Sprague-Dawley Research Articles

Study of the Cardioprotective Properties of Uridine-5'-Monophosphate and Uridine in a Rat Model of Myocardial Damage Induced by Isoprenaline

Study of the Cardioprotective Properties of Uridine-5'-Monophosphate and Uridine in a Rat Model of Myocardial Damage Induced by Isoprenaline

Non-invasive point-of-care optical technique for continuous invivo assessment of microcirculatory function: Application to a preclinical model of early sepsis.

Increased amplitude of peripheral vasomotion is a potential early marker of sepsis-related microcirculatory impairment; however, previous reports relied on clinically unsuitable invasive techniques. Hyperspectral near-infrared spectroscopy (hsNIRS) and diffuse correlation spectroscopy (DCS) are non-invasive, bedside techniques that can be paired to continuously monitor tissue hemoglobin content (HbT), oxygenation (StO2), and perfusion (rBF) to detect vasomotion as low-frequency microhemodynamic oscillations. While previous studies have primarily focused on the peripheral microcirculation, cerebral injury is also a common occurrence in sepsis and hsNIRS-DCS could be used to assess cerebral microcirculatory function. This work aimed to use a hybrid hsNIRS-DCS system to continuously monitor changes in the peripheral and cerebral microcirculation in a rat model of early sepsis. It was hypothesized that the skeletal muscle would be a more sensitive early indicator of sepsis-related changes in microhemodynamics than the brain. Control animals received saline while the experimental group received fecal slurry to induce sepsis. Subsequently, hsNIRS-DCS measurements were acquired from the skeletal muscle and brain for 6 h. Peripheral rBF rapidly decreased in septic animals, but there were no significant changes in peripheral HbT or StO2, nor cerebral HbT, rBF, or StO2. The power of low-frequency peripheral oscillations in all parameters (i.e., HbT, StO2, and rBF) as well as cerebral HbT oscillations were elevated in septic animals during the final 4 h. These findings suggest that in the early stages of sepsis, while vital organs like the brain are partly protected, changes in peripheral perfusion and vasomotor activity can be detected using hsNIRS-DCS. Future work will apply the technique to ICU patients.

Content of Nitrogen Monoxide and Copper in the Hippocampus of a Rat Model of Short-Term Cerebral Ischemia Followed by Reperfusion

Content of Nitrogen Monoxide and Copper in the Hippocampus of a Rat Model of Short-Term Cerebral Ischemia Followed by Reperfusion

Histological Evaluation of the Effects of Intra-Articular Injection of Caffeic Acid on Cartilage Repair in a Rat Knee Microfracture Model.

BACKGROUND Cartilage injuries are challenging to treat due to limited self-healing. Standard treatments often lead to the formation of less durable fibrocartilage. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound, can improve cartilage repair. This animal study aimed to evaluate the histological effects of intra-articular injection of CAPE on cartilage repair in a rat model of microfracture of the knee joint. MATERIAL AND METHODS Twenty-four male Sprague-Dawley rats were divided into 4 groups. A cartilage defect was created in all groups, but Group A received no further intervention. Group B underwent a microfracture. Group C received intra-articular CAPE in the presence of a defect, without microfracture. Group D underwent both microfracture and CAPE treatment. Also, each rat underwent bilateral surgery, with one knee receiving CAPE (150 µg/kg) and the other receiving a control solution. After 28 days, histological analysis was performed on the cartilage tissue samples obtained from the defect sites by using the International Cartilage Research Society (ICRS-I and -II) visual assessment scale. Statistical analysis was performed using appropriate tests to compare histological scores between groups, with significance set at P<0.05. RESULTS Intra-articular CAPE significantly improved histopathological outcomes across several parameters, including reduced inflammation (P<0.05), enhanced tissue morphology (P<0.05), and improved cartilage matrix staining (P<0.05). No significant difference was observed in chondrocyte clustering or surface architecture among the groups. CONCLUSIONS Intra-articular CAPE enhances cartilage healing by improving tissue morphology and cartilage matrix quality.

Comparison of Early-Stage Knee Osteoarthritis Induced by Medial Meniscus Tear Versus Tibial Osteotomy in the Rat Model.

Medial meniscus tear (MMT) is a common method to induce osteoarthritis in rats, but mimics secondary osteoarthritis. A novel method of carrying out a medial wedge closing tibial osteotomy (TO) has been recently developed to induce primary osteoarthritis. This study aims to validate it, compared to MMT. Twenty rats were divided equally into 2 groups. Outcome measures such as histology graded according to Osteoarthritis Research Society International (OARSI) guidelines and computed tomography (CT) scans were analyzed at 6 weeks post-operatively. Observational gait analysis and serum biomarkers such as C-terminal cross-linked telopeptides of type II collagen (CTX-II) and interleukin-1 beta (IL-1β) were collected at 2-weekly intervals up to 6 weeks post-operatively. Serum CTX-II and IL-1β levels did not reveal a statistically significant difference across all time points between the 2 groups. CT grading was significantly more severe (2.80 ± 1.10 vs 1.40 ± 0.548, P = 0.0389) in the MMT group compared to the TO group. In addition, histological gradings such as calcified cartilage score (2.10 ± 1.91 vs 0.00 ± 0.00, P < 0.01) and cartilage degeneration score (4.80 ± 5.18 vs 0.00 ± 0.00, P < 0.01) revealed significantly more severe osteoarthritis in the MMT compared to TO group. Synovial membrane score did not reveal a statistically significant difference (1.10 ± 0.994 vs 1.00 ± 0.00, P = 1.00). TO is a novel method in inducing primary osteoarthritis in the rat model compared to MMT between the 6 and 12 weeks' time frame.

Discovery and Optimization of Dihydroquinolin-2(1H)-ones as Novel Highly Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.

Phosphodiesterase 5 (PDE5) is a cGMP-specific hydrolytic enzyme and widely distributed in versatile tissues. PDE5 has been identified as a valid therapeutic target for treating erectile dysfunction and pulmonary arterial hypertension (PAH). Herein, a hit-to-lead structural optimizations were performed on the PDE1 inhibitor 10c, leading to compound 14b possessing great potency against PDE5A (IC50 = 3 nM) with high selectivity over PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11 by more than 1125-fold, and remarkable safety properties. Furthermore, oral administration of 14b (5.0 mg/kg) exerted much better pharmacodynamics effects on both mPAP (mean pulmonary artery pressure) and RVHI (index of right ventricle hypertrophy) than sildenafil citrate (10.0 mg/kg) in a monocrotaline-induced PAH rat model. Overall, these results proposed a novel highly selective PDE5 inhibitor 14b which could serve as a potential candidate for treatment of PAH.

Oxidative stress and apoptosis of the spinal cord in a rat model of retinoic acid-induced neural tube defects.

Neural tube defects (NTDs) are severe congenital anomalies that significantly impact the central nervous system, arising from the neural tube's failure to close during early embryogenesis. In this study, we investigated NTDs and associated pathophysiological mechanisms in foetal rats following exposure to all-trans retinoic acid (atRA). Out of 168 embryos from 15 pregnant rats in the experimental group, 78% displayed NTDs with notable spinal deformities, primarily in the lumbar-sacral region, similar to human cases. Body weight and crown-rump length (CRL) measurements indicated significant growth impairment in the NTD group compared to controls, while the atRA-treated group without NTDs showed no notable differences in growth. Immunohistochemistry (IHC) results demonstrated decreased NeuN and PCNA expression in the NTD group's spinal cord. Oxidative stress markers showed markedly reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity, alongside increased malondialdehyde (MDA) levels in the NTD group, indicating heightened oxidative stress. Analysis of apoptosis-related proteins revealed elevated Bax and caspase-3 levels, reduced Bcl-2 and lower poly (ADP-ribose) polymerase (PARP) in the NTD group, suggesting a pronounced shift towards proapoptotic pathways, potentially contributing to NTD progression. Our findings indicate that oxidative stress and apoptosis play significant roles in the development of NTDs. Future investigations should aim to pinpoint critical regulatory genes or proteins that might be targeted for therapeutic interventions to alleviate oxidative stress and apoptosis in NTD development.

Isoquercitrin Loaded PEGylated Long Circulating Liposomes Improve Bone Mass and Reduce Oxidative Stress After Osteoporosis.

Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis.

Glutathione's Role in Liver Metabolism and Hangover Symptom Relief: Dysregulation of Protein S-Glutathionylation and Antioxidant Enzymes.

Hangovers from alcohol consumption cause symptoms like headaches, nausea, and fatigue, disrupting daily activities and overall well-being. Over time, they can also lead to inflammation and oxidative stress. Effective hangover relief alleviates symptoms, prevents dehydration, and replenishes energy needed for daily tasks. Natural foods considered high in antioxidants and antiinflammatory properties may aid in the hepatic breakdown of alcohol. The study aims to investigate the impact of glutathione or its enriched yeast extract, which is recognized for its antioxidant characteristics, on alcohol metabolism and alleviating hangovers in a rat model exposed to binge drinking. In this study, glutathione and its enriched yeast extract controlled hangover behaviour patterns, including locomotor activity. Additionally, it enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) following ethanol ingestion (3 g/kg). Further, the incorporation of glutathione led to an increase in the expression of antioxidant enzymes, such as SOD and catalase, by activating the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway. This activation reduced the excessive production of reactive oxygen species (ROS) and malondialdehyde. Next, glutathione modulated the activity of cytochrome P450 2E1 (CYP2E1) and the protein expressions of Bax and Bcl2. Besides, in vitro and in vivo investigations with glutathione demonstrated a regulating effect on the pan-s-glutathionylation and its associated protein expression, glutaredoxin 1 (Grx1), glutathione-S-transferase Pi (GST-π), and glutathione reductase (GR). Together, these findings suggest that glutathione or its enriched yeast extract as a beneficial dietary supplement for alleviating hangover symptoms by enhancing alcohol metabolism and its associated Nrf2/Keap1 signalings.

Dietary Antrodia cinnamomea Polysaccharide Intervention Modulates Clinical Symptoms by Regulating Ovarian Metabolites and Restructuring the Intestinal Microbiota in Rats with Letrozole-Induced PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.

Preventing epileptogenesis by interaction between inositol isomers and proteins.

Inositols play significant roles in biological systems. Myo-inositol (MI), the most prevalent isomer, functions as an osmolyte and mediates cell signal transduction. Other notable isomers include Scyllo-inositol (SCI) and D-Chiro-inositol (DCHI). Our previous investigations have highlighted MI's potential antiepileptogenic effects, although its exact mechanisms of action during epileptogenesis remain unclear. A critical, unexplored area is how inositols interact with proteins. Additionally, the antiepileptogenic capabilities of SCI and DCHI have yet to be determined. This study seeks to address these gaps. Inositol interacting proteins were identified by cellular thermal shift assay. Status epilepticus (SE) in rats was induced using kainic acid (KA), followed by a 28-day treatment with either MI, SCI, DCHI, or saline. The duration and frequencies of behavioral spontaneous recurrent seizures (SRS) were scored for 8 weeks by 24 h video monitoring system. The effects of inositol treatment on spatial learning and memory deficits associated with epileptogenesis were evaluated by Morris water maze test. The changes in protein amounts were studied by Western immunoblotting. We identified several proteins that interact with inositols, noting both commonalities and isomer-specific associations. For the first time, we demonstrated that the treatment with SCI and DCHI, alongside MI, significantly reduces the frequency and duration of behavioral SRS in a KA-induced post-status epilepsy model in rats. This reduction persisted for 4 weeks post-treatment. Moreover, all three inositol isomers mitigated spatial learning and memory deficits associated with epileptogenesis. Alterations in the inositol interacting proteins: alpha synuclein and 14-3-3 theta were further examined 8 weeks post-SE in the hippocampus and neocortex of rats. Myo-inositol, SCI and DCHI interact with a number of proteins involved in different biological pathways. All studied inositol isomers express long-term beneficial effects on KA-induced SRS and the associated comorbidities. Inositols can be successfully used in the future for translational research. Epilepsy is a common neurological disorder characterized by spontaneous recurrent seizures and a range of associated comorbidities. The process that leads to the development of epilepsy is called epileptogenesis, and currently, no medication can effectively prevent it. Our study investigated the effects of a group of compounds-myo-inositol, scyllo-inositol, and D-chiro-inositol-that have potential antiepileptogenic properties on epilepsy induced by kainic acid. We found that: (i) the three inositol isomers share some common target proteins and also have unique ones and (ii) all of them counteract epileptogenesis and the related cognitive impairments.

Pharmacological and Phytochemical investigation of plant Zingiber Zerumbet having anti-ulcer activity

This study investigates the anti-ulcerogenic properties of Zingiber zerumbet using a rat model subjected to ulcerogenic agents. The hydroalcoholic extract of Zingiber zerumbet was evaluated for its efficacy in mitigating ulcer formation, measured through the number of ulcers, ulcer index, and gastric pH levels. Results demonstrated that the extract significantly reduced both the number of ulcers (from 9.80 ± 0.75 in the control group to 0.25 in the treated groups) and the ulcer index (from 6.25 ± 0.30 in the control to 0.52 ± 0.15 in the extract-treated group). Additionally, the gastric pH improved markedly, with treated groups showing pH levels of 6.85 ± 0.75 and 6.75 ± 0.35, compared to 3.45 ± 0.32 in the control group. The qualitative phytochemical analysis revealed the presence of flavonoids, saponins, and alkaloids, which are known for their therapeutic effects. These findings underscore the potential of Zingiber zerumbet as a natural remedy for gastric ulcers, providing a basis for further research into its active constituents and mechanisms of action Keywords: Zingiber zerumbet, anti-ulcerogenic, gastric ulcers, rat model, ulcer index, gastric pH, phytotherapy, herbal medicine, flavonoids

Dexamethasone alleviates acute lung injury in a rat model with venovenous extracorporeal membrane oxygenation support

BackgroundIn recent years, dexamethasone (Dex) has been used to treat acute respiratory distress syndrome (ARDS) in patients with COVID-19 and achieved promising outcomes. Venovenous extracorporeal membrane oxygenation (VV ECMO) support...

The histological investigation of the effects of electromagnetic radiation on rat ovaries.

People are now exposed to higher levels of electromagnetic radiation (EMR) due to the widespread use of mobile phones in recent years. The possible effects of this exposure on human health are related to EMR. It has been suggested that exposure to EMR has serious effects on reproduction. The study aimed to investigate the impact of exposure to EMR (4.5GB; 2600MHz) emitted by mobile phones on rat ovaries. 18 adult female Wistar albino rats were used in the study, and the animals were divided into three groups (n = 6): control, stand-by, and dialing. For 8weeks, the experimental groups were subjected to 4.5GB EMR at 2600MHz while on standby and making 10-min calls every hour. The rats in the control group received no exposure. Hematoxylin-eosin (H&E) staining of ovarian tissues was performed for histomorphological examinations. Additionally, immunoexpression of autophagy-related protein Beclin-1, apoptosis marker Caspase-3, ovarian reserve marker FSH, and oxidative stress marker iNOS were investigated in the rat ovaries. Microscopic examinations showed follicular degeneration in the ovaries of the rats in the stand-by and dialing groups. The immunoexpression of Beclin-1, Caspase-3, FSH, and iNOS was detected in granulosa cells and the corpus luteum in ovarian tissues obtained from the two EMR-exposed groups. There was a significant increase in the immunoexpression of Beclin-1 and Caspase-3 in the dialing group compared to the other two groups. Additionally, the iNOS and FSH expressions were increased in both EMR exposure groups compared to the control. Our results suggest that EMR exposure harms the ovaries, and autophagy and apoptosis are involved in this process.

Boron-Doped Nano Hydroxyapatite Grafts for Bone Regeneration in Rat Mandibular Defects.

The aim of this study was to evaluate the potential effects of boron-doped nano hydroxyapatite grafts on craniofacial bone regeneration in critical bone defects in the mandibular corpus of rats, in terms of scintigraphic and histopathological aspects. Forty Wistar albino rats, with an average weight of 200-220g, aged 16-18weeks, and all male, were used in the study. The rats were randomly assigned to five groups, each containing 8 rats, as follows: group C1 (no procedure applied to the mandible), group C2 (surgical defect created in the mandible but no treatment applied), group nHA (nano hydroxyapatite applied to the surgical defect area), group nHA + B1 (nano hydroxyapatite + 1% boron applied to the surgical defect area), and group nHA + B2 (nano hydroxyapatite + 2% boron applied to the surgical defect area). A standard 4 × 4mm full-thickness transosseous bone defect was created in the mandibular corpus of all rats, except for those in group C1. The bone defect in the rats in group C2 was left to heal naturally. Nano hydroxyapatite (nHA), nano hydroxyapatite + 1% boron, and nano hydroxyapatite + 2% boron were applied to the surgical defect areas of the other three groups, respectively. Bone scintigraphy was performed on all rats on days 0 (following the surgical procedure) and 28 of the experimental period. At the end of the 28th day, the animals were sacrificed, and tissue samples were collected for histological examination. A standard grading system was used to evaluate fracture healing. When the groups were compared in terms of bone healing histopathological scores, a statistically significant difference was observed between group C1 and the other groups (p < 0.005). In the statistical evaluation made according to the histopathological mean scores, the least improvement was observed in group C2. No statistically significant difference was observed between group nHA and group nHA + B1 and group C2 and between group nHA and group nHA + B1 in terms of bone healing scores (p > 0.005). A statistically significant difference was found between group nHA + B2 and group C2 (p = 0.026). Although there was no statistically significant difference in histopathological scores, the mean score closest to group C1 was observed in group nHA + B2. A statistically significant difference was observed between the groups in the scintigraphic evaluation performed on the 28th day of the experimental procedure, and the difference was between group C1 and group nHA + B1 and between group nHA and group nHA + B1 (p = 0.004; p = 0.028, p < 0.005). In the comparison of the values obtained on days 0 and 28 within the group, a statistically significant change was observed in group nHA + B1 and group nHA + B2 (p < 0.005). When the results of the present study were evaluated, it was thought that the boron-doped nHA graft biomaterials may have positive effects on bone healing. Providing a different perspective for the development of an alternative new treatment modality that can be locally applied in the treatment of fractures a serious and common health problem can be interpreted as an important outcome of the present study. We believe that this study will serve as a preliminary study for more comprehensive future studies on this subject.

Role of intermittent hypoxic training combined with methazolamide in the prevention of high-altitude cerebral edema in rats

Although intermittent hypoxia training (IHT) and methazolamide (MTZ) alone can prevent high-altitude cerebral edema (HACE) to varying degrees, their efficacy and dispersion remain limited. However, only a handful of trials have explored the effectiveness of the IHT and MTZ combination in preventing HACE. Rats were first exposed to hypobaric hypoxia (5000 m, 54.02 kPa, 10.8% fraction of inspired oxygen (FiO2)) with simultaneous exhaustive exercise (EE) for different durations to determine the ideal condition for establishing a rat model of HACE. Rats receiving various courses of IHT were subjected to this condition, and changes in behaviour, brain water content (BWC), pathology and brain protein expression were evaluated. Meanwhile, rats received different doses of MTZ before and during hypoxia exposure with simultaneous EE. Finally, rats receiving the IHT and MTZ combination were then exposed to hypoxia with simultaneous EE. Systemic inflammation and mild cerebral edema developed in rats after 6 h of hypobaric hypoxia with simultaneous EE. Rats showed severe impairment of spatial and memory functions after 2 days of hypobaric hypoxia with simultaneous EE, and the pathology of their brain showed significant dilated perivascular spaces, cell swelling, vacuolar degeneration and reduced neuron count. BWC, serum inflammatory factors and expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) proteins in the hippocampus increased significantly. Both IHT and MTZ differentially counteracted hypobaric hypoxia-induced spatial and memory function impairments and increased BWC, pathological changes and expression of AQP4 and VEGF proteins in the hippocampus. Among these, the long-course IHT (BID, 14 d) combined with MTZ (200 mg/kg/d) showed the most significant improvement, restoring the rats’ indices to normal levels. Continuous hypobaric hypoxia with simultaneous EE for 2 days resulted in significant HACE in rats, which may be used to establish a rat model of HACE. Both IHT and MTZ alleviated HACE in rats to varying degrees, among which long-course IHT (BID, 14 d) combined with MTZ (200 mg/kg/d) effectively prevented HACE in rats.

DNA methylation profiling of CpG islands in trigeminal ganglion of rats with orofacial pain induced by experimental tooth movement

BackgroundTooth movement induced orofacial pain is the most cited negative effect during orthodontic treatment, while treatment options without side effects are limited. The differential expression of pain-related genes due to DNA methylation and demethylation is instrumental in pain. The purpose of the study was to evaluate the DNA methylation profiling of CpG islands (CGI) and CGI shores in promoter regions in trigeminal ganglions (TG) of tooth movement induced orofacial pain rats, thus to further insight the DNA methylation regulation in orofacial pain.Materials and methodsAn orofacial pain rat model was constructed by ligating coil springs between the incisor and first maxillary molar with 40 g of force. The Rat Grimace Score (RGS) was used for pain evaluation. The genome methylation status was analyzed by the reduced representation bisulfite sequencing (RRBS) technique. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted in the differentially methylated regions (DMRs). Moreover, a protein-protein interaction (PPI) network was established to detect annotated genes associated with pain.ResultsRGS was significantly higher in orofacial pain rats than in sham rats. RRBS showed widespread methylation changes in CGI and CGI shores in TG promoter regions. Both 902 hypermethylated DMRs and 862 hypomethylated DMRs were found in the CGIs of promoter regions. KEGG analysis revealed that annotated genes are participated in endocrine, nervous, immune, and sensory systems. Moreover, the “Calcium signaling pathway”, “Wnt signaling pathway” and “Neuroactive ligand-receptor interaction” were significantly enriched pathways. Furthermore, PPI network showed several genes (Ctnnb1, Dlg4, Creb1, Camk2g, Bmp2, etc.) with different methylation statuses were reported to be associated with pain.ConclusionsThis study demonstrated methylation changes were existed in CGI and CGI shores in TG promoter regions when pain occurs, thus providing a basis for further study on the mechanism of DNA methylation in orofacial pain.

E3 ubiquitination ligase XIAP lightens diabetes-induced cognitive impairment by inactivating TXNIP-ERS-mediated neuronal injury.

Diabetes-induced cognitive dysfunction (DCD) is a neurological disorder associated with diabetes, characterized by cognitive impairment driven by neuronal injury from chronic high glucose (HG) exposure. This study aims to elucidate the role and mechanisms of the X-linked inhibitor of apoptosis protein (XIAP)/thioredoxin-interacting protein (TXNIP) in hippocampal neuron cell death and cognitive function within DCD models. A diabetic rat model was established using a high-fat/sucrose diet and streptozotocin injection. Primary hippocampal neurons were stimulated with HG to mimic diabetic conditions. Cognitive and memory functions were assessed using the Morris water maze (MWM) and novel object recognition test (ORT).

Rat models of frozen shoulder: Classification and evaluation.

Frozen shoulder (FS), also known as adhesive capsulitis, is a condition that causes contraction and stiffness of the shoulder joint capsule. The main symptoms are persistent shoulder pain and a limited range of motion in all directions. These symptoms and poor prognosis affect people's physical health and quality of life. Currently, the specific mechanisms of FS remain unclear, and there is variability in treatment methods and their efficacy. Additionally, the early symptoms of FS are difficult to distinguish from those of other shoulder diseases, complicating early diagnosis and treatment. Therefore, it is necessary to develop and utilize animal models to understand the pathogenesis of FS and to explore treatment strategies, providing insights into the prevention and treatment of human FS. This paper reviews the rat models available for FS research, including external immobilization models, surgical internal immobilization models, injection modeling models, and endocrine modeling models. It introduces the basic procedures for these models and compares and analyzes the advantages, disadvantages, and applicability of each modeling method. Finally, our paper summarizes the common methods for evaluating FS rat models.

Pentoxifylline ameliorates carbamazepine-induced hepatotoxicity via down expression of CYP3A4 and NF-kB gene expression in the rat: in vivo study

Drug-induced liver injury (DILI) is a serious complication of many drugs, including carbamazepine; this study investigates the protective effect of pentoxifylline (PTX) against DILI induced by carbamazepine in rat models by attenuating CYP3A4 and NF-κB gene expression. Forty rats were divided into five groups: the control group received no treatment, the induction group received 50 mg/kg carbamazepine orally for 28 days, and three groups received PTX (100, 200, and 300 mg/kg) once daily for one hour before carbamazepine induction for 28 days. Then, the rats were euthanized, and blood and liver tissue were collected for biochemical, gene expression, and histopathology. PTX attenuates the carbamazepine-induced increased CYP3A4 and NF-κB gene expression, with the highest dose showing the best result. PTX also reduced aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, while glutathione levels increased. In conclusion, PTX is highly efficacious in preventing and restoring the liver cells’ normal morphology and cellular function caused by carbamazepine hepatotoxicity. A possible mechanism of the PTC effect is hindering oxidative stress by scavenging free radicals and enhancing the body’s natural defense antioxidant system. Additionally, it exerts an anti-inflammatory impact by modulating NF-κB gene expression.