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

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimers disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aβ42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events. We conducted kinetic analyses of γ-secretase activity in cell-free systems in the presence of Aβ, as well as cell-based and ex vivo assays in neuronal cell lines, neurons, and brain synaptosomes to assess the impact of Aβ on γ-secretases. We show that human Aβ42 peptides, but neither murine Aβ42 nor human Aβ17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75, and pan-cadherin. Moreover, Aβ42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems. Our findings raise the possibility that pathological elevations in Aβ42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aβ toxicity in the context of γ-secretase-dependent homeostatic signaling.

Brain microvessels possess the unique properties of a blood-brain barrier (BBB), tightly regulating the passage of molecules from the blood to the brain neuropil and vice versa. In models of brain injury, BBB dysfunction and the associated leakage of serum albumin to the neuropil have been shown to induce pathological plasticity, neuronal hyper-excitability, and seizures. The effect of neuronal activity on BBB function and whether it plays a role in plasticity in the healthy brain remain unclear. Here we show that neuronal activity induces modulation of microvascular permeability in the healthy brain and that it has a role in local network reorganization. Combining simultaneous electrophysiological recording and vascular imaging with transcriptomic analysis in rats, and functional and BBB-mapping MRI in human subjects, we show that prolonged stimulation of the limb induces a focal increase in BBB permeability in the corresponding somatosensory cortex that is associated with long-term synaptic plasticity. We further show that the increased microvascular permeability depends on neuronal activity and involves caveolae-mediated transcytosis and transforming growth factor β signaling. Our results reveal a role of BBB modulation in cortical plasticity in the healthy brain, highlighting the importance of neurovascular interactions for sensory experience and learning.

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

This study aimed to assess the antioxidant capacity of lemon flavonoid extract Eriomin® (LE) and its impact on cholesterol metabolism in the context of healthy aging. We orally treated 24-month-old male Wistar rats with an LE (40 mg/kg) suspended in 0.3 mL of sunflower oil. At the same time, control groups received an equal volume of sunflower oil (CON) or remained untreated (ICON) daily for 4 weeks. We examined LEs effects on superoxide dismutase and catalase- and glutathione-related enzyme activities, the concentration of lipid peroxides and protein carbonyls, total oxidant status (TOS) and antioxidant status (TAS), and oxidative stress index (OSI) in the liver, jejunum, and ileum. We also measured total cholesterol, its biosynthetic precursors (lanosterol, lathosterol, desmosterol), its degradation products (bile acid precursors) in the serum, liver, jejunum, and ileum, and serum phytosterols (intestinal absorption markers). LE reduced TOS, TAS, and OSI (p < 0.05) compared with control values, indicating its consistent antioxidant action in all examined organs. LE lowered hepatic desmosterol (p < 0.05) while also reducing 7α- and 24-hydroxycholesterol levels in the liver and ileum (p < 0.01). Serum cholesterol, hepatic gene expression, and the immunostaining intensity of CYP7A1 were unchanged. In conclusion, LE exerted non-enzymatic antioxidant effects and reduced cholesterol degradation, reducing its biosynthesis products, thereby maintaining serum cholesterol levels.

Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain.

Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting an estimated 283 million individuals worldwide, with substantial health and economic consequences. Peroxisome proliferator-activated receptors (PPARs), particularly PPAR-α and PPAR-γ, have shown promise in preclinical studies as potential therapeutic targets for AUD. In this human laboratory study, we aimed to translate preclinical findings on the PPAR-α agonist fenofibrate to a human population with current AUD. We hypothesized that, relative to placebo, fenofibrate at the highest FDA-approved dose of 145 mg/d would attenuate responsiveness to in vivo alcohol cues in the lab and reduce drinking under natural conditions. However, the results did not show significant differences in craving and alcohol consumption between the fenofibrate and placebo groups. Reverse translational studies in rodent models confirmed the lack of fenofibrate effect at human-equivalent doses. These findings suggest that inadequate translation of drug dose from rodents to humans may account for the lack of fenofibrate effects on alcohol craving and consumption in humans with AUD. The results highlight the need for new brain-penetrant PPAR-α agonists to adequately test the therapeutic potential of PPAR-α agonists for AUD, and the importance of reverse translational approaches and selection of human-equivalent doses in drug development.

A peptic ulcer is a stomach lesion. It is generally caused by malnutrition, the use of anti-inflammatory medications, and an imbalance between mucosal defense systems. In fishes, the lubricous substance that called mucus secreted from the skin, prevents the entry of microorganisms that can enter the body through the skin. That mucus contains immune components such as antimicrobial peptides, lysozymes, lectins, proteases, and mucin. This study investigated the antiulcer activity of Rainbow Trout skin Mucus (RTM) in indomethacin induced ulcer model of rats and compared with famotidine as standard antiulcer drug. We administered 50, 100 and 200 mg/kg RTM dose on indomethacin-induced gastric ulcer model in rats and evaluated the numerical density of ulcer areas, histopathologic parameters and oxidative stress parameters (SOD, GSH, MDA) in the rat stomach. RTM was able to inhibit indomethacin-induced ulcer formation and exhibited a similar effect to 40 mg/kg dose of standard drug famotidine. 200 mg/kg dose of RTM had positive effects on oxidative stress biomarkers and histopathological results in the stomach tissue of rats. This is the first time we have fully demonstrated the gastroprotective effects of RTM as a waste product in rats. Analyses have shown that mucin, which has a positive regulatory effect on oxidative stress parameters, may be responsible for the gastroprotective effect. [ABSTRACT FROM AUTHOR]

People are now exposed to higher levels of electromagnetic radiation (EMR) due to the widespread use of mobile phones in recent years. The possible effects of this exposure on human health are related to EMR. It has been suggested that exposure to EMR has serious effects on reproduction. The study aimed to investigate the impact of exposure to EMR (4.5 GB; 2600 MHz) emitted by mobile phones on rat ovaries. 18 adult female Wistar albino rats were used in the study, and the animals were divided into three groups (n = 6): control, stand-by, and dialing. For 8 weeks, the experimental groups were subjected to 4.5 GB EMR at 2600 MHz while on standby and making 10-min calls every hour. The rats in the control group received no exposure. Hematoxylin–eosin (H&E) staining of ovarian tissues was performed for histomorphological examinations. Additionally, immunoexpression of autophagy-related protein Beclin-1, apoptosis marker Caspase-3, ovarian reserve marker FSH, and oxidative stress marker iNOS were investigated in the rat ovaries. Microscopic examinations showed follicular degeneration in the ovaries of the rats in the stand-by and dialing groups. The immunoexpression of Beclin-1, Caspase-3, FSH, and iNOS was detected in granulosa cells and the corpus luteum in ovarian tissues obtained from the two EMR-exposed groups. There was a significant increase in the immunoexpression of Beclin-1 and Caspase-3 in the dialing group compared to the other two groups. Additionally, the iNOS and FSH expressions were increased in both EMR exposure groups compared to the control. Our results suggest that EMR exposure harms the ovaries, and autophagy and apoptosis are involved in this process. [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]

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]

Stellate ganglion blockade (SGB) is a practical approach to managing many clinical disorders. Ultrasound-guided SGB is currently adopted as a more effective and safer method in humans. Developing this technique in rats would facilitate further study of SGB application. The present study examined physiological responses following ultrasound-guided SGB in Sprague-Dawley rats. Under general anesthesia, lidocaine containing Chicago blue dye (1.0%–1.5% in 40–60 µL) was injected into the unilateral stellate ganglion (SG). Ptosis was observed on the ipsilateral right (n = 8) or left (n = 7) side of lidocaine administration. No ptosis was noted in any controls by 0.9% normal saline injection into the right (n = 6) or left (n = 6) SG. Heart rate (HR) was significantly decreased after administration of lidocaine (344 ± 32 to 289 ± 47 bpm; p = 0.015, pre-vs. after-injection), but not after normal saline, into the right SG. HR was unaltered after injecting lidocaine or normal saline into the left SG. Heart rate variability analysis showed that SGB with lidocaine on the right or left side caused a decrease in the ratio of the power of low-frequency over high-frequency. Respiratory rate, body temperature, and general conditions were unchanged in all rats, regardless of left or right SGB. Chicago blue dye was confirmed to be distributed in the SG region. No bleeding or tissue damage was evident in the injected SG area. Our findings suggest that ultrasound-guided unilateral SGB effectively inhibits cervicothoracic sympathetic nerves in rats and enhances heart rate variability, and sympathetic nerves controlling HR are likely predominantly associated with the right SG in the rat. [ABSTRACT FROM AUTHOR]

Primary cell cultures from rodent brain are widely used to investigate molecular and cellular mechanisms of neurotoxicity. To date, however, it has been challenging to reliably culture endogenous microglia in dissociated mixed cultures. This is a significant limitation of most in vitro neural cell models given the growing awareness of the importance of interactions between neurons, astrocytes and microglia in defining responses to neurotoxic exposures. We recently developed a tri-culture model consisting of neurons, astrocytes and microglia dissociated from the developing rat neocortex and demonstrated that this tri-culture model more faithfully mimics in vivo neuroinflammatory responses then standard neuron-only or neuron-astrocyte co-cultures. Here, we describe our protocol for generating tri-cultures of rat cortical neurons, astrocytes and microglia in which all 3 cell types can be maintained for up to 1 month in culture at the same relative ratio observed in the developing rat neocortex. We also discuss applications of this model for neurotoxicity testing, as well as the potential of this model to fill a current gap for assessing neuroinflammation in the in vitro testing battery for developmental neurotoxicity. [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]

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]

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]

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]

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]

Simple Summary: This study involved anesthetizing 20 rats, which were then fixed in a stereotactic frame. A 26G scalp needle, in conjunction with a 1 mL syringe, was used to puncture the atlanto-occipital membrane for cerebrospinal fluid (CSF) collection, with an approximate volume of 170 μL. CSF was collected twice within 14 days, and during this period, daily observations were made to monitor food intake, body weight, and hematological indicators. At the end of the study, a histopathological examination was conducted. The results confirmed that large-scale CSF collection had no significant effect on the health status of the rats, and repeated collections were feasible. The success rate of the procedure was 100%, and the blood contamination of CSF decreased from 70% in the first collection to 35% in the second, demonstrating that this technique is convenient, accurate, and suitable for wider application. The aim of this study was to explore an improved method for extracting rat cerebrospinal fluid (CSF), observing the impact on animal health under conditions of large-scale CSF collection and evaluating the feasibility of repeated collections. A total of 20 rats were anesthetized and fixed in a stereotactic frame. A 26G scalp needle, combined with a 1 mL syringe, was used to puncture the atlanto-occipital membrane and collect approximately 170 μL of CSF. CSF was collected twice within 14 days. During the study, animals were monitored daily for food intake, body weight, and hematological parameters, and at the end of the study, histopathological examination was performed. The health of the animals remained good, and repeated CSF collections were feasible. The success rate of the procedure was 100%, with blood contamination in the CSF decreasing from 70% in the first collection to 35% in the second. This technique is convenient, accurate, and suitable for widespread applications. [ABSTRACT FROM AUTHOR]