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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]

Decreased sperm quality has been reported in men with different clinical conditions, including aging and hypertension. In the male reproductive tract, it has been suggested that the α1-adrenergic receptor influences fertility and spermatogenesis, and important functions are also attributed to the renin–angiotensin axis, such as regulation of steroidogenesis, spermatogenesis, and sperm function. Previously, our group demonstrated impaired testicular vasomotion via α1-adrenergic receptor activation and increased hypoxia-related proteins in the testes of spontaneously hypertensive rats (SHRs) compared to Wistar normotensive rats. In this study, we aimed to investigate the effect of hypertension and inhibition of systemic α1-adrenergic receptor or angiotensin II AT1 receptor on sperm quality, sperm functional characteristics, and testicular microcirculation in rats from three different ages: young (8–10-week-old), adult (20–24-week-old) and older adult (60–66-week-old). We observed higher blood pressure in SHRs of all ages compared to age-matched Wistar rats. Lower blood pressure was observed either in prazosin or losartan-treated adult or aged SHRs. Additionally, lower sperm concentration, impaired motility and higher acrosome damage were demonstrated in SHRs. Prazosin treatment alleviated the effects of hypertension on sperm concentration and motility but not acrosome damage. Higher vasomotion was noticed in testicular blood vessels of adult and aged SHRs compared to Wistar rats. Thus, impaired sperm quality was observed in SHRs of different ages and was improved by sub-chronically blocking the α1-adrenergic receptor. [ABSTRACT FROM AUTHOR]

The transverse dimensions of internasal and nasopremaxillary sutures in rats were assessed at different ages and following different dietary functional demands.Eighty‐four male Wistar rats were divided into two groups fed either a hard or a soft diet from 4 weeks of age, and sacrificed at 4 weeks (baseline: n = 12),16 weeks (n = 24), 26 weeks (n = 24), or 38 weeks (n = 24) of age. High‐resolution micro‐computed tomograms of the internasal and left nasopremaxillary sutures were obtained with 10 µm voxel size and 5 × 5 mm field of view. The endocranial and ectocranial suture widths, the mean suture width, and the suture height were measured. Linear regression analysis was used to estimate the effects of age and type of diet on suture dimensions. Internasal and nasopremaxillary suture dimensions were influenced by age, with a generally lower width and a larger height in the older animal. Regarding diet consistency, internasal suture widths were on average larger in the hard‐diet group (e.g., mean suture width 43 µm in the hard‐ versus 30 µm in the soft‐diet group at 26 weeks). In conclusion, the internasal and nasopremaxillary sutures tend to become narrower with age, while being influenced by masticatory functional demands. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acupotomy is effective in the treatment of knee osteoarthritis, but its mechanism is not very clear. OBJECTIVE: To observe the effect of acupotomy on the apoptosis of knee chondrocytes in knee osteoarthritis rats based on osteoclast associated receptor (OSCAR)-tumor necrosis factor-associated apoptosis-inducing ligand (TRAIL)-osteoprotetin (OPG) pathway. METHODS: Twenty-seven Sprague-Dawley rats were randomly divided into normal group (n=9), model group (n=9) and acupotomy group (n=9). Rats in the normal group were routinely housed without any treatment. Animal models of knee osteoarthritis were established by knee injection of papain. Acupotomy intervention was performed 1 week after modeling, once a week for a total of three times. Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION: The Lequesne MG behavioral scores of rats in the model group were elevated compared with the normal group (P < 0.01), while the Lequesne MG behavioral scores of rats in the acupotomy group were decreased compared with the model group (P < 0.01). Hematoxylin-eosin staining results showed that compared with the normal group, the cartilage surface of the rat’s knee joints in the model group was worn and uneven and the chondrocytes were swollen, ruptured, reduced in number, and arranged disorderly; while the cartilage surface of the rat’s knee joints in the acupotomy group was relatively smooth, and the chondrocytes were high in number and arranged in an orderly manner, with the structure basically clear. Immunohistochemical staining results showed that compared with the normal group, the positive expressions of OSCAR and TRAIL were increased in the model group (P < 0.01), while the positive expression of OPG was decreased (P < 0.01). Compared with the model group, the positive expressions of OSCAR and TRAIL in the acupotomy group were decreased (P < 0.01), while the positive expression of OPG was increased (P < 0.01). TUNEL staining results showed that compared with the normal group, the number of apoptotic cells in the model group were increased (P < 0.01); compared with the model group, the number of apoptotic cells in the acupotomy group decreased (P < 0.01). RT-qRCR and western blot results showed that compared with the normal group, the protein expressions of OSCAR, TRAIL and Bax in the model group were increased (P < 0.01), and the protein expressions of OPG and Bcl-2 were decreased (P < 0.01); compared with the model group, the protein expressions of OSCAR, TRAIL, and Bax in the acupotomy group were decreased (P < 0.01), and the protein expressions of OPG and Bcl-2 were increased (P < 0.01). To conclude, acupotomy can reduce cartilage injury of the knee joint in rats with knee osteoarthritis, which may be related to the blockage of mitochondrial pathway apoptotic signaling release by the OSCAR-TRAIL-OPG pathway. [ABSTRACT FROM AUTHOR]

How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole‐brain functional magnetic resonance imaging (fMRI) are conducted in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. The results reveal that upon the loss of consciousness (LOC), there is a sharp increase in low‐frequency power of the electrophysiological signal. Additionally, fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus‐thalamus‐mPFC pathway preceding LOC. These data suggest that LOC may be triggered by sequential activities in the hippocampus, thalamus, and mPFC, while wide‐spread activity increases in other cortical regions commonly observed during anesthesia‐induced unconsciousness may be a consequence, rather than a cause of LOC. Taken together, the study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering insight into the systems‐level neural mechanisms underpinning LOC. [ABSTRACT FROM AUTHOR]

Resveratrol, which is thought to have a preventive effect on the formation of different types of cancer, is abundant in grapes and other foods. Resveratrol has been shown to have anti‐cancer effects by in vitro andin vivo studies, however this is the first time its effect on atypical acinar cell foci (AACF), known as precursor forms of pancreatic carcinoma, has been experimentally investigated. Male Sprague Dawley rats, each consisting of 5 experimental groups (Cont, AzCont, AzRes10, AzRes15, and AzRes20), 10 of which were 14 days old, were used in the study. In the azaserine groups (AzCont, AzRes10, AzRes15, and AzRes20), it was investigated how the development of Atypical Cell Foci (AACF) resulting from intraperitoneal injection (i.p.) of azaserine (30 mg/kg bw) in 14‐day‐old rats was affected by dietary restoration. Male rats in the resveratrol group (AzRes10, AzRes15, and AzRes20) were fed diets containing 10%, 15%, or 20% mmol resveratrol for an 8‐month experimental period 1 week after the last azaserine injection. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One‐way analysis of variance (ANOVA) non‐parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and control groups. The AACF load in the azaserine group (AzCont) compared to the control group (Cont) was found to be statistically significant in all categories (p < 0.05). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont) (p < 0.05). In addition, the calculated estimated mean AACF diameter (mm) in the AzRes10 and AzRes15 groups, in the AzRes15 group the calculated estimated mean AACF number in the whole organ and the calculated average AACF number per unit area were found to be statistically significant compared to the azaserine control group (AzCont) (p < 0.05). According to the results of our study, it has been shown that atypical acinar cell foci (AACF) formed in the exocrine pancreas of rats with azaserine can be reduced by a diet containing resveratrol. It was determined that the tumor burden decreased statistically significantly (p ≤ 0.05) in resveratrol‐treated rats. Accordingly, it is thought that the inhibitory effects of resveratrol may contribute to studies that reduce the occurrence of pancreatic cancer. [ABSTRACT FROM AUTHOR]

• Female rats show faster and more effective trauma extinction than males. • Shock reminder reactivates fear memory only in male rats. • Ultrasonic vocalizations mirror fear behavior profiles in both sexes. • Study underscores the need for female inclusion in preclinical PTSD research. Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric condition arising from traumatic experiences, marked by abnormal fear memories. Despite women are twice as likely as men to develop PTSD, the biological mechanisms underlying this disparity remain inadequately explored, particularly in preclinical studies involving female subjects. Previous research shows that female rats exhibit active fear responses, while males display passive behaviors. Additionally, sex differences in ultrasonic vocalizations (USVs) during fear conditioning have been observed, indicating varying emotional responses. Here, we validated a traumatic stress model consisting of footshock exposure paired with social isolation − originally developed in male rats − on females for the first time, focusing on sex differences in fear memory expression, retention and extinction. Our findings reveal that only during trauma exposure, males predominantly exhibited passive responses, whereas females demonstrated more active responses, despite both sexes emitting similar numbers of alarm USVs. Females also showed lower levels of freezing and USV emissions throughout extinction sessions and displayed a higher extinction rate compared to males. Notably, only males displayed a conditioned fear response when triggered by a single mild stressor. These findings highlight sex differences in trauma responses and fear memory processes. The study emphasizes the importance of incorporating 22-kHz USV evaluations along with other behavioral metrics for a comprehensive understanding of fear memory. This research contributes to the existing literature on traumatic stress models as well as underscores the necessity of including female subjects in preclinical studies to better inform treatment and prevention strategies tailored to both sexes. [ABSTRACT FROM AUTHOR]

Pharmaceutical companies routinely screen compounds for hemodynamics related safety risk. In vitro secondary pharmacology is initially used to prioritize compounds while in vivo studies are later used to quantify and translate risk to humans. This strategy has shown limitations but could be improved via the incorporation of molecular findings in the animal-based toxicological risk assessment. The aim of this study is to develop a mathematical model for rat and dog species that can integrate secondary pharmacology modulation and therefore facilitate the overall pre-clinical safety translation assessment. Following an extensive literature review, we built two separate models recapitulating known regulation processes in dogs and rats. We describe the resulting models and show that they can reproduce a variety of interventions in both species. We also show that the models can incorporate the mechanisms of action of a pre-defined list of 50 pharmacological mechanisms whose modulation predict results consistent with known pharmacology. In conclusion, a mechanistic model of hemodynamics regulations in rat and dog species has been developed to support mechanism-based safety translation in drug discovery and development. [ABSTRACT FROM AUTHOR]

BACKGROUND: At present, bone marrow mesenchymal stem cells are the main seed cells used in cell therapy for the treatment of intervertebral disc degeneration. However, the use of bone marrow mesenchymal stem cells as seed cells for the regeneration of fibrous rings is at risk of heterotopic ossification and teratoma at the repair site. Therefore, it is of great economic and social significance to find a new kind of seed cells for tissue engineering of annulus fibrosus for the treatment of intervertebral disc degeneration. OBJECTIVE: To isolate and purify rat annulus fibrosus-derived stem cells by adherent method combined with fibronectin differential adhesion screening method, and to observe its purification effect and biological characteristics. METHODS: Annulus fibrosus tissue was obtained from a SD rat intervertebral disc. Primary annulus fibrosus-derived stem cells were obtained by the mechanical-enzymatic digestion method. Annulus fibronectin differential adhesion method was used to purify annulus fibrosus-derived stem cells. Morphological changes and proliferation of cells were observed through a microscope. The expression levels of stem cell markers were detected by immunofluorescence technique and qPCR. The screened cells were subjected to multi-lineage cell differentiation and characteristic gene detection. RESULTS AND CONCLUSION: (1) The purified cells grew well, and most of them were angular and star-shaped multi-process cells, which had good proliferation ability. (2) Cells were positive for cell membrane surface antigens CD73, CD90 and CD105, while negative for CD45 and CD34. (3) After specific induction, cells could successfully differentiate into osteoblasts, chondroblasts and lipoblasts. (4) Collagen-I, Runx-2 after osteogenic induction, Collagen II, Sox-9 after chondrogenic induction, and PPAR -γ and LPL after lipogenic induction were highly expressed in cells, and the difference was significant compared with that before induction (P < 0.05). (5) These findings confirm that the adherent method combined with fibronectin differential adhesion method is effective enough to screen, isolate and purify rat annulus fibrosus-derived stem cells, and has good cell biological properties, good proliferation ability and multiple differentiation potential. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. Methods: We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. Results: GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). Conclusion: The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders. [ABSTRACT FROM AUTHOR]

Obesity stands out as one of the most significant health problems in the modern world. The prevalence of high‐calorie diets (HCDs) globally exacerbates this condition. Throughout history, plants and plant‐derived food products have been utilized for medicinal purposes, demonstrating their efficacy in the treatment and prevention of various diseases. Gundelia tournefortii (GT), a plant of interest, is known to possess beneficial properties. Hence, this study aimed to investigate the immunotoxic and neurotoxic effects of two different doses of GT plant extract on the liver, brain, and heart tissues of obese rats. For this purpose, Wistar male rats were divided into four groups: “CG,” “HCDG,” “HCDGUN1,” and “HCDGUN2” At the conclusion of the study, adenosine deaminase (ADA) and myeloperoxidase (MPO) activities, as well as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) biomarkers, were evaluated in the liver, heart, and brain tissues. The study results revealed a statistically significant increase in ADA and MPO activities in the HCDG group compared to the CG group, alongside a significant decrease in the HCDGUN groups compared to the HCDG group. Regarding AChE and BChE activities, a statistically significant decrease was observed in the HCDG group compared to the CG group, whereas an increase was noted in the HCDGUN groups relative to the HCDG group, with the latter approaching values similar to those of the control group. In conclusion, the intake of GT plant extract exhibited positive effects on the immunotoxic and neurotoxic effects induced by HCD in rats with an experimental obesity model, as evidenced by tissue biomarker evaluations. [ABSTRACT FROM AUTHOR]

In the brains of adult rodents, the cells arising in the subventricular zone of the lateral ventricles maintain the ability to divide when migrating to the olfactory bulb along the rostral migratory stream (RMS). Dividing cells in the RMS are most frequently revealed through immunohistochemical detection of an exogenous marker of proliferation, 5-Bromo-2-deoxyuridine (BrdU), which incorporates into DNA during the S-phase of mitosis. The more recently recognized antigen Ki-67 (also known as Kiel-67 and MKI67), an endogenous protein expressed in nuclei at all stages of mitosis, is also used for proliferation detection. BrdU and Ki-67 are often used as alternative methods, but they have not previously been compared in the RMS. We analyzed the numbers and distribution of cells labeled either with BrdU or Ki-67 within the RMS of adult rats. The first group of animals received a single i.p. dose of BrdU. In the second group, dividing cells were visualized by Ki-67 immunohistochemistry. Some sections from brains of BrdU-treated rats were also immunostained for Ki-67. Labeled cells were counted in the three anatomical parts of the RMS (vertical arm, elbow and horizontal arm) using a method for unbiased estimation of cell density. The distribution of proliferating cells was similar for both markers. Most BrdU and Ki-67 positive cells were located in the vertical arm and in the elbow, but a caudo-rostral reduction in cell divisions was more evident with Ki-67 labeling. The number of Ki-67 positive cells significantly exceeded the number of BrdU positive cells in all parts of the RMS. Our results indicate that BrdU and Ki-67 are not interchangeable markers for evaluation of proliferative activity in the RMS. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1β), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1β). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene. [ABSTRACT FROM AUTHOR]

Depression is a persistent illness affecting health, behavior, and performance in life. Worldwide morbidity and mortality are caused by depression. The current study intended to explore fumaric acid's potential protective effect against ciprofloxacin-provoked depression in rats and to determine its mechanism of action by studying its antioxidant and anti-inflammatory properties. Five groups of male Wistar albino rats (120 g ± 20) were employed; the first group received physiological saline, the second group received fumaric acid (80 mg/kg/day; orally) for 3 weeks, the third group was administered ciprofloxacin (50 mg/kg/day; orally) for 3 weeks to induce depression, the fourth group received a daily low dose of fumaric acid (40 mg/kg; orally) concurrent with ciprofloxacin and the fifth group received a daily high dose of fumaric acid (80 mg/kg; orally) concurrent with ciprofloxacin for 21 days. Then, behavior tests, oxidative stress indicators, inflammatory biomarkers, neurotransmitters, p190 Rho GTP, and histopathological examination were evaluated. Ciprofloxacin significantly increased oxidative stress biomarkers [malondialdehyde (MDA) as a lipid peroxidation marker and nitric oxide (NO)] and biomarkers of inflammation [Toll-like receptor4 (TLR-4)] and tumor necrosis factor-alpha (TNF-α) with reduction in the activities of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and catalase as well as brain contents of neurotransmitters and P190-RHO GTP. In addition, it causes necrosis of neurons and mild loss of Purkinje cells. Fumaric acid eliminates these effects of ciprofloxacin. Fumaric acid has beneficial effects as an anti-depressant in Wistar albino male rats that received ciprofloxacin. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase. [ABSTRACT FROM AUTHOR]

The current study explored a free‐operant analogue of discrete‐trial procedures to study the effects of amount and delay of reinforcement on choice and response rate. Rats responded on a multiple variable‐interval (VI) 45‐s, 45‐s schedule, with interspersed choice probe trials. Comparison of relative response rates and percentage of choice revealed some discrepancies between the free‐operant analogue and discrete‐trial procedures. Amount of reward controlled choice behavior when the ratios of delays were similar. When reward delays were more discrepant, delay length controlled choice behavior. Whereas the percentage of choice was larger for the larger magnitude reward, the relative rate of response for the larger magnitude was less than.50. In contrast, when the percentage of choice generally fell to below 50% (with large amount and large delay differences between alternatives), relative response rate indicated a preference for the larger amount alternative. This study shows the feasibility and utility of a free‐operant analogue of discrete‐choice studies that could be used to develop an analysis of preference. [ABSTRACT FROM AUTHOR]

The potential of silver-containing hydroxyapatite (Ag-HA) coatings to prevent orthopaedic implant-associated infection was explored previously; however, the resistance of Ag-HA coatings to late-onset orthopaedic infections is unknown. This study aimed to evaluate the long-term Ag+ elution and antibacterial properties of the Ag-HA coatings through in vitro and in vivo experiments. Ag-HA-coated disc specimens were immersed in fetal bovine serum (FBS) for six months. Ag concentration was measured over time using inductively coupled plasma-mass spectrometry to evaluate Ag release. The hydroxyapatite (HA)- or Ag-HA-coated disc specimens were immersed in FBS for 3 months to elute Ag+ for in vitro experiments. Methicillin-resistant Staphylococcus aureus (MRSA) suspensions were inoculated onto each disc; after 48 h, the number of colonies and the biofilm volume were measured. HA- or Ag-HA-coated disc specimens were inserted under the skin of Sprague-Dawley rats for three months for in vivo experiments. In in vivo experiment 1, specimens were inoculated with MRSA and the number of colonies was counted after 48 h. In in vivo experiment 2, the specimens were inoculated with bioluminescent S. aureus Xen36 cells, and bioluminescence was measured using an in vivo imaging system. The Ag-HA-coated disc specimens continued to elute Ag+ after six months. The biofilm volume in the Ag-HA group was lower than in the HA group. In in vitro and in vivo experiment 1, the bacterial counts in the Ag-HA group were lower than those in the HA group. In in vivo experiment 2, the bioluminescence in the Ag-HA group was lower than that in the HA group on days 1–7 after inoculation. The Ag-HA-coated discs continued to elute Ag+ for a long period and exhibited antibacterial activity and inhibition of biofilm formation against S. aureus. The Ag-HA coatings have the potential to reduce late-onset orthopaedic implant-associated infections. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine the single and combined antidiabetic activity and side effects of the retinoid X receptor agonist bexarotene and the thioredoxin-interacting protein inhibitor and peroxisome proliferator-activated receptor γ and AMP-activated protein kinase activator icariin. Methods The rats were grouped as healthy (control), diabetes, diabetes + bexarotene (20 mg/kg), diabetes + icariin (60 mg/kg), diabetes + bexarotene (10 mg/kg) + icariin (30 mg/kg) low-dose combination and diabetes + bexarotene (20 mg/kg) + icariin (60 mg/kg) high-dose combination groups. Key findings Icariin treatment led to a significant reduction in glucose levels compared with the diabetes control group, a remarkable outcome observed 45 days after the initial application. HbA1c levels of the icariin and low-dose combination treatment groups were significantly lower than in the diabetes group. Notably, icariin treatment also significantly elevated HOMA-β levels, which is indicative of improved β-cell function. Icariin significantly decreased glucose levels at 30 and 120 min in the oral glucose tolerance test. Moreover, it ameliorated hepatocyte degeneration, hepatic cord dissociation, congestion, mononuclear cell infiltration in the liver, and degeneration in the pancreas. Conclusions Icariin treatment exhibited robust antidiabetic effects with fewer side effects than other treatment options in this study. In future studies, long-term and varying doses of icariin will contribute to the development of novel antidiabetic drugs. [ABSTRACT FROM AUTHOR]

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial (MT) Chromosomes. We genotyped the Y and MT Chromosomes in heterogeneous stock (HS) rats (Rattus norvegicus), an outbred population created from 8 inbred strains. We identified 8 distinct Y and 4 distinct MT Chromosomes among the 8 founders. However, only 2 types of each nonrecombinant chromosome were observed in our modern HS rat population (generations 81–97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and MT Chromosomes were strongly associated with the expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern HS rats there are no Y and MT Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and MT Chromosomes that do not appear in modern HS rats, nor do they address effects that may exist in other rat populations, or in other species. [ABSTRACT FROM AUTHOR]

This experimental study was performed to evaluate the alterations in the expression of a few subunits composing glutamate AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartate) receptors in the hippocampal cells of Wistar rats in response to long-term fluoride (F-) exposure. The animals were given water with background 0.4 (control), 5, 20, and 50 ppm F- (as NaF) for 12 months. The cognitive capacities of rats were examined by novel object recognition (NOR), Y-maze test, and Morris water maze tests. RT-qPCR and Western blotting techniques were used to evaluate the expression of different AMPA and NMDA subunits at transcriptional and translational levels, respectively. Long-term F- poisoning disturbed the formation of hippocampus-dependent working spatial and long-term non-spatial memory. The expression of Gria1, Gria2, and Gria3 genes encoding different subunits of AMPA receptors were comparable in hippocampi of control and F--exposed animals, although the levels of both Grin2a and Grin2b mRNA increased. Long-term F- intake enhanced the ratio of phospho-GluA1/total-GluA1 proteins in subcellular fraction enriched with cytosolic proteins, while decreased content of GluA2 but elevated level of GluA3 were observed in subcellular fraction enriched with membrane proteins. Such changes were accompanied by increased phosphorylation of GluN2A and GluN2B subunits, higher ratios of GluN2A/GluN1 and GluN2B/GluN1 proteins in the cytosol, and GluN2A/GluN2B ratio in membranes. These changes indicate the predominance of Ca2+-permeable AMPARs in membranes and a shift between different NMDARs subunits in hippocampal cells of F--exposed rats, which is typical for neurodegeneration and can at least partially underly the observed disturbances in cognitive capacities of animals. [ABSTRACT FROM AUTHOR]

Background: After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated. Aims: To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study. Materials and methods: Forty‐four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out. Results: There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram). Conclusion: Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation. [ABSTRACT FROM AUTHOR]

• Oral acute and subchronic toxicities of Ziziphus jujuba were evaluated in rats. • No major signs of toxicity were observed in the liver and kidney. • Repeated oral administration is safe at up to 1000 mg kg-1 bw over a 28-day period. • Ziziphus jujuba bark is relatively safe at lower dose. Ziziphus jujuba is a medicinal botanical with various pharmacological properties against cardiovascular diseases, respiratory system diseases, gastrointestinal problems, dysentery, and diarrhea. Despite its exhaustive use for medicinal aims, no study has yet been directed to evaluate this plant's potentially toxic profile. The present work focused on the acute and subchronic toxicity of Z. jujuba bark extract. The acute oral toxicity was performed using the OECD guideline 425; Z. jujuba bark extract was administered to female rats at a single dose of 5000 mg kg-1 body weight. The subchronic acute oral toxicity was carried out according to OECD guidelines 407; Z. jujuba bark extract was administered to male and female rats at doses of 250, 500, and 1000 mg kg-1 bw; after 28 days of Z. jujuba bark extract daily administration, the animals were sacrificed. Hematological parameters, serum and urinary biochemical parameters, and histological sections of the liver and kidneys were assessed. Administration of the single-oral dose of Z. jujuba bark methanolic extract did not cause any death in rats, and the LD 50 was found to be greater than 5000 mg kg-1 bw. The repeated administration of Z. jujuba bark methanolic extract at 250, 500, and 1000 mg kg-1 bw did not induce any significant perturbation of the white blood cells, lymphocytes, red blood cells, hemoglobin, hematocrit, and platelets in rats as compared to the controls. For the lipid parameters, namely triglycerides and cholesterol, no significant difference was recorded between the profiles of the treated and untreated groups of animals. Likewise, we registered non-significant changes in renal parameters such as creatinine, urea, and proteins; this was confirmed by the histological sections, which showed a normal kidney structure. Besides, we did not observe any significant modification in the values of liver parameters, ALT and AST. This finding was further confirmed by the histological examination of the liver, which revealed the organ's normal structure. Finally, for single-oral administration, Z. jujuba bark extract is almost non-toxic. For repeated oral administration, Z. jujuba bark extract is safe at doses up to 1000 mg kg-1 bw over a 28-day period. [ABSTRACT FROM AUTHOR]

ABSTRACT Honey has a rich history of treating gastrointestinal diseases due to its diverse bioactive compounds. This study evaluated the protective effects of select Iranian honeys against cold water immersion stress (CWIS)‐induced ulcers in rats. Forty male Wistar rats (250–280 g) were randomly assigned to eight groups (n = 5): control, CWIS, and groups treated with strong (eucalyptus, Annaab, and Jangale) and weak honeys (Chand Giah, Sumaq, Gaz) + CWIS. Honey selection was based on antioxidant capacity, phenolic content, and protein concentration. Rats received 20% honey in water (1 mL/kg) orally twice daily for 14 days; controls received water. After a 24‐h fast, rats underwent 3‐h CWIS to induce ulcers. Serum samples were analyzed for malondialdehyde (MDA), total antioxidant capacity (TAC), thiol groups, tumor necrosis factor alpha (TNF‐α), and interleukin 6 (IL‐6) levels. Stomachs were assessed for ulcer severity (gastric ulcer index), gastric juice volume, and histopathological changes. Honey types were categorized as strong (eucalyptus, Annaab, and Jangale) or weak (Chand Giah, Sumaq, and Gaz) based on total phenolic content, antioxidant effects (FRAP and DPPH), and protein levels. Ulcer group showed significant increases in MDA (64%) and TNF‐α and IL‐6 levels (98.5% and 111.6%), and decreases in ferric reducing antioxidant power and 2,2‐diphenyl‐1 picrylhydrazyl (FRAP, DPPH, and thiol levels [26%, 14.39%, and 26%]) compared to controls. Strong honey groups exhibited 50% lower gastric ulcer index compared to weak honey groups. This study showed that strong honeys, due to their higher phenolic, total protein, and antioxidant content, offer greater protection against gastric damage and oxidative stress compared to weaker honeys. These results highlight the importance of bioactive compounds in honey's therapeutic properties. Therefore, high‐quality honeys with higher phenolic content can be considered as therapeutic supplements for gastrointestinal disorders, especially those caused by oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Objective(s): Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue. Materials and Methods: In this experimental study, twenty pregnant rats were randomly allocated into control and streptozotocin (STZ)-induced diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of STZ (40 mg/kg/bw) on the 5th day of gestation. At day 19 of gestation, fetal livers were separated and subjected to histological, transmission electron microscopic, and quantitative morphometric examinations. Results: In the GDM group, PAS staining was positive, revealing scattered eosinophilic inclusions in some hepatocytes. Masson trichrome staining was also positive and showed some fibrous tissue as fine fibers in the portal spaces that extended to the central vein. Reticulin staining in the GDM group was focally positive in the areas of fibrosis and the portal spaces. Ultrastructural examination showed pyknotic nuclei, karyolysis, degranulation and vesiculation of the rough endoplasmic reticulum, and degeneration of mitochondria in the GDM group. The morphometric examination demonstrated that the mean area of hepatocytes was significantly lower in the GDM group than in the control group (P<0.05). Moreover, the mean diameter of the central vein and the density of megakaryocytes were significantly higher in the GDM group than in the control group (P<0.05). Conclusion: Uncontrolled mild GDM induced the histological, ultrastructural and morphometric alterations in the fetal liver. [ABSTRACT FROM AUTHOR]

The regulatory role of estrogen receptor beta (ERβ) and the JNK signaling pathway in the effect of high-dose boron on rat splenic lymphocytes has been examined by measuring proliferation, apoptosis, and immune function. The results showed that, compared with the control group, the addition of high-dose boron (40 mmol/L) reduced the proportion of CD3+, CD4+, and CD8+ T lymphocytes, the concentrations of IgG, IL-2, IFN-γ, and IL-4, the proliferation rate of splenic lymphocytes, and the expression levels of PCNA and Bcl-2 mRNA (P < 0.01 or P < 0.05), and increased the apoptosis rate of splenic lymphocytes, caspase-3, and BAX mRNA expression levels (P < 0.01 or P < 0.05). After specific blocking of ERβ, the addition of high-dose boron could not reduce the proportion of CD8+ T lymphocytes, the concentrations of IgG and cytokines IL-2, IFN-γ, and IL-4, the lymphocyte proliferation rate, or PCNA mRNA expression levels, nor could it increase BAX mRNA expression levels. After specific blocking of JNK, the addition of high-dose boron could not increase BAX mRNA expression levels. However, after specific blocking of ERβ and JNK, the addition of high-dose boron could neither reduce the proportion of CD4+ and CD8+ T lymphocytes, the concentrations of IgG and IL-2 (P > 0.05), nor increase caspase-3 and BAX mRNA expression levels (P < 0.01). The results suggest that the ERβ-mediated JNK signaling pathway participates in regulating the effects of high-dose boron on the expression of genes related to the proliferation and apoptosis of rat splenic lymphocytes. [ABSTRACT FROM AUTHOR]

This study aimed to determine the protective role of l‐ascorbic acid in a pregnant rat model of cadmium‐induced toxicity. Cadmium is a toxic heavy metal that can seriously harm placenta and fetus tissue in pregnant women. Forty‐two healthy female Wistar albino rats (250–300 g weight and 14–16 weeks) were randomly distributed into six equal groups (n = 7): control, cadmium 1 mg (CD1), cadmium 5 mg (CD5), ascorbic acid (AA), CD1+AA, CD5+AA. Cadmium was administered to pregnant rats by oral gavage every other day, and/or AA (200 mg) was administered every day. At the end of pregnancy (Day 21), blood, placenta, and fetuses were collected from rats. The results indicated that cadmium‐induced oxidative stress by increasing the level of MDA and by decreasing the levels of GSH, SOD, and CAT activity in the serum of maternal. However, AA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). Cadmium (5 mg/kg) exposure significantly increased creatinine levels compared to AA and CD1+AA groups (p < 0.05). In addition, AA (200 mg/kg) significantly attenuated cadmium‐induced histopathological alteration in the placental and fetal tissues. In conclusion, AA may prevent cadmium toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat tissues and alleviates histopathological changes. [ABSTRACT FROM AUTHOR]

Past studies in animal models have extensively investigated the impact of early life experiences on behavioral development, yet relatively few have specifically examined the implications of peripubertal experiences on the evolution of competitive behavior across distinct stages of adulthood. In the current research, we probed potential differences in competitive behavior during emerging adulthood (3 months old) and middle adulthood (12 months old) in 81 Sprague‐Dawley male rats exposed to three different peripubertal (postnatal Days 37–60) environments: an enriched environment (EE), a chronic unpredictable mild stress (CUMS) condition, and a control condition. Anxiety‐like behavior served as a positive control in our study. Results revealed significant variations in competitive behavior among the groups during emerging adulthood. The EE group displayed the least anxiety and outperformed their peers in food‐reward‐oriented competition, whereas the CUMS group excelled in status‐driven, agonistic competition. However, these behavioral differentiations gradually attenuated by middle adulthood, at which point the control group began to show an advantage. Our findings suggest that although peripubertal experiences significantly shape competitive behavior in the emerging adulthood stage, this effect diminishes over time and is nearly non‐detectable during mid‐adulthood, underscoring the fluidity of behavioral development and demonstrating that the effects of peripubertal experiences can be modulated by subsequent life experiences. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation caused by cisplatin, which is frequently used in the treatment of many cancers, damage healthy tissues as well as cancer cells. In this study, we aimed to investigate the effect of epigallocatechin-3-gallate (EGCG) and infliximab (INF) administration on pancreatic endocrine cells in rats treated with systemic cisplatin (CDDP). The rats were randomly divided into 6 groups: group 1 (control group), group 2 (EGCG group), group 3 (CDDP group), group 4 (EGCG + CDDP group), group 5 (CDDP + INF group), and group 6 (EGCG + CDDP + INF group). The study's findings demonstrated that EGCG and INF effectively reduced the cellular damage induced by CDDP in histopathologic investigations of the pancreas. EGCG and INF, whether used individually or in combination, demonstrated a significant reduction in malondialdehyde (MDA) levels and an increase in glutathione (GSH) levels in the rat pancreas compared to the CDDP group. Immunohistochemically, the enhanced presence of insulin and glucagon positivity in the EGCG and INF groups, along with the absence of TUNEL immunopositivity, indicate that both treatments reduced CDDP-induced apoptosis. Furthermore, the observed lack of immunopositivity in TNF-α and 8-OHdG in the groups treated with EGCG and INF, compared to those treated with CDDP, indicates that these substances can inhibit inflammation. EGCG and INF, whether provided alone or together, can potentially reduce the damage caused to pancreatic islet cells by cisplatin. This effect is achieved through their anti-inflammatory and antioxidant properties during the early stages of the condition. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal with significant environmental health hazards. It enters the body through various routes with tissue accumulation. The relatively longer half-life with slow body clearance significantly results in hepatotoxicity during its liver detoxification. Therefore, researchers are exploring the potential use of herbal-derived phytocomponents to mitigate their toxicity. Here, we investigated, for the first time, the possible ameliorative effect of the phytochemical Morin (3,5,7,29,49-pentahydroxyflavone) against acute Cd-induced hepatotoxicity while resolving its underlying cellular mechanisms in a rat animal model. The study involved 50 adult male Sprague–Dawley rats weighing 200–250 g. The animals were divided into five equal groups: control, Cd, Morin100 + Cd, Morin200 + Cd, and Morin200. The 2nd, 3rd, and 4th groups were intraperitoneally treated with Cd (6.5 mg/kg), while the 3rd, 4th, and 5th groups were orally treated with Morin (100 and 200 mg/kg) for 5 consecutive days. On the 6th day, hepatic function (serum ALT, AST, ALP, LDH enzyme activities, and total bilirubin level) testing, transcriptome analysis, and immunohistochemistry were performed to elucidate the ameliorative effect of Morin on hepatotoxicity. In addition to restoring liver function and tissue injury, Morin alleviated Cd-induced hepatic oxidative/endoplasmic reticulum stress in a dose-dependent manner, as revealed by upregulating the expression of antioxidants (SOD, GSH, Gpx, CAT, and Nrf2) and decreasing the expression of ER stress markers. The expression of the proinflammatory mediators (TNF-α, IL-1-β, and IL-6) was also downregulated while improving the anti-inflammatory (IL-10 and IL-4) expression levels. Morin further slowed the apoptotic cascades by deregulating the expression of pro-apoptotic Bax and Caspase 12 markers concomitant with an increase in anti-apoptotic Blc2 mRNA expression. Furthermore, Morin restored Cd-induced tissue damage and markedly suppressed the cytoplasmic expression of JNK and p-PERK immunostained proteins. This study demonstrated the dose-dependent antioxidant hepatoprotective effect of Morin against acute hepatic Cd intoxication. This effect is likely linked with the modulation of upstream p-GRP78/PERK/ATF6 pro-apoptotic oxidative/ER stress and the downstream JNK/BAX/caspase 12 apoptotic signaling pathways. [ABSTRACT FROM AUTHOR]

The mammalian cerebral cortex is composed of a rich diversity of cell types. Sensory cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions for perception, learning, and memory. The auditory cortex (AC) has been most extensively studied for its experience-dependent effects, including for perceptual learning and associative memory. Here, we used single-nucleus RNA sequencing (snRNA-seq) in the AC of the adult rat to investigate the breadth of transcriptionally diverse cell types that likely support the role of AC in experience-dependent functions. A variety of unique excitatory and inhibitory neuron subtypes were identified that harbor unique transcriptional profiles of genes with putative relevance for the adaptive neuroplasticity of cortical microcircuits. In addition, we report for the first time a diversity of astrocytes in AC that may represent functionally unique subtypes, including those that could integrate experience-dependent adult neuroplasticity at cortical synapses. Together, these results pave the way for building models of how cortical neurons work in concert with astrocytes to fulfill dynamic and experience-dependent cognitive functions. [ABSTRACT FROM AUTHOR]

Background: The autonomic nervous system (ANS) is affected by several factors, including major nutrients. However, their effects on the ANS remains unclear. Most studies had several limitations. They focused on humans, therefore they had difficulties excluding factors other than the nutrients. Their observation periods were too short (<4 hours) to align with typical absorption times of carbohydrates versus fats. They assessed the effects compared with the pre-prandial state rather than comparisons between different nutrient types. Objective: We aimed to investigate the effects of carbohydrates and fats on the ANS. Method: We employed a rat model to exclude the effects of external stimuli, used sufficient observation period, and compared the ANS parameters among animals fed 3 different diets. The rats were divided into carbohydrate-rich-diet (carb group) and fat-rich-diet (fat group) groups. We investigated the effects of carbohydrates and fats on the ANS by measuring heart rate variability parameters in rats. Electrodes and electrocardiography (ECG) transmitters were implanted in 14 Wistar rats maintained on a standard diet for 2 days followed by the experimental diets for 2 days. ECG readings were continuously recorded for 4 days. The R waves, function of the R-R interval, and time were calculated. A fast Fourier transform was used to obtain the power spectrum of the fluctuation (low frequency [LF: 0.2-0.75 Hz]; high frequency [HF: 0.75-3.0 Hz]; LF/HF ratio). Result: Compared with the standard-diet group, the carb group showed significantly increased HF activity, while the fat group showed a significantly increased LF/HF ratio. Conclusion: The results reveal a link between macronutrients and ANS activity. [ABSTRACT FROM AUTHOR]

The Raphe Pallidus (RPa) is a brainstem nucleus containing sympathetic premotor neurons that control thermogenesis and modulate cardiovascular function. It receives inputs from various hypothalamic areas, including the Lateral Hypothalamus (LH), a heterogeneous region intricately involved in several autonomic and behavioral functions. A key subpopulation of neurons in the LH expresses orexin/hypocretin, a neuropeptide which is crucially involved in the regulation of the wake-sleep states and feeding behavior. The RPa receives orexinergic projections from the LH and orexinergic signalling in the RPa has been shown to enhance thermogenesis in the anaesthetized rat, but only in the presence of an already existing thermogenic drive, without significantly affecting cardiovascular function. The present work was aimed at exploring the effects on thermoregulation and autonomic function and the possible role in the modulation of the wake-sleep states and feeding behavior of orexin injection in the RPa in the free-behaving rat. In order to assess the influence of an already present thermogenic drive on orexinergic signalling in the RPa, animals were studied at three different ambient temperatures (Ta, 10°C, 24°C, and 32°C). We found that orexin injection into the RPa variably affected the wake-sleep states, autonomic functions, motor activity, and feeding behavior, at the different Tas. In particular, in the first post-injection hour, we observed an increase in wakefulness, which was large at Ta 24°C and Ta 10°C and rather mild at Ta 32°C. Deep brain temperature was increased by orexin injection at Ta 10°C, but not at either Ta 24°C or Ta 32°C. Moreover, an increase in mean arterial blood pressure occurred at Ta 24°C, which was probably masked by the high baseline levels at Ta 10°C and was completely absent at Ta 32°C. Finally, an enhancement in feeding behavior was observed at Ta 24°C and 10°C only. In accordance with what observed in anaesthetized rats, orexinergic signalling in the RPa seems to be ineffective in the absence of any thermogenic drive. Moreover, the effects observed on the wake-sleep states and feeding behavior introduce the RPa as a novel player in the central neural network promoting wakefulness and feeding. [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]

The aim of the present study was to establish a simple and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method and apply it for the determination of pharmacokinetics of moxidectin-loaded microspheres (MOX-MS) in rats. Plasma samples were processed using a simplified liquid–liquid extraction method and were separated using an Agilent Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of a 10 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.4 mL/min for 5 min. Avermectin B1a was used as an internal standard (IS). The sample was injected at a volume of 10 μL with a column temperature of 35 °C and detected in a positive ion mode. A good linear response across the concentration range of 1.00–200 ng/mL (r2 > 0.99) and a lower limit of quantification (LLOQ) of 1.00 ng/mL were achieved. The extraction recovery of moxidectin exceeded 94.1%, the matrix effect was between 91.2% and 96.2%, the accuracy ranged from 100.1 to 103.6%, and the relative standard deviation (RSD) did not exceed 15% for the intra- and inter-day accuracy and precision. The pharmacokinetic results showed that MOX-MS significantly decreased Cmax, prolonged T1/2, and improved bioavailability. The developed method significantly reduced the assay volume, shortened detection time, simplified sample processing methods and saved assay costs, which may contribute to the development of the new antiparasitic drug. [ABSTRACT FROM AUTHOR]

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To ensure the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression levels were Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model. [ABSTRACT FROM AUTHOR]

Head direction (HD) neurons, signalling facing direction, generate a signal that is primarily anchored to the outside world by visual inputs. We investigated the route for visual landmark information into the HD system in rats. There are two candidates: an evolutionarily older, larger subcortical retino‐tectal pathway and a more recently evolved, smaller cortical retino‐geniculo‐striate pathway. We disrupted the cortical pathway by lesioning the dorsal lateral geniculate thalamic nuclei bilaterally, and recorded HD cells in the postsubicular cortex as rats foraged in a visual‐cue‐controlled enclosure. In lesioned rats we found the expected number of postsubicular HD cells. Although directional tuning curves were broader across a trial, this was attributable to the increased instability of otherwise normal‐width tuning curves. Tuning curves were also poorly responsive to polarizing visual landmarks and did not distinguish cues based on their visual pattern. Thus, the retino‐geniculo‐striate pathway is not crucial for the generation of an underlying, tightly tuned directional signal but does provide the main route for vision‐based anchoring of the signal to the outside world, even when visual cues are high in contrast and low in detail. Key points: Head direction (HD) cells indicate the facing direction of the head, using visual landmarks to distinguish directions.In rats, we investigated whether this visual information is routed through the thalamus to the visual cortex or arrives via the superior colliculus, which is a phylogenetically older and (in rodents) larger pathway.We lesioned the thalamic dorsal lateral geniculate nucleus (dLGN) in rats and recorded the responsiveness of cortical HD cells to visual cues.We found that cortical HD cells had normal tuning curves, but these were slightly more unstable during a trial. Most notably, HD cells in dLGN‐lesioned animals showed little ability to distinguish highly distinct cues and none to distinguish more similar cues.These results suggest that directional processing of visual landmarks in mammals requires the geniculo‐cortical pathway, which raises questions about when and how visual directional landmark processing appeared during evolution. [ABSTRACT FROM AUTHOR]

The cryopreservation of rat embryos is useful for efficiently archiving rat resources in bioresource repositories. The cryopreserved fertilized oocytes can be quickly reanimated to rats with homozygous mutations using embryo transfer. In addition, cryopreserved rat fertilized oocytes are easier to transport than live animals. Before cryopreservation, fertilized oocytes are obtained by mating or in vitro fertilization. However, it is not clear which fertilized oocytes are most suited to cryopreservation. In this study, we performed a systematic comparison of the fertilizing ability, cryotolerance, and developmental ability of cryopreserved fertilized oocytes at the pronuclear stage produced either by mating (in vivo) or in vitro fertilization (in vitro) in SD and F344 rats. In vivo-fertilized oocytes had higher cryotolerance and developmental ability than in vitro-fertilized oocytes in SD and F344 rats. Furthermore, the fertilization ability, cryotolerance, and developmental ability of vitrified-warmed fertilized oocytes differed between SD and F344 rats. In conclusion, our study suggests that in vivo-fertilized rat oocytes were more suitable for cryopreservation. Our protocol provides an optimized system for the management of rat colonies using fertilized oocytes cryopreservation and contributes to the 3Rs principle by reducing the number of animals used for research. [ABSTRACT FROM AUTHOR]

This study evaluates silver-doped carbon dots (AgCDs) as a novel agent for chemical castration using a rat model. Six groups of rats (five males and ten females each, except for the surgical group which had only males) were utilized to compare the effects of different concentrations of AgCDs. The groups included control, sham, and three experimental groups injected with 1.25, 50, and 200 µg/mL AgCDs, respectively, along with a surgical castration group. Testosterone levels, sperm parameters, fertility index, oxidative damage, histopathological parameters, and gene expression of P53, Bax, Bcl-2, caspase-3, AKT, and PI3K were analyzed. Results demonstrated that the high-dose AgCDs group significantly reduced testosterone levels, sperm concentration, and motility, resulting in a decreased fertility index. MDA and NO significantly increased, while CAT, SOD, GPx, and TAC significantly reduced in the chemically castrated groups. Histological and genes expression analysis also revealed apoptosis and testicular damage in the AgCDs groups, indicated by significant increases in P53, Bax, and Caspase-3 levels, and significant reductions in AKT, PI3K, and Bcl-2. Based on these findings, AgCDs could be considered a potent and efficient agent for chemical castration, offering a less invasive, cost-effective solution with potential applications for population control. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF‐H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy.Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF‐H by enzyme‐linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video‐electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T2 magnetic resonance imaging were performed to assess comorbidities and lesion severity.Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI−). Plasma pNF‐H concentrations were higher in TBI+ rats than in TBI− rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF‐H concentration distinguished TBI+ rats from TBI− rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF‐H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF‐H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF‐H concentration on D2 correlated with greater T2 signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF‐H concentration on D2 did not correlate with Morris water maze performance on D37–D39.Plasma pNF‐H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters. [ABSTRACT FROM AUTHOR]

Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50 mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke, and its mechanism of action is still unclear. OBJECTIVE: To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats.METHODS: Fifty Sprague-Dawley rats were divided into sham-operated group, model group, positive control group, high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method, with 10 rats in each group. Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group. Administration in each group started on the 3rd day after surgery, and the rats in the positive control group were intraperitoneally injected with edaravone injection (6 mg/kg), the rats in the high- and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively, and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline. After 14 days of continuous treatment in each group, the pathological changes in rat brain tissue were observed, and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected. RESULTS AND CONCLUSION: Compared with the sham-operated group, the volume of cerebral infarction became larger in the model group; the structure of brain tissue was loose, irregular cavities could be observed, and the number of neurons was reduced and irregularly arranged; the positive expression of NLRP3 inflammasome increased (P < 0.01); and the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β increased (P < 0.01). Compared with the model group, the volume of cerebral infarction became smaller in the high- and low-dose gastrodin groups; the neurons were regularly arranged, increased in number, and uniformly distributed; the positive expression of NLRP3 inflammasome was decreased (P < 0.05); the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β were decreased in the high-dose gastrodin group (P < 0.01); Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group, and the protein and mRNA expression of the other inflammatory response-associated factors decreased (P < 0.05, P < 0.01). To conclude, gastrodin attenuates inflammatory injury in ischemic stroke rats, and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy. Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital, Beijing University of Chinese Medicine. OBJECTIVE: To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy. METHODS: Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups. There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group, and the low-, medium-, and high-dose groups of Shujin Jiannao Prescription. The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group. After successful modeling, rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4, 8, and 16 g/kg per day for 1 week. Body mass of rats was measured and behavioral changes were detected before and after drug administration. Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue, and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2, Bax, and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION: Compared with the model group, medium- and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats (P < 0.05). Compared with the model group, minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats (P < 0.05), while medium- and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time, shortened the inclined plane test time, and increased the Longa score of rats (P < 0.05). The pathological results showed that after drug intervention, only a small number of neuronal cells in the brain tissue of rats were necrotic, the cells were more neatly arranged, the cell structure was more complete, and only part of the cell nuclei became smaller. Compared with the model group, minocycline and medium- and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3 (P < 0.05), medium- and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2 (P < 0.05), and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups (P < 0.05). In addition, the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription, and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups (P > 0.05). To conclude, the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl2, inhibit the expression of pro-apoptotic protein Bax, and reduce the expression of Caspase-3, ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy. Within a certain range, the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect, and the high-dose Shujin Jiannao Prescription is as effective as minocycline. [ABSTRACT FROM AUTHOR]

Background: Testicular torsion is a surgical emergency leads to severe acute ischemia injuries, and may eventually cause male infertility. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is involved in testicular torsion pathophysiology. The aim of this study was to evaluate the effects of nanocurcumin (nCur) on testicular tissue and the NLRP3 inflammasome components. Materials and Methods: In this experimental study, male Wistar rats (n=36) were randomly divided into six equal groups: controls, ischemia-reperfusion (I/R), I/R+nCur (50 or 100 mg/kg thirty minutes before reperfusion), and I/ R+nCur (50 or 100 mg/kg thirty minutes before reperfusion and continued for seven days). The left testis was rotated 720 (2x360) degrees counterclockwise to induce testicular torsion. After two hours of ischemia, detorsion was performed. At the end of treatment, an orchiectomy was carried out. The testis histopathology and the mRNA levels of NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 were evaluated. Results: Our results revealed that, testicular I/R had a detrimental effect on testis histology such as the number of spermatogonia (14.5 ± 0.57, P<0.001) and the seminiferous tubules epithelium thickness (28.5 ± 11.7, P=0.007). It also significantly increased the expression of the NLRP3 inflammasome components (P<0.001). Treatment with nCur (in both doses) improved testicular damage and significantly reduced the expression of NLRP3 (P=0.007), ASC (P=0.003), and Caspase-1 (P<0.001). Conclusion: These results imply that nCur might be a useful therapeutic strategy in the field of reproductive medicine to diminish the side effects of testicular I/R via its anti-inflammatory properties and may be employed as adjuvant therapy to lessen testicular torsion complications. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the duration required for endothelium dysfunction to develop in the fructose drinkinginduced hypertension and examine the relative contributions of endothelium-dependent relaxing factors to changes in mesenteric arterial reactivity in male Wistar Albino rats. Materials and Methods: Metabolic parameters (water intake and food consumption) and hemodynamic parameters systolic blood pressure (SBP) and diastolic blood pressure (DBP)-were monitored in vivo. Vascular reactivity was examined in the isolated organ bath. Endothelium-dependent relaxation (EDR) to acetylcholine was observed in the absence and presence of pharmacological inhibitors of endothelial nitric oxide (NO) synthase, cyclooxygenase, and KCa2.3 channels. Contractile responses to phenylephrine and relaxation of sodium nitroprusside (SNP) were also determined. Results: A significant increase in daily water intake and decrease in food consumption were typically observed in rats treated with 10% fructose for 4 weeks (p < 0.05). SBP and DBP increased significantly as early as 2 weeks of induction and continued to rise gradually throughout the induction period (p < 0.05). Fructose consumption significantly impaired EDR at week 3 and worsened at week 4 (p < 0.05). Impairment of the KCa3.1 channel-mediated component of endothelium-dependent hyperpolarisation (EDH)-type relaxation contributed to worsening EDR, whereas the contribution of NO-mediated relaxation was not apparent compared with the controls. The reduction in EDH-type relaxation in fructose-fed rats appears to be partially compensated by increased NO sensitivity in the smooth muscle region, as fructose induction increased SNP relaxation compared with the control. Conclusion: These data provide evidence of early endothelial dysfunction developing concurrently with increased blood pressure in 10% fructose-fed rats. Decreased KCa3.1-mediated part of EDH-type relaxation appears to contribute to the impairment of endothelium-dependent vasorelaxation over time in this model. [ABSTRACT FROM AUTHOR]

Objective To analyze the ECG manifestations of each lead of myocardial infarction (MI) model in rats established by injection of isoproterenol (ISO), and to explore the observation leads suitable for this model to judge whether MI has been formed. Methods Twenty rats were injected with ISO subcutaneously, and then were given the drug again after 24 hours. ECGs of limb and chest leads were recorded every 24 hours, while the deviation value of J-point of each lead except that of lead aVR was measured, and compared with those before and after administration. After 48 hours, the rats were killed, and their hearts were obtained for pathological examination. Results On the 2nd day before medication, the elevation of J-point in lead V2 was more obvious than that in leads Ⅱ, Ⅲ and aVF (P<0. 01), and there was no statistical difference of the value in pairwise comparison of leads Ⅱ, Ⅲ and aVF ( P > 0. 05). Conclusion The infarct areas of MI model in rats established by ISO method are scattered; J-point elevation could appear in multiple leads, of which lead V2 is the most obvious. One of the above leads could be selected for observation in the experiment; limb and chest leads could also be monitored synchronously. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the impact of sulpiride and PMSG hormone treatments on estrus and the number of offspring produced in female rats. Thirty mature rats were divided into three groups, each consisting of 10 females. The first group was treated intraperitoneally with sulpiride (0.25 mg/kg), the second group with PMSG hormone (20 IU/kg), and the third group with normal saline. Treatments were administered after the onset of estrus. Following treatment, natural mating occurred. The results of the study showed no significant differences between the PMSG hormone, sulpiride, and normal saline treatment groups regarding the number of females that showed estrus and mated. However, a significant difference (P < 0.05) was observed between the PMSG treatment group and the other groups with respect to the average number of embryos, which were 128, 75, and 55, respectively. The Luteinizing Hormone (LH) concentration was significantly higher (P < 0.05) in the sulpiride-treated group (1.44 ±0.12 ng/ml) compared to the PMSG hormone (1.23 ± 0.14 ng/ml) and normal saline treatment groups (0.76 ± 0.08 ng/ml). In conclusion, the application of PMSG was more effective in inducing ovulation and increasing the average number of offspring compared to sulpiride treatment in female rats. [ABSTRACT FROM AUTHOR]

In recent years, a significant research effort has been underway to explore the effects of low-dose radiation (LDR). Animal models play a key role in various fields of research, including biomedicine, pharmaceutical, environmental, and behavioral studies. The use of animal models has been an invaluable tool in radiation research for understanding radiation biology, assessing radiation risks, and developing strategies for radiation protection and medical management. In the present review, the initial part focuses on the deleterious effects of high-dose radiation, and in correlation to that, in the later part of the review, the emphasis has been given to experimental approaches to explore the beneficial effects of LDR using animal models. This review could help explore the innovative approach for future research targeting the therapeutic role of LDR in various diseases, including depression, Cancer, Parkinson's disease, and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

High-fat diets have detrimental health impacts that increase the likelihood of developing obesity and metabolic syndrome. This study aimed to examine the potential antioxidant and anti-inflammatory effects of orlistat and white tea in rats fed a high-fat diet. Thirty-two rats were randomized into four groups: control (standard diet), HFD (high-fat diet), HFD+Orlistat (high-fat diet+orlistat), and HFD+WT (high-fat diet+white tea extract). A significant increase in malondialdehyde (MDA) levels and a decrease in total thiol (TT) levels were detected in the HFD group (p < 0.001). On the other hand, a decrease in the MDA level (p < 0.001) and an increase in the TT level were observed in the orlistat and white tea groups compared with those in the HFD group (p < 0.001). Histopathological examinations revealed that, compared with the HFD alone, orlistat and white tea reduced fat accumulation, prevented degenerative changes in hepatocytes, and decreased the histopathological damage score (p = 0.001). Immunohistochemical examinations of nuclear factor-kappa B (NF-kB/p65) revealed that compared with the HFD, orlistat and white tea reduced immunopositivity (p = 0.001). White tea decreases lipid peroxidation and oxidative stress. Both white tea and orlistat decreased fat formation and inflammation in the liver and regulated inflammation by reducing Nf-kB positivity. Nevertheless, further research is needed to assess their impact on human subjects. [ABSTRACT FROM AUTHOR]