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Background: Diarrhea is the leading contributory factor of sickness and mortality among children under five and an economic burden for families. This study aimed to investigate the effects of mixed probiotics supplementation at different times (consecutive and alternate-hour) on intestinal microecology in Sprague-Dawley (SD) rats with acute diarrhea. Methods: A total of 40 SD rats were randomly assigned to four groups, including the control group, model group, probiotic group A, and probiotic group B. An acute diarrhea model was induced by administration of 5% dextran sulfate sodium. Rats in probiotic group A and probiotic group B were fed with Clostridium butyricum (C. butyricum), Bifidobacterium infantis (B. infantis), and Saccharomyces boulardii (S. boulardii) for a total of 7 days. Probiotic group A was fed with all probiotics simultaneously. Probiotic group B was fed with C. butyricum and B. infantis simultaneously, and then after a 2-hour interval, with S. boulardii. Metagenomic next-generation sequencing was used to analyze the fecal samples from every rat. The metagenomic sequencing used in this experiment was used to evaluate the effect of probiotics on the composition as well as function of the gut microbiota in order to gain a deeper comprehension of probiotic-host interactions on health and disease. Results: The structure of the gut microbiota in probiotic group A showed significant changes. Compared to the model group, the abundance of some beneficial bacteria had increased, including Actinobacteria (P=0.048), Lactobacillus (P=0.050), and Lactobacillus johnsonii (P=0.042), and many opportunistic pathogenic bacteria has decreased, such as Ruminococcus (P=0.001). Compared to the control group, the abundance of some beneficial bacteria had increased, including Fusobacteria (P=0.02) and Phascolarium (P=0.002), and there was a reduction in the abundance of many opportunistic pathogenic bacteria such as Roseburia (P=0.03), Lachnoclosterium (P=0.009), and Oscillibacter_sp_1-3 (P=0.002). In addition, metagenomic analysis showed that as well as an up-regulation of glycoside hydrolase expression, amino acid and inorganic ion transport, and metabolism-related pathways, there was a down-regulation of cell motility. Conclusions: Simultaneous administration of probiotics may have more positive implications in improving the gut microbiota of acute diarrhea rats.

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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.

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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.

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Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

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Aim: To assess the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with porcine small intestinal submucosa (SIS) on full-thickness skin injuries in rats. Methods: We established full-thickness skin injury models in Sprague-Dawley rats, dividing them into blank control, SIS, hUCMSCs and hUCMSCs combined with SIS. We monitored wound healing, scores and area, and analyzed inflammatory cells, microvessel density and collagen fibers after 12 days. Results: The blank group showed no healing, forming a scar of 0.6 × 0.5 cm2, while SIS and hUCMSCs groups exhibited incomplete healing with 0.4 × 0.5 cm2 scabs. Wound healing was significantly better in the hUCMSCs combined with the SIS group. Conclusion: Local application of hUCMSCs combined with SIS enhances full-thickness skin injury wound healing in rats.

Our skin protects us from infections and injuries, but severe damage can lead to health problems. In this study, we explored a promising new treatment to enhance skin healing. We used mesenchymal stem cells derived from umbilical cords in combination with a biological material called porcine small intestinal submucosa (SIS) to conduct experiemnts on rats with skin wounds. This treatment led to much better healing in rats with deep skin wounds compared with standard approaches. This approach is promising for treating severe skin injuries, offering hope for quicker recovery and better outcome, including faster recovery, reduced pain and inflammation and less scarring.

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BACKGROUND: The process of wound healing is complex, and expediting it remains a challenge. The advantages of extremely low frequency electric and magnetic fields (ELF-EMF) are its non-invasive treatment, promotes healing and promotes myogenesis of C2C12 cells. Epidermal growth factor (EGF) is known to play a vital role in promoting wound healing, so a combination of ELF-EMF and EGF can have far-reaching significance. OBJECTIVE: To study the effect of recombinant murine epidermal growth factor (rmEGF) combined with ELF-EMF on wound healing. METHODS: Thirty-six rats were randomly divided into three groups: normal control group, EGF group, and ELF-EMF+EGF group, and a 20 mm × 20 mm dorsal wound was made. The wound healing rate of rats was calculated on the 3rd, 7th, 11th and 15th day. HE staining was used to observe the micro-morphological changes during the wound healing process. RESULTS: The wound healing rate of EGF+ELF-EMF group was better than other groups. On the 15th day of wound healing, the wounds of each group were completely healed. On the 3rd, 7th, 11th and 15th day of HE staining, the early inflammatory cell infiltration, the arrangement of fibroblasts and the number of new capillaries in the wounds of EGF+ELF-EMF group were better than those of the other groups. CONCLUSIONS: rmEGF combined with ELF-EMF significantly promotes wound healing in SD rats.

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Background: This study investigated the IgG-specific humoral immune responses against specific antigen-like whole-cell antigen (WCA), outer membrane protein (OMP), periplasmic protein (PP), and cytoplasmic protein (CP) during the acute and subacute stages of Brucella abortus biotype 1 infection in Sprague Dawley (SD) rats. Materials and Methods: The intraperitoneal method was used to experimentally infect forty-four 6- to 8-week-old SD rats with 1 × 109 colony-forming units (CFUs) of B. abortus biotype 1. Following inoculation, the rat was serially sampled for serum at 0, 3, 7, 14, 21, 28, 35, 42, 60, 90, and 120 days. The IgG-specific immune responses and recognition of immunodominant antigens in WCA, OMP, PP, and CP of B. abortus were assessed by indirect enzyme-linked immunosorbent assay (IELISA) and western blot (WB) assay using infected rat sera. Results: The IgG antibody response was detectable at 3 days after infection. The peak serum IgG antibody titers were recorded against CP and PP at 28 days after infection. The highest serum IgG antibody titers were recorded at 42 days after infection against WCA and 90 days after infection only against OMP. WB assay revealed a wide array of protein bands between molecular weight of 13 and 95 kDa for WCA, 13 and 95 kDa for OMP, 15 and 65 kDa for PP, and 12 and 85 kDa for CP. Proteins bands of 10, 13, 20, 24, 46, and 76 kDa for WCA; 28, 35, 39, 85, and 95 for OMP; 20, 30, 40, 43, 46, and 65 kDa for PP, and 12, 23, 68, and 85 for CP were intensely recognized. Conclusion: Data of this study indicated that WCA, CP, and PP of B. abortus could be useful for diagnosis of acute and subacute brucellosis in SD rat model. OMP of B. abortus could be useful for differential diagnosis of subacute brucellosis.

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Periodontitis is an oral disease with the highest incidence globally, and plaque control is the key to its treatment. In this study, Microcin C7 was used to treat periodontitis, and a novel injectable temperature-sensitive sustained-release hydrogel was synthesized as an environmentally sensitive carrier for drug delivery. First, modified gelatin was formed from gelatin and glycidyl methacrylate. Then, Microcin C7-laden hydrogel was formed from cross-linking with double bonds between modified gelatin, N-isopropyl acrylamide, and 2-Methacryloyloxyethyl phosphorylcholine through radical polymerization, and the model drug Microcin C7 was loaded by electrostatic adsorption. The hydrogel has good temperature sensitivity, self-healing, and injectable properties. In vitro results showed that the hydrogel could slowly and continuously release Microcin C7 with good biocompatibility and biodegradability, with a remarkable antibacterial effect on Porphyromonas gingivalis. It also confirmed the antibacterial and anti-inflammatory effects of Microcin C7-laden hydrogel in a periodontitis rat model. The results showed that Microcin C7-laden hydrogel is a promising candidate for local drug delivery systems in periodontitis.

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Maternal immune activation (MIA), defined as elevated levels of inflammatory markers beyond the normal range, can occur due to psychological stress, infection, and other disruptions during pregnancy. MIA affects the immune system development in offspring and increases the risk of immune-related disorders. Limited studies have investigated the effects of prenatal stress on offspring's immune system. In this study, pregnant rats were exposed to chronic unpredictable mild stress (CUMS) during pregnancy, involving seven different stressors. We examined the impact of prenatal stress stimuli on the offspring's immune system and observed activation of the PI3K/Akt/NF-κB signaling pathway, resulting in an imbalance of Th17/Treg cells in the offspring's spleen. Our findings revealed increased plasma levels of corticosterone, IL-1ß, and IL-6 in female rats exposed to prenatal stress, as well as elevated serum levels of IL-6 and TNF-α in the offspring. Furthermore, we identified a correlation between cytokine levels in female rats and their offspring. Transcriptome sequencing and qPCR experiments indicated differentially expressed mRNAs in offspring exposed to prenatal stress, which may contribute to the imbalance of Th17/Treg cells through the activation of the Gng3-related PI3K/Akt/NF-κB pathway.

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Protein is the most important macro-nutrient when it comes to maximizing health, body composition, muscle growth, and recovery of body tissue. In recent years, it has been found that protein also plays an important role in metabolism and gut microbiota. This study was performed to investigate the effects of an isocaloric diet with different crude protein contents on the energy metabolism of Sprague-Dawley (SD) rats. Results revealed that compared with the 20% crude protein (CP; control) diet, the 38% CP diet improved serum parameters that are associated with dyslipidemia and glucose metabolic disorders in SD rats, whereas the 50% CP diet increased liver injury indicators and fatty acid synthesis-related genes and protein expression in the liver. Compared with the control diet, the 14% CP diet increased the abundance of colonic short-chain fatty acid-producing bacteria (Lachnospiraceae_NK4A136_group and Ruminiclostridium_9) and promoted colonic microbial cysteine and methionine metabolism, the 38% CP diet up-regulated colonic microbial lysine biosynthesis and degradation pathways, and the 50% CP diet down-regulated colonic mucosal cholesterol metabolism. Furthermore, the increase of multiple colonic enteropathogenic bacteria in the 50% CP group was associated with higher palmitic acid and stearic acid concentrations in the colonic microbes and lower cholesterol and arachidonic acid concentrations in the colonic mucosa. These findings revealed that the 14% CP and 38% CP diets improved rats' energy metabolism, while the 50% CP diet was accompanied by lipid metabolism imbalances and an increase in the abundance of multiple enteropathogenic bacteria.

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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.

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Background: This study aimed to determine the effects of Indomethacin (IMC) treatment on embryo implantation and histomorphology of uterus, ovary, and other vital organs and its effective dosage in establishing embryo implantation dysfunction model in Sprague-Dawley (SD) rats. Materials and Methods: The experiments were performed on 24 (6 × 4 groups) adult female SD rats aged 12 weeks old. G1 was the control group and received a normal diet with normal saline. However, on pregnancy days 3 (Pd3) and 4 (Pd4), G2, G3, and G4 were given normal saline and subcutaneously administered IMC twice daily at different doses of 4.33, 4.66 and 5.00 mg/kg body weight, respectively. The rats were euthanized on day 8 of pregnancy (Pd8). The uterus was excised and examined for signs of pregnancy, followed by tissue samples from liver, kidney, and ovary (for histomorphological examination using haematoxylin and eosin stain). Results: All IMC treatment doses disrupted the implantation process and caused a significant reduction in embryo development. Analysis for histopathological changes revealed that IMC doses above 4.33 mg/kg body weight caused more adverse reproductive health effects in rats. Vasoconstriction and micro vascularization were detected in the liver, while degenerative Bowman's capsules and inflammatory cells were observed in kidney sections from IMC-treated rats. Conclusion: IMC therapy interfered with implantation and embryo development in rats, resulting in significant uterine vasoconstriction and atrophy, 4.33 mg/kg bwt dose appeared to be optimum to establish embryo implantation dysfunction in SD rats.

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Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated-dose toxicity of Hu7691 in male and female Sprague Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg/day, while female rats received doses of 12.5, 25, 50, and 75 mg/kg/day for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg/day. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg/day, while for female animals, it should be less than 50 mg/kg/day.

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A short synthetic peptide from the C-terminal part of the caveolin-3 structure was tested for experimental autoimmune encephalomyelitis (EAE) treatment in rats. The structure-function similarity established between the novel synthetic peptide of pCav3 and the well-known immunomodulator immunocortin determined pCav3's ability to reduce EAE symptoms in Dark Agouti (DA) rats injected with pCav3 (500 µg/kg). pCav3 was found to interfere with the proliferation of lymphocytes extracted from the LNs of DA rats primed with homogenate injection, with IC50 = 0.42 µM (2.35 mcg/mL). pCav3 affected EAE in a very similar manner as immunocortin. The high degree of homology between the amino acid sequences of pCav3 and immunocortin corresponded well with the therapeutic activities of both peptides, as demonstrated on EAE. The latter peptide, possessing a homologous structure to pCav3, was also tested on EAE to explore whether there were structural restrictions between these peptides implied by the MHC-involved cell machinery. Consequently, immunocortin was further examined with a different autoimmune disease model, collagen-induced arthritis (CIA), established in Sprague-Dawley rats. CIA was established using an intentionally different genetic platform than EAE. Based on the results, it was concluded that the effectiveness of pCav3 and immunocortin peptides in EAE rat model was almost identical, but differed in the rat model of rheumatoid arthritis; thus, efficacy may be sensitive to the MHC type of animals used to establish the autoimmune disease model.

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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.

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As an alternative to octabromodiphenyl ether (octa-BDE), 1, 2-bis (2,4, 6-tribromophenoxy) ethane (BTBPE) has been widely used in a variety of combustible materials, such as plastics, textiles and furniture. Previous studies have demonstrated the thyroid toxicity of traditional brominated flame retardants for example octa-BDE clearly. Nevertheless, little is known about the thyroid toxicity of alternative novel brominated flame retardants BTBPE. In this study, it was demonstrated that BTBPE in vivo exposure induced FT4 reduction in 2.5, 25 and 250 mg/kg bw treated group and TT4 reduction in 25 mg/kg bw treated group. TG, TPO and NIS are key proteins of thyroid hormone synthesis. The results of Western blot and RT-PCR from thyroid tissue showed decreased protein levels and gene expression levels of TG, TPO and NIS as well as regulatory proteins PAX8 and TTF2. To investigate whether the effect also occurred in humans, anthropogenic Nthy-ori 3-1 cells were selected. Similar results were seen in vitro condition. 2.5 mg/L BTBPE reduced the protein levels of PAX8, TTF1 and TTF2, which in turn inhibited the protein levels of TG and NIS. The results in vitro experiment were consistent with that in vivo, suggesting possible thyrotoxic effects of BTBPE on humans. It was indicated that BTBPE had the potential interference of T4 generation and the study provided more evidence of the effects on endocrine disorders.

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BACKGROUND: Each eccrine sweat gland (ESG) is a single-tubular structure with a central lumen, and the formation of hollow lumen in the initial solid cell mass is a key developmental process. To date, there are no reports on the mechanism of native ESG lumen formation. METHODS: To investigate the lumen morphogenesis and the lumen formation mechanisms of Sprague-Dawley (SD) rat ESGs, SD rat hind-footpads at E20.5, P1-P5, P7, P9, P12, P21, P28 and P56 were obtained. The lumen morphogenesis of ESGs was examined by HE staining and immunofluorescence staining for polarity markers. The possible mechanisms of lumen formation were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay and autophagy marker LC3B immunofluorescence staining, and further explored by ouabain intervention experiment. RESULTS: In SD rat ESGs, the microlumen was formed at P1, and the small intact lumen with apical-basal polarity appeared at P3. The expression of apical marker F-actin, basal marker Laminin, basolateral marker E-cadherin was consistent with the timing of lumen formation of SD rat ESGs. During rat ESG development, apoptosis and autophagy were not detected. However, inhibition of Na+-K+-ATPase (NKA) with ouabain resulted in decreased lumen size, although neither the timing of lumen formation nor the expression of polarity proteins was altered. CONCLUSIONS: Epithelial polarity-driven membrane separation but not cavitation regulates lumen formation of SD rat ESGs. NKA-regulated fluid accumulation drives lumen expansion.

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Cadmium (Cd) is a toxic element that can negatively affect both humans and animals. It enters the human and animal bodies through the respiratory and digestive tracts, following which it tends to accumulate in different organs, thereby seriously affecting human and animal health, as well as hampering social and economic development. Cd exposure can alter the composition of intestinal microbiota. In addition, it can damage the peripheral organs by causing the translocation of intestinal microbiota. However, the relationship between translocation-induced changes in the composition of microbiome in the blood and metabolic changes remains unclear. In the present study, we investigated the effects of Cd exposure on microbiota and serum metabolism in rats by omics analysis. The results demonstrated that Cd exposure disrupted the balance between the blood and intestinal flora in Sprague-Dawley (SD) rats, with a significant increase in gut microbiota (Clostridia_UCG_014, NK4A214_group) and blood microbiome (Corynebacterium, Muribaculaceae). However, Cd exposure caused the translocation of Corynebacterium and Muribaculaceae from the gut into the blood. In addition, Cd exposure was associated with the up-regulation of serum indoxyl sulfate, phenyl sulfate, and p-cresol sulfate; down-regulation of δ-tocopherol and L-glutamine; and changes in blood microbiome and metabolites. In conclusion, we identified novel metabolic biomarkers for Cd toxicity, which will also expand our understanding of the role of blood microbiome in Cd-induced injury.

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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.

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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.

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