Search Results (298)

Objective: This study aimed to determine the possibility of creating a new animal model in which diabetic retinopathy (DR) progresses due to hypertension caused by salt loading. Methods: Male Spontaneously Diabetic Torii (SDT) fatty rats were divided into two groups: one group received 0.3% saline water starting at 8 weeks of age for a duration of 16 weeks (salt SDT fatty group), while the control group was provided with tap water (SDT fatty group). In addition, Sprague-Dawley (SD) rats receiving tap water served as normal controls. Retinal function was assessed by electroretinography (ERG) at 8 and 24 weeks of age. At 24 weeks, following perfusion with fluorescein dextran, the eyes were enucleated, and retinal flat mounts were prepared for vascular evaluation. Retinal thickness and the number of retinal folds were assessed histologically, and ultrastructural changes in the retina were examined using transmission electron microscopy. Results: Saline administration did not lead to significant changes in food consumption or body weight among the groups. In the salt SDT fatty group, blood pressure was significantly elevated, while blood glucose levels showed a slight reduction. ERG analysis showed that the amplitude of oscillatory potential (OP)1 waves was suppressed, and the latencies of OP3, OP4, and OP5 waves were prolonged. Although no significant changes were noted in retinal thickness or the number of retinal folds, thickening of the retinal capillary basement membrane was evident in the salt SDT fatty group. Conclusions: Hypertension induced by 0.3% saline promotes DR progression in SDT fatty rats. This model may help clarify the role of hypertension in DR. Full article

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD^® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection. Full article

Umbilical cord mesenchymal stem cells (UCMSCs)-derived small extracellular vehicles (sEVs) are reported to offer therapeutic effects in regenerative medicine, but they lack safety and biodistribution profiles to support smooth translation at the clinical stage and regulatory requirements. Our study aimed to determine the safety and biodistribution profile in a healthy animal model before application in the metabolic syndrome model. Method: Healthy male Sprague Dawley (SD) rats were given an intravenous (IV) injection of normal saline (control group) or pooled fetal UCMSCs-derived sEVs (treated group) every three weeks for 90 days. Morbidity and mortality observation (daily), physical measurements (weekly), selected serum biochemistry (every three weeks), and hematology (every three weeks) were performed for 90 days. Acute toxicity (on day 14) and sub-chronic toxicity (on day 90) were assessed for gross necropsy, relative organ weight, and histopathological assessment of lungs, liver, spleen, kidney, and lymph nodes. Separately, a biodistribution study was conducted with the sEVs preparations labeled with PKH26 fluorescent dye, given intravenously to the rats. The organs were harvested 24 h post-injection. There were no drastic changes in either group’s morbidity or mortality, physical, hematological, and biochemistry evaluation. The histopathological assessment concluded moderate (focal) inflammation in the treated group’s kidneys and signs of recovery from the inflammation and vascular congestion in the liver. A biodistribution study revealed a higher accumulation of sEVs in the spleen. Multiple IV injections of the pooled fetal UCMSCs-derived sEVs in healthy male SD rats were deemed safe. The sEVs were abundantly distributed in the spleen 24 h post-injection. Full article

Background: The combined diphtheria–tetanus–acellular pertussis (three-component), Haemophilus influenzae type b (Hib, conjugate), and ACYW135 meningococcal (conjugate) vaccine (DTaP-Hib-MCV4) offers a promising alternative to single-component vaccines, potentially simplifying immunization schedules and improving vaccination coverage. Methods: We evaluated the safety, immunogenicity, and protective efficacy of DTaP-Hib-MCV4 in animal models. Acute and long-term toxicity studies were conducted in Sprague-Dawley (SD) rats with equal numbers of male and female animals. Immunogenicity was assessed in female NIH mice and SD rats using a three-dose regimen at 14-day intervals. Orbital blood was collected 14 days post-immunization to measure IgG titers against pertussis, diphtheria, tetanus, Hib, and meningococcal antigens. The protective efficacy was determined using potency tests for the pertussis, diphtheria, and tetanus components; passive protection studies for Hib; and serum bactericidal antibody (SBA) titers against A/C/Y/W135 meningococcal serogroups. Results: Acute and repeated-dose toxicity studies in SD rats showed no signs of abnormal toxicity or irritation at either high (three doses/rat) or low (one dose/rat) doses levels. The no-observed-adverse-effect level (NOAEL) for DTaP-Hib-MCV4 was established at three doses/rat after 8 weeks of repeated intramuscular administration and a 4-week recovery period. Specific IgG antibodies against all the vaccine components were detected in animal sera at both one and three doses/rat, with no evidence of immunotoxicity. Following two-dose primary immunization in murine models, the combined vaccine elicited robust antigen-specific antibody responses, with geometric mean titers (GMTs) as follows: 1,280,000 for pertussis toxin (PT); 761,093 for filamentous hemagglutinin (FHA); 1,159,326 for pertactin (PRN); 1,659,955 for diphtheria toxoid (DT); 1,522,185 for tetanus toxoid (TT); 99 for Haemophilus influenzae type b (Hib); and 25,600, 33,199, 8300, and 9051 for serogroups A, C, Y, and W135 of Neisseria meningitidis, respectively. In the rat models, three-dose primary immunization also elicited robust antigen-specific antibody responses. Protection studies demonstrated efficacy against pertussis, tetanus toxin, and diphtheria toxin challenges. In the Hib challenge study, none of the 10 animals given anti-DTaP-Hib-MCV4 antiserum developed bacteremia after the live Hib challenge (vs. 5814/0.1 mL in the negative control, p < 0.001). In addition, the SBA titers against meningococcal serogroups exceeded the protective threshold (≥1:8) in 92.2% of the immunized mice and 100% of the immunized rats. Crucially, the combined vaccine induced potent immune responses and protective efficacy, with antibody levels and protection against each component antigen comparable to or greater than those of the individual components: DTaP, Hib, and MCV4. Conclusions: These findings demonstrate that the DTaP-Hib-MCV4 combined vaccine is both safe and immunogenic, supporting its potential as a viable alternative to individual vaccines. This combined vaccine may streamline immunization programs and enhance vaccination coverage. Full article

Stroke is still considered a predominant cause of morbidity and mortality, for which research on prevention and cure has been sought to prevent neuronal damage after a stroke incident. In this research, we evaluated the protective effects of virgin coconut oil (VCO) using behavioral, morphophysiological, and gene expression parameters using an ischemic stroke surgical rat model using Sprague Dawley (SD) rats. Eight-week-old SD rats were subjected to repeated oral administration (5 mL/kg/day) of either 1% Tween 80 or VCO. For behavioral and morphophysiological parameters, surgery was performed for each group, after which neurological scoring was performed at 4 h, 24 h, 48 h, 5 d, and 10 d. Further, hematological and brain morphology assessment was performed after euthanasia and necropsy of the animals. For gene expression studies, surgery was performed with animals sacrificed at different time points (baseline, before surgery, 4 h, 24 h, and 48 h after surgery) to collect the brain. Results of the study showed that there are differences in the neurological scores between the two treatments 24 h, 48 h, and 5 d after surgery. Brain morphology assessment also showed favorable results for VCO for infarct size, edema, and hypoxic neurons. Gene expression studies also showed positive results with an increase in the relative expression of angiogenin (Ang), angiopoietin (Angpt 1), Parkin, dynamin-related protein 1 (Drp 1), mitofusin 2 (Mfn 2), and mitochondrial rho (Miro) and decreased relative expression of caspase 3, receptor for advanced glycation end-product (Rage), and glyceraldehyde-3-phosphate dehydrogenase (Gapdh). In summary, the current study shows that VCO may have protective effects on the brain after stroke, which may be explained by the results of the gene expression studies. Full article

Medium chain triglycerides (MCTs) are regarded as an important ingredient for functional foods and nutraceuticals. Cinnamomum camphora seed kernel oil (CCSKO) contains more than 95% medium chain fatty acids (MCFAs), which is a significantly higher level than palm kernel oil (62%) and coconut oil (55%). However, the safety assessment of CCSKO, as the only natural MCT oil rich in capric acid and lauric acid found so far in the world, has not been fully verified. The study aimed to investigate the 90-day sub-chronic oral toxicity and teratogenicity of CCSKO. In the sub-chronic oral toxicity study, no clinically significant adverse events occurred in male or female Sprague–Dawley (SD) rats with CCSKO daily administration for 13 weeks. Moreover, there were no dose–response relationships between CCSKO and body-weight gain, food intake and food utilization in male or female SD rats. No significant differences (p > 0.05) were found in the hematological properties or organ weights between the male and female SD rats. In the teratogenicity test, no toxicological signs were observed in either Wister pregnant rats or fetuses. The no-observed-adverse-effect level of CCSKO was determined to be more than 4 mL/kg body weight. These results suggested that CCSKO may be an excellent edible oil with high oral safety. Full article

Objective: Growth retardation in adolescents caused by nutritional deficiency requires effective intervention. A novel dietary supplement containing bamboo shoot extract, amino acids, and calcium citrate (Kidtal + Ca, KDTCa) was evaluated for its growth-promoting effects. Methods: After acclimatization, sixty-three 3-week-old male Sprague-Dawley (SD) rats were randomly divided into a normal control group and model groups. Growth retardation was induced in the modeling groups through calcium-deficient feeding, followed by administration of KDTCa, bamboo shoot extract and amino acids (Kidtal), or calcium citrate (CC). After 6 weeks of intragastric administration, the mechanical properties, microstructure, and growth plate development of bone were evaluated using three-point bending, micro-CT, and H&E staining, respectively. Bone calcium/phosphorus distribution and fecal calcium apparent absorption rate were measured by ICP-MS. Results: All inter-group differences were analyzed using one-way analysis of variance and checked using the Tuckey test. KDTCa treatment dose-dependently enhanced bone development in calcium-deficient rats. Compared to the model group, H-KDTCa significantly restored naso-anal length (p < 0.05) and body weight (p < 0.01). KDTCa supplementation significantly restored calcium and phosphorus levels in blood and bone. Three-point bending experiments showed that the stiffness and bending energy were increased by 142.58% and 384.7%. In bone microarchitecture, both bone mineral density (BMD) and microstructural parameters were significantly improved. These findings were consistent with the increased long bone length (p < 0.05) and decreased serum BALP/TRACP levels (p < 0.001). Dose-dependent IGF-1 elevation (p < 0.01) potentially mediated growth plate elongation by 35.34%. Notably, KDTCa increased calcium apparent absorption by 6.1% versus calcium-only supplementation at equal intake. Conclusions: KDTCa improves bone microstructure and strength, restores bone metabolism, and enhances growth plate height via promoting IGF-1 secretion to facilitate bone development. Further studies are needed to determine whether the components and calcium in Kidtal have a synergistic effect. Full article

Background/Objectives: Dihydromyricetin (DHM), a flavonoid with abundant natural sources, potent bioactivity, and high safety, holds promise for translational applications, particularly in mitigating skin aging. However, its role and underlying mechanisms in counteracting skin aging induced by advanced glycation end products (AGEs) remain unclear. Methods: Eight-week-old male Sprague-Dawley (SD) rats were subcutaneously injected with 500 mg/kg D-galactose and administered DHM via gavage for 11 weeks. Additionally, senescent human skin fibroblasts (HFF-1) induced by AGEs were used for further investigation. Results: DHM treatment significantly alleviated D-galactose-induced skin aging in rats, with the most pronounced effects observed in the moderate-dose group (100 mg/kg). Compared to the aging group, DHM enhanced skin elasticity and preserved collagen levels. Moreover, DHM promoted cell proliferation in the skin. Further studies on AGE-induced senescent fibroblasts revealed that DHM markedly reduced multiple senescence-associated markers and stimulated cell proliferation by approximately a 1.5-fold increase. Transcriptomic analysis indicated that DHM upregulated genes related to the cell cycle and DNA repair while suppressing AGE-RAGE signaling and its downstream pathways. Notably, DHM downregulated AGER, the gene encoding the receptor for AGEs (RAGE). Molecular docking analysis demonstrated that DHM shares a binding site with other known RAGE inhibitors. Surface plasmon resonance (SPR) analysis further confirmed the high binding affinity of DHM to RAGE (K_D = 28.7 μM), which was stronger and more stable than that of FPS-ZM1 (K_D = 40.7 μM). Conclusions: DHM may attenuate glycation-induced skin aging in rats by functioning as a RAGE inhibitor, thereby suppressing AGE-RAGE signaling, delaying cellular senescence, and promoting cell proliferation. Full article

As the proportion of the elderly population increases, there is an urgent need for anti-aging technologies. Since the skin is the most visibly aging organ in the human body, it is crucial to develop active ingredients to slow down skin aging. Currently, identified anti-aging active substances include antioxidants, retinoids, peptides, growth factors, and compounds derived from biofermentation. However, they have limitations such as poor stability, low transdermal permeability, skin irritation, high effective concentrations, slow onset of efficacy, single-action mechanisms, and high production costs. These limitations highlight the necessity of developing new anti-aging technologies that are multifunctional and cause low irritation. This study aimed to investigate the anti-aging effects and mechanisms of fructosazine (FZ) and deoxyfructosazine (DOF) on the skin as well as their potential applications in skincare. The methods included ELISA tests to assess the viability of human dermal fibroblast (NHDF) cells and related factors, and monitoring in Sprague-Dawley (SD) rats. The results showed that FZ promoted cell viability. Both FZ and DOF enhanced the secretion of type I collagen (Col I) and hyaluronic acid (HA), inhibited matrix metalloproteinase-1 (MMP-1), boosted catalase (CAT), and reduced malondialdehyde (MDA), reactive oxygen species (ROS), and β-galactosidase. They also nourished the epidermis and increased fiber content. In conclusion, FZ and DOF can stimulate the production of anti-aging substances, exhibit antioxidant activity, and have potential in skincare. Full article

Sublancin, an S-linked antimicrobial (glycol) peptide produced by Bacillus subtilis, has emerged as a novel and promising veterinary drug due to its unique antibacterial mechanism, low risk of resistance, and properties that modulate the immune system, reduce inflammation, and promote gut health. This study comprehensively assessed the subchronic (90-day) and chronic (180-day) toxicity of Sprague–Dawley (SD) rats, following the guidelines issued by the Ministry of Agriculture of China. Rats were orally administered sublancin at doses of 2000, 10,000, or 50,000 mg/kg feed, representing 1666–5000 times the efficacious dose (1.0–1.2 mg/kg) reported in mice via the same administration route. Throughout this study, a wide range of physiological and behavioral parameters were monitored to access the toxicity of sublancin, including appetite, water intake, body weight gain, and organ weights. Hematological and biochemical analyses, as well as histopathological examinations of the major organs, were conducted at the end of each study period. The results indicated no adverse effects on any measured parameters at any dose level, with no significant differences observed between the sublancin-treated groups and the control group (p > 0.05). Notably, even the highest dose of 50,000 mg/kg did not induce growth inhibition or physiological dysfunction. A histopathological examination also revealed no tissue abnormalities in the major organs. The no-observed-effect level (NOEL) was determined to be 50,000 mg/kg for both study periods. These results demonstrate the long-term safety of sublancin in Sprague–Dawley rats, with no adverse effects during 180 days of oral administration at doses 1666–5000-fold the documented antimicrobially effective and immune-enhancing doses. Full article

Objective: The aim of this work is to investigate the impact of exercise on gut microbiome composition, serum metabolites, and their correlation with osteoarthritis (OA) severity. Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into four groups: Sham rats without treadmill walking (Sham/Sed group, n = 9), Sham rats with treadmill walking 2 months (Sham/TW2M group, n = 9), PTOA rats without treadmill walking (PTOA/Sed group, n = 9), and PTOA rats with treadmill walking 2 months (PTOA/TW2M group, n = 9). The PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and destabilization of the medial meniscus (DMM). Histological evaluation and micro-CT analysis were performed to observe the pathological changes in cartilage and subchondral bone, respectively. Additionally, we conducted 16S rDNA sequencing of fecal samples and untargeted metabolomic analysis using liquid chromatography–mass spectrometry (LC–MS) of serum samples to detect the alteration of gut microbiota composition and metabolites. Results: Exercise effectively mitigated OA-related pathological changes, including articular cartilage degeneration and subchondral bone loss. Moreover, 16S rDNA sequencing analysis of gut microbiome revealed a decreased abundance of Bacteroidetes (p < 0.01), Bacteroidia (p < 0.01), Rikenellaceae (p < 0.01), [Paraprevotellaceae] (p < 0.01), and Paraprevotella (p < 0.01) but an increase in Firmicutes (p < 0.01) in PTOA/TW2M group rats compared with PTOA/Sed group as a response to exercise. In addition, the results of metabolomics analysis showed that exercise treatment contributed to the upregulation of Daidzein and Anthranilic acid and downregulation of 1-Palmitoyllysophosphatidylcholine. Moreover, the correlation analysis showed that Rikenellaceae significantly positively correlated with both OARSI (r = 0.81, p < 0.01) and Mankin score (r = 0.83, p < 0.01) and negatively correlated with the serum level of Anthranilic acid (r = −0.56, p < 0.01) and Daidzein (r = −0.46, p < 0.01). Conclusions: Exercise can effectively mitigate OA through slowing down articular cartilage degeneration and subchondral bone loss, modulating gut microbiota composition, and increasing beneficial metabolites. Full article

Poly (methyl methacrylate) (PMMA) bone cement is widely used in percutaneous vertebroplasty to stabilize osteoporotic vertebral compression fractures. However, its clinical application is limited by its high compressive modulus, risk of thermal necrosis, and poor bone integration, unlike conventional PMMA formulations used in vertebrae or joint arthroplasty, which can reach polymerization temperatures exceeding 100 °C. Spine-specific PMMA is formulated to cure at a reduced polymerization temperature, thereby minimizing the rise in core temperature during the setting process. Consistent with our hypothesis, this moderate thermal output induces localized thermal injury that triggers osteogenic responses and extracellular matrix production, thereby enhancing osteoblast activity in the surrounding bone. This study aimed to evaluate bone remodeling following spine-specific PMMA injection in an osteoporotic Sprague-Dawley (SD) rat model. Twenty-four osteoporotic female SD rats were randomly assigned to three groups: Control (untreated), OVX + spine-specific PMMA (OVX + PMMA), and OVX (OVX + Defect). Bone regeneration was assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (Micro-CT), quantitative PCR (qPCR), immunohistochemistry (IHC), and Western blotting. At 12 weeks post-injection, the OVX + PMMA group exhibited significantly greater bone regeneration than the OVX group. Micro-CT analysis demonstrated a marked increase in trabecular thickness in the PMMA-treated group. Notably, bone formation was more pronounced in regions surrounding the cement compared to adjacent untreated areas. This suggests that spine-specific PMMA promotes osteogenesis via localized thermal necrosis and subsequent osteoblast recruitment. These findings highlight the dual role of spine-specific PMMA in both structural stabilization and biologically driven bone regeneration. Further research is warranted to optimize its clinical applications while minimizing potential adverse effects. Full article

The aim of this study was to achieve the high secretion and expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris, as well as to investigate its antibacterial properties and biological effects in promoting wound healing. The recombinant thymosin β4 protein (rTβ4) exhibited no hemolytic activity on rabbit red blood cells and demonstrated significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 25 μg/mL. It effectively inhibited bacterial growth and disrupted the cell wall and membrane structure of the bacteria. In the Sprague Dawley (SD) rat wound healing model, the wound healing rate in the rTβ4 treatment groups (at concentrations of 12.5 and 25 μg/mL) was significantly higher than that in the control group (p < 0.05), and the healing effect was comparable to that of the positive control group (Kangfu Xin solution, KFX). The histopathological study demonstrated that rTβ4 could reduce the infiltration of inflammatory cells and promote the proliferation and re-epithelialization of granulation tissue. In conclusion, this study successfully achieved the high expression of thymosin β4 derived from Pinctada fucata in Pichia pastoris and validated its antibacterial and wound healing potential through both In vitro and In vivo experiments. Full article

Dimethyl phthalate (DMP) can enter the human body and be absorbed into the bloodstream to produce monomethyl phthalate (MMP). MMP in the environment can also enter the bloodstream. However, little is known about the toxicity of the phthalate metabolite MMP in most organisms. In this study, the erythrocyte toxicity of MMP and a preventive approach were investigated using Sprague–Dawley (SD) rats as the model animal under MMP concentrations of 5–250 mg/kg (sub-chronic exposure in vivo) and 1.25–100 μg/mL (acute exposure in vitro). The experimental results indicate that the interaction of MMP with erythrocytes caused oxidative damage, which decreased the number of red blood cells and the hemoglobin content and increased the content of methemoglobin and the iron release of hemoglobin in rat blood. However, the above results were not observed when MMP directly interacted with hemoglobin. The antioxidants vitamin C and vitamin E improved the above blood indicators in rats. The results of this study provide certain theoretical guidance for the evaluation of the potential risks of phthalate metabolites. Full article