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BACKGROUND: A network-based pharmacological approach has identified multifunctional effects of the main bioactive compounds in the Trichosanthis Fructus-Allii Macrostemonis Bulbus on coronary heart disease; however, the mechanism of its therapeutic effect on coronary heart disease has not been fully elucidated. OBJECTIVE: To investigate the role and mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus in improving coronary heart disease by regulating the composition of gut microbiota. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups: blank control group (n=10), model group (n=10), positive drug group (n=10), and medicine pair group (n=10). A rat model of coronary heart disease was established by continuous gastric perfusion of fat emulsion and injection of pituitrin. After modeling, rats in the model group were gavaged with distilled water (10 mL/kg) for control, rats in the positive drug group were gavaged with simvastatin 4 mg/kg per day, and rats in the medicine pair group were gavaged with Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs 7.56 g/kg per day. All interventions lasted for 14 days. Electrocardiograms and myocardial pathology were observed, and blood lipid levels were measured. The structure of gut microbiota was analyzed using 16S rDNA sequencing technology. RESULTS AND CONCLUSION: Electrocardiogram results showed ST segment elevation in the model group. There were no significant abnormalities in the electrocardiograms of the positive drug group and medicine pair group. Compared with the blank control group, the levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol were significantly higher in the model group (P < 0.05). Compared with the model group, the levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol were significantly lower in the positive drug group and medicine pair group (P < 0.05). Compared with the blank control group, focal myocardial cell necrosis was observed in the model group, while partial myocardial cell disarray was observed in the positive drug group and medicine pair group. Compared with the blank control group, the Ace, Shannon, and Chao indices were increased (P < 0.05) and the Simpson index was decreased (P < 0.05) in the model group, positive drug group and medicine pair group. Compared with the model group, the Ace and Chao indices were decreased (P < 0.05), while the Shannon index showed no significant difference (P > 0.05) and the Simpson index was also decreased (P < 0.05) in the positive drug group and medicine pair group. Compared with the blank control group, the relative abundances of Desulfovibrionia, Muribaculaceae_norank, etc. were increased in the model group, while those of Clostridia, [Eubacterium]_coprostanoligenes_group_norank, etc. were decreased. Compared with the model group, the relative abundances of WPS-2_norank, Muribaculaceae_norank, etc. were increased in the medicine pair group, while those of Clostridia, [Eubacterium]_coprostanoligenes_group_norank, etc. were decreased; the relative abundances of Desulfobacterota, [Eubacterium]_coprostanoligenes_group_ norank, etc. were increased in the positive drug group, while those of Firmicutes, Muribaculaceae_norank, etc. were decreased. Compared with the positive drug group, the relative abundances of Desulfobacterota, Bacteroides, etc. were increased in the medicine pair group, while those of Firmicutes, [Eubacterium]_ coprostanoligenes_group_norank, etc. were decreased. The LEfSe results showed that the medicine pair group had the highest microbial enrichment, followed by the blank control group and positive drug group, with the model group having the lowest microbial enrichment. To conclude, Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs can improve the development of coronary heart disease by regulating gut microbiota composition, providing new insights for further research and development of Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs. [ABSTRACT FROM AUTHOR]

• Reproductive hormones may affect cognition by rapidly modulating synaptic responses in the infralimbic cortex. • Stimulation of infralimbic cortex layer I evoked field EPSPs generated by a current sink in layer I. • Both progesterone and allopregnanolone increased EPSP amplitudes in layer I. • The membrane progesterone receptor agonist Org OD 02–0 increased synaptic responses. • Org OD 02–0 also occluded increases in synaptic responses induced by progesterone or allopregnanolone. Estrogens and progesterone can have rapid effects on neuronal function and can modify the use of spatial navigation strategies dependent upon the prefrontal cortex, striatum, and hippocampus. Here, we assessed the effects of 17β-estradiol (E2), progesterone, and its metabolite allopregnanolone, on evoked excitatory postsynaptic potentials in the infralimbic region of the female rat prefrontal cortex. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of layer I were first characterized by recording responses at multiple depths between the cortical surface and the underlying white matter. Current source density analysis showed that the short-latency negative component was generated by activation of synaptic currents within layer I, and that putative polysynaptic responses were generated in layers III to V. The amplitude of evoked field EPSPs in layer I was not significantly affected by 20 min application of 17β-estradiol (10 nM), but both 100 nM progesterone and 1 µM allopregnanolone caused lasting increases in field EPSP amplitude. The effects of progesterone were not blocked by the nuclear progesterone receptor antagonist RU486 (1 µM). Both progesterone and allopregnanolone are known to activate membrane progesterone receptors, and we found that the membrane progesterone receptor agonist Org OD 02–0 facilitated EPSPs, and also occluded further increases induced by either progesterone or allopregnanolone. These results provide evidence that both progesterone and allopregnanolone facilitate synaptic responses in layer I of the infralimbic cortex by activating membrane progesterone receptors. [ABSTRACT FROM AUTHOR]

The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and neurological function after spinal cord injury, we prepared a rat spinal cord injury model using Allen’s percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly suppressed the expression of glial fibrillary acidic protein (Gfap) and vimentin, hallmark molecules of glial scarring, and increased the expression of neurofilament protein-200 (Nf-200) and growth-associated protein (Gap43), key molecules of axon regeneration, as well as Synaptophysin, a key molecule of synapse formation expression. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results suggest that Ski is able to inhibit the expression of key molecules of glial scar formation, and at the same time promotes the expression of molecules that are markers of axonal regeneration and synapse formation after spinal cord injury, making it a potential target for targeted therapy after spinal cord injury. [ABSTRACT FROM AUTHOR]

The glial scar that forms at the site of injury after spinal cord injury (SCI) is an important physical and biochemical barrier that prevents axonal regeneration and thus delays functional recovery. Ski is a multifunctional transcriptional co-regulator that is involved in a wide range of physiological and pathological processes in humans. Previous studies by our group found that Ski is significantly upregulated in the spinal cord after in vivo injury and in astrocytes after in vitro activation, suggesting that Ski may be a novel molecule regulating astrocyte activation after spinal cord injury. Further studies revealed that knockdown or overexpression intervention of Ski expression could significantly affect the proliferation and migration of activated astrocytes. To further verify the effect of knockdown of Ski expression in vivo on glial scar formation and neurological function after spinal cord injury, we prepared a rat spinal cord injury model using Allen’s percussion method and used lentivirus as a vector to mediate the downregulation of Ski in the injured spinal cord. The results showed that knockdown of Ski expression after spinal cord injury significantly suppressed the expression of glial fibrillary acidic protein (Gfap) and vimentin, hallmark molecules of glial scarring, and increased the expression of neurofilament protein-200 (Nf-200) and growth-associated protein (Gap43), key molecules of axon regeneration, as well as Synaptophysin, a key molecule of synapse formation expression. In addition, knockdown of Ski after spinal cord injury also promoted the recovery of motor function. Taken together, these results suggest that Ski is able to inhibit the expression of key molecules of glial scar formation, and at the same time promotes the expression of molecules that are markers of axonal regeneration and synapse formation after spinal cord injury, making it a potential target for targeted therapy after spinal cord injury. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH's abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH's rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG. [ABSTRACT FROM AUTHOR]

AbstractThe purpose of this trial was to assess the effects of methylphenidate on the kidney tissues and to investigate the protective effect of adenosine triphosphate (ATP) against possible methylphenidate nephrotoxicity in rats. The rats were separated into; healthy control (HG), methylphenidate (MPHG), ATP (ATPG), and ATP+ methylphenidate (AMPG). The ATPG and AMPG groups were administered ATP 4 mg/kg bw/d, and the HG and MPHG groups received distilled water intraperitoneally. One hour from, ATP and distilled water administration, methylphenidate 10 mg/kg bw/d was applied via oral gavage to the AMPG and MPHG groups once daily for 30 d (1 × 1). Animals were euthanized after 30 d and tissues were collected. The levels of certain oxidant/antioxidant parameters, pro-inflammatory cytokines, and Blood urea nitrogen (BUN) and creatinine levels were measured. Kidneys were also examined histopathologically. ATP inhibited the increase in oxidant and decrease antioxidant levels induced by methylphenidate. The amounts of pro-inflammatory cytokines were increased in methylphenidate-treated kidney tissue compared with the HG and AMPG groups. However, ATP increased oxidative damage markers and cytokines levels close to the healthy group. Serum BUN and creatinine levels increased with methylphenidate but ATP prevented BUN and creatinine from rising in the ATPG and MPHG groups. ATP also reduced the histopathological damage increased by methylphenidate. The potential efficacy of ATP in treating kidney damage induced by methylphenidate use. [ABSTRACT FROM AUTHOR]

Polyacrylic acid (PAA) with different concentrations of cross-linker was instilled into the trachea of rats to examine the effect of PAA crosslink density on lung disorders. Methods: F344 rats were intratracheally exposed to low and high doses of PAA with cross-linker concentrations of 0.1, 1.0, and 5.0% (CL0.1%, CL1.0%, and CL5.0%, respectively). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure. PAA with different cross-linker concentrations caused an increase in neutrophil influx, cytokine-induced neutrophils, and chemotactic factor (CINC) in bronchoalveolar lavage fluid (BALF) from 3 days to 1 week after instillation. Lactate dehydrogenase (LDH) activity in BALF and heme oxygenase-1 (HO-1) release in lung tissue were higher in the CL0.1% exposure group during the acute phase. Lung histopathological findings also showed that severe fibrotic changes induced by CL0.1% were greater than those observed in CL1.0% and CL5.0% exposure during the observation period. CL0.1% was associated with more severe lung fibrosis, and a decrease in lung fibrosis was observed with increasing cross-linker concentrations, suggesting that the cross-link density of PAA is a physicochemical feature that affects lung disorders. [ABSTRACT FROM AUTHOR]

• Effects of ovariectomy on mitochondrial function and synaptic proteins were examined in rat entorhinal cortex. • Ovariectomy reduced respiration and the expression of the mitochondrial membrane protein VDAC1. • Ovariectomy increased cytochrome c and superoxide dismutase, suggesting an increase in oxidative stress. • Synaptic markers PSD95 and synaptophysin were reduced by ovariectomy. • Estradiol supplementation in ovariectomized animals prevented changes in mitochondial and synaptic proteins. Reductions in circulating estrogens can contribute to cognitive decline, in part by impairing mitochondrial function within the hippocampal region. The entorhinal cortex provides the hippocampus with its main cortical inputs. To assess the impact of estrogen deficiency on mitochondrial respiration and synaptic proteins in the entorhinal cortex, female wildtype rats received either sham surgery, bilateral ovariectomy, or ovariectomy with implantation of a subdermal capsule to maintain low levels of circulating 17β-estradiol (E2). Mitochondrial respiration in the entorhinal cortex was not significantly affected two weeks following ovariectomy, but there was a reduction in oxygen consumption four weeks after ovariectomy that was prevented by E2 supplementation. The expression of mitochondrial membrane integrity element voltage-dependent anion channel protein (VDAC1) was also reduced four weeks after ovariectomy, suggesting that respiration was reduced due to a decline in mitochondrial density. Ovariectomy also increased mitochondrial and cytoplasmic cytochrome c and upregulated superoxide dismutase 2 (SOD2) both two and four weeks after ovariectomy, reflecting mitochondrial electron leakage and oxidative redox imbalance. Further, the ovariectomy-induced changes in mitochondrial proteins were associated with reductions in postsynaptic density protein 95 (PSD95) and the presynaptic protein synaptophysin. There were no changes in mitochondrial or synaptic proteins in ovariectomized animals that received E2 supplementation. Our findings indicate that reductions in circulating 17β-estradiol induced by ovariectomy disrupt mitochondrial functions in the entorhinal cortex, and suggest that a resulting increase in oxidative stress contributes to the degradation in synaptic proteins that may affect cognitive functions mediated by the hippocampal region. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mercaptomethylimidazole (MMI) affects the evolution of total neonatal development. • Hypothyroidism alter neonatal expression of neuronal and inducible nitric oxide synthases. • Changes of perinatal nitic oxide synthase expression influence protein nitration. • Thyroid hormones are crucial for nitric oxide production during postnatal development. Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal development and plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals. [ABSTRACT FROM AUTHOR]

Urinary tract injuries represent a significant clinical challenge, necessitating precise diagnosis and effective treatment strategies. Rat models are preferred for studying urinary tract injuries due to their size, visibility of external genitalia, and robust reproductive and growth capabilities. However, there is a lack of standardized methodologies for evaluating the endpoints of rat urinary tract injury models. This study aimed to investigate the methodology of model establishment, imaging evaluation techniques, and endpoint effectiveness. Twenty-four male Sprague-Dawley rats were randomly assigned to groups, including a blank control group and surgical groups. The surgical groups underwent urethral injury induced by recombinant transforming growth factor-β1 (TGF-β1) solution, followed by the random selection of one surgical group (n = 6) to receive treatment with mesenchymal stem cell (MSC) exosomes. High-frequency ultrasonography using a GE E10 device combined with a water bath method was employed to evaluate the urethral conditions of all rats. Ultrasonographic characteristics were scored for all surgical group rats, and an intergroup analysis was conducted between the surgical group and the control group rats. Statistical analysis was conducted using SPSS 22.0 software. Ultrasonographic assessment revealed significant differences in urethral echogenicity between the normal group and the surgical group, with noticeable changes in urethral morphology post-injury. Histopathological examination confirmed more severe urethral stenosis in the TGF group compared to the MSC group. High-frequency ultrasound could effectively differentiate between the two groups of rats. Additionally, there were significant differences in the scoring of ultrasonographic characteristics between the two groups. Urethral stricture presents a complex challenge in urology, often requiring invasive treatment modalities. The establishment of animal models plays a crucial role in understanding and addressing this condition. TGF-β1 induced fibrosis and MSC therapy represent promising avenues for urethral stricture management. High-frequency ultrasound combined with the immersion method offers a non-invasive and cost-effective approach for evaluating rat urethral stricture models. This study highlights the practicality of high-frequency ultrasound combined with the water bath method in evaluating rat urethral stricture models, as it can effectively differentiate between rats in the pure TGF-β1 induced group and those in the MSC treatment group based on urethral changes. The results underscore the importance of standardized methodologies for model assessment and the potential of non-invasive imaging techniques in preclinical research. Overall, this study contributes to advancing our understanding of urinary system injuries and holds implications for future therapeutic interventions in urology. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus. Swimming may be a potential intervention for joint contracture due to the special physical properties of water. OBJECTIVE: To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into a blank control group (n=8) and a joint contracture group (n=16). After the surgical operation of knee joint contracture rat models, the joint contracture group was randomly subdivided into a surgical control group (n=8) and a swimming treatment group (n=8). Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks. At the 6th week after surgery, the body mass, knee joint range of motion, and quadriceps diameter were tested, and the diameter/body mass index was calculated. Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle, and Masson staining was used to observe fibrotic changes in the knee joint capsule. Furthermore, the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris. RESULTS AND CONCLUSION: Compared with the blank control group, the knee range of motion decreased in the surgical control and swimming treatment groups (P < 0.01), and knee extension deficit and arthrogenic extension deficit were significantly increased (P < 0.01), the diameter of the quadriceps muscle was decreased (P < 0.01), the joint capsule showed significant fibrosis, the quadriceps muscle was atrophied, and the diameter/body mass index was decreased (P < 0.01). Compared with the surgical control group, the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter (P < 0.01), and significant improvement in joint capsule fibrosis and quadriceps atrophy. Compared with the blank control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group (P < 0.01). Compared with the surgical control group, collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group. Compared with the blank control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased (P < 0.05). Compared with the surgical control group, the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased (P < 0.05). To conclude, early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats, decreases MuRF1 expression in the quadriceps muscle, and increases joint range of motion and quadriceps diameter, thereby inhibiting the development of joint contracture. [ABSTRACT FROM AUTHOR]

Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of metabolic dysfunction-associated steatotic liver disease (MASLD). In humans and mice, the cellular heterogeneity and diverse function of hepatic macrophages in MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their roles in rats. Here, we collected liver tissues at the postnatal week 16, when our previously characterized Lep∆I14/∆I14 rats developed MASH phenotypes. By scRNA-seq, we found an increase in the number of macrophages and endothelial cells and a decrease in that of NK and B cells. Hepatic macrophages in rats underwent a unique M1 to M2 transition without expression of the classical markers such as Arg1 and Nos2, except for Cd163. Lipid-associated macrophages (LAMs) were increased, which could be detected by the antibody against Cd63. In the microenvironment, macrophages had an increased number of interactions with hepatocytes, myofibroblasts, T cells, neutrophils, and dendritic cells, while their interaction strengths remained unchanged. Finally, the macrophage migration inhibitory factor (MIF) pathway was identified as the top upregulated cell-communication pathway in MASH. In conclusion, we dissected hepatic macrophage dynamics during MASH at single cell resolution and provided fundamental tools for the investigation of MASH in rat models. [ABSTRACT FROM AUTHOR]

Background: Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome. Methods: The negative effects of secondary metabolites extracted from selected multidrug-resistant Gram-negative bacteria within the cancer microbiota were evaluated. These effects included carcinogenicity, mutagenicity, hepatotoxicity, nephrotoxicity, and sperm deformities observed in albino rats after one month of oral ingestion of these microbial extracts. Results: Our findings in the present investigation revealed that among the bacterial community derived from the microbiota, Gram-negative bacteria accounted for 74.87% the total microbiota (146 out of 195) and their spectrum including Escherichia sp. (n = 36, 24.66%) followed by Acinetobacter sp. (n = 34, 23.29%), Stenotrophomonas sp. (n = 29, 19.86%), Pseudomonas sp. (n = 26, 17.81%) and Serratia sp. (n = 21, 14.38%), as the most prevalent pathogens. All isolates derived from the cancer microbiome exhibited multidrug resistance to a large number of conventional therapies. Out of them Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 strains showed multidrug resistant profile against all antibiotic classes under study including penicillins, cephalosporins, carbapenems, fluoroquinolones, β-lactamase inhibitors combinations, folate synthesis pathway inhibitors, phosphonic, aminoglycosides, polymyxins, tetracyclines, macrolides, and chloramphenicol antibiotics. The adverse effects of oral ingestion of their metabolites were evaluated in albino rats. They induced pronounced carcinogenesis along with severe raise in the inflammatory cytokines, hepatotoxicity, nephrotoxicity, mutagenicity along with sperm deformities in treated animals. Moreover, all metabolites showed marked cytotoxicity against human normal cell lines; human mammary epithelial (MCF10A), human lung fibroblasts (WI38) and human dermal fibroblasts (HDFs). Conclusion: These bacterial strains isolated from the cancer microbiome may play significant roles in inducing cancer, inflammation, mutagenesis, hepatotoxicity, nephrotoxicity, and sperm abnormalities, along with histopathological changes in the treated animal groups by orally administrated metabolites in compared to the untreated group. [ABSTRACT FROM AUTHOR]

Context: The Developmental Origins of Health and Disease (DOHaD) concept suggests that early-life interventions significantly influence the long-term health outcomes of offspring. Emerging evidence supports that maternal physical exercise and balanced nutrition can positively impact the health of the next generation. Aims: This study investigated the effects of maternal swimming combined with postnatal high-fat, high-sugar (HFHS) diet on the ovarian health of adult female Wistar rat offspring. Methods: Adult female Wistar rats performed swimming exercise in a controlled temperature environment (32°C, 2% bodyweight overload adjusted daily) during 4 weeks, starting 1 week prior mating. The female offspring received a control or HFHS diet from postnatal day (PND) 21 to PND 90. We analyzed offspring's body weight, ovarian histomorphology, redox status, and associated molecular pathways 5′ adenosine monophosphate-activated protein kinase (AMPKα), forkhead box O3 (FoxO3), and mitofusin 1 (Mfn-1). Key results: Our findings reveal that maternal swimming exerted an effect on offspring body weight gain, delaying it. Individually, maternal exercise reduced superoxide dismutase (SOD) activity and mitofusin-1 levels, while the postnatal HFHS diet alone decreased both SOD and glutathione peroxidase (GPx) activities and increased the pFOXO3a/FOXO3a ratio in the ovaries. Conclusions: We showed that combination of maternal swimming with a 2% overload and a postnatal HFHS diet can negatively affect the ovarian redox balance in offspring. Implications: Prenatal and postnatal lifestyle might affect reproductive function in females. This study explores how a mother's physical activity and diet during pregnancy can shape the long-term health of her offspring, using a rat model. We found that swimming during pregnancy helped protect against weight gain in the offspring, but when combined with a high-fat, high-sugar diet after birth, it disrupted important antioxidant defenses in the offspring's ovaries. These findings highlight the complex impact of maternal habits on the future health of the next generation. Image by Cristiane Matté using BioRender. [ABSTRACT FROM AUTHOR]

Oxidative stress and apoptosis are highly engaged in development of diabetic nephropathy (DN). In monotherapy, dapagliflozin and pioglitazone positively modulate target organ damage even independently of their hypoglycaemic effect. This study evaluated whether a simultaneous PPARγ activation and SGLT cotransporter inhibition offer superior protection against DN-related oxidative and apoptotic processes in a T1DM rat model. Diabetes was induced in Wistar rats using streptozotocin (55 mg/kg, i.p.). The rats received daily chow containing dapagliflozin (10 mg/kg), pioglitazone (12 mg/kg) or their combination. Six weeks after STZ administration, histological and molecular analyses were performed in excised kidneys. STZ-induced DN was demonstrated by the propagation of apoptotic (Bax, p53, Casp3) and oxidative reactions (Gp91phox, MnSOD) and disrupted nitric oxide signalling (eNOS, Hsp90, Cav1). Kidney damage molecule expression (Kim1, Nphs1) revealed a deceleration of kidney damage by pioglitazone and dapagliflozine monotherapies. The monotherapy also reduced apoptosis, oxidative stress, and partially restored NO signalling. The combined therapy ameliorated glomerulosclerosis but in other measured parameters, it reached the effect of the monotherapies except for Hsp90 expression modulation. Both dapagliflozin and pioglitazone exert protective character in kidneys when used in monotherapy. The combined therapy does not exhibit an expected additive effect within modulating oxidative stress, NO signalling or apoptosis. [ABSTRACT FROM AUTHOR]

This research seeks to address the gap in past studies by examining the role of the Nrf2 (nuclear factor erythroid 2-related factor 2) and HO-1 (heme oxygenase-1) signaling pathways in hypoxia and the potential effects of alpha-pinene on these factors. Wistar rats were divided into 7 experimental groups (n = 7): 1) control, 2 and 3) groups receiving alpha-pinene 5 and 10 mg/kg (i.p., for 21 days), 4) hypoxia group (7% O2 and 93 N2, 3 h, GD14 to GD18), 5 and 6) groups receiving alpha-pinene 5 and 10 after hypoxia. Memory and cognition were evaluated using the Morris water maze and novel object recognition tests. Inflammation was assessed by ELISA method and Nrf2 and HO-1 Nrf2 gene expression was evaluated using real-time PCR in the hippocampus. Recognition index, spatial memory, and Nrf2-H0-1 gene expression significantly reduced in the hypoxia group compared to the control group, and alpha-pinene injection in the offspring improved cognition, memory, and Nrf2- HO-1 gene expression in the groups were affected by hypoxia. Inflammation factors in the hypoxia group were higher than the control, but alpha-pinene significantly decreased inflammation (all cases p < 0.05). Based on the results, it seems that alpha-pinene prevents cognitive and memory loss by increasing Nrf2 and H0-1 gene expression and reducing inflammation. [ABSTRACT FROM AUTHOR]

Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment. We highlight a key case study for the Organization for Economic Cooperation and Development (OECD), in which a 3D model was used to assess human toxicity and replace the requirement for a 90-day inhalation toxicity study in rats. Finally, we consider the regulatory guidelines for the application of NAMs and potential use of different lung models for aerosol toxicity studies depending on the regulatory requirement/context of use. [ABSTRACT FROM AUTHOR]

Sepsis, a life-threatening condition characterized by dysregulated host responses to infection, often leads to multi-organ dysfunction, including kidney injury. Kidney damage in sepsis can have severe consequences and is associated with high mortality rates. This study aimed to investigate the potential therapeutic effects of fosfomycin (FOS), a broad-spectrum antibiotic with immunomodulatory properties, on kidney damage induced by cecal ligation and puncture (CLP)-induced sepsis in a rodent model. In total, 24 rats were randomly divided into three groups. Group 1 (n = 8), the healthy control group (C), received a single dose of 0.9% NaCl (saline) solution via an intraperitoneal (i.p.) route. To group 2 (n = 8), the CLP group, CLP-induced sepsis was applied without medication, and a single dose of 0.9% NaCl (saline) solution was applied i.p. before induction. To group 3 (n = 8), the CLP + FOS (500 mg/kg) group, a single dose of 500 mg/kg FOS was administered i.p. before sepsis induction. The effects of fosfomycin on kidney function, histopathological changes, inflammatory markers, oxidative stress, and apoptosis were assessed. In the fosfomycin-treated group, the histological analysis results demonstrated reduction in kidney tissue damage and inflammation. Additionally, fosfomycin attenuated the upregulation of pro-inflammatory cytokines and reduced oxidative stress markers in kidney tissue. Furthermore, fosfomycin treatment was associated with a decrease in apoptotic cell death in the kidney. These findings suggest that fosfomycin may have a protective effect on kidney damage caused by CLP-induced sepsis. The potential mechanisms underlying this protection include the modulation of inflammation, reduction of oxidative stress, and inhibition of apoptosis. [ABSTRACT FROM AUTHOR]

The Rat-1 cell line was established as a subclone of the parental rat fibroblastoid line F2408, derived from Fisher 344 rat embryos. Rat-1 cells are widely used in various research fields, especially in cancer biology, to study the effects of oncogenes on cell proliferation. They are also crucial for investigating signal transduction pathways and play a key role in drug testing and pharmacological studies due to their rapid proliferation. Therefore, Rat-1 cells are an indispensable research tool. While some cytogenetic information on their basic chromosomal features is available, detailed genomic analyses, such as karyotype analysis, short tandem repeat (STR) profiling, and whole-genome sequencing, have not been thoroughly conducted. As a result, the genetic stability and potential variations in Rat-1 cells over extended culture periods are poorly understood. This lack of comprehensive genetic characterization can limit the interpretation of experimental results and requires caution when generalizing findings from studies using this cell line. In this study, we describe the genetic characterization of the Rat-1 cell line. We established a karyotype, performed multicolor fluorescence in situ hybridization (mFISH), identified chromosomal losses and gains, and defined an STR profile for Rat-1 with 31 species-specific markers. Interestingly, the chromosomal imbalances found in Rat-1 cells resemble those found in human epithelioid sarcoma or liposarcoma. Additionally, we analyzed the transcriptome of Rat-1 cells through mRNA sequencing (mRNA-Seq) using next-generation sequencing (NGS). Finally, typical features of these fibroblastic cells were determined using electron microscopy, Western blotting, and fluorescent phalloidin conjugates. [ABSTRACT FROM AUTHOR]

Background: Perturbations of intestinal serotonergic neurotransmission seem to be involved in bowel dysmotility associated with irritable bowel syndrome (IBS) with diarrhea. Oral administration of probiotics is an emerging strategy to improve IBS symptoms, possibly via influencing local serotonin metabolism and neurotransmission. In the present study, we evaluated the effects of the yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) on intestinal motility and serotonergic receptors. Methods: Isolated rat ileum was contracted in a cumulative concentration way by serotonin (5-HT), various 5-HT agonists or by acetylcholine to determine their effective concentration 50% (EC50). Single concentrations of S. boulardii or 5-HT antagonists were added before agonists to identify the receptors targeted by S. boulardii. Results: The serotonin antagonists 5-HT1A WAY100635, 5-HT2A ketanserin and 5-HT4 GR113808 inhibited 5-HT-induced contractions in a concentration-dependent manner. S. boulardii between 0.05 and 1.5 mg/mL increased the EC50 value of 5-HT suggesting an inhibitory effect against serotonin-induced contraction. Ileum contractions induced by the serotonin agonist 5-HT1 carboxamidotryptamine or by the serotonin agonist 5-HT2 alpha-methyl-5-HT were significantly reduced by S. boulardii at 1.5 mg/mL. The yeast did not affect acetylcholine-induced ileum contraction. Conclusion: S. boulardii CNCM I-745 possesses relaxant properties on the rat ileum involving the inhibition of 5-HT and more specifically 5-HT1A and 5-HT2A/2B/2C receptor-induced contractions. These data suggest that the attenuation of 5-HT-induced ileal contractions by S. boulardii represents a probable mechanism of action sustaining its efficacy in patients affected by IBS with diarrhea. [ABSTRACT FROM AUTHOR]

Protein deficiency in the diet during pregnancy and lactation has a serious impact on the offspring by programming a predisposition to such serious diseases as hypertension and type 2 diabetes mellitus. In our study, we examined liver ultrastructure of rat pups at ages 2, 21, and 40 days with maternal protein deficiency. Body weight of the pups progressively lagged behind the control throughout the experiment, and the timing of eye opening indicated a slowdown of development. In the liver of 2-day-old animals, the proportion of hematopoietic cells at early stages of differentiation was higher as compared to the control. At the ultrastructural level, no obvious pathological changes were revealed, but a decrease in the amount of organelles was observed simultaneously with accumulation of lipids and glycogen. In the course of the experiment, a progressive decrease in the amount of the rough endoplasmic reticulum and ribosomes and increasing accumulation of glycogen in the cytoplasm of hepatocytes were noted. The most pronounced difference in ultrastructure between periportal and pericentral hepatocytes of control rat pups was detected on the 40th day of development, whereas in the low-protein diet group, the difference was weakly pronounced throughout the experiment. Thus, we showed that with prenatal and early postnatal protein deficiency, the growth and development of rat pups slows down, and glycogen accumulates excessively in the liver concurrently with a decrease in the amount of organelles. [ABSTRACT FROM AUTHOR]

Background: The mechanism by which laparoscopic operations induce lower post-operative inflammatory response compared to open surgery was investigated with regard to the effect of the type of gas environment. Methods: Rats were subjected to midline laparotomy at either CO2 (group CO2) or room-air environment (group Air) or to anesthesia only (group Control) under atmospheric pressure conditions. At various timepoints after surgery (1, 3, 6, 24, or 48 h), the expression of inflammation biomarkers interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and nuclear factor-κΒ (NFκΒ) were assessed immunohistochemically in tissue samples excised from the liver, intestine, and kidneys, accompanied by histopathologic analysis, and their levels were measured by ELISA in blood samples. Results: Tissue expression of IL-6, TNFα, and NFκΒ was downregulated in the liver and intestine in group CO2 compared to group Air and in the kidneys in group Air compared to group CO2. However, no differences were noted among groups regarding the histopathologic score of organ tissues and the blood serum levels of inflammation biomarkers. Conclusion: Post-operative local inflammatory response was lower in intra-peritoneal organs of rats subjected to laparotomy at CO2 rather than room-air environment under atmospheric pressure conditions. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT) plays an important role in many physiological and pathological processes, such as regulation of vascular tone. The aim of this study is to evaluate the effects of pioglitazone on functional, structural, and biochemical properties of PVAT in an experimental model of type-2 diabetes (T2DM). T2DM was induced by high-fat-diet/low-dose-streptozotocin in rats, and pioglitazone (20 mg/kg/p.o.) was administered for 6 weeks. Changes in biochemical parameters, PVAT-mass, vascular-reactivity in thoracic-aorta, as well as PVAT adipocytokine and PPARG-expression levels, and histopathology were evaluated. Pioglitazone administration improved blood glucose and lipid profiles in T2DM. Pioglitazone did not change the anticontractile effect of PVAT on aortic contractile reactivity and besides, had no influence on endothelium-dependent and -independent relaxation responses. Pioglitazone administration increased PVAT-mass and tumor necrotizing factor-α levels, while adiponectin, leptin, and interleukin-6 levels were unchanged. Also, a prominent increase was observed in PPARG-expression in T2DM-Pio group. Moreover, pioglitazone decreased liver steatosis, aortic wall thickening, and myocardial damage, whereas increased adipocyte size and adiposity in PVAT. Overall, pioglitazone treatment changed the mass and in part the inflammatory profile of PVAT but did not modify vasoreactivity in T2DM. This study provides novel findings in relationship with the adipogenic effect of pioglitazone and PVAT function. [ABSTRACT FROM AUTHOR]

Prodromal signs of Parkinson's disease (PD), including vocal communication deficits, are poorly understood and do not respond adequately to current pharmacologic treatments. Norepinephrine dysfunction is involved early in PD; thus, drug therapies targeting norepinephrine may be useful as a treatment of prodromal signs. This study used a validated, translational rodent model of prodromal PD, the male Pink1−/− rat, which exhibits ultrasonic vocalization (USV) deficits as early as 2 months of age. The purpose of this preclinical study was to investigate a dose-dependent (2.5, 5.0, 7.5, 10 mg/kg) response of methylphenidate on USV parameters with the hypothesis that methylphenidate would increase vocalization output. Because methylphenidate is a psychostimulant with known adverse side effects, we also hypothesized that potential side effects including anxietylike behavior and spontaneous activity would be increased in a dose-dependent manner. To accomplish this, wild-type (WT) and Pink1−/− rats were administered a dose of a vehicle (saline) and a methylphenidate dose in a randomized within-subjects design and then assessed for USVs, anxiety behavior (open field), and limb motor (cylinder) activity. The results suggest that methylphenidate does not alter USV emissions in Pink1−/− rats; however, methylphenidate increased the total number of vocalizations and duration of frequency-modulated calls in WT rats. Methylphenidate dose dependently influenced spontaneous movements in both WT and Pink1−/− rats, as expected, while methylphenidate increased anxiety in Pink1−/− rats and not WT rats. This study demonstrates a difference in response to a psychostimulant between Pink1−/− rats and WT rats. [ABSTRACT FROM AUTHOR]

• A single topical application of Imiquimod induces psoriasis-like skin inflammation. • Plasmid IL-10 gene therapy is known to be therapeutic after intrathecal dosing. • Transcutaneous delivery of therapeutic plasmid DNA for psoriasis is challenging. • Lipoderm HMW enabled transcutaneous delivery of plasmid IL-10 gene therapy. • This combination provides initial indication of therapeutic potential for psoriasis. Psoriasis is a chronic immune-mediated skin disorder characterized by intense local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current treatment approaches for psoriasis aim to alleviate symptoms and prevent disease progression, including systemically administered drugs with whole body side effects. Despite some advances in psoriasis treatment, success has been quite limited. To begin to address this challenge, we undertook an initial investigation of whether transcutaneous delivery of an endogenous anti-inflammatory cytokine could provide an effective, local treatment of psoriatic-like skin conditions. To do this, we utilized a previously documented rodent model of psoriasis, induced via a single topical application of Imiquimod (IMQ) to the shaved back of rats. The therapeutic approach used for this initial investigation was delivery of plasmid DNA encoding rat interleukin-10 (pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective in suppressing neuroinflammatory disorders after localized delivery either intracerebrally or intrathecally. Translation of this CNS therapeutic for use in psoriatic-like skin disorders required reformulation to enable transcutaneous delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a base explicitly designed to deliver higher molecular weight compounds into skin. Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was effective in decreasing mRNA levels of pro-inflammatory cytokines as well as reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this transcutaneous IL-10 gene therapy decreased signs of skin inflammation, reflected by reduced erythema. Moreover, the results provide an initial indication that IL10 may stimulate hair regrowth in psoriatic-like skin. [ABSTRACT FROM AUTHOR]

• Translocator protein 18 kDa (TSPO) is upregulated with neuroimmune signaling. • TSPO is upregulated in brains of male and female rats with peripheral nerve injury. • TSPO is expressed predominantly by microglia. • TSPO is downregulated by treatment with Nrf2 activator. Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was increased in discrete brain regions, including medial prefrontal cortex, somatosensory cortex, insular cortex, anterior cingulate cortex, motor cortex, ventral tegmental area, amygdala, midbrain, pons, medulla, and nucleus accumbens. TSPO was broadly upregulated across these regions at 4 weeks post CCI in males, and 10 weeks in females, though there were regional differences between the sexes. Using immunohistochemistry, we confirmed TSPO expression in these regions. We further demonstrated that TSPO was upregulated principally in microglia in the nucleus accumbens core, and astrocytes and endothelial cells in the nucleus accumbens shell. Finally, we tested whether TSPO upregulation was sensitive to diroximel fumarate, a drug that induces endogenous antioxidants via nuclear factor E2-related factor 2 (Nrf2). Diroximel fumarate alleviated neuropathic pain and reduced TSPO upregulation. Our findings indicate that TSPO is upregulated over the course of neuropathic pain development and is resolved by an antinociceptive intervention in animals with peripheral nerve injury. [ABSTRACT FROM AUTHOR]

The aim of the research was to determine possible changes in the morphology of cells of the leukocyte order of peripheral blood, using geometric morphometric tests, after the application of calcium-aluminate and calcium-silicate cements to the dental pulp in rats. The study included 27 Wistar rats, divided into an experimental group (n=18) and a control group (n=9). Trepanation of the tip of the pulp cavity was performed, and placement of calcium-aluminate and calcium-silicate dental cements directly on the pulp. Peripheral blood samples were collected by vena caudalis puncture, with the aim of making blood smears. In the tpsUtil program, two-dimensional models of the examined leukocytes were created and they were converted into tps files, on which sixteen specific points were marked in the tpsDig program. We analyzed their shape in the MorphoJ program. The results of discriminant functional analysis determined that there was a statistically significant difference in the shape of the lymphocytes between the experimental animals, to which dental cements were applied, compared to the lymphocytes from the control group. Morphological differences were determined between the lymphocytes to which calcium aluminate and calcium silicate were applied. The results indicate that there were statistically significant morphological differences between these two groups of lymphocytes (P=0.02). The results obtained indicate the possibly unfavorable influence of the tested dental cements, especially calcium silicate, on leukocytic cells. [ABSTRACT FROM AUTHOR]

In 2022, para-fluorofentanyl (pFF) rose to the 6th most reported drug and the most reported fentanyl analog in the United States according to the Drug Enforcement Administration (DEA). pFF differs from fentanyl by the addition of a single fluorine group. To date, pFF has not been extensively evaluated in vivo and is frequently seen in combination with fentanyl. In the present study, the pharmacodynamic (PD) and pharmacokinetic (PK) properties and brain region-specific concentrations of pFF were evaluated in male Sprague–Dawley rats and compared to fentanyl. A 300 μg/kg subcutaneous dose of fentanyl or pFF was administered to assess PD and PK parameters as well as brain region concentrations. PD parameters were evaluated via a tail flick test to evaluate analgesia and core body temperature to measure hypothermia, a surrogate marker of overall opioid toxicity. Fentanyl and pFF were found to be equally active at the tested dose in terms of tail flick response with both compounds producing an analgesic response that lasted up to 240 min post-drug treatment. pFF induced a significantly greater hypothermic effect compared to fentanyl with a maximum temperature decrease of −5.6 ℃. Plasma PK parameters (T1/2, AUC, etc.) did not differ between fentanyl and pFF. However, pFF concentrations in the medulla, hippocampus, frontal cortex and striatum were more than two times the fentanyl concentrations. The increase in brain concentrations and greater hypothermic effect suggests that pFF is potentially more dangerous than fentanyl. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the effect of the recommended (6.5 mg/kg) or enhanced (13 mg/kg) level of CuNPs in the diet in combination with different types of dietary fibre – cellulose (control), inulin, pectin, or psyllium on the Cu biodistribution and level of selected minerals parameters in the blood of rats. Rats were randomly divided into 10 groups. The first two groups were fed control diets containing cellulose and a mineral mixture with standard or enhanced content of CuCO3. Experimental groups were fed a diet supplemented with CuNPs (6.5 or 13 mg/kg) and combined with different types of fibre (cellulose, pectin, inulin, or psyllium). After the feeding period blood, liver, brain, and thigh samples were collected. In the samples of water, diet, urine, faeces, liver, brain, and thigh the Cu content was determined to assess Cu biodistribution in the body. Additionally, the concentrations of minerals (Cu, P, Ca, Mg, Fe, and Zn) in the blood plasma samples were measured. The replacement of CuCO3 with CuNPs in the diet beneficially influenced the biodistribution of Cu in the body by reducing its excretion, improving its digestibility, and utilization, reducing its accumulation in the brain and muscle, and increasing levels of Ca, P, Mg, Zn and Fe in the blood. Increasing the level of CuNPs in the diet increased total Cu intake. The addition of pectin, inulin and psyllium to the diet with a high content of CuNPs significantly increased the excretion of Cu, with no negative effect on its digestibility, and utilization, and prevented its excessive accumulation in the brain and muscle of rats, especially in the case of inulin. The results suggest that the addition of dietary fibre to the diet of rats ensures homeostasis of this element in the case of excessive intake of CuNPs by modifying the bioavailability of Cu. [ABSTRACT FROM AUTHOR]

Background: Rats are an important reservoir animal for several zoonotic pathogens worldwide, including hantaviruses and Leptospira spp., which are the causative agents of hemorrhagic fever with renal syndrome, hantavirus cardiopulmonary syndrome, and leptospirosis. Although a previous study indicated a high frequency of antihantaviral antibodies in patients with acute fever in Indonesia, circulating hantaviruses and their reservoir animals in the country remain limited. Materials and Methods: The presence of hantavirus in rats captured in the urban area of Bogor, Indonesia, from which Leptospira spp. were isolated using PCR, followed by DNA sequencing. Immunohistochemical analyses were performed to detect hantaviral and leptospiral antigens in rat kidney tissues. Results: Seoul of Orthohantavirus seoulense (SEOV) RNA was detected from 24 of 80 Rattus norvegicus (30%). SEOV and Leptospira coinfection was detected in 10 of 80 rats (12.5%). Immunohistochemistry revealed that hantavirus antigens were positively stained in the interstitial capillaries and cells, whereas Leptospira antigens were stained in the luminal side of the renal tubules. Conclusion: This study revealed a high prevalence of SEOV and SEOV and Leptospira coinfection among rats in the urban areas of Bogor, Indonesia, indicating a potential risk of rat-borne zoonotic diseases in the area. [ABSTRACT FROM AUTHOR]

The present study has investigated whether circulating estrogen level variations in the pro-estrus and estrus phases of the intact rats and estrogen depletion in the ovariectomized animals (OVX) adjust the formalin-induced nociceptive behaviors. During the pro-estrus and estrus phases of rats' estrus cycle and in the OVX rats, 17β-estradiol and ICI 182,780 (estrogen receptor antagonist) were administered into the right paragigantocellularis lateralis (LPGi) nucleus. Then, the formalin-induced flexing and licking responses were recorded for 60 min. The findings of this study revealed that intra-LPGi administration of 17β-estradiol (0.8 μmol) reduced the formalin-induced flexing and licking duration in pro-estrus and estrus rats (P < 0.001), suggesting an analgesic effect. 17β-Estradiol injection into the LPGi nucleus of OVX rats increased the flexing duration (P < 0.05) while decreasing the licking duration (P < 0.05) of the formalin test. The pain modulatory effect of 17β-estradiol on the flexing response was reversed by ICI 182,780 (15 nmol) in the pro-estrus (P < 0.001) and estrus rats (P < 0.001) but not in the OVX rats. Also, pretreatment of LPGi nucleus with ICI 182,780 reversed the analgesic effect of 17β-estradiol on the licking response in the pro-estrus (P < 0.05), estrus (P < 0.001), and OVX rats (P < 0.001). These results suggest that the pain threshold in intact female rats is modulated independently of the estrus state. Still, the basal level of plasma estrogen and the activation of its receptors are necessary for pain modulation. [ABSTRACT FROM AUTHOR]

This study explored the therapeutic potential hydroalcoholic extract derived from Origanum vulgare leaf in mitigating ethanol-induced working memory impairments and hippocampal oxidative stress in rats. Eight groups, including controls, ethanol-exposed rats, and those treated with extract (100, 200, and 300 mg/kg) alone or combined with ethanol, were assessed using the radial arm maze (RAM) for behavioral tests. Ethanol increased working memory errors and time spent in error zones, effects notably reduced by the extract, especially at 300 mg/kg dose (P≤0.001). Biochemical tests showed ethanol suppressed catalase (CAT), superoxide dismutase (SOD), and acetylcholinesterase (AChE) activities within the hippocampus and cortex. while the extract elevated CAT and SOD activities and reduced AChE activity. These results suggest the extract’s neuroprotective properties, including oxidative stress reduction and neurotransmitter modulation, which mitigate ethanol-induced hippocampal damage. This highlights Origanum vulgare extract potential as a therapeutic adjunct for memory deficits and oxidative stress-related conditions. [ABSTRACT FROM AUTHOR]

High consumption of ultra-processed foods, rich in sugar and unhealthy fats, has been linked to the onset of numerous chronic diseases. Consequently, there has been a growing shift towards a fiber-rich diet, abundant in fruits, vegetables, seeds, and nuts, to enhance longevity and quality of life. The primary bioactive components in these plant-based foods are polyphenols, which exert significant effects on modulating the gastrointestinal microbiota through their antioxidant and anti-inflammatory activities. This modulation has preventive effects on neurodegenerative, metabolic, and cardiovascular diseases, and even cancer. The antimicrobial properties of polyphenols against pathogenic bacteria have significantly reduced the need for antibiotics, thereby lowering the risk of antibiotic resistance. This paper advances the field by offering novel insights into the beneficial effects of polyphenols, both directly through the metabolites produced during digestion and indirectly through changes in the host's gastrointestinal microbiota, uniquely emphasizing swine as a model highly relevant to human health, a topic that, to our knowledge, has not been thoroughly explored in previous reviews. This review also addresses aspects related to both other animal models (mice, rabbits, and rats), and humans, providing guidelines for future research into the benefits of polyphenol consumption. By linking agricultural and biomedical perspectives, it proposes strategies for utilizing these bioactive compounds as therapeutic agents in both veterinary and human health sciences. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is defined as a neurodevelopmental condition. The precise underlying mechanisms remain incompletely elucidated. A body of research suggests disruptions in both the cellular architecture and neuronal function within the brain regions of individuals with ADHD, coupled with disturbances in the biochemical parameters. This study seeks to evaluate the morphological characteristics with a volume measurement of the striatal regions and a neuron density assessment within the studied areas across different developmental stages in Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Furthermore, the investigation aims to scrutinize the levels and activities of specific markers related to immune function, oxidative stress, and metabolism within the striatum of juvenile and maturing SHRs compared to WKYs. The findings reveal that the most pronounced reductions in striatal volume occur during the juvenile stage in SHRs, alongside alterations in neuronal density within these brain regions compared to WKYs. Additionally, SHRs exhibit heightened levels and activities of various markers, including RAC-alpha serine/threonine-protein kinase (AKT-1), glucocorticoid receptor (GCsRβ), malondialdehyde (MDA), sulfhydryl groups (-SH), glucose (G), iron (Fe), lactate dehydrogenase (LDH). alanine transaminase (ALT), and aspartate transaminase (AST). In summary, notable changes in striatal morphology and elevated levels of inflammatory, oxidative, and metabolic markers within the striatum may be linked to the disrupted brain development and maturation observed in ADHD. [ABSTRACT FROM AUTHOR]

Two experiments in rats examined how training where a stimulus signaled when to respond for reward, conditions that should favour S-R learning, might lead to habitual control of behaviour. Experiment 1 investigated how animals trained with a stimulus preceding lever insertion would impact learning relative to a group that was self-paced and could control lever insertion with a second, distinct response. Rats were then tested for sensitivity to outcome devaluation to distinguish between goal-directed and habitual control. We found that free-operant, self-paced conditions promoted goal-directed control while signaling trials with a stimulus promoted habitual control evidenced as insensitivity to outcome devaluation. Experiment 2 assessed whether the stimulus-outcome association is important for driving habitual responding when training occurs with a traditional discriminative stimulus. A comparison group was trained under free-operant conditions and experienced the same stimulus presented alongside the earned reward. Following devaluation, animals trained under discriminated-operant conditions had reduced goal-directed control, but only after extended training. The free-operant group remained goal-directed, even after extended training, and their performance was not altered by stimulus presentations, suggesting effects of a stimulus-outcome association were unlikely to account for the deficit in the discriminative stimulus group. These results extend understanding of how stimuli present during instrumental training promote the development of habitual control. [ABSTRACT FROM AUTHOR]

Aerobic exercise training is aimed to prevent and correct various cardiovascular disorders. To study its effects, various rodent models are currently in use, among which the rat model of voluntary wheel running is of particular interest, as its pattern of motor activity is close to natural rat locomotion, while being non-stressful. This work was aimed at a comprehensive investigation of wheel running effects on the neural control of heart rate (HR) in rats. The animals, aged 6 weeks, were divided into two groups: training (TR, free access to wheels, n = 11) and sedentary control (CON, n = 12). After a 6-week training, ECG was recorded in freely moving rats using skin electrodes in three modes: at rest, after autonomic blockade of cardiotropic influences, and during 4-min air-jet stress. Autonomic neural influences were analyzed by administering the β1-adrenoceptor blocker atenolol (2 mg/kg) and the peripheral M-cholinoceptor antagonist methylatropine (1 mg/kg), as well as by analyzing HR variability via spectral and wavelet analyses. At rest, the TR group showed a decrease in the baseline HR level vs. CON group. Аtenolol decreased HR equally in two groups, but methylatropine elicited a more significant increase in HR in the TR vs. CON group. After atenolol and methylatropine co-administration, HR levels in two groups were similar. TR rats showed an increased contribution of high-frequency (0.75–3 Hz) oscillations to the total RR interval power spectrum. During emotional (air-jet) stress, the TR group demonstrated a more pronounced increase in HR vs. CON group. In addition, stressed TR rats exhibited a decrease in the amplitude of HR high-frequency oscillations, which was absent in the CON group. Thus, voluntary wheel running in rats is accompanied by an increase in parasympathetic influences on the heart, as manifested in an increase both in respiratory sinus arrhythmia and in vagal effects on the resting HR level (increased tachycardia). Moderate resting bradycardia promotes a more pronounced increase in HR under emotional stress conditions due to suppression of parasympathetic cardiac influences. [ABSTRACT FROM AUTHOR]

Objective(s): Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells. Materials and Methods: Ninety adult male Wistar rats were divided into six main groups (n=15) and three subgroups (2, 4, and 8 weeks). Groups: control; without surgery, Tr; sciatic nerve transected in silicone tube, S; collagen gel put inside the silicone tube, MC; placed 3x104 mast cells mixed with scaffold, MSC; placed 3x104 mesenchymal stem cells mixed with scaffold, and MC+MSC; 3x104 of each of the mast cell and mesenchymal stem cells along with scaffold. Animals were euthanized and sampled for muscle and nerve histological and nerve immunohistochemical evaluations. Results: Diameter of muscle fibers, ratio of the muscle fiber's nuclei to the fibrocyte nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fiber's number (mn/mf), and ratio of the blood vessels number to the number of muscle fibers (v/mf) in all treatment groups, especially the MC + MSC group, increased compared to the Tr group but the number of mast cells, the percentage of sarcoplasmolysis, and necrosis fibers decreased. Histomorphometric results of the nerve in its various parts and immunohistochemistry results also showed improved nerve conduction, especially in the MC + MSC group. Conclusion: In this study, nerve improvement happened mainly for two reasons: cells and time. So, the most obvious improvement occurred in the group with mast and mesenchymal cells in the 8th week. [ABSTRACT FROM AUTHOR]

Objective(s): Activating apoptosis and oxidative stress contributes to the pathogenesis of diabetes. Evening primrose oil (EPO) has been shown to regulate lipid profiles and hyperglycemia under metabolic conditions. This study aimed to examine the effect of EPO on miR-21 expression, oxidative stress, apoptosis, and histological changes in the pancreas of male rats with experimental diabetes induced by streptozotocin (STZ). Materials and Methods: Thirty-two Wistar rats were divided into four distinct groups: control, diabetic, diabetic + EPO, and EPO. EPO was administered orally at a dose of 500 mg/kg, and STZ was administered intraperitoneally at a dose of 35 mg/kg for 28 days. In the end, the effects of treatments were assessed by measuring expressions of miR-21 in the pancreas with real-time PCR, pancreatic histological and immunohistochemical changes examinations, and oxidative stress assessment. Results: In the diabetic group, miR-21 expression and the levels of caspase-3 and malondialdehyde (MDA) were increased compared to the control group, while insulin expression and superoxide dismutase activity (SOD) levels were decreased significantly. Treatment with EPO resulted in a reduction of miR-21 and caspase-3 expression, as well as MDA levels, and an increase in insulin expression and SOD levels compared to the diabetic group. Additionally, supplementation with EPO demonstrated the ability to restore pancreatic tissue features, serum insulin levels, and blood glucose fluctuations. Conclusion: Collectively, the protective impacts of EPO in diabetic rats may be linked to the inhibition of miR-21/caspase-3/oxidative stress pathway, leading to the restoration of pancreatic β-cell function and structure. [ABSTRACT FROM AUTHOR]

Increasing interest in identifying the causes of and treatments for heart failure with preserved ejection fraction and cardiac fibrosis has spawned a focus on measures of cardiac diastolic function. The methods, their underlying principals and mechanics, and caveats to their measurement were largely worked out decades ago, but some of this seems a bit forgotten as scientists working in the field now have backgrounds more in molecular and cellular biology. This perspective was spawned by seeing the growing number of studies where diastolic function analysis is a key parameter used to justify a given pre-clinical model or to show the consequences of a particular genetic or pharmacological therapy. The goals are to discuss what comprises and influences diastolic function, how it is measured, what the parameters mean and what their limitations are, and what comprises evidence for pathophysiologically meaningful diastolic dysfunction. • Assessing diastolic function requires measuring different phases of diastole. • Each metric makes assumptions and often has load dependence to be considered. • Math models often used by indexes should be chosen to best match the actual data. • Finding diastolic dysfunction does not imply heart failure per se. • The severity of dysfunction and impact on cardiopulmonary disease is important. [ABSTRACT FROM AUTHOR]

Diabetes is one of the leading causes of endometrial diseases in women. No study has addressed the influence of hydrogen sulphide (H2S) donors on endometrial injury on top of type 1 diabetes. This research was conducted to study either the effect of sodium hydrosulphide (NaHS), the H2S donor, or DL-propargylglycine (PAG), the inhibitor of endogenous H2S production, on the endometrium of diabetic rats. A total of 40 female Wistar rats were separated into control group, diabetic group, diabetic group treated with NaHS and diabetic group treated with PAG. Serum levels of insulin, glucose, total cholesterol (TC) and triglycerides (TG) were assessed. Uterine tissue markers of oxidative stress, inflammation, apoptosis and cell proliferation were analysed. Diabetes-induced endometrial overgrowth associated with oxidative stress, inflammation and inhibition of apoptosis. NaHS administration reversed the previous conditions while PAG administration got them worse. We concluded that H2S prevented endometrial overgrowth in a rat model of type 1 diabetes through modulation of PPARγ/mTOR and Nrf-2/NF-κB pathways. [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]

This study explored long-term retention of spatial memory in rats using an eight-arm radial maze. Crystal and Babb (Learning and motivation, 39(4), 278–284, 2008) previously demonstrated that rats could retain spatial memory for up to 25 h in the radial maze. Notably, they found performance improved with 48-h intertrial intervals compared with 24-h intervals. Our study investigated the effects of extending intertrial intervals on long-term retention of spatial memory by reducing the potential for proactive interference. Each trial comprised a learning phase, during which subjects were required to sequentially visit four randomly selected arms, followed by a free-choice test that included all eight arms, conducted after increasing the retention and intertrial intervals. The retention intervals were systematically increased from 1 h to 24, 48, and, ultimately, 72 h, with corresponding intertrial intervals expanding from 24 to 48, 120, and 144 h. Performance significantly surpassed chance levels across all conditions, demonstrating that rats are capable of retaining spatial memory for up to 72 h. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) as a neurodegenerative disease can cause behavioral impairments due to oxidative stress. Aging and oxidative conditions are some AD risk factors. Objective: We assessed the influence of geraniol (GR), an acyclic monoterpene alcohol, on behavioral functions, hippocampal oxidative status, and histological alterations in AD rats induced by amyloid-β (Aβ). Methods: Male Wistar rats (n = 70) were randomly allocated to the control, sham, AD, control-GR (100 mg/kg; per oral: P.O.), AD-GR (100 mg/kg; P.O.; treatment), GR-AD (100 mg/kg; P.O.; pretreatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment + treatment) groups. GR administration was done for four continuous weeks. After treatments, novel object recognition (NOR) and Morris water maze (MWM) tests assessed the animals' behavior. Then, hippocampal specimens were collected for biochemical assessment. Finally, the number of intact neurons was identified in the hippocampus using hematoxylin and eosin staining. Results: Aβ microinjection increased learning and memory deficits in both NOR and MWM tests, oxidative stress status, and neuronal loss. Oral GR administration improved behavioral deficits and reduced oxidative stress status and neuronal loss in the Aβ-infused animals. Conclusions: GR ameliorates behavioral impairments through a decrease in neuronal degeneration and oxidative stress. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the potential anti-obesity benefits of blackcurrant extract, specifically its hydro-alcoholic leaf extract, in comparison to quercetin, one of its main active compounds. The rats fed with a high-fat diet developed a moderate obesity, gut imbalance, and changes in antioxidant capacity. Over 12 weeks, rats were given either blackcurrant extract or quercetin in two different doses. The results show that the extract and quercetin supplementations prevented weight gain and partially improved glucose tolerance and antioxidant activity disrupted by the high-fat diet. Importantly, the extract also helped to improve gut health, which was negatively impacted by the diet. These findings suggest that the extract may offer broader health benefits than quercetin alone, potentially making it valuable for preventing obesity and its related health issues. This study is promising, as it highlights the potential of the blackcurrant leaf extract in developing natural approaches to manage and prevent obesity, which could be beneficial for overall public health. Blackcurrant (BC) extract was reported to exert anti-obesity effects. However, it is unknown whether BC extract with a composition close to the totum differentially affects obesity when compared to one of its active compounds. We evaluated the anti-obesity effects of a BC standardized hydro-alcoholic leaf extract (BC-HLE) in an HFD-induced obesity rat model and compared them with quercetin (QUE). Thirty-six 12-week-old Wistar rats were divided into six groups: control, HFD, BC-HLE- (41 and 50 mg/kg) and QUE- (0.9 and 50 mg/kg) supplemented HFD rats for 12 weeks. HFD rats developed a moderate obesity, associated with a gut dysbiosis and a change in their total antioxidant capacity. The increase in body weight gain was prevented only by the low dose of BC-HLE and the high dose of QUE. The impaired glucose tolerance by HFD was attenuated by the low dose of QUE. Hepatic glutathione peroxidase activity was increased in the HFD group and only BC-HLE supplementation counteracted this change. The low BC-HLE dose tended to reduce the HFD-induced gut dysbiosis. These findings suggest that while QUE has beneficial effects on obesity-related disorders, the BC-HLE may offer even greater overall benefits and could contribute to preventing obesity and related conditions. [ABSTRACT FROM AUTHOR]

Objective: Cisplatin (CP) is a chemotherapeutic drug that causes cardiotoxicity. Melatonin (MEL) is secreted by the pineal gland throughout the night. This study aimed to investigate the protective effect of MEL against cardiotoxicity associated with CP exposure. Methods: Physiological saline was applied to Group 1 (control) throughout the experiment. A single dose of CP (7 mg/kg) was administered to Group 2 on the 5th day of the experiment. Group 3 received MEL (10 mg/kg) for 7 days and CP (7 mg/kg) on day 5. MEL (10 mg/kg) was administered to group 4 for 7 days. On the 8th day of the experiment, the hearts were removed under anesthesia. Sections taken from heart tissue samples were stained with hematoxylin and eosin for histopathological evaluation. Additionally, heart tissue sections were immunohistochemically stained for 78-kDa glucose-regulated protein (GRP-78), growth arrest and DNA damage-inducible gene 153 (GADD 153), and connexins (Cx 43) expression. Results: CP application caused cellular damage and disrupted heart tissue tissue integrity. At the same time, CP application caused an increase in the expression of GRP-78 and GADD 153, whereas it caused a decrease in the expression of Cx43. MEL application heals cell damage and impaired tissue integrity. However, while reducing GRP-78 and GADD153 expression; CX had an effect of increasing expression. Conclusion: MEL may have a protective effect against CP-induced cardiotoxicity in rats. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the potential role of immunization against INH on testicular development, serum reproductive hormone (FSH, LH and T) concentrations, testicular biochemical indexes (GGT, ALP, ACP, LDH, α-neutral glucosidase and carnitine) and testicular cell apoptosis in rats. Forty healthy male rats were randomly divided into four groups (n = 10 per group), and respectively immunized with 0.5 mL of C500/pVAX-asd-IS-L (108 CFU/ mL), C500/pVAX-asd-IS-M (109 CFU/ mL), C500/pVAX-asd-IS-H (1010 CFU/ mL) or C500 (1010 CFU/ mL) (thrice with an interval of 2 weeks). P/N values increased after vaccination and differed (p < 0.05) at 1 week and sharply increased at 2 weeks following the booster vaccination (p < 0.01); P/N values indicated that the immune response was induced and production of anti-INH antibodies in rats; Immunization of INH vaccines enhanced serum concentrations of T and FSH, while reduced LH concentrations (p < 0.05); The testis weight, volume, testis coefficient, epididymal weight, sperm count in the epididymis, and the sperm deformity results indicated that INH gene vaccine immunization could promote testicular development and enhance sperm production rate in rats. After immunization of INH gene vaccines, GGT activity was markedly increased, but ALP, LDH and α-neutral glucosidase activities were observably reduced (p < 0.05). Furthermore, flow cytometry results demonstrated that the apoptosis rate of the testicular cells was extremely increased in the C500/pVAX-asd-IS-M group (p < 0.01). These findings illustrate a functional cross-link between FSH, T, LH and spermatogenic markers via inhibin to maintain spermatogenesis. INH immunization may have a positive effect on spermatogenesis and testicular development in male rats. [ABSTRACT FROM AUTHOR]

Background/Objectives: Alzheimer's disease (AD) remains incurable, highlighting the need for new and diverse animal models to better understand its complex mechanisms. This study compares various injected animal models of AD, focusing on the main theories that explain the disease; Methods: Female Wistar rats (10-months old) were administered intracebroventricularly by artificial cerebrospinal fluid (aCSF) (Control), beta amyloid Aβ1-42 (BA), okadaic acid (OKA), lipopolysaccharides (LPS), buthionine sulfoximine (BSO) or by a mixture of these different molecules (MLG). Cognitive performance was assessed one week or one month after stereotaxic surgery; Results: Our results, show that only the Aβ and the MLG induced a persistence and progressive deficits in the working memory, recognition memory and spatial memory in rats. As the hippocampus (HIP) and the prefrontal cortex (PFC) are particularly involved in memory behavior, we analyzed long-term neuroadaptations in these brain subregions using spectrophotometric and histological methods to assess oxidative stress changes and neuronal loss, respectively. We found that the behavioral impairments in memory and learning were accompanied by irreversible oxidative stress changes and neurodegenerescence, particularly in the HIP; Conclusions: This study provides promising data on the modeling of AD in order to develop an effective therapeutic approach. [ABSTRACT FROM AUTHOR]

The rat is one of the most employed animal models in biomedicine. Traditionally, weight gain has been utilized to gauge development and compare across species. Numerous studies have conducted longitudinal analyses of rat development, with emphasis on weight gain analysis. Given the high variability in these patterns, experimental data from a single laboratory may not be reliable for generalized estimation. This study aimed to analyze the effect of different factors on the pattern of weight gain during rat development. A literature survey was conducted to compile a database comprising nearly 300 data points of age and weight from 15 longitudinal studies. The database comprised both pre- and postnatal data. Utilizing the Gompertz equation, the data was analyzed to formulate a comprehensive model describing rat development. Differences in growth patterns became increasingly evident at later developmental stages, when significant differences in the maximum asymptote between sexes and strains were reached. [ABSTRACT FROM AUTHOR]

Objective To establish a rat model of moderate-to-severe knee osteoarthritis, laying the foundation for studying the pathogenesis of moderate-to-severe knee osteoarthritis and its prevention and treatment methods. Methods Thirty male SD rats were randomly divided into three groups: a sham surgery group, an 8-week model group, and a 20-week model group, with 10 rats in each group. Rats in the 8-week and 20-week model groups underwent surgery to cut the anterior and posterior cruciate ligaments and medial collateral ligament of the right knee joint, and remove the medial and lateral menisci. After surgery, the rats were allowed to move freely. The rats in the sham surgery group had only skin incisions to expose the joint without any surgical treatment. At 8 and 20 weeks post-surgery, Micro-CT scans were performed to analyze the femoral osteoporosis in the rats. After euthanizing the rats, gross observations of the knee joints were made, and the cartilage of the joint surface was scored using the Pelletier scoring system. The knee joints were collected for hematoxylin and eosin (HE) staining and safranin O-fast green staining to observe changes in cartilage morphology. The modified Mankin's scoring system was used to assess the tissue pathology of the joint surface. Immunohistochemical staining was used to detect the expression of type II collagen and matrix metalloproteinase 13 (MMP13), reflecting the anabolic and catabolic metabolism of the knee joint cartilage. Results The knee joint cartilage in the 8-week and 20-week model groups was severely damaged, with Pelletier and modified Mankin's scores significantly higher than those in the sham surgery group (both P<0.01). The Pelletier and modified Mankin's scores in the 20-week model group were significantly higher than those in the 8-week model group (P<0.01). Micro-CT observations revealed irregular joint surfaces, osteophyte formation, and signs of osteoporosis in both the 8-week and 20-week model groups, with the 20-week model group showing more loose bodies around the knee joints. Immunohistochemical staining showed increased expression of MMP13 and decreased expression of type II collagen in the knee joint tissues of the model groups, indicating that the balance of anabolic and catabolic metabolism in the joint cartilage was disrupted. MMP13 increased while type II collagen decreased. Conclusion The surgical method of cutting the anterior and posterior cruciate ligaments and medial collateral ligament and removing the medial and lateral menisci successfully creates a moderate-to-severe knee osteoarthritis model in rats. Imaging examinations reveal osteophytes, osteoporosis, and loose bodies in the knee joints, while pathological observations show a reduction or even disappearance of joint cartilage, with a disruption in the balance of cartilage anabolic and catabolic metabolism. [ABSTRACT FROM AUTHOR]