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Osteoporosis (OP) represents a global health challenge. Certain functional food has the potential to mitigate OP. Honeysuckle (Lonicera japonica) solution has medicinal effects, such as anti-inflammatory and immune enhancement, and can be used in functional foods such as health drinks and functional snacks. The composition of honeysuckle changed significantly after fermentation, and 376 metabolites were enriched. In this study, we used dexamethasone to induce OP in the rat model. Research has confirmed the ability of FS (fermented Lonicera japonica solution) to enhance bone mineral density (BMD), repair bone microarchitectural damage, and increase blood calcium levels. Markers such as tartrate-resistant acid phosphatase-5b (TRACP-5b) and pro-inflammatory cytokines (TNF-α and IL-6) were notably decreased, whereas osteocalcin (OCN) levels increased after FS treatment. FS intervention in OP rats restored the abundance of 6 bacterial genera and the contents of 17 serum metabolites. The results of the Spearman correlation analysis showed that FS may alleviate OP by restoring the abundance of 6 bacterial genera and the contents of 17 serum metabolites, reducing osteoclast differentiation, promoting osteoblast differentiation, and reducing the inflammatory response. This study revealed that Lactobacillus plantarum-fermented honeysuckle alleviated OP through intestinal bacteria and serum metabolites and provided a theoretical basis for the development of related functional foods. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) represents a global health challenge. Certain functional food has the potential to mitigate OP. Honeysuckle (Lonicera japonica) solution has medicinal effects, such as anti-inflammatory and immune enhancement, and can be used in functional foods such as health drinks and functional snacks. The composition of honeysuckle changed significantly after fermentation, and 376 metabolites were enriched. In this study, we used dexamethasone to induce OP in the rat model. Research has confirmed the ability of FS (fermented Lonicera japonica solution) to enhance bone mineral density (BMD), repair bone microarchitectural damage, and increase blood calcium levels. Markers such as tartrate-resistant acid phosphatase-5b (TRACP-5b) and pro-inflammatory cytokines (TNF-α and IL-6) were notably decreased, whereas osteocalcin (OCN) levels increased after FS treatment. FS intervention in OP rats restored the abundance of 6 bacterial genera and the contents of 17 serum metabolites. The results of the Spearman correlation analysis showed that FS may alleviate OP by restoring the abundance of 6 bacterial genera and the contents of 17 serum metabolites, reducing osteoclast differentiation, promoting osteoblast differentiation, and reducing the inflammatory response. This study revealed that Lactobacillus plantarum-fermented honeysuckle alleviated OP through intestinal bacteria and serum metabolites and provided a theoretical basis for the development of related functional foods.

Pentachlorophenol (PCP), a ubiquitous environmental pollutant, has been reported as a possible contributor to diabetes. However, evidence for general population is scarce while related mechanisms are largely unknown. Using a representative population-based case-control study in Beijing (n = 1796), we found a positive association between PCP exposure and diabetes risk with the odds ratio reaching 1.68 (95 % confidence interval: 1.30 to 2.18). A further rat experiment revealed that low-dose PCP mimicking real-world human exposure can significantly impair glycemic homeostasis by inducing pancreatic β-cell dysfunction, with non-linear dose-response relationships. Subsequent multi-omics analysis suggested that low-dose PCP led to notable gut microbiota dysbiosis (especially the species from genus Prevotella , such as intermedia, dentalis, ruminicola, denticola, melaninogenica, and oris), decreased serum amino acids (L-phenylalanine, L-tyrosine, and L-tryptophan) and increased serum fatty acids (oleic and palmitic acid) in rats, while strong correlations were observed among alterations of gut microbes, serum metabolites and glycemic-related biomarkers (e.g., fasting blood glucose and insulin). Collectively, these results imply PCP may increase diabetes risk by disrupting gut microbial-related amino acids and fatty acids biosynthesis. This will help guide future in-depth studies on the roles of PCP in the development of human diabetes. [Display omitted] • Epidemiological study reveals a positive correlation between PCP and diabetes risk. • Human exposure doses of PCP significantly impair glycemic homeostasis in rats. • Impairment of β-cell secretory function may underlie PCP-induced hyperglycemia. • PCP destroys gut microbiota balance and perturbs amino/fatty acids metabolism. [ABSTRACT FROM AUTHOR]

Previous studies suggest that exposure to thiamethoxam (TMX) may cause adverse effects to human. However, the distribution of TMX in various organs of human body and the associated risk are little-known. This study aimed to explore the distribution of TMX in human organs by extrapolation from a toxicokinetic experiment in rats and to assess the associated risk based on literature data. The rat exposure experiment was performed using 6-week female SD rats. Five groups of rats were oral-exposed to 1 mg/kg TMX (water as solvent) and executed at 1 h, 2 h, 4 h, 8 h and 24 h after treatment, respectively. The concentrations of TMX and its metabolites in rat liver, kidney, blood, brain, muscle, uterus and urine were measured in different time points using LC-MS. Data on concentrations of TMX in food, human urine and blood as well as human cell-based in vitro toxicity of TMX were collected from the literature. After oral exposure, TMX and its metabolite clothianidin (CLO) were detected in all organs of the rats. The steady-state tissue-plasma partition coefficients of TMX for liver, kidney, brain, uterus and muscle were 0.96, 1.53, 0.47, 0.60 and 1.10, respectively. Based on literature analysis, the concentration of TMX in human urine and blood for general population were 0.06–0.5 ng/mL and 0.04–0.6 ng/mL, respectively. For some people, the concentration of TMX in human urine reached 222 ng/mL. By extraplation from rat experiment, the estimated concentrations of TMX in human liver, kidney, brain, uterus and muscle for general population were 0.038–0.58, 0.061–0.92, 0.019–0.28, 0.024–0.36 and 0.044–0.66 ng/g, respectively, well below the relevant concentrations for cytotoxic endpoints (HQs ≤ 0.012); however, for some people they could be up to 253.44, 403.92, 124.08, 158.40 and 290.40 ng/g, respectively, with very high developmental toxicity (HQ = 5.4). Therefore, the risk for highly exposed people should not be neglected.

First, the bioinformatics database was used to predict the potential targets and signaling pathways of pulmonary fibrosis (PF) leading to erectile dysfunction (ED), and bleomycin sulfate was used to create a PF rat model. Then, enzyme‐linked immunosorbent assay (ELISA), Western blotting, Real‐time fluorescent quantitative reverse transcription polymerase chain reaction (RT‐qPCR) were used to detect the expression of sex hormones and related proteins and mRNA, and Hematoxylin and eosin (H&E) staining was used to compare the pathological changes of penile tissue. The results showed that, compared with group A, cyclic guanosine phosphate (cGMP) content in group B decreased, protein kinase CGMP‐dependent 1(PKG1) and nitric oxide synthase 3 (eNOS) protein and mRNA expression were down‐regulated, and phosphodiesterase 5A (PDE5A) protein and mRNA expression was up‐regulated (p <.05); the penile tissue of rats in group B had pathological damage. And there was no change in sex hormone‐related indicators in the two groups (p >.05). Therefore, PF inhibits erectile function by inhibiting the cGMP‐PKG pathway and reducing the expression of eNOS and PKG1 protein and mRNA. And by up‐regulating the expression of PDE5A to impair erectile function. [ABSTRACT FROM AUTHOR]

The effects of liposome‐encapsulated hemoglobin with high O2 affinity (h‐LEH), an artificial O2 carrier in skeletal muscle, were studied by in situ fatigue resistance test in fast‐type plantaris (PLT) and slow‐type soleus (SOL) muscles with or without ischemia in the rat. The distal tendons of PLT and SOL muscles were isolated in situ and individually attached to the force transducers to record the developed tension in response to stimuli (80 Hz tetanus train, 1.5 minutes) to the ipsilateral sciatic nerve. The fatigue resistance test (five sets separated by 2‐minute rests) was evaluated in terms of tension attenuation (fatigue) from the initial to the last tension (A) during each set, attenuation of the initial (B) or last tension (C) in each set, as compared to the first set in the presence or absence of ischemia or h‐LEH (10 mL/kg). While ischemia significantly enhanced fatigue only in PLT, h‐LEH showed no effect regardless of the perfusion pattern (normal/ischemia) or muscle‐type (PLT/SOL) during each set (A). In parameter (B), set‐by‐set fatigue development was observed in PLT, whereas h‐LEH‐SOL showed a trend of advanced fatigue resistance. Such trends became clear in the parameter C (last tension), because h‐LEH‐SOL exerted, rather than decreased, the tension enhancement regardless of the presence or absence of ischemia, whereas there were no h‐LEH effects in PLT. In addition, faster recovery of the nicotinamide adenine dinucleotide content in the muscle after 10 minutes of all fatigue tests was observed in h‐LEH‐SOL, while saline‐SOL still showed a significantly higher value than that of control. These results suggested that additional O2 supply by h‐LEH may accelerate the tricarboxylic acid cycle/electron transport chain in slow‐type aerobic SOL muscle containing abundant mitochondria and contribute to the faster removal of muscle fatigue substances such as lactate. [ABSTRACT FROM AUTHOR]

[Display omitted] • The tissue-plasma partition coefficients of TMX for organs in rats were obtained. • The concentrations of TMX in human organs were extrapolated from the rat experiment. • The hazard quotients were low for general population but high for particular person. Previous studies suggest that exposure to thiamethoxam (TMX) may cause adverse effects to human. However, the distribution of TMX in various organs of human body and the associated risk are little-known. This study aimed to explore the distribution of TMX in human organs by extrapolation from a toxicokinetic experiment in rats and to assess the associated risk based on literature data. The rat exposure experiment was performed using 6-week female SD rats. Five groups of rats were oral-exposed to 1 mg/kg TMX (water as solvent) and executed at 1 h, 2 h, 4 h, 8 h and 24 h after treatment, respectively. The concentrations of TMX and its metabolites in rat liver, kidney, blood, brain, muscle, uterus and urine were measured in different time points using LC-MS. Data on concentrations of TMX in food, human urine and blood as well as human cell-based in vitro toxicity of TMX were collected from the literature. After oral exposure, TMX and its metabolite clothianidin (CLO) were detected in all organs of the rats. The steady-state tissue-plasma partition coefficients of TMX for liver, kidney, brain, uterus and muscle were 0.96, 1.53, 0.47, 0.60 and 1.10, respectively. Based on literature analysis, the concentration of TMX in human urine and blood for general population were 0.06–0.5 ng/mL and 0.04–0.6 ng/mL, respectively. For some people, the concentration of TMX in human urine reached 222 ng/mL. By extraplation from rat experiment, the estimated concentrations of TMX in human liver, kidney, brain, uterus and muscle for general population were 0.038–0.58, 0.061–0.92, 0.019–0.28, 0.024–0.36 and 0.044–0.66 ng/g, respectively, well below the relevant concentrations for cytotoxic endpoints (HQs ≤ 0.012); however, for some people they could be up to 253.44, 403.92, 124.08, 158.40 and 290.40 ng/g, respectively, with very high developmental toxicity (HQ = 5.4). Therefore, the risk for highly exposed people should not be neglected. [ABSTRACT FROM AUTHOR]

We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6–24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40–50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., “O” type of hyperintense rim in group I and “C” type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA. [ABSTRACT FROM AUTHOR]

Phytoestrogen isoflavones (IFs) are considered to suppress estrogen-related cancers through their antiestrogenic activity. The antioxidant effect of IFs, however, has not been confirmed in an in vivo system, so suppression of hydroperoxide formation and resultant DNA adduct formation were studied. The antioxidant effects of the soya-hypocotyl tea (SHT), which contained daidzein (14+/−1.5 mg/l) and genistein (3+/−0.5 mg/l), were examined in Wistar rats fed the AIN-76 control diet or iron deficient diet (FeD) for 4 weeks. The intake amount of the diet and IFs were measured daily. Urinary excretion of IFs was measured for 3 days before sacrifice. In addition to the serum lipid analyses, phosphatidylcholine hydroperoxide (PCOOH), and phosphatidylethanolamine hydroperoxide (PEOOH) production in red blood cells and the liver were measured as a biomarker of oxidants. Production of DNA adducts by oxidative stress was measured by the amount of 8-hydroxy-2′-deoxyguanosine (oh8dG) in the liver and kidney, and urine. Histological changes were checked by H&E staining and immunohistochemistry for oh8dG. FeD rats showed anemia, growth retardation, hyperlipidemia. IFs only lowered the triacylglycerol level and did not change the cholesterol level. Rats fed the normal diet did not show suppression of PCOOH and PEOOH production in either red blood cells or the liver, while groups administered SHT showed suppressed production of PCOOH and PEOOH in the liver. The cumulative intake of daidzein, genistein and the total amount of IFs showed significant inverse associations with urinary excretion of oh8dG. oh8dG in the kidney showed an inverse association with the amount of oh8dG in the urine. Enzymehistochemically, a strong localization of oh8dG was found in the epithelial cells of the bile canaliculi and proximal tubules of the kidney. IFs and SHT showed antioxidant effects at physiological concentrations in an in vivo system. The antioxidant effects of IFs decreased oxidation stress to the nuclear DNA, which was shown by the decreased oh8dG production. It is suggested that to prevent various cancers, in addition to the known antiestrogenie, antityrosin kinase, and other effects. IFs appeared to promote excretion of oh8dG. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effect of bovine bone mineral placement as an adjunct to a guided bone regeneration (GBR)-barrier in experimental bone augmentation. Some 18 Sprague-Dawley rats underwent flap surgery in which non-permeable silicone domes were placed on the calvaria. A test group of 9 animals received domes filled with cancellous deproteinized bovine bone mineral (Bio-Oss®). The domes of 9 control animals were left empty. The experiment was terminated after 8 weeks of healing. Inspection after histologic preparation found no signs of any foreign body reaction to the implanted bovine bone mineral, which seemed to be well integrated with the augmented tissue. The control specimens healed uniformly with new bone inside the domes at the base of the calvaria. The tissue inside the domes of the test specimens had a completely different architecture with new bone both at the base of the calvaria and at a distance from the base, surrounded by and in close contact with non-mineralized tissue and remaining bovine bone mineral. Some ingrowth of soft connective tissue, most likely from the sagittal skull suture could be seen in most test and control specimens. Histomorphometric analysis revealed that the total amount of augmented tissue was significantly greater in the test group (x=1.93±O.21 mm2) than in the control group (x=0.99±0.22 mm2), P<0.00l). The control domes contained 0.73±0.28 mm2 augmented bone, while the corresponding value for the test specimens was 0.35±0.13 mm2, significantly less than the controls (P<0.01). The test domes contained 0.83±0.15 mm2 newly-formed non-mineralized calvarial tissue, significantly more than the controls (x=0.26±0.16 mm2), P<0.00l). Remaining particles of bovine bone mineral constituted 0.76±0.14 mm2, or 39%, of the total amount of augmented tissue in the test group. A considerable... [ABSTRACT FROM AUTHOR]

Decamethylcyclopentasiloxane (D5) is a cyclic siloxane used in the production of industrial and consumer products. Four groups of 60 Fischer-344 female rats were analyzed for uterine endometrial adenocarcinoma (inhalation study with exposure levels in ppm/number of observed cases: 0/0, 10/1, 40/0, and 160/5) by exact regression (logistic, Poisson), the max poly-3 trend test, and a random effects probit model. When comparing the 160 ppm group to controls after 24 months, the incidence of adenocarcinomas was elevated (borderline significant); it was significant when all exposure levels were included. Four sets of (historical) control groups were formed, with varying heterogeneity. The effect of D5 was either significant or borderline significant when comparing all control sets to the 160 ppm group. When considering all exposure groups using any of the analysis methods, a significant effect was observed when the high dose group was included in the analysis; the effect was not significant when the high dose group was not included. The evidence tends to support the conclusion that D5 at the highest dose level (160 ppm) results in an increased incidence of adenocarcinomas. However, it is important to verify any potential effect through a biological investigation. [ABSTRACT FROM AUTHOR]

Background: Human amniotic membranes (HAMs) are assumed to have a number of unique characteristics including durability, hypoallergenic and anti-inflammatory properties. Materials and Methods: Multilayer HAMs from caesarian sections were applied to repair defined bladder defects in male Sprague-Dawley rats. The animals were sacrificed at 7, 21 and 42 days after implantation. Bladder volume capacity after grafting was measured. Histological analyses were performed to asses a number of parameters including HAM degradation, inflammatory reaction, graft rejection and smooth muscle ingrowth. Results: One rat died from sepsis in the treated group. No severe complications or signs of leakage were observed. Bladder capacity did not change over time. The initially increased inflammation in the HAM group diminished significantly over time (p<0.05). No signs of HAM degradation were observed and smooth muscle staining increased over time. Conclusions: HAMs appear to be durable and hypoallergenic grafts. The assumed suitability for the reconstruction of urinary tract justifies further research on detailed immunological process in larger grafts., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.