Being Stung Once or Twice by Bees (Apis mellifera L.) Slightly Disturbed the Serum Metabolome of SD Rats to a Similar Extent.

In most cases, the number of honeybee stings received by the body is generally small, but honeybee stings can still cause serious allergic reactions. This study fully simulated bee stings under natural conditions and used 1H Nuclear Magnetic Resonance (1H NMR) to analyze the changes in the serum metabolome of Sprague-Dawley (SD) rats stung once or twice by honeybees to verify the impact of this mild sting on the body and its underlying mechanism. The differentially abundant metabolites between the blank control rats and the rats stung by honeybees included four amino acids (aspartate, glutamate, glutamine, and valine) and four organic acids (ascorbic acid, lactate, malate, and pyruvate). There was no separation between the sting groups, indicating that the impact of stinging once or twice on the serum metabolome was similar. Using the Principal Component Discriminant Analysis ( PCA-DA) and Variable Importance in Projection (VIP) methods, glucose, lactate, and pyruvate were identified to help distinguish between sting groups and non-sting groups. Metabolic pathway analysis revealed that four metabolic pathways, namely, the tricarboxylic acid cycle, pyruvate metabolism, glutamate metabolism, and alanine, aspartate, and glutamate metabolism, were significantly affected by bee stings. The above results can provide a theoretical basis for future epidemiological studies of bee stings and medical treatment of patients stung by honeybees.

Polysaccharides from Dendrobium officinale improve obesity-induced insulin resistance through the gut microbiota and the SOCS3-mediated insulin receptor substrate-1 signaling pathway.

BACKGROUND: Obesity induces insulin resistance and chronic inflammation, impacting human health. The relationship between obesity, gut microbiota, and regulatory mechanisms has been studied extensively. Dendrobium officinale polysaccharide (DOP), a traditional Chinese herbal medicine, potentially reduces insulin resistance. However, the mechanism through which DOP affects gut microbiota and alleviates obesity-induced insulin resistance in rats requires further investigation. RESULTS: The current study aimed to assess the impact of DOP on gut microbiota and insulin resistance in rats on a high-fat diet. The results revealed that DOP effectively reduced blood lipids, glucose disorders, oxidative stress, and inflammatory infiltration in the liver of obese Sprague Dawley rats. This was achieved by downregulating SOCS3 expression and upregulating insulin receptor substrate-1 (IRS-1) by regulating the JAK/STAT/SOCS3 signaling pathway. Notably, DOP intervention enhanced the abundance of beneficial gut microbiota and reduced harmful microbiota. Correlation analysis demonstrated significant associations among intestinal microbiota, SOCS3-mediated IRS-1 expression, and inflammatory factors. CONCLUSION: Dendrobium officinale polysaccharide regulated the gut microbiota, enhanced IRS-1 expression, and mitigated liver injury and insulin resistance due to a high-fat diet. These findings depict the potential anti-insulin resistance properties of DOP and offer further evidence for addressing obesity and its complications. © 2023 Society of Chemical Industry.

Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

Organ distribution of Nano-WC particles after repeated intratracheal instillation into the lungs of SD rats and subsequent organ injury.

Nano-tungsten carbide (nano-WC) is widely used in composite materials due to its special physical and chemical properties. Owing to their small size, nano-WC nanoparticles easily enter organisms through the respiratory tract, which may cause health hazards. However, only a few studies have reported the toxicity of nano-WC. In this study, a 10 mg/kg nano-WC suspension and 0.9% normal saline were quantitatively perfused into the lungs of two groups of healthy male SD rats by tracheal instillation, and the in vivo pulmonary toxic effects were systematically evaluated. Additionally, as multiple organs and tissues are involved, systemic effects were observed throughout the body and mainly manifested as inflammatory damage. The concentrations of tungsten ions in various organs and alveolar lavage fluid were measured by ICP-MS, and the results showed that the lung was the target organ, as it had the highest concentration of ions. In addition, the abnormal increases in the tungsten ion concentrations in the liver and kidney may be closely related to the immune damage we observed. This study provides a theoretical basis and data support for the systematic evaluation of the health hazards of nano-WC and a reference for the safe use of nanomaterials.

Naringenin improves ovarian health by reducing the serum androgen and eliminating follicular cysts in letrozole-induced polycystic ovary syndrome in the Sprague Dawley rats.

Polycystic ovary syndrome (PCOS) is most common in women of reproductive age, giving rise to androgen excess and anovulation, leading to infertility and non-reproductive complications. We explored the ameliorating effect of naringenin in PCOS using the Sprague Dawley (SD) rat model and human granulosa cells. Letrozole-induced PCOS rats were given either naringenin (50 mg/kg/day) alone or in combination with metformin (300 mg/kg/day), followed by the estrous cycle, hormonal analysis, and glucose sensitivity test. To evaluate the effect of naringenin on granulosa cell (hGC) steroidogenesis, we treated cells with naringenin (2.5 µM) alone or in combination with metformin (1 mM) in the presence of forskolin (10 µM). To determine the steroidogenesis of CYP-17A1, -19A1, and 3ßHSD2, the protein expression levels were examined. Treatment with naringenin in the PCOS animal groups increased ovulation potential and decreased cystic follicles and levels of androgens. The expression levels of CYP-17A1, -19A1, and 3ßHSD2, were seen restored in the ovary of PCOS SD rats' model and in the human ovarian cells in response to the naringenin. We found an increased expression level of phosphorylated-AKT in the ovary and hGCs by naringenin. Naringenin improves ovulation and suppress androgens and cystic follicles, involving AKT activation.

Acute and 13 weeks subchronic toxicological evaluation of the flavonoid-rich extract of Sophora flavescens.

The roots of Sophora flavescens have a long history of use in Chinese medicine for the treatment of various medical conditions. Flavonoids from the ethyl acetate extract of S. flavescens have shown anti-inflammatory, anticancer, and antidiabetic properties. The objective of this study was to evaluate the toxicological profile of a flavonoid-rich extract of S. flavescens (SFEA). We conducted acute and sub-chronic oral toxicity studies of SFEA in Kunming (KM) mice and Sprague-Dawley (SD) rats. Acute oral administration of 9.0 g/kg SFEA did not result in mortality, clinical signs of toxicity, or abnormal changes in the body weight or food consumption patterns. No significant changes in hematological, blood biochemical, or histopathological parameters were observed. A 13-week sub-chronic toxicity study was conducted in SD rats; the rats were orally administrated with various doses of SFEA (in mg/kg): 0 (control), 40, 80, 400, 800, and 1200. Mortality, clinical signs, or treatment-related changes in body weight, food consumption, hematological parameters, blood biochemical parameters, organ weights, or histopathological parameters were not observed. We found that SFEA is practically nontoxic to KM mice at a dose of 9.0 g/kg and that the no-observed-adverse-effect-level (NOAEL) of SFEA in SD rats is greater than 1200 mg/kg.

Preparation, characterization and biocompatibility of calcium peroxide-loaded polycaprolactone microparticles. / èšå·±å† é ¯åŒ è½½è¿‡æ°§åŒ–é’™å¾®ç²’çš„åˆ¶å¤‡ã€è¡¨å¾åŠå ¶ç”Ÿç‰©ç›¸å®¹æ€§ç ”ç©¶.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O2 and H2O2 after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O2 and H2O2 released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS: CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.

Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/IκBα/NF-κB signaling pathway. / 降浊合剂通过调节TLR4/IκBα/NF-κBä¿¡å·é€šè·¯å½±å“è‚¥èƒ–å¤§é¼ ç³–è„‚ä»£è°¢.

OBJECTIVES: To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats. METHODS: Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues. RESULTS: Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05). CONCLUSIONS: Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.

Estimation of the post-mortem interval by modelling the changes in oral bacterial diversity during decomposition.

AIMS: Decomposition, a complicated process, depends on several factors, including carrion insects, bacteria and the environment. However, the composition of and variation in oral bacteria over long periods of decomposition remain unclear. The current study aims to illustrate the composition of oral bacteria and construct an informative model for estimating the post-mortem interval (PMI) during decomposition. METHODS AND RESULTS: Samples were collected from rats' oral cavities for 59 days, and 12 time points in the PMI were selected to detect bacterial community structure by sequencing the V3-V4 region of the bacterial 16S ribosomal RNA (16S rRNA) gene on the Ion S5 XL platform. The results indicated that microorganisms in the oral cavity underwent great changes during decomposition, with a tendency for variation to first decrease and then increase at day 24. Additionally, to predict the PMI, an informative model was established using the random forest algorithm. Three genera of bacteria (Atopostipes, Facklamia and Cerasibacillus) were linearly correlated at all 12 time points in the 59-day period. Planococcaceae was selected as the best feature for the last 6 time points. The R2 of the model reached 93.94%, which suggested high predictive accuracy. Furthermore, to predict the functions of the oral microbiota, PICRUSt results showed that energy metabolism was increased on day 3 post-mortem and carbohydrate metabolism surged significantly on days 3 and 24 post-mortem. CONCLUSIONS: Overall, our results suggested that post-mortem oral microbial community data can serve as a forensic resource to estimate the PMI over long time periods. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study are beneficial for estimating the PMI. Identifying changes in the bacterial community is of great significance for further understanding the applicability of oral flora in forensic medicine.

Differential distribution and genetic determination of eccrine sweat glands and hair follicles in the volar skin of C57BL/6 mice and SD rats.

BACKGROUND: Eccrine sweat glands (ESGs) and hair follicles (HFs) are the prominent skin appendages regulating human body temperature. C57BL/6 mice and Sprague-Dawley (SD) rats are the most commonly used model animals for studying ESGs and HFs. Previous studies have shown the distribution of ESGs and HFs in volar hindfeet of C57BL/6 mice, but there are few or no reports on the distribution of ESGs and HFs in volar forefeet of C57BL/6 mice and volar feet of SD rats. Here, we investigated the differential distribution and genetic determination of ESGs and HFs in the volar skin of C57BL/6 mice and SD rats through gross observation, iodine-starch sweat test, double staining with Nile Blue A and Oil Red O, hematoxylin and eosin (HE) staining, double immunofluorescence staining of LIM Homeobox 2 (LHX2)/Na+-K+-ATPase α1(NKA) or LHX2/Na+-K+-2Cl－ cotransporter 1 (NKCC1), and qRT-PCR detection of ESG-related gene Engrailed 1 (En1) and HF-related gene LHX2. RESULTS: The results showed ESGs but no HFs in the footpads of C57BL/6 mice and SD rats, both ESGs and HFs in the inter-footpads (IFPs) of C57BL/6 mice, and neither ESGs nor HFs in the IFPs of SD rats. The relative quantitative change in En1 was consistent with the differential distribution of ESGs, and the relative quantitative change of LHX2 was consistent with the differential distribution of HFs. CONCLUSION: C57BL/6 mice and SD rats had their own characteristics in the distribution of ESGs and HFs in the volar skin, and researchers should choose mice or rats, and even forefeet or hindfeet as their research object according to different purposes. The study provides a basis for selection of optimal animal models to study development, wound healing and regeneration of skin appendages.

Flaxseed-derived peptides ameliorate hepatic cholesterol metabolism in Sprague-Dawley rats fed a high-cholesterol and high-fat diet.

BACKGROUND: Plant peptides have been reported to have cholesterol-lowering activities. Previous research has found that ≤1 kDa flaxseed peptide (FP5 ) reduces cholesterol absorption and synthesis in vitro. In this research, we investigated the cholesterol-lowering activity of FP5 in Sprague-Dawley (SD) rats fed a high-cholesterol and high-fat diet. In addition, amino acid sequences of FP5 were determined by high-performance liquid chromatography-electrospray ionization-Orbitrap mass spectrometry. RESULTS: FP5 supplement significantly decreased the serum and hepatic cholesterol levels and modulated the hepatic gene and protein expression of cholesterol metabolism-related enzymes or regulators (3-hydroxy-3-methylglutaryl coenzyme A reductase, Low-Density Lipoprotein Receptor (LDLR), Cholesterol 7 α-hydroxylase, Niemann-Pick C1-like 1, ATP-binding cassette transporters G5 and G8). Eleven peptides were identified from FP5 . These peptides were characterized as hydrophobic amino acids such as leucine (L), proline (P), glycine (G), isoleucine (I) and continuous sequences, including LP, LL, LG and II, with low molecular weights. CONCLUSION: FP5 has a certain cholesterol-lowering activity in SD rats fed a high-cholesterol and high-fat diet. The possible mechanism for ameliorating hepatic cholesterol metabolism of FP5 includes inhibiting hepatic cholesterol de novo synthesis, promoting the synthesis and excretion of bile acids, and inhibiting the reabsorption of bile acids during enterohepatic circulation. © 2022 Society of Chemical Industry.

Toxicity and Local Tolerance of COVID- eVax, a Plasmid DNA Vaccine for SARS-CoV-2, Delivered by Electroporation.

COVID-19 is a rapidly spreading disease, posing a huge hazard to global health. The plasmid vaccine pTK1A-TPA-SpikeA (named COVID-eVax) encodes the severe acute respiratory syndrome coronavirus 2 S protein receptor-binding domain, developed for intramuscular injection followed by electroporation (EP). The aim of this study was to assess the systemic toxicity and local tolerance of COVID-eVax delivered intramuscularly followed by EP in Sprague Dawley (SD) rats. The animals were killed 2 days and 4 weeks after the last injection (30-day and 57-day, respectively). No mortality was observed, and no signs of toxicity were evident, including injection site reactions. A lasting and specific immune response was observed in all treated animals, confirming the relevance of the rat as a toxicological model for this vaccine. Histopathological evaluation revealed muscle fiber necrosis associated with subchronic inflammation at the injection sites (at the 30-day time point), with a clear trend for recovery at the 57-day time point, which is expected following EP, and considered a desirable effect to mount the immune response against the target antigen. In conclusion, the intramuscular EP-assisted DNA vaccine, COVID-eVax showed an excellent safety profile in SD rats under these experimental conditions and supports its further development for use in humans.

Development of in-vitro maturation protocol for rat oocytes; under simple culture vs co-culture with cumulus cell monolayer and its developmental potential via Parthenogenetic/artificial activation.

BACKGROUND: Murine is the most abundantly used as laboratory animal models. There has been a tremendous amount of research including; their evolution, growth, physiology, disease modeling as well as genomic mapping. Rats and mice are the most widely used among them. Although both rats and mice fall under the same category still both are different a lot too. As regarding in vitro maturation and development mouse studies are well established as compared to rats which still lies in the early phase of development. So, we tried to figure out rat oocytes in vitro maturation and their developmental potential by performing 3 experiments i.e. superovulation, in vitro Maturation as simple culture (COC's only), and COC's & cumulus cells co-culture, which later further developed using parthenogenetic activation after IVM. Female Sprague Dawley rat 3-4 week used for these studies, we hyper-stimulated their ovaries using PMSG and hCG 150 IU/kg each. After that, we collected ovaries via dissection and retrieved oocytes. We matured them in TCM 199 supplemented with FSH, Estrogen, EGF, and Pyruvate. After maturation, we activated them using two types of activators i.e. Ethanol 7%, Ionomycin. After that, we saw and compared their developmental potential in vitro. RESULTS: Oocytes matured in COC's and Cumulus cell monolayer co-culture (59% ± 4*) showed significantly more even growth and extrusion of the first polar body as compared to the COC's only culture (53.8 ± 7%*). While oocytes activated using Ionomycin showed more promising development until 8 cells/blastocyst level compared to ethanol 7%. CONCLUSION: we concluded that COC's and cumulus monolayer co-culture is better than COC's only culture. Cumulus monolayer provides extra aid in the absorption of nutrients and supplements thus providing a better environment for oocytes growth. Also, we concluded that matured oocytes showed more developmental capacity after activation via ionomycin compared to ethanol.

Treatment of contaminated radial fracture in Sprague-Dawley rats by application of a degradable polymer releasing gentamicin.

Fracture-related infections remain a leading cause of morbidity and mortality. We aimed to establish a simple contaminated radial osteotomy model to assess the efficacy of a biodegradable polymer poly(sebacic-co-ricinoleic acid) [p(SA-RA)] containing 20% w/w gentamicin. A unilateral transverse osteotomy was induced in Sprague-Dawley (SD) rats, followed by application of Staphylococcus aureus suspension over the fracture. After successfully establishing the contaminated open fracture model, we treated the rats either systemically (intraperitoneal cefuroxime), locally with p(SA-RA) containing gentamicin, or both. Control groups included non-contaminated group and contaminated groups that were either untreated or treated with the polymer alone. After 4 weeks, the bones were subjected to micro-CT scanning and microbiological and histopathology evaluations. Micro-CT analysis revealed similar changes in the group subjected to both local and systemic treatment as in the non-contaminated control group. Lack of detectable bacterial growth was noted in most animals of the group subjected to both local and systemic treatment, and all samples were negative for S. aureus. Histopathological evaluation revealed that all treatment modalities containing antibiotics were highly effective in reducing infection and promoting callus repair, resulting in early bone healing. While p(SA-RA) containing gentamicin treatment showed better results than cefuroxime, the combination of local and systemic treatment displayed the highest therapeutic potential in this model.

Molecular characterization of gut microbial shift in SD rats after death for 30 days.

To observe the temporal shifts of the intestinal microbial community structure and diversity in rats for 30 days after death. Rectal swabs were collected from rats before death (BD) and on day 1, 5, 10, 15, 20, 25, and 30 after death (AD). Bacteria genomic DNA was extracted and V3 + V4 regions of 16S rRNA gene were amplified by PCR. The amplicons were sequenced at Illumina MiSeq sequencing platform. The bacterial diversity and richness showed similar results from day 1 to 5 and day 10 to 25 all presenting downtrend, while from day 5 to 10 showed slightly increased. The relative abundance of Firmicutes and Proteobacteria displayed inverse variation in day 1, 5, 10 and that was the former decreased, the latter increased. Bacteroidetes, Spirochaete and TM7 in day 15, 20, 25, 30 was significantly decline comparing with BD. Enterococcus and Proteus displayed reduced trend over day 1, 5, 10 and day 10, 15, 20, 25, respectively, while Sporosarcina showed obvious elevation during day 15, 20, 25. Accordingly, there was a certain correlation between intestinal flora succession and the time of death. The results suggested that intestinal flora may be potential indicator to aid estimation of post-mortem interval (PMI).

Chicory fibre improves reproductive performance of pregnant rats involving in altering intestinal microbiota composition.

AIM: Chicory fibre (CF) is rich in fructan, which always functions as a quality dietary fibre source during mammalian pregnancy; however, its effect on reproductive performance remains unclear. METHODS AND RESULTS: 40 pregnant SD rats were randomly allotted to receive one of four diets: basal diet (control group), basal diet + 5% CF, basal diet + 10% CF, and basal diet + 15% CF, respectively. We found that CF significantly increased the number born alive and total litter birth weight (P < 0·05), increased the expression of intestinal tight junction proteins, mucins and antimicrobial peptides, accompanied by the increase of villi height and the decrease of crypts depth of pregnant SD rats (P < 0·05). We also observed that CF markedly increased the acetic acid, propanoic acid, butyric acid and total SCFAs concentrations in caecum contents and promoted the expression of SCFAs-related receptors (P < 0·05). Notably, rats fed CF increased the relative abundance of Bacteroidetes (P < 0·001), decreased the relative abundance of Firmicutes and Proteobacteria, while markedly lowered the Firmicutes/ Bacteroidetes ratio (F/B ratio) (P < 0·05). Intriguingly, the number born alive and total litter birth weight were positively correlated with some probiotics and negatively correlated with other harmful bacteria by Pearson correlation analysis. CONCLUSION: Collectively, CF can enhance intestinal barrier function and maintain intestinal health, and may improve reproductive performance by altering intestinal microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY: Adding suitable dietary fibre to the diet can improve the reproductive performance of sows. Indeed, there exist various problems in the application of traditional dietary fibres, including high insoluble fibre content and anti-nutritional factor level, and mycotoxin contamination. This study demonstrates that dietary CF supplementation improves reproductive performance and intestinal health. Thus, CF can be applied in pregnancy animals as a new dietary fibre additive in animal husbandry.

Quinazolinone derivative BNUA-3 ameliorated [NDEA+2-AAF]-induced liver carcinogenesis in SD rats by modulating AhR-CYP1B1-Nrf2-Keap1 pathway.

Cytochrome P450 1B1, considered as one of the novel chemotherapeutic targets involved in cancer prevention and therapy is also associated with the conversion of procarcinogens into their active metabolites. The aryl hydrocarbon receptor (AhR) is responsible for mediating different biological responses to a wide variety of environmental pollutants and also causes transcriptional activation of cytochrome P450 enzymes including CYP1B1 and thus plays a pivotal role for initiating cancer and its progression. On the other hand, active carcinogenic metabolites and reactive oxygen species-mediated stress alter different molecular signalling pathways and gene expressions. Quinazoline derivatives are recognized for their diversified biological activities including anticancer properties. The current study was designed for evaluation of chemotherapeutic efficacy of a synthetic quinazolinone derivative BNUA-3 against hepatocellular cancer in Sprague-Dawley (SD) rats. A detailed in vivo analysis was performed by administrating BNUA-3 (15, 30 mg/kg b.w. for 28 days, i.p.) in N-Nitrosodiethylamine + 2-Acetylaminofluorene induced partially hepatectomized liver cancer in SD rats. This was followed by morphological evaluations, biochemical estimations and analysis of different mRNA and protein expressions. The results demonstrated the potency of BNUA-3 in efficient restoration of the altered morphology of liver, its protective effect against lipid peroxidation, enzymic and non-enzymic antioxidants levels in liver tissue which was disrupted after cancer induction. The study also demonstrated downregulation of AhR, CYP1B1 and Keap1 expressions with subsequent augmentation of protective Nrf2, HO-1, NQO1 and GSTA1 expressions thus, revealing the chemotherapeutic potency of BNUA-3 in inhibiting liver carcinogenesis through AhR/CYP1B1/Nrf2/Keap1 pathway.

Rat 90-day oral toxicity study of a novel coccidiostat - Ethanamizuril.

In the current study, to support the safety assessment of ethanamizuril as a new potent anticoccidial agent of triazine compounds, a 90-day repeated-dose oral toxicity assay of ethanamizuril was investigated. Treatment related clinical signs of alopecia on back and neck have been observed in some male and female at the 65 and 130 mg/kg dose groups. The body weight and feed conversion efficacy of 65 and 130 mg/kg females and 65 mg/kg males were significantly increase than those of the control in treatment time, but noted decreased in the 130 mg/kg males. Dose related changes of hematologic and biochemical parameters such as MCV, MCH, TG, and the significant increased in the organ weight and the relative organ weight of the liver, kidney, heart, lung and spleen in both genders in the 65 and 130 mg/kg treated groups were observed. Furthermore, histopathological observations revealed that 65 and 130 mg/kg ethanamizuril induced pathological damage such as hepatocyte steatosis and focal necrosis, renal tubular atrophy, tubule protein casts. Fortunately, the observed toxicities were recoverable in convalescence. The results indicated that liver, kidneys and lung were the main target organs. The NOAEL of ethanamizuril for rats was estimated to be 20 mg/kg dietary dose level.

A Pilot Safety Assessment for Recombinant Epinephelus lanceolatus Piscidin Yeast Powder as a Drug Food Additive after Subacute and Subchronic Administration to SD Rats.

Recombinant Epinephelus lanceolatus piscidin (RELP) was previously shown to improve growth performance and immune response when used as a feed additive for Gallus gallus domesticus. However, the long-term toxicity of RELP has not be thoroughly investigated. In the present study, we evaluated the subacute and subchronic oral toxicities of RELP in SD rats by hematological, biochemical, and histopathological analyses. To determine subacute and subchronic toxicities, male and female rats were fed with RELP 1000 mg/kg bodyweight/day for 28 and 90 days, respectively. Bodyweight and food intake were unchanged by RELP treatment over the course of the studies. After exposure, samples of blood, heart, lung, liver, and kidney were collected and analyzed. Results demonstrated that RELP exposure did not cause any observable hematological, biochemical, or histological abnormalities in SD rats. Thus, RELP may be a safe feed additive for use in agriculture and aquaculture.

Arctigenin improves lipid metabolism by regulating AMP-activated protein kinase and downstream signaling pathways.

Although it has been reported that arctigenin (ARG) can reduce the body weight and inhibit adipogenic differentiation by activating AMP-activated protein kinase (AMPK), the exact signals responsible for the ARG-mediated antiobesity mechanism through AMPK are not well understood. In this study, we investigated the potential improvement of AGR on lipid metabolism using a high-fat diet (HFD)-induced hyperlipidemia rats and 3T3-L1 mature adipocytes. The levels of AMPK and its downstream factors were examined by Western blot analysis and real-time fluorescent quantitative polymerase chain reaction. We observed that ARG lowered the HFD-induced body weight and the levels of serum lipid. Moreover, ARG clearly alleviated fat deposition in the liver and reduced epididymal fat accumulation. ARG also suppressed lipogenesis and lipolysis but promoted fatty acid ß-oxidation in adipocytes. Most importantly, ARG increased the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and upregulated the messenger RNA levels of downstream genes related to fatty acid ß-oxidation, such as carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 but downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1c) and their targets, including lipogenesis-related genes such as CCAAT/enhancer-binding protein α, lipoprotein lipase, adipocyte protein 2, and fatty acid synthase (FAS), as well as lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase. The activity of FAS was also decreased by ARG. We conclude that AMPK activation is important for the pharmacological effects of ARG. ARG may improve lipid metabolism by regulating the AMPK-ACC and AMPK-PPARγ/SREBP1c signaling pathways.