Diffusion-tensor magnetic resonance imaging as a non-invasive assessment of extracellular matrix remodeling in lumbar paravertebral muscles of rats with sarcopenia.

BACKGROUND: Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. METHODS: Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. RESULTS: The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were - 0.71, -0.94, -0.85, and - 0.88, respectively (p < 0.05 for all). CONCLUSIONS: The fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia.

Towards an Objective Measurement Tool for ADHD-like Traits in Family Dogs: A Comprehensive Test Battery.

Family dogs exhibit neuropsychological deficits similar to attention-deficit/hyperactivity disorder (ADHD) symptoms in humans. Questionnaire methods have mostly been used to assess ADHD-like behaviours in dogs. In addition to our validated questionnaire (Dog ADHD and Functionality Rating Scale-DAFRS; 2024), we developed a simple behavioural test battery covering the ADHD symptom domains (i.e., inattention, hyperactivity, and impulsivity) in dogs. Our main aim was (i) to provide a final external validation step to the DAFRS by examining its associations with the test variables (N = 59); and (ii) to compare owner- and trainer-rated factor scores' associations with the test variables (n = 38). We developed four tests covering the ADHD symptom domains: the attention test (inattention), the plush dog test (impulsivity), the leash test, and the sit test (hyperactivity). All four behavioural variables correlated with their respective questionnaire scores, i.e., the strongest for hyperactivity, and the least strong for inattention. Both owner- and trainer-rated scores (n = 38) correlated with the relevant test variables in an expected direction. Dogs' training status was linked only to the sit test results. Test-retest analyses (n = 34) indicated moderate-to-excellent agreement across all behavioural variables. Our findings support the validity of our novel human-analogue questionnaire for dogs as the behavioural tests strongly correlate with the relevant questionnaire scores, indicating that the two constructs together can effectively assess inattention, hyperactivity, and impulsivity in dogs.

Still to ARRIVE at adequate reporting of orthodontic studies involving animal models.

BACKGROUND: The ARRIVE 2.0 guidelines were introduced to improve the reporting of animal studies. The aim of this study was to assess the reporting adherence of orthodontic speciality animal studies in relation to ARRIVE 2.0 guidelines. Associations between the reporting and study characteristics were explored. MATERIALS AND METHOD: An electronic database search was undertaken using Medline via PubMed (www.pubmed.ncbi.nlm.nih.gov) to identify studies meeting the eligibility criteria published between 1 January 2018 and 31 December 2023. Data extraction was performed in duplicate and independently. Descriptive statistics and frequency distributions for the responses to each checklist item were calculated. Mean values for adequate reporting per ARRIVE item were calculated. A sum score was calculated by adding the responses (0 = not reported, 1 = inadequate reporting, 2 = adequate reporting) per item and sub-questions. On an exploratory basis, univariable linear regression between summary score and study characteristics (year of publication, continent of authorship, type of centre, and number of authors) was performed. RESULTS: Three hundred and eighty-four studies were analysed. Variability in the adequate reporting of the ARRIVE 2.0 guideline items was evident. In particular, in 32% of studies, there was a lack of reporting of the priori sample size calculation. Overall, the mean reporting score for the sample was 57.9 (SD 6.7 and range 34-74). There were no associations between score and study characteristics except for a weak association for year of publication with a small improvement over time (each additional year). CONCLUSIONS: The reporting of animal studies relevant to the speciality of orthodontics is sub-optimal in relation to the ARRIVE 2.0 guidelines. There was a tendency for the non-reporting of items pertaining to study sample size, eligibility, methods to reduce bias and interpretation/scientific implications. Greater awareness and reporting adherence to the ARRIVE 2.0 guidelines are required to reduce research waste involving animal models.

In vivo experimental study comparing alveolar ridge preservation versus guided bone regeneration after unassisted socket healing at intact and damaged sites in narrow alveolar ridges.

BACKGROUND: To compare bone regeneration and dimensional alteration of alveolar ridge at intact and damaged extraction sockets after alveolar ridge preservation (ARP) and implant placement versus unassisted socket healing followed by guided bone regeneration (GBR) with simultaneous implant placement. METHODS: In 6 beagle dogs, 3 types of extraction sockets in the mandible were created: (1) intact sockets, (2) 1-wall defect sockets and (3) 2-wall defect sockets. The sockets were allocated to undergo either (1) ARP and implant placement 8 weeks later (ARP group) or (2) GBR with simultaneous implant placement after 8 weeks of unassisted socket healing (GBR group). After an additional healing period of 8 weeks, bone regeneration and dimensional changes were evaluated radiographically and histologically. RESULTS: GBR showed superior bone formation and greater bone gains compared to ARP, regardless of the initial extraction-socket configuration. Although ARP maintained the preexisting alveolar ridge dimensions, peri-implant bone defects were still detected at 8 weeks of follow-up. Histomorphometric analyses confirmed that GBR increased dimensions of the alveolar ridge compared to baseline, and the augmentation and bone regeneration were greater with GBR than with ARP. CONCLUSION: Early implant placement with ARP can mitigate alveolar ridge changes in the narrow alveolar ridge. However, early implant placement with simultaneous GBR creates the conditions for enhanced bone regeneration around the implant and greater ridge augmentation compared to ARP, irrespective of the extraction-socket configuration.

Establishment of an animal model of immune-related adverse events induced by immune checkpoint inhibitors.

OBJECTIVE: Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. METHODS: Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. RESULTS: Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. CONCLUSIONS: The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.

Transcatheter pseudo-vascular isolation for localization and concentration of a large molecule theranostic probe into a transgenic OncoPIG kidney tumor.

INTRODUCTION: Great strides have been made identifying molecular and genetic changes expressed by various tumor types. These molecular and genetic changes are used as pharmacologic targets for precision treatment using large molecule (LM) proteins with high specificity. Theranostics exploits these LM biomolecules via radiochemistry, creating sensitive diagnostic and therapeutic agents. Intravenous (i.v.) LM drugs have an extended biopharmaceutical half-life thus resulting in an insufficient therapeutic index, permitting only palliative brachytherapy due to unacceptably high rates of systemic nontarget radiation doses to normal tissue. We employ tumor arteriole embolization isolating a tumor from the systemic circulation, and local intra-arterial (i.a.) infusion to improve uptake of a LM drug within a porcine renal tumor (RT). METHODS: In an oncopig RT we assess the in vivo biodistribution of 99mTc-labeled macroaggregated albumin (MAA) a surrogate for a LM theranostics agent in the RT, kidney, liver, spleen, muscle, blood, and urine. Control animals underwent i.v. infusion and experimental group undergoing arteriography with pseudovascular isolation (PVI) followed by direct i.a. injection. RESULTS: Injected dose per gram (%ID/g) of the LM at 1 min was 86.75 ± 3.76 and remained elevated up to 120 min (89.35 ± 5.77) with i.a. PVI, this increase was statistically significant (SS) compared to i.v. (13.38 ± 1.56 and 12.02 ± 1.05; p = 0.0003 p = 0.0006 at 1 and 120 min respectively). The circulating distribution of LM in the blood was less with i.a. vs i.v. infusion (2.28 ± 0.31 vs 25.17 ± 1.84 for i.v. p = 0.033 at 1 min). Other organs displayed a trend towards less exposure to radiation for i.a. with PVI compared to i.v. which was not SS. CONCLUSION: PVI followed by i.a. infusion of a LM drug has the potential to significantly increase the first pass uptake within a tumor. This minimally invasive technique can be translated into clinical practice, potentially rendering monoclonal antibody based radioimmunotherapy a viable treatment for renal tumors.

Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice.

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Assessing genetic parameters for first parity reproductive traits for early selection in Saanen × Beetal goats of India.

The present study aimed to evaluate the genetic parameters of first parity reproductive traits. Information on 762 reproductive records on Saanen × Beetal (S × B) goats reared for approximately five decades was collected from ICAR-National Dairy Research Institute, Karnal, Haryana (1973-2020). For genetic analysis, single-trait and multiple-trait animal models were used. Gibbs sampler for animal model (GSAM) approach was used for estimating (co)variance components of reproductive traits. Six different single-trait animal models (with or without maternal and environmental effects) were used and the deviance information criterion (DIC) determined the best model. The least squares mean for age at first service (AFS), age at first kidding (AFK), service period (SP), dry period (DP), gestation length (GL), kidding interval (KI), litter weight (LW), number of kids born (NKB) and number of female kids born (NFKB) in first parity were 526.99 ± 4.86, 662.96 ± 5.03, 219.11 ± 6.25, 109.38 ± 6.00, 150.48 ± 0.27, 356.63 ± 4.80 days, 3.87 ± 0.05 kg, 1.27 ± 0.02 and 0.67 ± 0.03, respectively. Lower heritability estimates for these reproductive traits revealed a sparse scope for genetic improvement. Multivariate analysis using Model 1 was carried out to evaluate the genetic and phenotypic correlation of these nine reproductive traits. The genetic correlation of DP and SP was negatively with LW, NKB and NFKB, which is favourable as reduction in SP and DP can improve these economically important traits through indirect selection. Consistent efforts towards genetic improvement of these goat flock poses a promising future for meat industry owing to high prolificacy and good reproductive potential in this flock.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats.

BACKGROUND: Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism-like behavior of IMH offspring. METHODS: The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid-stimulating hormone (TSH) were detected using enzyme-linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open-field test, three-chamber sociability test, and Morris water maze, to explore the autistic-like behavior of 40-day-old offspring rats. RESULTS: The ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly. CONCLUSION: The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic-like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

Current status and perspective on molecular targets and therapeutic intervention strategy in hepatic ischemia-reperfusion injury.

Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.

Establishment of an acute arterial mesenteric ischaemia model in canines with an endovascular approach.

Purpose: This study aimed to evaluate the feasibility of establishing an arterial acute mesenteric ischemia (AMI) model in canines using transcatheter autologous thrombus administration. Materials and methods: Ten canines were divided into the experimental group (Group A, n = 5) and the sham group (Group B, n = 5). The canines in Group A received thrombus administration to the superior mesenteric artery (SMA) through a guiding catheter, while the canines in Group B received normal saline administration. Blood samples were collected and tested at baseline and 2 h after modelling. Canines in Group A underwent manual thromboaspiration after blood and intestine samples were collected. Ischaemic grades of intestinal mucosa were evaluated under light microscopes. Results: The AMI models were successfully conducted in all canines without procedure-related vessel injury or death. At the 2-h follow-up, the high-sensitivity C-reactive protein and D-dimer in Group A were significantly higher than in Group B (5.72 ± 1.8 mg/L vs. 2.82 ± 1.5 mg/L, p = 0.024; 2.25 ± 0.8 µg/mL vs. 0.27 ± 0.10 µg/mL, p = 0.005; respectively). The mean histopathologic intestinal ischaemic grade in Group A was significantly higher than in Group B (2.4 ± 0.5 vs. 0.8 ± 0.4, p < 0.001). After a median of 2 times of thromboaspiration, 80% (4/5) of the canines achieved complete SMA revascularisation. Conclusion: This experimental study demonstrated that establishing an arterial model in canines using endovascular approaches was feasible. The present model may play an important role in the investigation of endovascular techniques in the treatment of arterial AMI.

Intervertebral disc degeneration produced by vertebral body fracture associated with microcirculation disruption of the sub-endplate.

BACKGROUND: Among the causes of the progression of intervertebral disc (IVD) degeneration (IDD) is the loss of nutrient intake to the IVD through the microcirculation disruption of the sub-endplate. Also, the vertebral body fracture intervenes in degenerating the adjacent IVD. This research aimed to create an animal model of IDD using these two strategies. METHODS: 30 male Sprague-Dawley rats were split into 3 groups: a control group, a middle vertebral body injury (MI) associated with ethanol injection (MI+EtOH) group, and an MI associated with phosphate-buffered saline injection (MI+PBS) group. A vertebral body fracture with or without endplate injection of ethanol was generated by either drilling a hole in the center of a caudal rat vertebral body to form a fracture with an unabated endplate or drilling a hole in the center of a rat coccygeal vertebral body with endplate injection of ethanol to establish a vertebral body fracture with endplate damage. X-ray, macroscopic, histologic, and biochemical evaluations were utilized to assess IDD at weeks 3 and 6. RESULTS: According to X-ray findings, the MI+EtOH group demonstrated a significant decrease in intervertebral space height over time in comparison to the 2 other groups. The water content also was significantly decreased. Macroscopic and histological analysis demonstrated progressive degenerative changes in the IVD of the MI+EtOH group. CONCLUSION: The caudal vertebra fracture with ethanol injection is more likely to induce degeneration of adjacent IVD. This model effectively repreduced IDD, which may serve as a theoretical basis for future clinical intervention for IDD.

Duct ligation/de-ligation model: exploring mechanisms for salivary gland injury and regeneration.

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/de-ligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders.

Genetic parameters of body weight traits in Mithun (Bos frontalis) using animal model.

Mithun (Bos frontalis), a domestically raised herbivore, holds significant economic importance for the farming community of Northeast India. This study aimed to elucidate the genetic parameters governing Mithun body weight traits across different ages using data from the sole organized semi-intensive Mithun farm in India. Information was gathered from 110 Mithuns born over a period spanning from 2011 to 2022. Body weight taken at week 1 (W1), 1-month (M1), 3-months (M3), 6-months (M6), 9-months (M9), 12-months (M12), 30-months (M30) and 45-months (M45) were considered for the study. The genetic parameters estimation employed the BLUPF90 suite of programs, incorporating univariate Gibbs sampler animal model with fixed effects; season and period of birth, and sex of the animal. Variance and covariance components, including direct additive genetic effects, were estimated. Heritability estimates for the eight body weight traits ranged from 0.47 ± 0.0050 to 0.50 ± 0.0043, indicating varying genetic influence across growth stages. Results revealed that Mithun herd has a substantial genetic variability for growth traits and therefore there is ample scope to select for a better growth rate. Here, we conclude that Month 12 (M12) and Month 9 (M9) body weights exhibit higher heritability, indicating potential for genetic improvement through selective breeding.

Unleashing the Neurotherapeutic Potential: The Crucial Role of miR-206-3p in Facilitating Hsp90aa1-Mediated Central Nervous System Injuries During Heat Stroke.

This study aims to explore the molecular mechanisms of miR-206-3p in regulating Hsp90aa1 and its involvement in the central nervous system (CNS) injury in heat stroke. Weighted gene co-expression network analysis (WGCNA) was performed on the GSE64778 dataset of heat stroke to identify module genes most closely associated with disease characteristics. Through the selection of key genes and predicting upstream miRNAs using RNAInter and miRWalk databases, the regulatory relationship between miR-206-3p and Hsp90aa1 was determined. Through in vitro experiments, various methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RIP experiment, and RNA pull-down experiment, were utilized to validate this regulatory relationship. Furthermore, functional experiments, including CCK-8 assay to test neuron cell viability and flow cytometry to assess neuron apoptosis levels, confirmed the role of miR-206-3p. Transmission electron microscopy, real-time quantitative PCR, DCFH-DA staining, and ATP assay were employed to verify neuronal mitochondrial damage. Heat stroke rat models were constructed, and mNSS scoring and cresyl violet staining were utilized to assess neural functional impairment. Biochemical experiments were conducted to evaluate inflammation, brain water content, and histopathological changes in brain tissue using H&E staining. TUNEL staining was applied to detect neuronal apoptosis in brain tissue. RT-qPCR and Western blot were performed to measure gene and protein expression levels, further validating the regulatory relationship in vivo. Bioinformatics analysis indicated that miR-206-3p regulation of Hsp90aa1 may be involved in CNS injury in heat stroke. In vivo, animal experiments demonstrated that miR-206-3p and Hsp90aa1 co-localized in neurons of the rat hippocampal CA3 region, and with prolonged heat stress, the expression of miR-206-3p gradually increased while the expression of Hsp90aa1 gradually decreased. Further in vitro cellular mechanism validation and functional experiments confirmed that miR-206-3p could inhibit neuronal cell viability and promote apoptosis and mitochondrial damage by targeting Hsp90aa1. In vivo, experiments confirmed that miR-206-3p promotes CNS injury in heat stroke. This study revealed the regulatory relationship between miR-206-3p and Hsp90aa1, suggesting that miR-206-3p could regulate the expression of Hsp90aa1, inhibit neuronal cell viability, and promote apoptosis, thereby contributing to CNS injury in heat stroke.

Redefining the Role of Ornithine Aspartate and Vitamin E in Metabolic-Dysfunction-Associated Steatotic Liver Disease through Its Biochemical Properties.

It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.

Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358.