Sprague-Dawley Research Articles

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.

The Effect of Zeolite Zinc on Memory Performance and Hippocampal Cell Death in a Rat Model of Alzheimer's-like Disease Induced by Aβ1-42.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, characterized by the slow and progressive loss of brain structure and function, primarily affecting older individuals. Evidence has shown that disruption of zinc homeostasis in the brain contributes to synaptic dysfunction, as well as impairments in learning and memory. In this study, we evaluated the effect of zeolite zinc on memory performance and hippocampal cell death in a rat model of Alzheimer's disease (AD) induced by intracerebroventricular administration of Aβ1-42. We employed the Morris water maze, shuttle box, and open field tests to assess spatial memory, passive avoidance memory, and anxiety-like behavior, respectively. P-Tau and the amyloid precursor protein (APP) expression, along with hippocampal cell death, were also evaluated. Both Aβ1-42 and zeolite zinc were injected intracerebroventricularly. The results showed that zeolite zinc partially reversed Aβ1-42-induced impairments in memory performance and mitigated the effects of Aβ1-42 on locomotor activity, although it did not fully restore baseline levels. In addition, Aβ1-42 increased the expression of APP and P-Tau, as well as the number of dead cells, whereas zeolite zinc reduced these effects. In conclusion, our findings suggest that while zeolite zinc plays a role in modulating the pathophysiology of AD, its therapeutic effects only partially reverse the progression or symptoms of AD, indicating the need for further investigation into optimal dosing or combination therapies.

A potential therapeutic strategy using a miniature, implantable, wireless nerve stimulation device for treating stress urinary incontinence in rats.

The present study examined the effects of a miniature, implantable, wireless stimulation device for treating stress urinary incontinence (SUI) in rats. Twenty-four female Sprague-Dawley rats were randomly assigned to three groups: Group 1 (Control), Group 2 (Sham), and Group 3 (Stimulation). All animals underwent vaginal distension (VD) to mimic postpartum SUI. Groups 2 and 3 were implanted with a stimulator in the pelvic floor muscle, but only Group 3 received continuous stimulation for two weeks. Multiple cystometrograms (CMGs) were performed to determine the leak point pressure (LPP) and maximal bladder capacity (MBC). In the rat model, LPP in Group 1 after VD and after two weeks decreased significantly from baseline (21.1 ± 2.5 and 30.8 ± 5.2 vs. 52.5 ± 6.3 cmH2O, P < 0.001). LPP improved after two weeks compared to after VD (P < 0.01), but did not return to baseline. In Group 2, LPP at baseline, after VD, and after two weeks were 50.8 ± 4.9, 23.1 ± 6.3, and 31.5 ± 6.9 cmH2O, respectively, showing similar changes to Group 1. In Group 3, LPP values were 48.4 ± 4.8, 17.8 ± 3.9, and 48.4 ± 8.5 cmH2O, with significant improvement after two weeks compared to after VD (P < 0.001), returning to baseline. MBC showed no significant differences across conditions. The current study demonstrated the effectiveness of the implantable stimulation device for treating SUI in a rat model. Further studies are needed to determine its long-term safety and action mechanism.

Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies

Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies

Flaxseed Linusorb Alleviates Collagen-Induced Rheumatoid Arthritis in Rats via Inhibiting the TLR4/NF-κb/MAPK Signal Pathway and Modulating Gut Microbiota.

Flaxseed linusorb (FL) has gradually garnered widespread attention in recent years because of its intriguing bioactivities like anti-inflammation, antimelanogenesis, and even anticancer effects. Based on its proven in vitro anti-inflammatory activity and mechanism, it is supposed that FL may also exhibit an in vivo effect in treating and preventing rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) rat models were established to investigate the potential therapeutic effect of FL, which were intervened with FL via gavage (50 and 100 mg/kg B.W.) and intraperitoneal injection (10 and 20 mg/kg B.W.). After FL treatment, RA clinical symptoms were significantly alleviated, including reduced toe swelling volume and mitigated bone damage in CIA rats. Moreover, a decline in the expression of pro-inflammatory factors (i.e., TNF-α, IL-1β, and IL-6) and RA-related proteins (i.e., MMP-3, COX-2, and 5-LOX) was observed to effectively block the TLR4/NF-κB/MAPK signaling pathway. In addition, FL was discovered to modulate the diversity and composition of intestinal microbiota in CIA rats, where the level of g_Parvibacte, g_Allobaculum, g_Enterococcus, and unclassified_o_Lactobacillales could be significantly increased, whereas the level of Gram-negative bacteria g_Parabacteroides, g_Parasutterella, and g_Paludicola was notably reduced. In conclusion, FL shows promise in RA treatment by inhibiting inflammatory pathways and regulating the gut microbiota.

Active Vitamin D Ameliorates Arsenite-Induced Thyroid Dysfunction in Sprague–Dawley Rats by Inhibiting the Toll-like Receptor 4/NF-KappaB-Mediated Inflammatory Response

Arsenic, a well-known environmental endocrine disruptor, exerts interference on the body’s endocrine system. Our previous investigations have demonstrated that chronic exposure to sodium arsenite (NaAsO2) can induce thyroid damage and dysfunction in Sprague–Dawley (SD) rats. Vitamin D (VD) is an indispensable fat-soluble vitamin that plays a crucial role in maintaining thyroid health. In recent years, numerous studies have demonstrated the association between VD deficiency and the development of various thyroid disorders. However, the precise intervention roles and mechanisms of VD in arsenic-induced thyroid injury remain elusive. This study aimed to investigate the intervention effect of VD on NaAsO2-induced thyroid dysfunction in SD rats. The results demonstrated that exposure to NaAsO2 activates the TLR4/NF-κB signaling pathway in thyroid tissue of rats, leading to apoptosis of thyroid cells and subsequent inflammatory damage and disruption of serum thyroid hormone secretion. Supplementation with TAK-242 (a TLR4 inhibitor) and VD effectively inhibits the activation of the TLR4/NF-κB signaling pathway in rat thyroid tissue exposed to NaAsO2, thereby reducing the inflammatory damage and dysfunction caused by arsenic exposure. In conclusion, the findings of this study offer innovative insights into the application of VD in the prevention and treatment of thyroid dysfunction caused by arsenic exposure.

3D printed β-TCP scaffolds loaded with SVVYGLR peptide for promoting revascularization and osteoinduction

It is crucial for the successful transplantation of large segmental bone defects to achieve rapid vascularization within bone scaffolds. However, there are certain limitations including uncontrolled angiogenesis and inadequate vascular function. Therefore, there is an urgent need to develop bone scaffolds with functional vascular networks. In our study, porousβ-tricalcium phosphate (β-TCP) scaffolds with varying pore sizes were prepared by 3D printing technology, loaded with osteopontin derived peptide Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) to induce osteoinduction and angiogenesis.In vitro, the proliferation and migration behaviors of human umbilical vein endothelial cell on scaffolds were assessed by Cell Counting Kit-8, confocal laser scanning microscopy and scanning electron microscopy. And the osteogenic ability of bone marrow mesenchymal stem cells was assessed using alkaline phosphatase staining and Alizarin Red S staining. The messenger ribonucleic acid (mRNA) expression levels of cell adhesion molecule (CD31), vascular endothelial growth factor and hypoxia inducible factor-1αin each group were detected by quantitative real-time fluorescence polymerase chain reaction (PCR) analysis.In vivo, cube scaffolds were subcutaneously implanted on the right hips of Sprague-Dawley (SD) rats for 6 weeks. Hematoxylin and Eosin staining, Masson's trichrome staining, and immunohistochemical analysis of osteocalcin and CD31 were performed on slices for every sample with three sections to explore the effect of SVVYGLR-loaded scaffolds on angiogenesis and osteogenic induction for bone reconstruction. The results indicate that 3D printedβ-TCP scaffolds loaded with the SVVYGLR peptide offer superior revascularization and osteoinduction to the scaffolds without the SVVYGLRin situ. Moreover, scaffolds with a pore size of 400 µm demonstrate higher effectiveness compared to those with a 150 µm pore size. The distinct hollow channel scaffolds and the specific SVVYGLR peptide substantially improve cell adhesion, spreading, and proliferation, as well as promote angiogenesis and bone formation. Furthermore, scaffolds with a pore size of 400 µm may exhibit greater efficacy compared to those with a pore size of 150 µm. The results of this study provide an idea for the development of practical applications for tissue-engineered bone scaffolds.

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.

THRA1/PGC-1α/SIRT3 pathway regulates oxidative stress and is implicated in hypertension of maternal hypothyroid rat offspring.

Many epidemiologic and animal studies have shown that maternal hypothyroidism is associated with an increased risk of hypertension in offspring in later life. In this study, we established a maternal hypothyroidism rat model to explore the underlying mechanism that contributes to elevated blood pressure in adult male offspring of hypothyroid mothers. The levels of thyroid hormones (THs) in the offspring were measured using ELISA kits. Blood pressure (BP) and depressor response were recorded in conscious, freely moving rats. Vascular reactivity was conducted in isolated mesenteric arteries (MAs) using a myograph. We used real-time quantitative PCR (RT-qPCR) and Western blots to examine the mRNA and protein expression of relevant molecules in MAs. The A7r5 cells were transfected with small interfering RNA (siRNA) to further investigate the gene functions. The following findings were observed: Basal systolic BP and diastolic BP was significantly increased, accompanied by attenuated depressor response and decreased vascular sensitivity to sodium nitroprusside (SNP). Reactive Oxygen Species (ROS) levels in the MAs were enhanced, along with decreased expression of the THRA1/PGC-1α/SIRT3 pathway. In A7r5 cells, triiodothyronine (T3) pretreatment improved the PGC-1α/SIRT3 pathway and reduced ROS levels after H2O2-induced oxidative stress. In contrast, the knockdown of THRA1 or SIRT3 diminished the above effects of T3. Down-regulation of THRA1 contributed to a decline in the PGC-1α/SIRT3 pathway, which causes an increased production of ROS. This indicates that the T3-THRA1/PGC-1α/SIRT3 pathway plays a protective role in the regulation of BP and may be a potential therapeutic strategy against hypertension.

Dehydroepiandrosterone and Bone Health: Mechanisms and Insights

Background/Objectives: Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal glands, plays a key role in various physiological processes, including bone health. Its age-related decline is linked to reduced bone density, though the mechanisms by which DHEA affects bone metabolism remain complex. This review summarises the diverse effects of DHEA on bone metabolism and density, highlighting its therapeutic potential; Methods: A literature search on the effects of DHEA on bone-related parameters was conducted from PubMed and Scopus using a specific search string, and after removing duplicates and irrelevant articles, 36 relevant full-text studies were included; Results: DHEA promotes osteoblast differentiation and proliferation, regulates the RANKL/OPG ratio, and inhibits osteoclastogenesis and bone resorption. Its osteogenic effects are mediated through multiple signalling pathways. In ovariectomised rat models, DHEA enhances trabecular bone volume, stimulates osteoblast proliferation, and increases oestradiol production and aromatase activity. In elderly individuals with low androgen levels, DHEA supplementation increases sulphated DHEA and oestradiol levels and improves bone mineral density, particularly in the ultra-distal radius of women and the femoral neck of men. However, the clinical use of DHEA remains debated due to inconsistent study results. Its effects on bone health may vary based on factors such as age, gender, and health conditions, emphasising the need for further research to clarify its mechanisms and optimise its use; Conclusions: In conclusion, while DHEA shows potential as a modulator of bone health, comprehensive clinical trials are required to assess its efficacy and safety, particularly in at-risk populations.

Fibro-adipogenic progenitor cells in skeletal muscle unloading: metabolic and functional impairments

BackgroundSkeletal muscle resident fibro-adipogenic progenitor cells (FAPs) control skeletal muscle regeneration providing a supportive role for muscle stem cells. Altered FAPs characteristics have been shown for a number of pathological conditions, but the influence of temporary functional unloading of healthy skeletal muscle on FAPs remains poorly studied. This work is aimed to investigate how skeletal muscle disuse affects the functionality and metabolism of FAPs.MethodsHindlimb suspension (HS) rat model employed to investigate muscle response to decreased usage. FAPs were purified from m. soleus functioning muscle (Contr) and after functional unloading for 7 and 14 days (HS7 and HS14). FAPs were expanded in vitro, and tested for: immunophenotype; in vitro expansion rate, and migration activity; ability to differentiate into adipocytes in vitro; metabolic changes. Crosstalk between FAPs and muscle stem cells was estimated by influence of medium conditioned by FAP’s on migration and myogenesis of C2C12 myoblasts. To reveal the molecular mechanisms behind unloading-induced alterations in FAP’s functionality transcriptome analysis was performed.ResultsFAPs isolated from Contr and HS muscles exhibited phenotype of MSC cells. FAPs in vitro expansion rate and migration were altered by functional unloading conditions. All samples of FAPs demonstrated the ability to adipogenic differentiation in vitro, however, HS FAPs formed fat droplets of smaller volume and transcriptome analysis showed fatty acids metabolism and PPAR signaling suppression. Skeletal muscle unloading resulted in metabolic reprogramming of FAPs: decreased spare respiratory capacity, decreased OCR/ECAR ratio detected in both HS7 and HS14 samples point to reduced oxygen consumption, decreased potential for substrate oxidation and a shift to glycolytic metabolism. Furthermore, C2C12 cultures treated with medium conditioned by FAPs showed diverse alterations: while the HS7 FAPs-derived paracrine factors supported the myoblasts fusion, the HS14-derived medium stimulated proliferation of C2C12 myoblasts; these observations were supported by increased expression of cytokines detected by transcriptome analysis.Conclusionthe results obtained in this work show that the skeletal muscle functional unloading affects properties of FAPs in time-dependent manner: in atrophying skeletal muscle FAPs act as the sensors for the regulatory signals that may stimulate the metabolic and transcriptional reprogramming to preserve FAPs properties associated with maintenance of skeletal muscle homeostasis during unloading and in course of rehabilitation.

SIRT1 Activation Suppresses Corneal Endothelial–Mesenchymal Transition via the TGF-β/Smad2/3 Pathway

Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na+/K+-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction.

Measurement of pulmonary hematocrit using oscillation of hyperpolarized 129Xe MR signals in blood.

To demonstrate the feasibility of measuring pulmonary hematocrit (Hct) in blood in vivo using oscillation of hyperpolarized 129Xe MR signals and its potential for disease assessment in animal models. Hyperpolarized 129Xe dynamic MR spectroscopy was performed on 10 anemia model rats and 10 control rats. A concise model based on hyperpolarized 129Xe MR signal oscillations was built for calculating pulmonary Hct. Blood tests and chemical shift saturation recovery were conducted on each rat to obtain Hct. Correlations of Hct obtained from different methods were analyzed using SPSS 22.0. Hct measurements were strongly correlated with blood test (Spearman correlation coefficient r = 0.871, p < 0.001) and chemical shift saturation recovery measurements (r = 0.956, p < 0.001). Hct was 0.198 ± 0.054 for the anemic cohort and 0.457 ± 0.039 for the control group (p < 0.001). We developed an approach that provided a way to quantify changes in pulmonary Hct using oscillations of hyperpolarized 129Xe signals. This method shows promise for noninvasive pulmonary Hct assessment and disease evaluation.

Oxidative and Endoplasmic Reticulum Stress Mediate Testicular Injury in a Rat Model of Varicocele.

Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced. Eight weeks postoperatively, the VCL group exhibited significant testicular damage and sperm abnormalities. Western blot analysis revealed upregulation of ER stress-related proteins and downstream apoptotic markers in the VCL group. For further investigation, we developed an in vitro oxidative stress model using GC-2 cells treated with 400 µM hydrogen peroxide (H2O2) for 12h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H2O2 and the ER stress inducer significantly reduced GC-2 cell viability and increased reactive oxygen species (ROS) production, ER stress, and apoptosis. Conversely, treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects. Our findings suggest a strong association between VCL-induced redox imbalance and ER stress-related injury driven by the UPR in this rat model. Furthermore, 4-PBA effectively reduced germ cell damage induced by ROS-mediated ER stress, offering potential therapeutic insights for treating VCL-related infertility.

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.