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Objective: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. Method and materials: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. Results: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. Conclusion: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures. [ABSTRACT FROM AUTHOR]

Purpose: To review experimental peri-implantitis studies using rat models and summarize different peri-implantitis induction techniques and evaluate their effectiveness. Materials and Methods: Electronic searches were conducted by two independent examiners to address the following issues. Meta-analyses explored the marginal bone loss (MBL) of four types of peri-implantitis induction methods in rats. The detailed induction tactics--such as the implant design, implant size, surgical process, time cost, induction methods, and endpoint measurements--were summarized. Results: Of the 18 included studies, 38.9% of the studies placed implants at the maxillary first molar, and 44.4% placed them at the alveolar ridge region anterior to the maxillary first molar. As for the induction method, the numbers of published studies on ligature methods, bacterial inoculation, and bacterial lipopolysaccharide inoculation were equally high among all selected studies. The total implant survival rate at the end was 160 out of 213 implants (75.11%). Eight studies with high pooled heterogeneity (I2 = 98, P < .01) in the meta-analysis reported an overall MBL (µ-CT) of 0.47 mm (95% CI = 0.14 to 0.81). A subgroup analysis estimated an MBL of 0.31 mm (95% CI = 0.12 to 0.50) for bacterial inoculation and 0.66 mm (95% CI = 0.07 to 1.26) for the ligature method. Histopathologic analysis revealed that peri-implantitis in rats was similar to peri-implantitis lesions in humans. Conclusions: Implant placement at the maxillary first molar with bacterial inoculation and the silk ligature method to build peri-implantitis rat models is reliable to use for research on peri-implantitis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. Materials and Methods: A total of 40 rats were randomly allocated into four groups (n = 10/group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). Results: There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). Conclusions: Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae. [ABSTRACT FROM AUTHOR]

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model. Materials and Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. Results: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. Conclusions: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression. Methods: Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry. Results: Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers. Conclusions: This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations. [ABSTRACT FROM AUTHOR]

Background: While the benefits of sonication for improving periprosthetic joint infection (PJI) are well-documented, its potential therapeutic effect against bacterial biofilm remains unstudied. This study aimed to investigate the safety and efficacy of a novel nanoparticle ultrasonication process on methicillin-resistant Staphylococcus aureus (MRSA) bacterial biofilm formation in a PJI rat model. Methods: This novel ultrasonication process was designed to remove attached bacterial biofilm from implant and peri-articular tissues, without damaging native tissues or compromising implant integrity. Twenty-five adult Sprague–Dawley rats underwent a surgical procedure and were colonized with intra-articular MRSA, followed by the insertion of a titanium screw. Three weeks after the index surgery, the animals received a second procedure during which the screws were explanted, and soft tissue was sampled. The intraoperative use of the nanoparticle sonication treatment was employed to assess the device's safety, while ex vivo treatment on the retrieved tissue and implants was used to evaluate its efficacy. Results: Clinical and histological assessments did not indicate any macro- or micro-damage to the host tissue. Sonication of the retrieved tissues demonstrated an average bacterial removal of 2 × 103 CFU/mL and 1 × 104 CFU/gram of tissue. Compared to the standard-of-care group (n = 10), implants treated with sonication (n = 15) had significantly lower remaining bacteria, as indicated by crystal violet absorbance measurements (P = 0.012). Conclusions: This study suggests that nanoparticle sonication technology can successfully remove attached bacterial biofilms from explanted orthopedic hardware and the joint capsule, without negatively affecting native tissue. The study provides initial results supporting the potential of nanoparticle sonication as an adjuvant treatment option during a DAIR (debridement, antibiotics, and implant retention) procedure for PJI, paving the way for future clinical trials. [ABSTRACT FROM AUTHOR]

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Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury. [ABSTRACT FROM AUTHOR]

Conditioned media (CM) is derived from mesenchymal stem cells (MSC) culture and contains biologically active components. CM is easy to handle and reduces inflammation while repairing injured joints. Combination therapy of the CM with cross-linked hyaluronic acid (HA) could ameliorate the beneficial effect of HA in treating degenerative changes of articulating surfaces associated with arthritic rats' temporomandibular joints (TMJs). This study aimed to evaluate the therapeutic potential of HA hydrogel combined with bone marrow stem cells-conditioned medium (BMSCs-CM) on the articulating surfaces of TMJs associated with complete Freund's adjuvant (CFA)-induced arthritis. Fifty female Sprague-Dawley rats were divided randomly into five equal groups. Rats of group I served as the negative controls and received intra-articular (IA) injections of 50 µl saline solution, whereas rats of group II were subjected to twice IA injections of 50 µg CFA in 50 µl; on day 1 of the experiment to induce persistent inflammation and on day 14 to induce arthritis. Rats of group III and IV were handled as group II and instead, they received an IA injection of 50 µl HA hydrogel and 50 µl of BMSCs-CM, respectively. Rats of group V were given combined IA injections of 50 µl HA hydrogel and BMSCs-CM. All rats were euthanized after the 4th week of inducing arthritis. The joints were processed for sectioning and histological staining using hematoxylin and eosin, Masson's trichrome and toluidine blue special staining, and immunohistochemical staining for nuclear factor-kappa B (NF-κB). SPSS software was used to analyze the data and one-way analysis of variance followed by post-hoc Tukey statistical tests were used to test the statistical significance at 0.05 for alpha and 0.2 for beta. In the pooled BMSC-CM, 197.14 pg/ml of platelet-derived growth factor and 112.22 pg/ml of interleukin-10 were detected. Compared to TMJs of groups III and IV, TMJs of group V showed significant improvements (P = 0.001) in all parameters tested as the disc thickness was decreased (331.79 ± 0.73), the fibrocartilaginous layer was broadened (0.96 ± 0.04), and the amount of the trabecular bone was distinctive (19.35 ± 1.07). The mean values for the collagen amount were increased (12.29 ± 1.38) whereas the mean values for the NF-κB expression were decreased (0.62 ± 0.15). Combination therapy of HA hydrogel and BMSCs-CM is better than using HA hydrogel or BMSCs-CM, separately to repair degenerative changes in rats' TMJs associated with CFA-induced arthritis. [ABSTRACT FROM AUTHOR]

Translational research in toxicology has significantly benefited from transcriptomic profiling, particularly in drug safety. However, its application has predominantly focused on limited organs, notably the liver, due to resource constraints. This paper presents TransTox, an innovative AI model using a generative adversarial network (GAN) method to facilitate the bidirectional translation of transcriptomic profiles between the liver and kidney under drug treatment. TransTox demonstrates robust performance, validated across independent datasets and laboratories. First, the concordance between real experimental data and synthetic data generated by TransTox was demonstrated in characterizing toxicity mechanisms compared to real experimental settings. Second, TransTox proved valuable in gene expression predictive models, where synthetic data could be used to develop gene expression predictive models or serve as "digital twins" for diagnostic applications. The TransTox approach holds the potential for multi-organ toxicity assessment with AI and advancing the field of precision toxicology. [ABSTRACT FROM AUTHOR]

Elevated blood pressure is the leading metabolic risk factor in attributable deaths, and hydrogen sulfide (H2S) regulates vascular tone and blood pressure. Thus, this study aims to evaluate the mechanism by which NaHS (H2S donor) produces inhibition of the vasopressor sympathetic outflow in obese rats. For that purpose, animals were fed a high‐fat diet (HFD) (60% calories from fat) for 12 weeks. They were anesthetized, pithed, and cannulated to evaluate the role of the potassium channel on NaHS‐induced sympathoinhibition. Animals received selective electrical stimulation of the vasopressor sympathetic outflow, an intravenous (i.v.) administration of (1) tetraethylammonium (TEA, non‐selective K+ channel blocker, 16.5 mg/kg), (2) 4‐aminopyridine (4‐AP, KV channel blocker, 5 mg/kg), (3) barium chloride (BaCl2, KIR channel blocker, 65 μg/kg), (4) saline solution (vehicle of TEA, 4‐AP, and BaCl2, 1 mL/kg), (5) glibenclamide (KATP channel blocker, 10 mg/kg), and (6) glibenclamide vehicle (DMSO + glucose 10% + NaOH, 1 mL/kg), and then a 310 μg/kg·min NaHS i.v. continuous infusion. We observed that (1) NaHS produced inhibition of the vasopressor sympathetic outflow and (2) the sympathoinhibitory effect by NaHS was reversed by the KIR channel blocker, BaCl2, in obese rats. The above data suggest that the potassium channel could be involved in the sympathoinhibition induced by NaHS. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains a significant global public health epidemic with adverse health and cost implications. Due to its complex, heterogeneous nature and wide-ranging impacts, definitive TBI treatments remain elusive. As such, continued laboratory research using animal models is warranted. In accordance with guidelines set forth for the humane treatment of research animals, TBI animal models are often administered analgesics for pain management. The choice of drug, timing, dose, and formulation of analgesic can vary depending on the study's unique needs and can potentially and unintentionally influence experimental results. In TBI studies utilizing rats as animal models, buprenorphine is a common analgesic administered. In addition to pain management in such studies, investigators must also monitor the research animals post-operatively and make the decision for humane euthanasia before intended experimental survival timepoint if the animals are assessed to be excessively suffering. This study investigated the differences in adult, male Sprague Dawley rats used for various TBI studies that reached weight-loss-induced humane endpoints following a single administration of buprenorphine slow-release LAB (bup-SR-LAB) or buprenorphine slow-release HCl (bup-SR-HCl). Our findings indicate that TBI-induced rats receiving bup-SR-LAB in conjunction with a secondary surgical insult such as artificial intracranial pressure elevation and/or osmotic pump implantation reach a weight-loss-induced humane euthanasia endpoint more often compared to sham-injured rats. When stratifying into the same groups, we did not find this pattern to hold true for rats administered bup-SR-HCl. Overall, this study contributes to the limited body of literature addressing different analgesic formulations' effects on laboratory animals. [ABSTRACT FROM AUTHOR]

Background: Injuries to the glenoid labrum have been recognized as a source of joint pain and discomfort, which may be associated with the inflammatory responses that lead to the deterioration of labral tissue. However, it is unclear whether the torn labrum prompts mast cell (MC) activation, resulting in synovial inflammatory responses that lead to labral tissue degeneration. Purpose: To determine the potential influence of activated MC on synovial inflammatory responses and subsequent labral tissue degeneration and shoulder function deterioration in a rat model by monitoring MC behavior and sequential inflammatory responses within the synovial tissue and labral tissue after injury, suture repair, and MC stabilizer administration. Study Design: Controlled laboratory study. Methods: Anteroinferior glenoid labral tears were generated in the right shoulder of rats (n = 20) and repaired using a tunneled suture technique. Synovial tissue inflammatory responses were modulated in some rats with intraperitoneal administration of an MC stabilizer—cromolyn (n = 10). At weeks 1 and 3, MC activation, synovial inflammatory responses, and labral degeneration were histologically evaluated. Simultaneously, gait analysis was performed before and after surgical repair to assess the worsening of the shoulder function after the injury and treatment. Results: Resident MC degranulation after labral injury (50.48% ± 8.23% activated at week 1) contributed to the initiation of synovial tissue inflammatory cell recruitment, inflammatory product release, matrix metalloproteinase-13, and subsequent labral tissue extracellular matrix degeneration. The administration of cromolyn, an MC stabilizer, was found to significantly diminish injury-mediated inflammatory responses (inflammatory cell infiltration and subsequent proinflammatory product secretion) and improve shoulder functional recovery. Conclusion: MC activation is responsible for labral tear–associated synovial inflammation and labral degeneration. The administration of cromolyn can significantly diminish the cascade of inflammatory reactions after labral injury. Clinical Relevance: Our findings support the concept that MC stabilizers may be used as a complementary therapeutic option in the treatment and repair of labral tears. [ABSTRACT FROM AUTHOR]

The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (by 50%) ethanol self-administration when injected 4 h before the session either intraperitoneally (1 mg/kg) or directly within the left nucleus accumbens (0.15 μg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra-left nucleus accumbens injection of 0.3 μg of the 5-HT2A receptor antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor (D2R) mRNA was increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while dopamine D1 receptor mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2A receptor within the left nucleus accumbens, possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects. [ABSTRACT FROM AUTHOR]

Background: The earliest manifestation of alcohol‐associated liver disease (ALD) is steatosis characterized by deposition of fat in specialized organelles called lipid droplets (LDs). While alcohol administration causes a rise in LD numbers in the hepatocytes, little is known regarding their characteristics that allow their accumulation and size to increase. The aim of the present study is to gain insights into underlying pathophysiological mechanisms by investigating the ethanol‐induced changes in hepatic LD proteome as a function of LD size. Methods: Adult male Wistar rats (180–200 g BW) were fed with ethanol liquid diet for 6 weeks. At sacrifice, large‐, medium‐, and small‐sized hepatic LD subpopulations (LD1, LD2, and LD3, respectively) were isolated and subjected to morphological and proteomic analyses. Results: Morphological analysis of LD1‐LD3 fractions of ethanol‐fed rats clearly demonstrated that LD1 contained larger LDs compared with LD2 and LD3 fractions. Our preliminary results from principal component analysis showed that the proteome of different‐sized hepatic LD fractions was distinctly different. Proteomic data analysis identified over 2000 proteins in each LD fraction with significant alterations in protein abundance among the three LD fractions. Among the altered proteins, several were related to fat metabolism, including synthesis, incorporation of fatty acid, and lipolysis. Ingenuity pathway analysis revealed increased fatty acid synthesis, fatty acid incorporation, LD fusion, and reduced lipolysis in LD1 compared to LD3. Overall, the proteomic findings indicate that the increased level of protein that facilitates fusion of LDs combined with an increased association of negative regulators of lipolysis dictates the generation of large‐sized LDs during the development of alcohol‐associated hepatic steatosis. Conclusion: Several significantly altered proteins were identified in different‐sized LDs isolated from livers of ethanol‐fed rats. Ethanol‐induced increases in specific proteins that hinder LD lipid metabolism led to the accumulation and persistence of large‐sized LDs in the liver. [ABSTRACT FROM AUTHOR]

Maternal exercise is beneficial for offspring brain development. Amyloid precursor protein (APP) influences neurogenesis and synaptic plasticity. Cleavage products of APP are implicated in the proliferation of neural progenitor cells and neuronal network development. Our study aimed to investigate differences in APP processing in active or sedentary offspring of dams who were exposed to voluntary wheel running with and without a western diet throughout gestation. Female Wistar rats (7–8 weeks old) were fed a normal chow or western diet and randomized into voluntary wheel run or sedentary conditions. Dams returned to sedentary conditions post-parturition. The pups were weaned at 6 weeks after which point half of the samples were collected, while the rest of the pups remained on a normal diet, separated into sedentary or voluntary wheel run groups, and collected 12 weeks later. In utero exposure to maternal exercise was associated with higher neuronal nuclear protein, higher soluble APPα and lower soluble APPβ in offspring prefrontal cortex tissue at 6, but not 18 weeks of age. Neuronal nuclear protein is exclusive to mature neurons implying that offspring of mothers who exercised could have more neuron maturation potentially influenced by the higher APPα content at this early developmental stage. The voluntary wheel run offspring groups had a higher mature/pro brain derived neurotrophic factor ratio compared to the sedentary counterparts. The maternal effects were isolated to the juvenile 6-week-old pups, while the differences in the adult offspring were caused by their own exercise status. [ABSTRACT FROM AUTHOR]

Rats and pigeons have shown striking differences in their behavior in the suboptimal choice procedure: while pigeons show a strong and consistent preference for the discriminative alternative, most studies performed with rats have found optimal preferences, and in the cases in which suboptimal preferences have been reported, those results have not been replicated. Currently, there is no consensus about the reasons for these discrepant results between species, but different explanations have been proposed either with an empirical base or exclusively in theoretical terms. In the latter category it has been proposed that the discrepancy might have arisen because of differences in the relationship between the natural foraging response of each species, and the response required in the laboratory. For analyzing this possibility, we conducted two experiments carried out within a maze that was specifically designed to allow rats to display behaviors related to their natural foraging. In experiment 1, we explored rats' preferences when facing a discriminative alternative with probability of reinforcement (p) = 0.5, and a non-discriminative alternative with p =.75. In experiment 2, we evaluated preferences when the discriminative alternative had p =.20 and the non-discriminative had p =.50, rats were evaluated in a closed economy, with longer terminal links, and were allowed to escape from the outcome found. In both studies, rats showed a strong preference for the non-discriminative alternative and showed very high levels of discrimination between the positive and the negative outcomes of the discriminative alternative. [ABSTRACT FROM AUTHOR]

Background: Mechanisms underlying psychostimulant euphoria remain poorly understood. In adult rats, positive emotional states are associated with alterations in 50-kHz ultrasonic vocalizations (USVs): specifically, "trill" calls are promoted over "flat" calls. Here, we investigated the effects of acute and repeated cocaine administration, and—based on previous findings with amphetamine—their possible dependence on beta-adrenergic receptors. Methods: Adult male Long-Evans rats received intraperitoneal drug or saline injections before daily USV recording. Fourteen 50-kHz call subtypes were analyzed. In Experiments 1 and 2, cocaine (1–10 mg/kg) and propranolol (10 mg/kg) were tested alone. In Experiment 3, propranolol/cocaine interactions were sought within a conditioned place preference (CPP) procedure. Experiment 4 investigated acute and chronic cocaine effects (Phase 1), and propranolol/cocaine interactions either in an open field (Phase 2) or within a CPP procedure (Phase 3). Results: In drug-naïve animals, cocaine increased the 50-kHz call rate, with sensitization developing rapidly. After more extended exposure, cocaine now also increased the relative prevalence of trill versus flat calls; effects on other subtypes were also revealed. The beta-blocker propranolol prevented neither cocaine CPP nor cocaine effects on USV emission or locomotion but exerted significant USV-related effects when given alone. CPP magnitude and USV-related measures were uncorrelated. Conclusions: With long-term intraperitoneal administration, cocaine can alter the relative prevalence of several 50-kHz call subtypes; its ability to promote trill versus flat calls, in particular, is consistent with a positive affect interpretation. Cocaine's behavioral effects (i.e., USV-related, locomotor, CPP) appear independent of beta-adrenergic receptor activity. [ABSTRACT FROM AUTHOR]

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25–160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis. [ABSTRACT FROM AUTHOR]

Background: Syndecan 4 (SDC4), a type I transmembrane proteoglycan, serves as a critical link between chondrocytes and the extracellular matrix. Objective: This study aimed to explore the role of SDC4 in cartilage degeneration of temporomandibular joint osteoathritis (TMJOA). Methods: Condylar chondrocytes were stimulated with varying concentrations of recombinant rat interleukin‐1β (rrIL‐1β) and SDC4 small interfering RNA (si‐SDC4). Anti‐SDC4 ectodomain‐specific antibodies or IgG were intra‐articularly administrated in a TMJOA model rats. SDC4 conditional knockout (SDC4‐cKO) and Sdc4flox/flox mice were induced TMJOA. Cartilage degeneration was assessed using haematoxylin & eosin (H&E) and safranin O (SO) staining. Protein levels of SDC4, matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with a thrombospondin motifs 5 (ADAMTS5), tumour necrosis factor α (TNFα), type II collagen (Col‐II), aggrecan (ACAN), cleaved caspase 3 (CASP3), Ki67 and related pathways in condylar cartilage were evaluated by immunohistochemical (IHC) staining or western blot assays. Results: SDC4 expression was evidently increased in MIA‐model animals compared to control groups. rrIL‐1β stimulation increased the expression of SDC4, MMP3 and ADAMTS5 expression in chondrocytes, while decreasing the expression of Col‐II. These effects were reversed by si‐SDC4 in vitro. In vivo, SDC4 blockade reduced the death of chondrocytes and the loss of cartilage matrix, which was evidenced by increased expression of Col‐II and ACAN, and a decrease in SDC4, MMP13 and cleaved‐CASP3‐positive cells. Furthermore, the protein levels of ACAN and Ki67 were elevated, and the ERK1/2 and P38 signalling pathways were activated following SDC4 inhibition. Conclusions: SDC4 inhibition significantly ameliorates condylar cartilage degeneration, which was mediated, at least partly, through P38 and ERK1/2 signalling. Inhibition of SDC4 may be of great value for the treatment of TMJOA. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety, the most prevalent neuropsychiatric manifestations in Parkinson's disease (PD), negatively impact their quality of life. Aims: To determine whether the chronic nasal administration of kisspeptin-54 (KP-54) could. Alleviate symptoms of anxiety and depression in hemi-Parkinsonian rats. Study Design: Experimental study. Methods: This study included adult Sprague Dawley male rats who were administered either a vehicle (artificial cerebrospinal fluid) or 6-hydroxydopamine (6-OHDA) unilaterally into the medial forebrain bundle. The vehicle, or KP-54 (3 nmol/kg, applied topically to the rhinarium), was administered daily for a seven-day period. The sucrose preference test (SPT), elevated plus maze test (EPMT), and open field test (OFT) were implemented to evaluate depression- and anxiety-like behaviors, respectively, seven days following the lesion surgery. Gamma-aminobutyric acid (GABA) concentrations in the amygdala were quantified using mass spectrometry. Tyrosine hydroxylase in substantia nigra was analyzed using immunohistochemistry. Results: The nasal delivery of KP-54 significantly reduced depressionand anxiety-like behaviors that were induced by 6-OHDA, as indicated by the results of the SPT, OFT, and EPMT. Moreover, it was observed that nasal KP-54 effectively mitigated 6-OHDA-induced motor deficits and the loss of nigral dopaminergic neurons. The nasal administration of KP- 54 augmented the decline in GABA levels in the amygdala induced by 6-OHDA. Furthermore, effective correlations were established between GABA concentrations and behavioral parameters. Conclusion: The nasal delivery of KP-54 could function as a viable therapeutic alternative for treating mood-related disorders in PD. [ABSTRACT FROM AUTHOR]

Objectives: We compared the cardioprotective capacity of Del Nido cardioplegia and warm Calafiore blood cardioplegia in an experimental setting during 90 min of ischaemia. Methods: 20 adult and 20 senescent rat hearts were isolated and mounted on a blood-perfused, pressure-controlled Langendorff apparatus. After a stabilization period, cardiac arrest (90 min) was induced by the administration of either Calafiore (Cala) or Del Nido solution (DNS). While Cala was given warm and intermittently, DNS was given as a cold single shot. During 90 min of reperfusion, cardiac function and metabolism were evaluated and biomarker levels were measured. After the end of the experiment, hearts were prepared for electronmicroscopic investigation. Results: Hearts exposed to Cala recovered faster during reperfusion compared with hearts administered DNS (Cala vs DNS at 30 min reperfusion: left ventricular developed pressure 72, SD: 22% of baseline (BL) versus 40, SD: 32% of BL, p <.001, and positive derived left ventricular pressure over time was better in both adult and senescent Cala groups (96, SD: 31% of BL) than in the DNS groups (39, SD: 27% of BL, p <.001). Ischaemic contractures were seen in the DNS groups starting after 30 min of ischaemia, whereas no rise in diastolic pressure was observed for the Cala groups. Accordingly, lactate production was higher after DNS (1.23 mg/dl (SD 0.87) than after Cala (0.33 mg/dl (SD 0.68), p =.015) at the beginning of reperfusion. Troponin I levels at the end of reperfusion were higher after DNS treatment in adult hearts (DNS: 287.9 SD: 147.7 ng/mL vs Cala 91.2: SD: 94.7 ng/mL, p =.02) and in senescent hearts (DNS: 376.5 (SD: 162.8) ng/ml versus Cala 104.7 (SD: 150.2) ng/ml, p =.025). Electron microscopy showed that the cellular oedema index was higher in adult DNS hearts (1.2 ± 0.2) than in adult Cala hearts (0.8 ± 0.1, p =.012), whereas the VS ratio was similar (0.18 ± 0.01 vs 0.17 ± 0.03). Conclusion: Calafiore cardioplegia offers better myocardial protection from ischaemia/reperfusion-related damage in isolated perfused adult and senescent rat hearts than Del Nido cardioplegia. [ABSTRACT FROM AUTHOR]

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Aim: This study aims to assess the effectiveness of therapy of human synovial membrane-derived MSCs (SM-MSC) from OA grade IV patients in treating knee OA. Methods: SM-MSC were isolated from patients undergoing total knee replacement surgery, cultured to the fourth passage, and characterized using flow cytometry. Differentiation potential was assessed through lineage-specific staining. Osteoarthritis was induced in 24 Wistar rats via monosodium iodoacetate (MIA). The rats were divided into three groups: negative control, OA control, and OA treated with SM-MSC. Radiological, histopathological, and molecular analyses were conducted to evaluate cartilage repair and gene expression. Results: Flow cytometry confirmed the MSC phenotype of SM-MSC, and successful differentiation was observed. Radiological and histopathological analyses showed significant improvement in the SM-MSC treated group, with reduced cartilage damage and higher Safranin O staining compared to the OA control group. Gene expression analysis indicated increased type-2 collagen (COL-2) expression in the SM-MSC treated group, although MMP-13 levels remained unchanged across all groups. Conclusion: Human SM-MSCs from OA grade IV patients significantly improved cartilage repair in an OA rat model, demonstrating their potential as a therapeutic option for OA. To enhance long-term efficacy and anti-inflammatory effects, further studies are needed to optimize treatment protocols, including injection frequency and dosage. [ABSTRACT FROM AUTHOR]

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial–mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions. [ABSTRACT FROM AUTHOR]

The posterior pituitary (PP) hormones oxytocin (OXT) and arginine vasopressin (AVP) are synthesized within the hypothalamic nucleus and released from the PP into systemic circulation. Hypothalamic AVP projects its axons into the external layer of median eminence (eME) and regulates anterior pituitary hormone secretion during stress responses. Although similar as PP hormones, we demonstrate distinct regulatory roles of estrogen in hypothalamic OXT and AVP dynamics. OXT dynamics in the hypothalamus exhibit sex‐dependent variations and that estrogen may influence dynamic OXT level changes, as observed in OXT‐mRFP1 transgenic rats. Estrogen was also observed to modulate dynamic changes in AVP levels in the axon terminals of eME in female AVP‐eGFP transgenic rats. Although OXT and AVP are produced within the similar hypothalamic region, both exhibit distinct dynamics within the hypothalamus. Estrogen acts on the hypothalamus, and further effects of estrogen replacement therapy can be expected. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rodent management with lethal methods (e.g., rodenticides) comes with downsides for rodent welfare, the environment and non‐target species. To reduce chemical use and prevent rodent nuisance, pest controllers in the Netherlands must work according to the principles of integrated pest management (IPM). A condition for the success of IPM is that there is sufficient engagement of all parties involved, including clients of pest controllers. The aim of this study was to gain insight into the attitudes of clients regarding rodent control, IPM and the application of preventive measures. Insight into their attitudes may contribute to a better implementation of IPM and with that to a more sustainable rodent management based on more effective prevention. An online survey among 248 clients of Dutch pest controllers from both the agricultural and other sectors was carried out. RESULTS: Respondents from the agricultural sector had a relatively negative attitude towards IPM, the new IPM regulations in the Netherlands and had little confidence in prevention. In other sectors, respondents were more positive about IPM and had more confidence in prevention. The respondents from the latter subgroup had a similar attitude compared to Dutch pest controllers who participated in a previous survey. CONCLUSION: The findings of the study provide information for the further development and practical implementation of IPM and preventive measures and with that a more sustainable and animal friendly rodent management. They can also be helpful for a better communication and cooperation between pest controllers and their clients. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rat eradication from islands is a very effective tool that can free entire ecosystems from the pressure of alien predators. In this study we present the case study of Ventotene (Ponziane Archipelago, central Italy), which to date is the island with by far the greatest number of human inhabitants ever freed from the negative implications of rats. Rat eradication was carried out in the framework of the Life PonDerat project, co‐financed by the European Union. Besides considering the conservation benefits due to the removal of rats, we also considered the socio‐economic and pathogenic impacts from introduced rats. RESULTS: The overall economic cost of the rats was quantified to be at least €18 500 per year to the residents of the island. Several zoonotic pathogens were detected in the rat population prior to eradication. A reduction in the rodenticide distributed over time on the island was also estimated. Identifying the origin of the rat population allowed for the development of more targeted and effective biosecurity measures. The eradication effort was challenged by the presence of domestic animals and variability in support for baiting in urbanised areas. CONCLUSIONS: The results of this study open up new perspectives on island restoration projects. We demonstrated the cost‐effectiveness of the action, including ecosystem restoration, reduction of rat impacts in agricultural systems, and improving overall health and food safety. Our findings will have implications for similar interventions on other islands, potentially bringing significant benefits. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Groundwater contamination in India exposes an estimated 70 million people to arsenic. Over 10 million people in the state of Bihar (India) are at risk of arsenic poisoning. As reported 27 districts of the state's thirty-eight districts are under a state of catastrophe. Symptoms noticed by those who have been exposed to the arsenic caused disease are-lack of appetite, neurobehavioral problems, hyperkeratosis, and melanosis on the skin. So, this study's primary objective is to find novel approaches to treat arsenic poisoning in rats using the Charles Foster model. Following permission from the Institutional Animal Ethics Committee, the animals were divided into three groups: one group served as a control, the second group received arsenic treatment, and the third group received Ganoderma lucidum extract after arsenic treatment. For the arsenic group, the rats were given 8 mg/kg body weight of sodium arsenite orally every day for 90 days, and then for 60 days, they were given 80 mg/Kg body weight of Ganoderma lucidum extract via gavage. Their biochemical values, including those of the liver and kidneys, were found to be increased. In addition, their levels of free radicals, including lipid peroxidation, were measured and found to be substantially higher. In addition, the levels of arsenic in the kidney and liver tissue were very high. However, biochemical and lipid peroxidation levels were significantly restored after administration of Ganoderma lucidum ethanolic extract. Arsenic levels in rat liver and kidney tissues were also found to be reduced. Ganoderma lucidum has a therapeutic impact against arsenicinduced toxicity, according to the present research. [ABSTRACT FROM AUTHOR]

Arsenic contamination is a serious issue throughout the world and is substantial risk factor in most of the countries including India. Chronic arsenic exposure from drinking water to humans is causing major public health related issues. The present study aims to investigate the ameliorative effect of Citrullus lanatus (Watermelon) seeds against arsenic induced reproductive function and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm). The study group includes group - I (n=6) as control, and group - II (n=18) treated with sodium arsenite (8 mg per Kg body weight per day) for 90 days. The group - II was furthermore divided into three sub-groups, Group - II-a, Group - II-b and Group - II-c. The group - II-a were sacrificed to see the effect of arsenic toxicity effect after arsenic exposure. Group - II-b was left with normal food and water for next 60 days to observe auto recovery. The group - II-c rats were administered with Citrullus lanatus (Watermelon) hydroxyl ethanolic seeds extract at the dose of 400 mg per Kg body weight per day for 60 days for 90 days upon pre-treated sodium arsenite treated group (8 mg per kg body weight). After completion of the experiment, all the treated group of animals were sacrificed for biochemical, hormonal assay, histopathological, testicular and reproductive functions study. In the arsenic treated rats' group, there was significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. There was decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance denotes infertility condition. In contrast, after the administration with C.lanatus (Watermelon) seeds hydroxy-ethanolic extract upon arsenic treated rats group, there was significant (p<0.001) improvement observed in the reproductive, hepatic and renal parameters. In the arsenic intoxicant rats' group, after administration with C. lanatus (Watermelon) seeds hydroxyl ethanolic extract, there was significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum lipid peroxidation. The histopathological study also showed the C. lanatus (Watermelon) seeds hydroxy ethanolic extract significantly restored the cellular integrity of testicular cells leading to normal functioning of it against arsenic induced toxicity. [ABSTRACT FROM AUTHOR]

Arsenic catastrophe has caused serious health hazards to the exposed population. An estimated 10 million people are exposed to arsenic poisoning through groundwater. The arsenic contamination through ground water has caused health diseases such as skin manifestations, loss of appetite, nausea, bowel disorders, neurological disorders etc. Therefore, there is need for search for proper therapeutic drug against arsenic induced toxicity in rats. In the present study, arsenic induced toxic model was developed by treating Charles Foster rats (n=18) with sodium arsenite orally at the dose of 8 mg/kg body weight daily for 60 days followed by administration of Bacopa moneri (Brahmi) leaf extract at the dose of 30mg/kg body weight daily by gavage method for 60 days. After the completion of the experiment, all the animals were sacrificed and their blood samples were collected along with their vital tissues. Following parameters were assayed such as haematological assay, biochemical assay and histopathological evaluation in the present study. The haematological study comprised of RBC counts, WBC counts, platelets counts and heamoglobin percentage. For biochemical evaluation, the liver function test and the kidney function test parameters along with free radical assay were carried out. The histopathological study also showed very high degree of degeneration in the hepatocytes and the nephrocytes in the vital organ's liver and kidney. But, after the administration of ethanolic leaf extract of Bacopa moneri, there was marked restoration in the studied parameters. The haematological parameters, the biochemical parameters as well as the histopathological study showed very significant outcomes. Therefore, the present studied medicinal plant Bacopa moneri possesses antidote effect against arsenic induced toxicity in Charles Foster rats which can be used as therapeutic drug in the future after clinical approval. [ABSTRACT FROM AUTHOR]

Objective OA is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA. Methods We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry and Alcian blue staining were performed. In vitro , immunofluorescence, quantitative real-time PCR (RT-qPCR), ELISA and western blot assays were performed. Results serpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioural responses and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1β and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation. Conclusions serpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA. [ABSTRACT FROM AUTHOR]

Background and aims: This study aimed to investigate the eect of iron overload on acetylcholinesterase activity in the frontal lobe tissue of rats with minimal hepatic encephalopathy (MHE) and its relation to cognitive ability. By elucidating the potential mechanisms of cognitive impairment, this study may oer insights into novel therapeutic targets for MHE. Materials and methods: Twelve Sprague-Dawley rats were purchased and randomly assigned to either the experimental or control group with six rats in each group. Following the induction of MHE, the Morris Water Maze (MWM) was utilized to assess spatial orientation and memory capacity. Subsequently, Magnetic Resonance Imaging (MRI) scans were performed to capture Quantitative Susceptibility Mapping (QSM) images of all rats’ heads. Results: Compared to the control group rats, the MHE model rats showed significantly reduced learning and memory capabilities as well as spatial orientation abilities (P < 0.05). Furthermore, the susceptibility values in the frontal lobe tissue of MHE model rats was significantly higher than that of the control group rats (P < 0.05), and the corresponding BuChE activity in the frontal lobe extract of model rats was significantly increased while BuChE activity in the peripheral blood serum was significantly decreased compared to the control group rats (P < 0.05). Meanwhile, our findings indicate a significant positive correlation between latency period and BuChE activity with susceptibility values in the MHE group. Conclusion: The changes in BuChE activity in frontal lobe extract may be related to changes in spatial orientation and behavioral changes in MHE, and iron overload in the frontal lobe tissue may regulate changes in BuChE activity, BuChE levels appear to be iron-dependen [ABSTRACT FROM AUTHOR]

Atomic magnetometer (AM) is utilized to non-invasively detect event-related magnetic fields (ERMFs) evoked by visual stimuli in rats. The aim of this study was to investigate the relationship between N2-like amplitude and visual attention. To achieve this, we combined the AM with a visual stimulation system and employed the passive single-stimulus paradigm. By measuring the ERMFs at various inter-stimulus intervals (ISIs) with a sensitivity of 20 fT/ Hz , we analyzed the effects of the ISI and the 'habituation' resulting from repeated stimuli on the N2-like amplitude. Our method serves as a valuable reference for studying the passive single-stimulus paradigm and the time course of mammalian attention. [ABSTRACT FROM AUTHOR]

Background: Taste buds' innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation. Methods: Twenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis. Results: Histopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds' number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds' number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II. Conclusion: BM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride. [ABSTRACT FROM AUTHOR]

Purpose: Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. Patients and methods: This study was set up as a double-blinded, placebocontrolled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. Results: A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Conclusion: Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to test the protective effect of Withania somnifera (WS) against the harmful effects of mercuric chloride (HgCl2)‐induced kidney failure at the histological, biochemical, and immune levels in Wistar rats. The study assessed the biochemical and immunological changes in five groups (n = 6): Group 1 (G1) was the negative control, and the other rats received a single subcutaneous dose of HgCl2 (2.5 mg/kg in 0.5 mL of 0.9% saline solution) and randomly divided into 4 groups. Group 2 (G2) was the positive control and left without treatment. Groups 3, 4, and 5 (G3, G4, and G5) were treated with different doses of WS root powder for 30 days. The HgCl2‐positive group showed significant signs of renal toxicity as reflected by increased levels of kidney function parameters (blood urea nitrogen, urea, and creatinine), inflammatory biomarkers, immunological indices (SDF‐1, IL‐6, NGAL, and KIM‐1), and oxidative stress (SOD, TAC, CAT, GSH, and MDA). The positive group rats also showed drastic pathological changes in renal tissues. Different doses of WS treatment significantly reduced the levels of all biochemical markers and decreased pathological damage to the kidney tissues. The antioxidant, phenolic, and flavonoid constituents of WS root powder helped protect rats' kidneys against HgCl2‐induced kidney toxicity in male rats. [ABSTRACT FROM AUTHOR]

Background: In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors. Methods: In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration. Results: Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP. Conclusions: The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine. [ABSTRACT FROM AUTHOR]

Background: Quercetin is a promising phytochemical in treating abnormalities associated with metabolic syndrome (MetS). This study aimed to explore the morphometric, metabolic, transcriptomic, and nutrigenetic responses to quercetin supplementation using two genetically distinct MetS models that only differ in the variant of the MetS-related Zbtb16 gene (Zinc Finger And BTB Domain Containing 16). Results: Quercetin supplementation led to a significant reduction in the relative weight of retroperitoneal adipose tissue in both investigated strains. A decrease in visceral (epididymal) fat mass, accompanied by an increase in brown fat mass after quercetin treatment, was observed exclusively in the SHR strain. While the levels of serum triglycerides decreased within both strains, the free fatty acids levels decreased in SHR-Zbtb16-Q rats only. The total serum cholesterol levels were not affected by quercetin in either of the two tested strains. While there were no significant changes in brown adipose tissue transcriptome, quercetin supplementation led to a pronounced gene expression shift in white retroperitoneal adipose tissue, particularly in SHR-Zbtb16-Q. Conclusion: Quercetin administration ameliorates certain MetS-related features; however, the efficacy of the treatment exhibits subtle variations depending on the specific variant of the Zbtb16 gene. [ABSTRACT FROM AUTHOR]

Background: Obesity is one of the public health issues that seriously threatens human health. This study aimed to investigate the effects of wheat bran oil (WBO) on body weight and fat/lipid accumulation in high-fat diet (HFD)-induced obese rats and further explore the possible mechanisms by microbiome and metabolome analyses. Methods: Fifty Sprague-Dawley (SD) rats were fed either a normal chow diet (B group, n = 10) or HFD (n = 40) for 14 weeks to establish an obesity model. The HFD-induced obese rats were further divided into four groups and given WBO at 0 mL/kg (M group), 1.25 mL/kg (WBO-L group), 2.5 mL/kg (WBO-M group), and 5 mL/kg (WBO-H group) by oral gavage for 9 weeks. The body weight of rats was weighed weekly. The gut microbiota structure was analyzed using 16 S rDNA high-throughput sequencing. The liver metabolite profile was determined using UHPLC-QE-MS non-target metabolomics technology. Results: In this study, WBO treatment reduced body weight gain, fat and lipid accumulation, and ameliorated hepatic steatosis and inflammation. WBO treatment increased the relative abundance of Romboutsia and Allobaculum and decreased that of Candidatus_Saccharimonas, Alloprevotella, Rikenellaceae_RC9_gut_group, Alistipes, Parabacteroides, UCG-005, Helicobacter, Colidextribacter, and Parasutterella compared with the M group. A total of 22 liver metabolites were significantly altered by WBO treatment, which were mainly involved in taurine and hypotaurine metabolism, nicotinate and nicotunamide metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and ether lipid metabolism. Conclusions: WBO alleviated body weight gain and fat/lipid accumulation in HFD-induced obese rats, which may be related to altered gut microbiota and liver metabolites. [ABSTRACT FROM AUTHOR]

Background: Acute compartment syndrome(ACS) is a perilous consequence of trauma. Acute compartment syndrome's precise cause is yet unknown. We performed studies to confirm that acute compartment syndrome can be relieved by suppressing ferroptosis and activating the Nrf2/Hmox1 pathway. Methods: We generated an ACS rat model and we conducted next-generation sequencing(NGS) of skeletal muscle tissue and identified differentially expressed target genes. Ultimately, we performed in vivo experiments to validate the presence of ferroptosis and the Nrf2/Hmox1 pathway in ACS rats. After the minocycline intervention, the drug was evaluated for its effects on ACS by examining changes associated with ferroptosis. Results: The bioinformatics analysis identified that the genetic changes in the disease were mostly focused on ferroptosis, with noticeable modifications in Nrf2/Hmox1. Based on the in vivo results, it was observed that ACS rats exhibited significantly elevated levels of ferroptosis compared to the control rats. The suppression of the Nrf2/Hmox1 pathway mediated by minocycline improves outcomes in ACS and reduces tissue damage after intervention. Conclusion: Minocycline hinders ferroptosis via stimulating the Nrf2/Hmox1 pathway, which slows down the advancement of acute compartment syndrome. [ABSTRACT FROM AUTHOR]

Background: Tetrapleura tetraptera, a widely used medicinal plant in West Africa, has been traditionally employed for various ailments. Despite its folkloric significance, scientific validation of its safety and potential neuroactive properties remains limited. Objectives: This study aimed to investigate the acute and subchronic toxicity of Tetrapleura tetraptera hot water extract (HWETTF) in rats and to elucidate its phytochemical composition. Methods: Acute oral toxicity was assessed in mice using the OECD guideline 423, while a 14-day repeat-dose toxicity study was conducted in rats. The phytochemical analysis included HPLC, FT-IR, and GC–MS. Results: HWETTF exhibited no significant toxicity in acute or subchronic studies, even at high doses. Phytochemical analysis revealed a diverse array of compounds, including those with potential GABAergic and CNS depressant activities. Conclusion: Tetrapleura tetraptera demonstrated a favourable safety profile in rodents and possesses a rich phytochemical composition. Further research is warranted to explore its potential neuroactive properties and develop therapeutic applications. [ABSTRACT FROM AUTHOR]

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal treatment of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose or single dose of EVs. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work at the tested dose and frequency, and that a single cumulative dose of EVs further improves the neurological function recovered during handling. These results show the importance of rehabilitation in combination with other treatments such as EVs, and highlight how extensive behavioral testing might influence functional recovery after stroke. [ABSTRACT FROM AUTHOR]

Purpose: Cumulating evidence supports the close association between periodontal diseases, neuroinflammation and neurodegenerative pathologies, except for peri-implantitis (PI). Thus, this study explored the association between experimental PI and neuropathological changes in the rat brain. Materials and methods: After bilateral first molars extraction, experimental PI was induced at titanium implants placed in the maxillae by lipopolysaccharide injections and ligature placement. Following 28-weeks of disease progression, the maxillae and brains were retrieved from 6 rats. Healthy brains from 3 rats were used as control. Brains were analyzed by immunohistochemistry to detect signs of neuroinflammation (interleukin (IL)-6 and tumor necrosis factor (TNF)-α)), microglial activation (IBA-1) and astrogliosis (GFAP). To explore signs of neurodegeneration, hematoxylin/eosin and Nissl stainings were used. Also, four different antibodies against amyloid beta (Aβ 1–42) were tested. Results: Chronic PI lesions showed peri-implant bone resorption accompanied by large inflammatory infiltrates. IL-6+ and TNF-α+ cells were found within the CA1 and Dentate Gyrus regions of the hippocampus of the PI-affected group, while almost no immune-positivity was detected in the control (p < 0.05). Detection of activated GFAP+ microglia and IBA-1+ astrocytes surface were significantly higher at the CA areas, and cerebral cortex of the PI-affected group, in comparison with control (p < 0.05). Shrunk neurons with pyknotic nuclei were inconsistently found among the PI-affected group, and these were almost not detected in control. No positive Aβ reactivity was detected in any of the samples. Conclusion: Chronic experimental PI lesions led to an increased detection of IL-6 and TNF-α, GFAP+ microgliosis and IBA-1+ astrocytosis, and in some cases, neurodegeneration, in the rat brain. [ABSTRACT FROM AUTHOR]

Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague–Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), a major cause of death and disability among young people, leads to significant public health and economic challenges. Despite its frequency, treatment options remain largely unsuitable. However, examination of the blood–brain barrier (BBB) can assist with understanding the mechanisms and dynamics of brain dysfunction, which affects TBI sufferers secondarily to the injury. Here, we present a rat model of TBI focused on two standard BBB assessment markers, high- and low-molecular-weight complexes, in order to understand BBB disruption. In addition, we tested a new technique to evaluate BBB disruption on a single brain set, comparing the new technique with neuroimaging. A total of 100 Sprague–Dawley rats were separated into the following five groups: naive rats (n = 20 rats), control rats with administration (n = 20 rats), and TBI rats (n = 60 rats). Rats were assessed at different time points after the injury to measure BBB disruption using low- and high-molecular-weight complexes. Neurological severity score was evaluated at baseline and at 24 h following TBI. During the neurological exam after TBI, the rats were scanned with magnetic resonance imaging and euthanized for assessment of the BBB permeability. We found that the two markers displayed different examples of BBB disruption in the same set of brain tissues over the period of a week. Our innovative protocol for assessing BBB permeability using high- and low-molecular-weight complexes markers in a single brain set showed appropriate results. Additionally, we determined the lower limit of sensitivity, therefore demonstrating the accuracy of this method. [ABSTRACT FROM AUTHOR]

A strict correlation among proximal tubule epithelial cell dysfunction, proteinuria, and modulation of the Renin-Angiotensin System and Kalikrein-Kinin System are crucial factors in the pathogenesis of Acute Kidney Injury (AKI). In this study, we investigated the potential protective effect of preconditioning by moderate-intensity aerobic exercise on gentamicin-induced AKI. Male Wistar rats were submitted to a moderate-intensity treadmill exercise protocol for 8 weeks, and then injected with 80 mg/kg/day s.c. gentamicin for 5 consecutive days. Four groups were generated: 1) NT+SAL (control); 2) NT+AKI (non-trained with AKI); 3) T+SAL (trained); and 4) T+AKI (trained with AKI). The NT+AKI group presented: 1) impairment in glomerular function parameters; 2) increased fractional excretion of Na+ , K+ , and water; 4) proteinuria and increased urinary γ-glutamyl transferase activity (a marker of tubular injury) accompanied by acute tubular necrosis; 5) an increased renal angiotensin-converting enzyme and bradykinin B1 receptor mRNA expression. Interestingly, the preconditioning by moderate-intensity aerobic exercise attenuated all alterations observed in gentamicin-induced AKI (T+AKI group). Taken together, our results show that the preconditioning by moderate-intensity aerobic exercise ameliorates the development of gentamicin-induced AKI. Our findings help to expand the current knowledge regarding the effect of physical exercise on kidneys during physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

Background: Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans, such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in West Africa are available. Our previous findings from a study investigating emerging pathogens in two localities in Mali has determined the prevalence of pathogens in small mammals (rodents and insectivores). We used the data collected from this small mammal population with different eco-climatic characteristics to test hypothesis that small mammal distribution in different eco-climatic settings could explain the diversity and frequency of pathogens they carry. Methods: Sessions of trapping were carried out in December 2016 in Faladjè and Bougouni with "Besançon tous services" (BTS) wire mesh traps baited with peanut butter and/or onion. All animals captured were identified morphologically. Results: Out of 123 small rodents and insectivores captured over 674 trap-nights, 75 (60.97%) were from Faladjè and 48 (39.02%) from Bougouni. Of these, six species of small rodents belonged to the family Muridae (Mastomys erythroleucus, Mastomys natalensis, Rattus rattus, Praomys daltoni, Gerbilliscus gambianus, Taterillus gracilis) and two species of insectivores associated with the genus Crocidura spp. belonged to the family Soricidae and Erinaceidae (Crocidura cf olivieri and Atelerix cf albiventris), respectively. There is low species diversity within these two areas, but the variation in relative abundance is significant (binomial test, p ˂ 0.05) between Faladjè and Bougouni. Mastomys erythroleucus was the most dominant species (57.33%, 43/75) in Faladjè, while R. rattus dominated (37.5%,18/48) in Bougouni. Conclusions: These two species of small mammals potentially involved in the transmission of bacteria, parasites and pathogenic viruses to humans are differently present in two distinct eco-climatic areas in Mali. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact of BNC on immune function, the intestinal microbiome, intestinal barrier integrity, and allergic sensitization in subacute experiments on rats. Male Wistar rats received BNC with a diet for eight weeks in a dose range of 1–100 mg/kg of body weight. The measurements of serum levels of cytokines, adipokines, iFABP2, indicators of cellular immunity, composition of the intestinal microbiome, and a histological study of the ileal mucosa were performed. In a separate four-week experiment on a model of systemic anaphylaxis to food antigen, BNC at a dose of 100 mg/kg of body weight did not increase the severity of the reaction or change the response of IgG antibodies. Based on dose–response effects on immune function, the non-observed adverse effect level for BNC was less than 100 mg/kg of body weight per day. The effects of BNC on the gut microbiome and the intestinal mucosal barrier were not dose-dependent. Data on the possible presence of prebiotic effects in BNC have been obtained. [ABSTRACT FROM AUTHOR]

Background: Ovarian cryopreservation is a promising technique despite being hindered by damage from freezing and thawing. Melatonin can mitigate this outcome. Objective: This study aimed to evaluate the effect of melatonin on the follicular dynamics of ovarian tissue in a cryopreserved cell culture. Methods: Three-month-old adult female Wistar rats (n = 24) weighing approximately 250 g were oophorectomized and divided into two groups (n = 12): the control group (CG) and the melatonin group (MG). In the CG, slow cryopreservation was performed according to the standard protocol with Medium M2 and dimethyl sulfoxide (DMSO). In MG, melatonin diluted in ethyl alcohol vehicle at a concentration of 0.1 μm was added to the culture medium. In both groups, the ovaries were cryopreserved by slow freezing and kept in liquid nitrogen for 24 h. Subsequently, after thawing, the ovaries were reimplanted in the retroperitoneum, one on each side of the great vessels (inferior vena cava and aorta). After 30 days, the animals were euthanized during the diestrus phase; then, the grafts were removed and processed for histomorphometric and immunohistochemical analyses, whereas the blood was subjected to biochemical analysis. Student's t test was used to assess the difference between the groups. Results: The FSH levels in MG (83.79 ± 32.37) were lower than those in CG (120.52 ± 36.59), p = 0.03. The FSH/AMH ratios were also lower in MG (3.53 ± 1.13) than in CG (6.52 ± 2.85), p = 0.001. The SOD2 immunoexpression was higher in MG than in CG regarding all parameters except for the degenerated follicles (follicular cells and internal thecal cells): CG (16.80 ± 4.80 [13.36–20.24]) and MG (14.91 ± 4.04 [12.01–17.79]) p = 0.351. Statistically, the difference in intact follicles (theca + interstitium) between CG (6.60 ± 2.59 [4.75–8.45]) and MG (9.31 ± 3.09 [7.09–11.51]) was significant (p = 0.049), with a small difference in the expression of regular antral follicles. Conclusions: Melatonin can improve the quality of cryopreserved tissues, as evidenced in this study, and the evaluation of cryopreserved ovarian grafts, as shown in the melatonin group with better hormonal parameters and greater immunohistochemical expression of the SOD2 antioxidant. Thus, damage is reduced during cryopreservation and transplantation is improved. [ABSTRACT FROM AUTHOR]