relative expression of IL-8 mRNA between the research group and the control group was statistically significant, of which a much higher level was detected in the research group (t=19.96, P<0.01). The apoptotic rate of smooth muscle cells in the research group was increased notably compared with that in the control group, and the difference was statistically significant (t=5.985, P<0.01). PDCD4 may participate in the formation of coronary AS plaque, and its possible function in the process is to inhibit the proliferation of vascular smooth muscle cells and promote the upregulation of IL-6 and IL-8. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the micro ribonucleic acid-138 (miR-138) expression in oral herpes simplex (HS) and its effect on the expression of herpes simplex virus type 1 (HSV-1) lytic gene trans-acting factor infected cell protein 0 (ICP0). Forty-five rat models with oral HS were successfully established (the observation group) and another 40 healthy rats were selected as the control group. The miR-138 expression in serum of rats in the two groups were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). 293T cells infected by HSV-1 were divided into Group A and Group B after 10 days of culture. Group A was transfected by miR-138 mimics and Group B was transfected by miR-138 complementary oligonucleotide inhibitor. The expression levels of miR-138 and ICP0 messenger RNA (mRNA) in the cells of the two groups were detected by RT-PCR, and the expression levels of ICP0 protein were detected by enzyme-linked immunosorbent assay (ELISA). A total of 85 rat models with oral HS were established in this study, but only 45 models were established successfully with a success rate of 56.25%. The expression level of miR-138 in the rat serum in the observation group was higher than that in the control group (P<0.05). In addition, the expression level of ICP0 mRNA in Group A was lower than that in Group B (P<0.05). Moreover, the expression level of ICP0 protein in Group A was lower than that in Group B (P<0.05). Finally, the expression level of miR-138 in HSV was increased, suggesting that the expression of miR-138 may inhibit the expression of ICP0, thus preventing the duplication of HSV-1. Therefore, the expression of miR-138 may be used as a potential therapeutic target for HSV. [ABSTRACT FROM AUTHOR]