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

Comparative mosquitocidal and repellence activities of essential oil, nanoemulsion and main terpenes of Deverra tortuosa against Aedes albopictus with insights into the non-target effects

There is an urgent and renewed interest in searching for effective and green pesticides to control mosquitoes. In this framework, the essential oil (EO) of the plant Deverra tortuosa was hydrodistilled, and analysed using gas chromatography-flame ionisation detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). Dillapiole (40.2%), elemicin (8.1%), and myristicin (6.3%), phenylpropanoids, and sabinene (4.3%) a common monoterpene, were found to be the major EO components. The oil nanoemulsion (ONE) was developed adopting a green protocol, and then characterised. The EO, ONE, and terpenes, particularly the phenylpropanoids possessed considerable mosquitocidal bioactivity against the Asian tiger mosquito, Aedes albopictus. A percentage of 100% larval mortality was recorded when insects were treated with a concentration of 40 μL/mL of ONE after 24 hours of treatment, while double of this concentration from EO and dillapiole was required to achieve the same activity. The LC50’s against larvae ranged between 7.6 and 60.7 μL/mL. For adults, LC50’s ranged between 6.4 and 50.9 μL/L. At sub-lethal concentrations (0.625-5.0 μL/cm2), EO materials significantly repelled Ae. albopictus, where a concentration of 5.0 μL/cm2 of EO and ONE provided 100% protection for up to180 min. As a proposed mechanism of action, the EO materials considerably inhibited the activity of acetylcholinesterase (AChE). The test materials were safe for the mosquitofish, Gambusia affinis, a common larvivorous fish, and Eisenia fetida earthworm. Test materials were also safe for the white albino rat in an oral bioassay at a limit dosage of 3500 mg/kg b.wt. The findings support the use of the EO, nanoemulsion, and phenylpropanoids of D. tortuosa as environmentally benign natural mosquitocodes to control Ae. albopictus.

Construction of an animal model of autism based on interaction between cerebellar histological, immunohistochemical, and biochemical changes in adult male albino rat

ABSTRACT Autism spectrum disorder (ASD) represents a heterogeneous group of neurodevelopmental conditions characterized by impaired social interaction, language deficit, and stereotype behavior. This study was designed to construct an autistic animal model on the basis of histological and immunohistochemical changes in the rat cerebellum. Methods Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining. Results The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group. Conclusion The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.

Male rats emit aversive 44-kHz ultrasonic vocalizations during prolonged Pavlovian fear conditioning.

Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long '22-kHz' vocalizations (>300 ms, <32-kHz) with constant frequency, signaling aversive states, and the second is short '50-kHz' calls (<150 ms, >32 kHz), often frequency-modulated, in appetitive situations. Here, we describe aversive vocalizations emitted at a higher pitch by male Wistar and spontaneously hypertensive rats (SHR) in an intensified aversive state - prolonged fear conditioning. These calls, which we named '44-kHz' vocalizations, are long (>150 ms), generally at a constant frequency (usually within 35-50-kHz range) and have an overall spectrographic image similar to 22-kHz calls. Some 44-kHz vocalizations are comprised of both 22-kHz-like and 44-kHz-like elements. Furthermore, two separate clustering methods confirmed that these 44-kHz calls can be separated from other vocalizations. We observed 44-kHz calls to be associated with freezing behavior during fear conditioning training, during which they constituted up to 19.4% of all calls and most of them appeared next to each other forming uniform groups of vocalizations (bouts). We also show that some of rats' responses to the playback of 44-kHz calls were more akin to that of aversive calls, for example, heart rate changes, whereas other responses were at an intermediate level between aversive and appetitive calls. Our results suggest that rats have a wider vocal repertoire than previously believed, and current definitions of major call types may require reevaluation. We hope that future investigations of 44-kHz calls in rat models of human diseases will contribute to expanding our understanding and therapeutic strategies related to human psychiatric conditions.

Bacopaside-I ameliorates motor dysfunction and neurodegeneration in rat model of Parkinson's disease.

Chronic administration of Bacopa monnieri extract exerts neuroprotective potential in multiple animal models of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), depression, and other cognitive impairments. However, the underlying mechanism of action remained unclear. Rotenone model of PD holds a great potential for investigating PD pathology and motor and nonmotor symptoms. Herein, we evaluated the neuroprotective effect of Bacopaside-I (BS-I), a major triterpenoid saponin of Bacopa monnieri extract, against rotenone-induced in vivo model of PD and explored the possible molecular mechanism. Rats were exposed to rotenone (2mg/kg body weight) for a period of 4 consecutive weeks to induce PD-like behavior. BS-I (5, 15, and 45mg/kg) was administered orally. Behavioral data (rotarod, foot printing, and grip strength test) suggest that BS-I plays a significant role in attenuating the motor function deficit. Exposure to rotenone reduces the dopamine level and increases oxidative stress, while BS-I treatment reversed these changes. Furthermore, chronic administration of BS-I increased the expression levels of dopamine transporter (DAT) and vesicular monoamine transporter (VMAT) genes and the numbers of tyrosine hydroxylase (TH)-positive neurons as compared to rotenone-exposed animals. Our study established the neuroprotective role of BS-I in PD model and laid the foundation for further evaluation of BS-I-based drug in future studies.

Exogenous Beta-guanidinopropionic acid administration enhances electromyostimulation-induced mitochondrial biogenesis in rat skeletal muscle

Abstract Objectives Exercise training induces several skeletal muscle adaptations. Beta-guanidinopropionic acid (β-GPA) is a creatine analog that simulates the effect of exercise to induce mitochondrial biogenesis. However, the effects of β-GPA on resistance training adaptation, such as muscle hypertrophy and mitochondrial biogenesis, are unclear. Therefore, using a resistance exercise model in rats, the present study was designed to investigate the effects of β-GPA administration on resistance training adaptations. Methods This study was approved by the Ethics Committee for Animal Experiments at Ritsumeikan University (approval number: BKC2022-009). Male Sprague Dawley rats were randomly divided into placebo or β-GPA groups. β-GPA (1000 mg/kg) was orally administered once daily, starting seven days before the initiation of electromyostimulation as a model for resistance exercise, and continued throughout the training period. Electromyostimulation was applied to the right gastrocnemius muscle via electrical stimulation every other day for a total of 12 sessions Results Peroxisome proliferators-activated receptor-γ co-activator-1α, a regulator of mitochondrial biogenesis, was significantly increased by the combination of training and β-GPA compared to the training leg (p&lt;0.05). Protein expression of Total OXPHOS, a marker of mitochondrial content, was significantly increased by the combination of training and β-GPA compared to the training leg (p&lt;0.05). β-GPA intake reduced muscle mass (main effect of β-GPA, p&lt;0.05) and was associated with muscle protein breakdown-related Fbx32 and LC3-II protein expression levels but did not counteract the increase in muscle mass caused by resistance training. Conclusions Administration of exogenous β-GPA enhanced resistance training-induced mitochondrial biogenesis. Moreover, β-GPA still permitted resistance electromyostimulation-induced muscle mass gains, but that effect was attenuated as compared to placebo.

A Comprehensive Study on the Renal Protective Effects of Polyherbal Extract Formulation and Their Impact on Kidney Function in Rats

Background: The nephroprotective effects of herbal extracts have increasingly gained attention due to the rise in kidney diseases and the limitations of conventional treatments. This study explores the renal protective properties of a polyherbal extract formulation composed of Ziziphus spina-christi, Trigonella foenum-graecum and Nigella sativa (ZTN) in Wistar albino rats. Methods: Three groups of adult male and female Wistar albino rats consisting of the control group that received only water, another group was administered with 100 mg/kg of the polyherbal (ZTN herbal) formulation, while the last group was administered with 250 mg/kg of the ZTN polyherbal extract formulation. The treatments administered for 14 days and thereafter Kidney weight, uric acid, Blood Urea Nitrogen (BUN) and creatinine levels were assessed to assess renal function. Histological analysis was conducted for tissue integrity evaluation. Result: The polyherbal extract formulation of ZTN induced a dose-dependent increase in kidney weight in both male and female rats. Uric acid levels decreased significantly in a dose-dependent manner, with the most substantial reduction at 250 mg/kg. BUN levels also showed a notable decrease, particularly at the higher dose, indicating enhanced renal function. Creatinine levels exhibited a significant dose-dependent reduction, with female rats showing higher baseline levels but greater overall reductions. Histological analysis revealed mild histological changes at 100 mg/mL and severe changes at 250 mg/mL. Histological changes include glomerular hypertrophy and tubular necrosis, more pronounced at higher doses. The polyherbal extract formulation of ZTN demonstrated significant nephroprotective effects, reducing uric acid, BUN and creatinine levels in a dose-dependent manner. Interestingly, an observation of gender-based differences occur in female rats showing higher baseline levels but greater reductions with treatment. These findings support the potential therapeutic use of polyherbal extracts in managing renal health, emphasizing the importance of dose regulation to avoid adverse effects.

Shensu IV maintains the integrity of the glomerular filtration barrier and exerts renal protective effects by regulating endogenous hydrogen sulfide levels

BackgroundNephrotic syndrome has a significant impact on global health, often leading to cardiovascular disease and high mortality due to limited effective treatments. This study investigates the efficacy of Shensu IV in a puromycin aminonucleoside (PAN)-induced rat model of nephropathy.MethodsRat models and in vitro podocyte PAN nephropathy models were established with PAN and treated with Shensu IV. Renal function was evaluated by measuring urine output and protein content, while hydrogen sulfide (H2S) and oxidative stress markers were quantified in serum and podocyte lysates. We conducted histological examination on kidney tissues and analyzed molecular markers (CD2AP, nephrin, and PI3K/AKT pathway) using RT-qPCR and Western blot.ResultsShensu IV significantly improved urine output and proteinuria, and attenuated glomerular damage, fibrosis, and mitochondrial swelling in PAN-treated rats. Mechanistically, Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.ConclusionShensu IV and NaHS confer renal protection primarily by modulating oxidative stress and restoring the integrity of the glomerular filtration barrier through mechanisms involving the enhancement of the PI3K/AKT pathway and modulation of H2S levels. These findings suggest a promising therapeutic potential for these metabolites in the treatment of nephrotic syndrome.

Kir4.1 and Aqp4 Contribution to Schisis Cystic Water Accumulation and Clearance in the Rs1 Exon-1 Del XLRS Rat Model

Background/Objective: The Rs1 exon-1-del rat (Rs1KO) XLRS model shows normal retinal development until postnatal day 12 (P12) when small cystic spaces start to form in the inner nuclear layer. These spaces enlarge rapidly, peak at P15, and then collapse by P19. Methods: We explored the possible involvement of Kir4.1 and Aqp4, the principal retina channels for water movement and homeostasis, along with Muller glia cells (MGCs), using semi-quantitative fluorescent immunohistochemistry at P7, P9, P12, and P30, in Rs1KO and WT littermates. Results: Kir4.1 expression was reduced in Rs1KO retinas at all the early time points—P7, P9, and P12—as the schisis cavities began to form; downregulation would reduce water egress from the retina. Aqp4 was upregulated at P30 in Rs1KO retinas during schisis cavity closure but not as cavities formed at P12. When examined by GFAP expression, MGCs were not activated at the preschisis P12 age but showed considerable GFAP expression at P30 following retinal cystic structural damage at P15, indicating that MGCs were activated during the period of retina water removal and cavity closure. Conclusions: The study results implicate the downregulation of Kir4.1 in schisis formation and a role for both Kir4.1 and Aqp4 upregulation in subsequent schisis closure.

Developmental Trajectory of Autistic-Like Behaviors in a Prenatal Valproic Acid Rat Model of Autism.

Autism spectrum disorders (ASDs) are characterized by deficits in social functioning, stereotyped patterns of behaviors, narrowed interests, and elevated anxiety. Certain ASD symptoms can persist, whereas others may improve throughout the lifespan, but the specific patterns of changes have not been clearly delineated. Using a valproic acid (VPA) rat model of ASD, the present study took a developmental approach and examined how autistic-like behaviors, including anxiety-like behavior, object obsession, and social functioning deficits, manifested differently in three critical periods representing preadolescent (postnatal day [PND] 25), adolescent (PND 45), and adulthood life stage (PND 75) in a sex-dependent manner. Starting on PNDs 25, 45, and 75, VPA- or saline-exposed male and female offspring were tested in an elevated plus maze (EPM) and a newly validated composite social and object interaction and a triple recognition test (object, spatial, and social recognition). Across the three age groups, VPA-exposed offspring did not exhibit enhanced anxiety-like behavior in the EPM nor enhanced object interaction ("object obsession") in the triple recognition test. However, both male and female preadolescent (PND 25) VPA-exposed offspring showed a significantly increased latency to initiate social contact than the saline-exposed controls, although their latencies to contact novel objects were comparable to those of the controls. Male preadolescent and adolescent VPA-exposed offspring, to a lesser extent the female preadolescent offspring, exhibited significantly lower levels of social interaction. These social functioning deficits were absent in adult VPA offspring. Additionally, prenatal VPA exposure did not cause an impairment of object recognition, spatial recognition, or social recognition of a familiar conspecific. Unexpectedly, it enhanced social recognition of a novel conspecific, but only in adolescent female offspring. These findings suggest that this rat model based on prenatal VPA exposure is valid in capturing early social motivational and functioning deficits but is limited in its capacity to model increased object obsession and enhanced anxiety as seen in ASD, as well as the developmental trajectory of non-social ASD symptoms. Recognizing these limitations is important as it informs us how to properly use this model to investigate the neurobiology of ASD and incentivizes us to develop better rodent models.

Histomorphometric analysis of external apical root resorption using L-loops and different intrusive forces

ABSTRACT Purpose This study aimed to conduct a histomorphometric analysis on the impact of varying intrusive forces on external apical root resorption (EARR) in rat molars, using an L-loop was employed to apply intrusion forces, artificially inducing EARR in the maxillary left first molar (M1) of rats. Materials and methods The L-loop was bent on a plaster rat model using stainless steel round wires with diameters of 0.014 and 0.016 inches. Using a universal test force measuring device, L-loops were calibrated to 4 N/mm and 6 N/mm for the 0.014-inch and 0.016-inch diameter stainless steel round wires, respectively. Fifteen-week-old Sprague-Dawley (SD) male rats were used and divided into the control (no loop) and experimental (0.014 and 0.016) groups (n = 5 for each group). The L-loop was attached to the left maxillary molar, applying an intrusive force to M1. After 15 days, the rats were euthanized. Maxillary bones were analysed using micro-computed tomography (μCT), evaluating M1 intrusive distance of vertical tooth movement and counting the number of tartrate-resistant acid phosphatase (TRAP)-positive cells on the surface of the mesial root apex and alveolar bone. Results The L-loop groups exhibited significantly increased M1 intrusive distance and TRAP-positive cell counts compared to controls. Specifically, the 0.016 group demonstrated greater M1 intrusive distance and more TRAP-positive cells than the 0.014 group. The M1 intrusive distance and TRAP-positive cells increased when intrusive forces were applied using L-loops of different diameters. Conclusion Greater intrusive forces enhance TRAP-positive cell activity, influencing EARR and vertical tooth movement.

Assessment of neurotoxicity of rotenone and the possible protective effect of alpha lipoic acid in adult male albino rats

ABSTRACT Background Parkinson’s disease (PD) results from neurodegeneration of the dopaminergic neurons present in the substantia nigra (SN) of midbrain, manifested as locomotor deficits and behavioral changes. Rotenone pesticide affects the central nervous system and causes oxidative stress and apoptosis, pathological cause of PD. Alpha lipoic acid (ALA), a potent antioxidant, crosses the blood–brain barrier. Objective This study aimed to assess the antioxidant properties of ALA in neurodegenerative model of Parkinsonism induced by rotenone. Material and Methods Twenty-four adult male albino rats 9–11 weeks of age were divided into four equal groups: A (control water), B (control DMSO), C (model group) received rotenone 2.5 mg/kg bwt/kg IP, D (treated group) received both rotenone & ALA at a dose of 200 mg/kg PO for 28 days. At the end of the experiment, all animals were weighed, and behavioral tests to assess locomotor activities were performed, then blood was collected to measure oxidant and antioxidant markers (MDA, TAC, GSH, SOD). All animals were sacrificed, and the midbrains were excised. Sections were prepared for H&E histopathological and immunohistochemical studies for caspase-3 monoclonal antibodies. Results Rotenone administration caused significant signs of neurotoxicity like deterioration in behavioral patterns such as rearing, line crossings in open field test. MDA level was increased while TAC, GSH, and SOD were decreased. Macroscopic and stereomicroscopic findings showed a significant reduction in the dark color of neuromelanin pigment in SN. H&E sections showed absence of pigmented neurons in the SN with necrotic changes and Lewy bodies. The immunoreaction of caspase-3 was significantly expressed. Administration of ALA showed significant improvement in behavioral test and oxidative stress markers, immunoreaction with nearly normal pigmented neurocytes. Conclusion Rotenone is capable of inducing PD due to its oxidant and apoptotic capacities; ALA could reduce oxidative stress and apoptosis in PD.

Chronic administration of Musa acuminata Colla (BANANA) to Wistar albino rats induces hyperkalemia

ABSTRACT Background Hyperkalemia is a medical condition characterized by excess potassium in the blood. Overindulgence in foods high in potassium can also result in hyperkalemia, particularly in individuals with severe kidney disease.. Aim of the study In this study, hyperkalemia was assessed in Wistar albino rats administered with M. acuminata. Material and Methods Thirty-six rats underwent various treatments over three months after being randomly divided into groups of six. Standard medications administered included Lisinopril and keyaxalate. The proximate and mineral content of raw banana (RB) and normal rat pellets (NRP) were compared and evaluated with that of cooked banana (CB). The rats’ serum and urine calcium and potassium levels were measured using established protocols. Results In comparison to RB, CB was found to have significantly higher levels of nutrients (proteins and fats) and minerals (calcium, sodium, and potassium). Administration of CB markedly significantly increased serum potassium levels however, keyaxalate decreased urine potassium levels; the treatment of kayexalate plus lisinopril markedly decreased urine Ca concentration (p<0.05). Conclusions Cooked banana has a higher mineral and nutritional content than raw banana. Continuous and daily consumption of cooked bananas led to hyperkalemia in Wistar rats as evidenced by elevated serum potassium levels.

99mTc-DTPA-Collagen Radiotracer for the Noninvasive Detection of Infective Endocarditis.

Infective endocarditis (IE) represents a significant concern among hospital-acquired infections, frequently caused by the Gram-positive bacterium Staphylococcus aureus. Nuclear imaging is emerging as a noninvasive and precise diagnostic tool. However, the gold standard radiotracer [18F]-FDG cannot distinguish between infection and inflammation, resulting in false positives. Based on the presence of collagen-binding proteins in the cell wall of S. aureus, we propose the radiolabeling of collagen for its evaluation in IE animal models by single-photon emission computed tomography (SPECT) imaging. We radiolabeled rat tail collagen I using DTPA chelator and [99mTc]NaTcO4. Selectivity was evaluated in vitro using 3 Gram-positive bacteria, 1 Gram-negative bacteria and 1 yeast. In vivo SPECT/computed tomography (CT) imaging was conducted on 8 SD rat models of IE and 8 sterile sham model as controls. Ex vivo biodistribution and autoradiography were performed following imaging. Diagnosis of IE was confirmed through microbiological studies and H&E histopathology. [99mTc]-DTPA-Collagen was synthesized successfully with a yield of 42.86 ± 6.35%, a purity of 95.84 ± 1.85% and a stability higher than 90% after 50 h postincubation. In vitro uptake demonstrated the selectivity for Gram-positive bacteria (63.85 ± 15.15%). Ex vivo analysis confirmed hepato-splenic excretion. In vivo SPECT/CT imaging revealed highly localized uptake within the aortic valve with a sensitivity of 62.5% and specificity of 87.5%. We successfully synthesized and characterized a new SPECT radiotracer based on [99mTc]Tc-radiolabeled collagen. In vitro studies demonstrated the selectivity of the radiotracer for Gram-positive bacteria. In vivo SPECT/CT-based assessment in an IE model confirmed the potential of this approach to detect active IE.

Oroxin B Resembles Bisoprolol in Attenuating Beta1-Adrenergic Receptor Autoantibody-Induced Atrial Remodelling via the PTEN/AKT/mTOR Signalling Pathway.

Beta1-adrenergic receptor autoantibodies (β1-AAbs) promote atrial remodelling and ultimately lead to the development of atrial fibrillation (AF). Oroxin B is a natural flavonoid glycoside with a variety of biological activities, including anti-inflammatory and autophagy-promoting effects, and has therapeutic benefits for a variety of diseases. The aim of this study was to investigate the potential therapeutic role of Oroxin B in the development of β1-AAb-induced atrial fibrillation and to elucidate the underlying mechanisms involved. We established a rat model of β1-AAb-induced atrial fibrillation via active immunisation. The first stage was divided into three groups: the control group, the β1-AAb group and the β1-AAb + bisoprolol group. The second stage was divided into three groups: the control group, the β1-AAb group and the β1-AAb + Oroxin B group. Serum levels of β1-AAbs, atrial tissue levels of cyclic monophosphate (cAMP), atrial electrophysiological parameters, cardiac structure and function, mitochondrial structure, autophagy levels, cardiomyocyte apoptosis and myocardial fibrosis were examined. The results showed that bisoprolol, a β1-blocker, improved β1-AAb-induced atrial electrical remodelling, reduced atrial collagen deposition, ameliorated the increase in LAD and regulated the balance of autophagy and apoptosis in atrial myocytes through the PTEN/AKT/mTOR signalling pathway. Oroxin B, a PTEN agonist, can improve the impairment of autophagy homeostasis and apoptosis in atrial tissue by activating the PTEN/AKT/mTOR signalling pathway, thereby improving atrial structure and electrical remodelling. Moreover, Oroxin B may play a therapeutic role in β1AAb-induced atrial fibrillation. In conclusion, our results demonstrate the potential therapeutic role of Oroxin B in β1AAb-induced atrial fibrillation and the underlying mechanisms, suggesting that Oroxin B may be an effective antiarrhythmic medication.

Tongmai Hypoglycemic Capsule Attenuates Myocardial Oxidative Stress and Fibrosis in the Development of Diabetic Cardiomyopathy in Rats.

To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.

Possible ameliorative effect of Dandelion Plant Leaf Extract on Paclitaxel Drug Induced Peripheral Neurotoxicity in adult male albino rats

Possible ameliorative effect of Dandelion Plant Leaf Extract on Paclitaxel Drug Induced Peripheral Neurotoxicity in adult male albino rats

Synthesis and preclinical evaluation of a novel Oxy133-infused biomimetic bone graft using a rat model of posterolateral spinal fusion.

To (1) create a novel tissue-engineered bone graft comprising the osteoinductive oxysterol Oxy133 and (2) compare the osteogenic capability of this novel bone graft with bone graft substitutes previously examined. Oxy133 was homogeneously incorporated into a biomimetic bone graft substitute (BioMim) comprising extracellular matrix and calcium phosphates. Two iterations of the graft were created: one corresponding to an implant-dose of 2.0mg Oxy133 (BioMim-Oxy133-Lo) and the other corresponding to an implant-dose of 20mg Oxy133 (BioMim-Oxy133-Hi). Thirty-two male Sprague Dawley rats were allocated randomly to four equally sized groups: 1) BioMim-Oxy133-Lo, 2) BioMim-Oxy133-Hi, 3) absorbable collagen sponge (ACS) with topically applied Oxy133 dissolved in dimethyl sulfoxide (ACS-Oxy133; 20mg Oxy133/graft), and 4) ACS with topically applied rhBMP-2 dissolved in water (ACS-rhBMP-2; 5.0μg rhBMP-2/graft). All animals underwent L4-L5 posterolateral spinal fusion. Spines were harvested 8 weeks postoperatively and analyzed using micro-CT imaging. Successful fusion was achieved in all animals. Grafts containing Oxy133 had significantly greater bone volume, percentage bone volume (%BV), bone surface density (BSD), and trabecular number (TbN) compared to ACS-rhBMP-2 (p<0.01 for each). Animals treated with BioMim-Oxy133-Lo had the greatest %BV, BSD, and TbN (p<0.001 for each), whereas animals treated with ACS-rhBMP-2 had the lowest %BV, BSD, TbN, and trabecular thickness (p<0.001 for each). BioMim-Oxy133 is a novel bone graft that led to superior bone volume and quality compared to ACS-rhBMP-2 in a clinically translatable rat model of spinal fusion. Future work is needed to further evaluate this material as a safe and efficacious bone graft substitute.